[{"title": "emdn_eudamed_nomenclature_en.pdf.txt", "text": "Medical Devices                January 2020  \nDG Health and Food Safety   \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \n \n \nPage 1 of 1 \n The European Medical Device  Nomenclature (EMDN)  \nThe European Medical Device Nomenclature (EMDN) will be the nomenclature of use by \nmanufacturers when registering their medical devices in the EUDAMED  database.  \nFounded on  pre-established criteria and requirements1 and based on orientations provided by \nthe Medical Device Coordination Group  (MDCG) , the European Commission decided in \nfavour of the use of the \u2018Classificazione Nazionale Dispositivi medici  (CND)\u20192 as the basis \nfor the EMDN . \nCurrently, a n extrao rdinary revision of the CND is ongoing so that  to release the first version \nof the EMDN, which will be i ntegrated in EUDAMED  for use by operators. The EMDN will \nbe fully available and accessible to any operators and will be copyright free.  \nTo the extent possible, t he Commission will map the EMDN to the G lobal Medical Device \nNomenclature (GMDN) . This task has been undertaken with th e hopes of  possibly facilitating \nEMDN code search by operators current ly using  GMDN . The correspondence between the \nnomenclatures is intended to be visible to operators and incorporated in the future database in \nthe form of a searching tool. Therefore, and  in cooperation with GMDN, t he mapping \nexercise is currently ongoing . The level of quality and reliability of this mapping is dependent \non the commitment of all relevant parties to work together in ma pping and validating the \nresult s.     \nA sub -group of the  MDCG on nomenclature which includes experts from National \nCompetent Authorities and stakeholders has been established to oversee  regulatory activities \nlinked to nomenclature . The sub -group will aim to define the rules and processes related to \nthe creation, update , maintenance and  use of  the European Medical Device  Nomenclature.  \nAdditionally, t he Commission is currently collaborating  with the World Health Organisation \n(WHO ) in the context of their work  and activities on a future international medic al device \nnomenclature.  \n                                                 \n1 (MDCG 2018 -2) \u2013 Future EU medical device nomenclature: Description of requirements  \n2 CND is currently used in Italy, Portugal and Greece."}, {"title": "FAQ_MDR_180117_V1.0-1.pdf.txt", "text": "Page 1 of 13 \n \nCAMD Transition Sub Group  \nFAQ \u2013 MDR Transitional provisions  \nDisclaimer : \nThe information presented in this document is for the purpose of general information only and is not intended to represent legal advice to any individual \nor entity. It reflects  the outcome of discussions within the Transition Sub Group (TSG) of the CAMD (established in May 2017) to establish \nrecommendations on the interpretation of transition -related provisions. It is not intended to be a guidance document . We recommend that you should \nobtain  your own legal advice before taking any action based on information given here. The content of this FAQ table will be updated cont inuously. While \nwe strive to provide the following information in as timely and accurate a manner as possible , this document does not make any claims or guarantees \nabout the accuracy, completeness or sufficiency of its contents. Participants of the Transit ion Sub Group, authors and reviewers of this document \nexpressly disclaim liability for any errors and omissions in the contents.  \n  \nPage 2 of 13 \n Glossary:  \n\u2022 AIMDD/MDD compliant device = device that is compliant with Directive 90/385/EEC/ Directive 93/42/EEC  \n\u2022 AIMDD/MDD certificates = certificates in accordance with Directive 90/385/EEC/ Directive 93/42/EEC  \n\u2022 DoA = date of application  of the MDR  \n\u2022 MDR = Medical Device Regulation (EU) 2017/745  \n\u2022 MDR compliant de vice = device that is compliant with the MDR  \n\u2022 MDCG = Medical Device Coordination Group  \n\u2022 MFR = manufacturer  \n\u2022 PRRC = person responsible for regulatory compliance  \n\u2022 NB = notified body  \n\u2022 \u201cold\u201d NB = NB that has issued an AIMDD/MDD certificate  \n\u2022 The Directives = Directives 90/385/EEC, 93/42/EEC  \nDocument History  \nVersion  Publication  Note  \nV1.0 17/01/18  Original publication  \n   \n   \n   \nConten ts: \nI - Issue: Transition in general  ................................ ................................ ................................ ................................ ................................ ..............................  3 \nII - Issue: Placing on the market of MDR compliant devices until 26 May 2020 (Art. 120 para 5 -7 MDR)  ................................ ................................ .............  4 \nIII - Issue: Placing on the market of devices in conformity with the Directives after 26 May 2020 (Art. 120 para 2 -3 MDR)  ................................ .................  7 \nIV - Issue: The so called \u201csell off\u201d provision of Art. 120 para 4 MDR  ................................ ................................ ................................ ................................ .. 11 \nV \u2013 Issue: EUDAMED and its relevance for the application of certain provisions of the MDR (Art. 123 para 3 d and e, Art. 120 para  8, Art. 122 MDR)  .... 12 \n \n   \nPage 3 of 13 \n  \nI - Issue: Transition in general  \n1 Question:  When does the Medical Devices Regulation (EU) 2017/745 (= MDR) apply?  \n Answer:  The MDR shall apply from 26 May 2020 (= date of application (DOA)) , see Art. 123 para 2  MDR .  \nThere are however exceptions to  that general rule. Some provisions apply earlier (e.g. regarding notified bodies or the \nMedical Device Coordination Group), some later (e.g. regarding UDI labelling). For the exceptions,  see Art. 123 para 3  \nMDR (earlier application: a -c, i; p ostponed application: d \u2013h). \n \n   \n2 Question:  When do the Directives 90/385/EEC , and 93/42/EEC [= the Directives] cease to apply ? \n Answer:  In general  the Directives 90/385/EEC and 93/42/EEC are repealed  with effect from 26 May 2020 (= DoA), see Art. 122  \nMDR . However there are some exceptions , e.g.  \n\u2022 in order to deal with devices that are compliant with the Directives or  \n\u2022 to serve as a \u201cback up\u201d in case EUDAMED is not fully functional at DoA  \n(see Art. 122 MDR).  \n   \n3 Question:  What is  the applicable legislation until  26 May 2020 (= DoA )? \n Answer:  Laws and regulations adopted by Member States in accordance with the Directives (= Directives regime). There are \nhowever exceptions (see for example Art. 123 para 3 a \u2013 c, i MDR and Art. 120 para 5 and 6  MDR ). \n   \n   \nPage 4 of 13 \n II - Issue: Placing on the market of MDR compliant  devices until 26 May 2020 (Art. 120 \npara 5 -7 MDR)  \n4 Question:  Is it possible to place a device, which is compliant with the MDR (= MDR compliant  \ndevice ), on the market prior to 26 May 2020  (= DoA) ? \n Answer:  Yes, see Art. 120 para 5 MDR.  \nManufacturer s (= MFR ) are \u2013 until 26 May 2020  (= DoA)  normally required to place devices on the market that comply with \nthe Directives  (= AIMDD/MDD compliant devices) , however Art. 120 para 5 MDR offers the option  to place MDR compliant \ndevices on the market before  DoA.  \n \n   \n5 Question:  Is it possible for all types  of devices  (for all different risk classes I \u2013 III) compliant with the MDR (= MDR compliant device) \nto be placed on the market prior to 26 May 2020  (according to Art. 120 para 5 MDR )? \n \n Answer:  Yes, all types  of devices  - regardless of their risk class \u2013 may be placed on the market according to Art. 120 para 5 MDR. \nThis includes for example custom made devices  (Art. 2 para 3  MDR ) and system s and procedure packs  (Art. 2 para 10  and \npara 11  MDR).  \nHowever , devices being subject to the \u201cclinical evaluation consultation procedure\u201d according to Art. 54 MDR (= certain \nclass III and class IIb devices) may not be placed on the market in ac cordance with Article 120 para 5 MDR  before  the \nMedical Device Coordination Group ( MDCG ) and the expert panels have been  established  (see Art. 120 para 7 MDR) . \nDepending on the risk class of the device, conformity assessment may requir e the involvement of a NB designated and \nnotified in accordance with the MDR  (see Art. 120 para 6 MDR). In this c ase, such devices cannot complete a  \nconformity assessment, and therefore may not be placed on the market, before  NBs have been designated and notified \nunder the MDR.  \n    \nPage 5 of 13 \n 6 Question:  As a MFR , which obligations of the MDR  do I need to fulfil in order to place  a MDR compliant  device on the market  \nbefore  the DoA according to Art. 120 para 5 MDR?  \n Answer:  As many obligations as are possible , while taking into account that   \n\u2022 EUDAMED is not fully functional and  \n\u2022 the MDR is not fully applicable  \nat that point in time .  \n \nGenerally speaking, that is to say that:  \n\u2022 first, the device  as such needs to be MDR compliant (see Annex I) and  \n\u2022 second, the  MFR  has to comply with the MDR.  \nIn particular, the MFR shall undertake an assessment of the conformity of that device in accordance with the \napplicable conformity assessment procedures set out in Art. 52 MDR . This may, depending on the risk class of the \ndevic e, necessitate the involvement of a notified body designated and notified in accordance with the MDR  (see Art. 120 \npara 6 MDR).  \n \nThe following requirements of the MDR  need to be fulfilled by t he MFR (non -exhaustive list) : \n\u2022 clinical evaluation  \n\u2022 risk management  \n\u2022 QMS  \n\u2022 Post-market surveillance  \n\u2022 Technical documentation and other reports  \n\u2022 Liability for defective devices  \n  \nPage 6 of 13 \n However, exceptions /adaptations  are possible /necessary , particularly due to the fact that EUDAMED may not  be fully \nfunctional before  the DoA . For example : \n \n\u2022 in the absence of a fully functional EUDAMED some requirements of the Directives  shall \u2013 where necessary - \napply in place of the relevant provisions of the Regulation (e.g. registration of d evices and economic operators).  \n \n\u2022 A person responsi ble for regulatory compliance  (PRRC, Art. 15 MDR) needs to be available  but not \nnecessarily registered until EUDAMED is available . . \n \n\u2022 The assignment of an UDI (Art. 27 para 3 MDR)   \nis not possible as long as there are  \n- no issuing entities  designated by the Commission according to Art. 27 para 2 MDR  or  \n- as long as the legal fiction according to Art. 120 para 12 does not apply (it shall apply from 26 May 2019 , see Art. \n123 para 3 i MDR ).  \nIt is of no significant use as long as there is no UDI database .  \n \n\u2022 An implant card and the information according to Art. 18 MDR  need to be provided, however without the UDI \nrelated content  (as the requirement to place the UDI carrier on the devices will be stepwise  introduced after the \nDoA).  \n   \n7 Question:  Are MDR compliant devices  placed on the market according to Art . 120 para 5 MDR subject to the so called \u201csell off\u201d \nprovision  in Art. 120 para 4 MDR (see below)?  \n Answer  No, the possibility of their being made available/put into service is not time-limited.  \n   \n  \nPage 7 of 13 \n III - Issue: Placing on the market of devices in conformity with the Directives  after 26 \nMay 2020 (Art. 120 para 2 -3 MDR)  \n8 Question:  Do certificates  issued by notified bodies in accordance with the Directives  (= AIMDD/MDD certificates ) prior to 25 May \n2020 remain valid after the DoA?  \n Answer:  Yes, as specified in Art. 120 para 2 MDR.  \nIn general , they remain valid until the end of the period indicated on the certificate. Certain AIMDD/MDD certificates (Annex \n4/IV, refer to Art. 120 para 2 first sentence MDR) become void at the latest on 27 May 2022, others (refer to Art. 120 para 2  \nsecond sentence  MDR) on 27 May 2024 at the latest. In other words, after 27 May 2024 there will be no more valid \nAIMDD/MDD certificates.   \n   \n9 Question:  What  kind of certificates remain valid  according to Art. 120 para 2 MDR?  \n Answer:  All certificates which are commonly issued by Notified Bodies  with reference to the Council Directives MDD and AIMDD.  \nThat is [see for example NBOG BPG 2010 -3, similar NB-MED/2.5. 1Rec 4]:  \n\uf02d EC Design -Examination Certificate  \n(Annex II section 4 MDD, Annex 2, section 4 AIMD)   \n\uf02d Certificate of Conformity  \n(Annex IV MDD, Annex 4 AIMD)  \n\uf02d EC Type Examination Certificate   \n(Annex III MDD; Annex 3 AIMD)  \n\uf02d EC Certificate Full Quality Assurance System  \n(Annex II excluding section 4  MDD; Annex 2 section 2 AIMD)  \n\uf02d EC Certificate Production Qualit y Assurance  \n(Annex V MDD, Annex 5 AIMD)   \nPage 8 of 13 \n \uf02d EC Certificate Product Quality Assurance System  \n(Annex VI MDD)  \n   \n10 Question:  May a \u201c declaration of conformity \u201d be considered as a \u201ccertificate\u201d  according  Art.120 para 2 MDR?  \n Answer:  No, since it is not a certificate issued by a NB.  \n   \n11 Question:  Is it possible for a MFR to have valid MDR and valid AIMDD/MDD certificates in parallel  until the 27 May 2024 expiry \ndate? \n Answer:  Yes.  \n   \n12 Question:  May devices, that are compliant with the Directives  (= MDD/AIMDD compliant devices ), be placed on the market/put into \nservice after 26 May 2020  (= DoA) ? \n Answer:  Yes, under certain conditions  (see answer on question 1 7) as specified in Art. 120 para 3 MDR.  \n \nIn general , after 26 M ay 2020 , devices need to comply with the MDR  in order to be placed on the market/put into service  \n(see Art. 5 MDR) . However , for a limited time (depending on the validity of the MDD/AIMDD  certificates) there is the option  \nto continue to place devices on the market  that are compliant with the Directives. Making use of this option  may postpone \nthe immediate need for a new certificate under the MDR.  \n   \n13 Question:  May MFR s of class I devices , that are compliant with the Directives , make use of the derogation in  Art. 120 para 3 \nMDR (= be placed on the market after the DoA)?  \n Answer:  No, they must comply with the MDR , unless the device  concerned is a class I device with measurement function or in \nsterile condition  covered by a valid  MDD certificate .  \n    \nPage 9 of 13 \n 14 Question:  May devices that are excluded  from the scope of the MDR (e.g. via Art. 1 para 6 lit h) nonetheless benefit from Art. 120 \npara 3 MDR ? \n Answer:  No, these devices do not fall under the MDR, thus Art. 120 para 3 MDR is not applicable.  \n   \n15 Question:  May MDD/AIMDD compliant devices , which  under the MDR will be subject to an \u201cupgrade\u201d in risk class  (\u201cup-\nclassification\u201d) , e.g. formerly class IIa -> then class III , benefit from Art. 120 para 3  MDR ? \n Answer:  Yes, under the conditions specified in Art. 120 para 3 MDR (e.g. valid AIMDD/MDD certificate ). Devices which are in a \ndifferent respectively higher risk class in MDR than under the Directives are not as such excluded from the scope of Art. \n120 para 3  MDR . \n   \n16 Question:  If, according to Art. 120 para 3 MDR, a MFR intend s to place  a MDD/ AIMDD compliant device  on the market after the \nDoA, that , under the MDR , will be subject to an \u201cupgrade\u201d in risk class  (\u201cup-classification\u201d) , what is the relevant risk \nclass  with regard to the applicable MDR requirements  listed in Article 120 para 3  MDR (e.g. PSUR)?  \n Answer:  The risk class under MDD/AIMDD . \n   \n17 Question:  What are the requirements  for the placing on the market/putting into service of MDD/AIMDD compliant devices  \naccording to Art. 120 para 3 MDR  after DoA? \n Answer:  See Art. 120 para 3 MDR.  \nIn short:  \n1. A valid AIMDD/MDD  certificate according to Art. 120 para 2 MDR  \n[All certificates necessary for the placing on the market of the device in question need to be valid , e.g. a class III \ndevice needs to have a valid QMS as well as product specific certificate .] \n2. Continuous compliance of the device  with the Directives    \nPage 10 of 13 \n 3. No signif icant changes  in the design and intended purpose  \n[If there is a significant change in either the design or the intended purpose , Art. 120 para 3  MDR cannot be \nclaimed .  Qualification  of a change as \u201csignificant \u201d according to Art. 120 para 3 MDR shall be determined on a \ncase by case basis. However,  \n- limitations of the intended purpose  \n- design changes related to corrective actions  assessed and accepted by the Competent Authority  \nare not considered \u201c significant \u201d in the sense of Art. 120 para 3 MDR. . \n4. Appl ication of MDR requirements  in place of the corresponding requirements of the Directives with regard to:  \na. Registration of economic operators and of devices   \n(see Art. 31 MDR and Art. 29 MDR)  \nb. Post market surveillance  (PMS)  \n(see Art. 83 -86, 92 MDR including Annex III but without the PMS having to be an integral part of the QMS)  \nc. Market surveillance   \n(see Art. 93 \u2013 100 MDR, but device s tandards to be met = Directives ) \nd. Vigilance   \n(see Art - 87-92 MDR)  \nHowever exceptions are possible in the case that EUDAMED is no t fully functional in time (then see Art. 123 \npara 3 d and e MDR).  \n \nMoreover, the \u201cold\u201d NB which issued the AIMDD/MDD certificate shall continue to be responsible for the appropriate \nsurveillance of all the applicable requirements relating to the devices it has certified. This should be agreed on between the \n\u201cold\u201d NB and the MFR on a contractual basis . \n   \n \n   \nPage 11 of 13 \n IV - Issue: The so called \u201csell off\u201d  provision  of Art. 120 para 4 MDR  \n18 Question:  What is the so called \u201csell off\u201d provision (Art. 120 para 4 MDR) about?  \n Answer:  It is intended to  limit the time  during which AIMDD/MDD compliant devices, that have already been placed on the \nmarket (either before the DoA or by virtue of Art. 120 para 3 after the DoA) , may be made available  e.g. by a \ndistributor . \nAfter May 27, 2025 these devices may not be made available/put into service (= deadline) . If such devices are still within \nthe supply chain by this date - i.e. have not reached the final user as being ready for use (e.g. the hospital) - they are not \n\u201cmarketable\u201d any more.  \n \nThis provision is thus primarily dealing with the \u201cmaking available\u201d  of AIMD/MDD compliant  devices once they have \nbeen placed on the market , e.g. within the supply chain . It does not apply to  the \u201cplacing on the market\u201d  of these \ndevices by the MFR . \n \nPlease  also note, that this provision is not intended to apply to second hand sales  (see recital 3).  This means , once a \ndevice has been made available to the final use r (e.g. the hospital) as being ready for use, the further making available  \nof this device is not subject to/covered by the MDR.  \n   \n19 Question:  Does Art. 120 para 4 MDR enable MFRs to place MDD/AIMDD compliant devices  on the market until May 27, 2025? \n Answer:  No. Art. 120 para 4 MDR is not applicable to  the \u201cplacing on the marke t\u201d of MDD/AIMDD compliant devices (see question \n18). The only way to place MDD/AIMDD compliant devices on the market after DoA is Art. 120 para 3  MDR (see \nquestion s 12-17). Given th at MDD/AIMDD certificate s will no longer be  valid after May 27 2024 , this option ceases to \nexist from that date onwards .  \n   \n   \nPage 12 of 13 \n V \u2013 Issue: EUDAMED  and its relevance for the application of certain provisions of the MDR \n(Art. 123 para 3 d and e, Art. 120 para 8, Art. 122 MDR)  \n20 Question:  Do all devices  have to be registered according to Art. 29 para 4 MDR  by the DoA? \n Answer:  No. Even if EUDAMED is  fully functional at the DoA there will be a n 18-month \u201cinterim  phase \u201d (= EUDAMED fully \nfunctional but Art. 29 para 4 MDR not yet applicable) during which the different devices to be placed on the market may \nbe registered \u201cstep by step\u201d  in EUDAMED  accordin g to Art. 29 para 4 MDR instead of nationally according to the \nDirectives (see Art. 123 para 3 e  and Art. 120 para 8 MDR) . However , at the end  of this \u201cinterim  phase \u201d it must be \nensured that  all devices of a MFR\u2019s portfolio have been registered in EUDAMED.  \n \nIf EUDAMED is not fully functional  until a date after the DoA,  the 18 -month \u201cinterim phase\u201d will be postponed accordingly \n(beginning at the later of the dates referred to in point d) of Art. 123 para 3 MDR).  \n   \n21 Question:  Must  NBs have entered all the certificate related information of all devices  according to Art. 56 para 5 MDR into \nEUDAMED by the DoA ? \n Answer:  No. Even if EUDAMED is fully functional at the DoA there will be an 18-month \u201cinterim phase\u201d  (= EUDAMED fully \nfunctional but Art. 56 para 5 MDR not yet applicable) during which the relevant information according to Art. 56 para 5 \nMDR may be registered in EUDAMED \u201cstep by step = certificate by certificate\u201d instead of nationally acco rding to the \nDirectives (see Art. 123 para 3 e and Art. 120 para 8 MDR). However , at the end of this \u201cinterim phase\u201d it must be \nensured that all the relevant data regarding all certificates  have been  registered in EUDAMED.  \n \nIf EUDAMED is not fully functio nal until a date after the DoA, the 18 -month \u201cinterim phase\u201d will be postponed accordingly \n(beginning at the later of the dates referred to in point d) of Art. 123 para 3 MDR).  \n    \nPage 13 of 13 \n 22 Question:  What happens if EUDAMED  is not fully functional  at the DoA?  How does this affect the application of obligations and \nrequirements of the MDR that relate to EUDAMED ? \n Answer:  The relevant provisions to refer to  are mainly Art. 123 para 3 d and e . \n \nArt. 123 para 3 d MDR:  \nThe different Articles  listed in Art. 123 para 3 d  (= dealing with e.g. the registration of devices and economic operators, \nclinical investigations, notified bodies, vigilance, post -market surveillance, market surveillance) are not fully  postponed \nwith regard to their applicati on but generally  remain applicable  from the DoA. However , their application is postponed as \nfar as  the obligations and requirements within these Articles relate to EUDAMED (which is not fully functional yet). To \nthat extent  they shall apply  from the date c orresponding to 6 months after the date of notice of full functionality . \nMeanwhile ( until EUDAMED is fully functional ) the corresponding provisions of the Directives regarding exchange of \ninformation  continue to apply .  \nThe principle is that the derogation applies to the electronic exchange of information/upload to EUDAMED. If the \nderogation is applicable this does not necessarily mean that the information itself does not need to be \nprepared/exchanged. This exchange of in formation e.g. reports will have to be done by other means in lieu  of exchange \nvia EUDAMED (Directives regime ). The underlying idea behind this paragraph was to ensure  compliance with the new \nobligations and requirements via the \u201cold\u201d systems  as far as pos sible.  \n \nThe actual practical implication of this concept with regard to the different Articles listed in Art. 123 para 3 d MDR needs a \ncloser look and further guidance , which is in progress.  \n \nArt. 123 para 3 e MDR : \nFor the application of Art. 29 para 4 MDR and Art. 56 para 5 MDR  in the case that EUDAMED is not fully functional in \ntime, see question  20 and 2 1."}, {"title": "ivd_mfr_stepbystep.pdf.txt", "text": "MEDICAL DEVICES  CHANGE OF LEGISLATION\nInternal market, \nIndustry,  \nEntrepreneurship  \nand SMEs1STEP  INTENTION / ACTION\nPre-assessmentBrief management to ensure a clear understanding of the importance and  \nbusiness implications of the IVDR\nConsider organisational challenges: management awareness, staffing capability \nand availability, budget implications\nGAP analysis and actions  \nresulting from thisAssess impact on products, internal resources, organisation and budget\nCheck new classification rules (IVDR Classes A\u2013D) and confirm conformity assess -\nment routes for existing and future products. Check the requirement for involving the \nNotified Bodies\nReview the changes needed to existing technical documentation (Technical Files)\nReview and upgrade quality management system (QMS) (point 3 below)\nCheck the adequacy of available clinical evidence and risk management and \nidentify any gaps (Article 56)\nReview product labelling (Annex I Chapter III)\nEnsure post-market surveillance (PMS) arrangements are adequate (Chapter VII \nSection 1)\nPrepare a post-market performance follow-up plan (PMPF, Annex XIII Part B) \nGet ready for the new vigilance requirements (Chapter VII Section 2)\nEnsure the respect of traceability obligations (Chapter III)\nQuality Management  \nSystem (QMS)Review adequacy of QMS to meet standards and processes for IVDs under the \nnew Regulation\nBuild new regulatory requirements into the QMS\nIdentify/hire the person responsible for regulatory compliance within your  \norganisation (Article 15) and be sure it is adequately qualified and trained1\n2\n3What you need to know!Implementation Model for\nIn-Vitro Diagnostic Medical \nDevices Regulation  \nStep by Step Guide\nRef. Ares(2018)3873813 - 20/07/20182Legal entitiesClarify how the company is affected: legal entities, obligation of economic  \noperators, organisational structures and resources\nConsider organisational challenges: management awareness, staffing capability \nand availability, budget implications\nEnsure product liability insurance is adequate\nPortfolioDo a cost/benefit analysis for your product portfolio; bear in mind costs related \nto the new risk classification system and the need of involving a Notified Body \nand costs for post-market surveillance and gaps in the technical documentation, \nand plan your transition to the IVDR accordingly\nReview supply chain provisions, and clarify roles and responsibilities of business \npartners (authorised representatives, importers, distributors)\nMaster implementation \nplanBuild a roadmap for implementation, including definition of sub-projects, re -\nsource requirements and a steering group, and ensure overall responsibility for \nIVDR implementation has been established\nGive special consideration to certificate expiry dates, bearing in mind the transi -\ntional period, transitional provisions and availability of your Notified Bodies\nNotified BodiesContact the selected Notified Bodies and determine their capacity and  \navailability to service the implementation plan \nRegulatory trainingEmpower and train staff through IVDR implementation and transition workshops\nExecute master  \nimplementation planImplement the various sub-projects (performance evaluation, technical  \ndocumentation, relations with other economic operators, Unique Device Identifica -\ntion, labelling, post-market surveillance, vigilance, and reporting IT systems)\nEnsure a cross-functional project management team is in place to cover all \naspects of implementation\nEnsure overall and individual responsibilities for IVDR implementation have been \nestablished\nReview efficiency and  \neffectivenessImplement regular meetings on project status and progress, discrepancy and \ngap analyses, risks, next steps and requirements\nHold regular progress reviews against the IVDR implementation plan and include \nthese in the management review process\nNotified Body submissionDiscuss submission dates to avoid delays in the approval process\nOngoing monitoringActively monitor the still-developing European regulatory environment and \nguidelines expected in the coming months (check DG GROW web pages on  \nmedical devices and subscribe to the newsletter)\nEstablish a procedure for dealing with unannounced inspections from Notified Bodies \nRegularly review the IVDR implementation plan, identifying and addressing key \nareas of risk4\n5\n6\n7\n8\n9\n10\n11\n12\n\u00a9 European Union, [2018]  Reuse is authorised provided the source is acknowledged.\nThe reuse policy of European Commission documents is regulated by Decision 2011/833/EU (OJ L 330, 14.12.2011, p. 39).\nISBN: 978-92-79-89124-3    DOI: 10.2873/41862\nET-04-18-659-EN-N"}, {"title": "scheer_o_015.pdf.txt", "text": "Final Version  \n \nGuidelines on the benefit -risk assessment of the presence of phthalates in certain \nmedical devices  \n  \n \n \n \n \n \nScientific Committee on Health, Environmental and Emerging Risks  \nSCHEER  \n \nGUIDELINES   \non the benefit -risk assessment of the presence of  \nphthalates in certain medical devices  \ncovering phthalates which are carcinogenic, mutagenic, toxic to \nreproduction (CMR) or have endocrine -disrupting (ED) \nproperties  \n \n \n \n \n \nThe SCHEER adopted this document at plenary meeting on 18 June 2019  \n  \nGuidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n2 \n ABSTRACT  \nThe SCHEER was requested to provide Guidelines on the benefit -risk assessment (BRA)  \nof the presence, in the medical devices specified in the regulation , of phthalates , which \nhave one or more of the following properties: carcinogenic, mutagenic, toxic to \nreproduction (CMR) or endocrine -disrupt ing (ED), according to the criteria outlined in the \nlegal obligation section from the mandate.  \n  \nPhthalates are widely used in industry as plastici sers of polymers, in a variety of \napplications such as coated fabrics and roofing membranes, as well as in me dical \ndevices, adhesives, paints, inks and enteric -coated tablets. Di -(2-(ethylhexyl) phthalate \n(DEHP) is the most widely used phthalate in medical devices. Dimethyl phthalate (DMP) \nand diethyl phthalate  (DEP) are not used as plasticis ers but e.g. as addit ives in \ncosmetics, medical devices, and household products.  \nThe interaction of phthalates with the polymers they are embedded in is weak, so they \nmay be released from the plastic product into the environment and into the human body \nif the product is in con tact with it.  \n \nThe Medical Device Regula tion, Regulation (EU) 2017/745 allows the use of CMR 1A/1B \nand/or ED substances in medical devices above a concentration of 0.1% w/w. when a \nproper justification can be provided (Annex I, Chapter II Section  10.4). Fo r such a \njustification several steps need to be considered including  the availability  of alternative \nsubstances, materials, designs, and medical treatments. In addition, the risk associated \nwith such alternatives should be weighed against the risk of the u se of CMR 1A/1B and/or \nED identified phthalates covered under MDR Annex I Chapter II Section  10.4.1 . However, \nthe risk by itself is not the only parameter to consider:  also the impact of the possible \nalternatives on the functionality, performance and the overall benefit -risk ratio of the \nmedical device shall be evaluated.  \n \nThese Guidelines describe the methodology on how to perform a BRA for the justification of \nthe presence of CMR 1A or 1B and/or ED phthalates (CMR/ED phthalates) in medical devices \nand/or or parts or materials used therein  at percentages above 0.1% by weight (w/w).  \nThey also describe  the evaluation of possible alternatives for these phthalates used in \nmedical devices , including  alternative materials, designs or medical treatments .  \nThey are intended to be used by the relevant stakeholders e.g. manufacturers, notified \nbodies and regulatory bodies.  \nThe approach of these Guidelines may also be used for a BRA of other CMR/ED \nsubstances present in medical devices.  \n \nDuring the preparation of these Guidelines for BRA of the use of CMR/ED phthalates in \nmedical devices, SCHEER noticed that a number of BRA methodologies are theoretically \navailable. However , there is a considerable lack of data  needed for the BRA  for potential \nrelevant  alternatives to be used in medical devices. Therefore, SCHEER encourages \nmanufacturers to generate data of high quality on  such alternatives  for CMR/ED \nphthalates in medical devices.  \nPending on new scientific evidence, it is recommended to evaluate the use and \nusefulness of these Guidelines after an application  period of three years.  \n \nKeywords: Guidelines, benefit -risk assessment , CMR/ED phthalates, medical devices, \nSCHEER . \nGuidelines  to be cited as:  SCHEER (Scientific Committee on Health, Environmental and \nEmerging Risks), Guidelines on the benefit -risk assessment of the presence of phthalates \nin certain medical devices  covering phthalates which are ca rcinogenic, mutagenic, toxic \nto reproduction (CMR)  or have endocrine -disrupting (ED) properties, final version \nadopted at  SCHEER plenary on 18 June 2019.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n3 \n  \nACKNOWLEDGMENTS  \n \n \nMembers of the Working Group are acknowledged for their valuable contribution to this \nopinion. The members of the Working Group are:  \n \nSCHEER members:  \nTeresa Borges  \nRodica Mariana Ion  \nWim H. de Jong    (Chair and Rapporteur)  \nDemosthenes Panagiotakos   \nEmanuela Testai  \nTheo Vermeire  \n \n \nSCCS members:  \nUlrike Bernauer  \nChristophe Rousselle  \n \n \nExternal experts:  \nSt\u00e9phane B\u00e9gu\u00e9  (Etablissement Fran\u00e7ais du Sang, EFS, Paris, France)  \nHilde B. M. Kopperud  (Nordic Institute of Dental Materials, Oslo, Norway)  \nMaria Rosaria Milana   (Istituto Superiore di Sanit\u00e0, Dip. Ambiente e Salute, Roma, Italy)  \nTanja Schmidt   (Ansbach University of Applied Science,  Ansbach,  Germany)  \n \n \nExperts from EU Agencies : \nFrancesco Pignatti   (European Medicines  Agency ) \nEvgenia Stoyanova   (European Chemicals Agency ) \nKatarina Volk    (European Food & Safety Authority ) \n  \n \n \n \n \nAll Declarations of Working Group members are available at  the following webpage:  \nhttp://ec.europa.eu/health/scientific_committees/experts/declarations/scheer_wg_en   \n \n \n \n \n \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n__________________________________________________________________________________\n4About the Scientific Committees (2016 -2021)  \nTwo independent non -food Scientific Committees provide the Commission with the \nscientific advice it needs when preparing policy and proposals relating to consumer \nsafety, public health and the environment. The Committees also draw the Commissio n's \nattention to the new or emerging problems which may pose an actual or potential threat . \nThey are: the Scientific Committee on Consumer Safety (SCCS) and the Scientific \nCommittee on Health, Environmental and Emerging Risks (SCHEER). The Scientific \nComm ittees review and evaluate relevant scientific data and assess potential risks. Each \nCommittee has top independent scientists from all over the world who are committed to \nwork in the public interest. \nIn addition, the Commission relies upon the work of other Union bodies, such as the \nEuropean Food Safety Authority (EFSA), the European Medicines Agency (EMA), the \nEuropean Centre for Disease prevention and Control (ECDC) and the European Chemicals \nAgency (ECHA).  \nSCHEER  \nThis Committee, on request of Commission services, provides Opinions on questions \nconcerning health, environmental and emerging risks. The Committees addresses \nquestions on: \n-health and environmental risks related to pollutants in the environmental media  and\nother biological and physical factors in relation to air quality, water, waste and soils.\n-complex or multidisciplinary issues requiring a comprehensive assessment of risks to\nconsumer safety or public health, for example antimicrobial resistance, n anotechnologies,\nmedical devices and physical hazards such as noise and electromagnetic fields.\nSCHEER members  \nRoberto Bertollini, Teresa Borges, Wim de Jong, Pim de Voogt, Raquel Duarte -Davidson, \nPeter Hoet, Rodica Mariana Ion, Renate Kraetke, Demosthen es Panagiotakos, Ana \nProykova, Theo Samaras, Marian Scott , Remy Slama, Emanuela Testai, Theo Vermeire, \nMarco Vighi, Sergey Zacharov  \nContact  \nEuropean Commission  \nDG Health and Food Safety  \nDirectorate C: Public Health, Country Knowledge, Crisis management  \nUnit C2 \u2013 Country Knowledge and Scientific Committees \nOffice: HTC 03/073   L -2920 Luxembourg\nSANTE- C2-SCHEER@ec.europa.eu   \nISBN 978-92-76-15387-0\u00a9 European Union, 2020 \nISSN 2467-4559\ndoi: 10.2875/784367 EW-CA-20-001-EN-N\nThe Opinions of the Scientific Committees present the views of the independent scientists \nwho are members of the committees. They do not necessarily reflect the views of the \nEuropean Commission. The Opinions are published by the European Commission in their \noriginal language only. \nhttp://ec.europa.eu/health/scientific_committees/policy/index_en.htm  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n5 \n  \nTABLE OF CONTENTS  \n \nACKNOWLEDGMENTS  ................................ ................................ ................................ ...........  3 \nA. GUIDELINES on benefit -risk assessment for CMR and/or endocrine -disrupting phthalates \nused in medical devices  ................................ ................................ ..............................  6 \n1. Introduction  ................................ ................................ ................................ ..............  7 \n2. Framework for Benefit -Risk Assessment  ................................ ................................ ..... 10 \n3. Assessment of the presence of phthalates in a medical device  ................................ ....... 15 \n4. Assessment of possible alternative substances, materials, designs or medical treatments  . 18 \n5. Assessment of potential relevant alternative substances, materials, designs or medical \ntreatments versus CMR/ED phthalates  ................................ ................................ ........  23 \n6. Justification for the use of CMR/ED phthalate  ................................ ..............................  25 \n7. Benefit assessment  ................................ ................................ ................................ .. 27 \n7.1 Material benefit  ................................ ................................ ................................ ....... 28 \n7.2 Clinical benefits  ................................ ................................ ................................ ....... 28 \n8. Methodologies for Benefit \u2013Risk Assessment  ................................ ...............................  29 \n9. Uncertainty analysis  ................................ ................................ ................................ . 30 \n10. Conclusions  ................................ ................................ ................................ .............  34 \n11. Consideration of the responses received during the public consultation process  ...............  35 \nB. REFERENCES  ................................ ................................ ................................ ...........  36 \nC. ANNEXES  ................................ ................................ ................................ ................  40 \nAnnex  1: SCHEER mandate on benefit -risk assessment on the use of CMR/ED phthalates  ...........  40 \nAnnex 2: Medical Device Regulation (Regulation 2017/745) on CMR and/or ED substances  .........  44 \nAnnex 3: Definitions/descriptions \u2013 References - Glossary  ................................ .......................  45 \nAnnex 4: CMR and/or ED substances  ................................ ................................ ....................  51 \nAnnex 5: Legislation on CMR and/or ED phthalates  ................................ ................................ . 53 \nAnnex 6: Use of phthalates in medical devices  ................................ ................................ ....... 57 \nAnnex 7: Approaches for Benefit -Risk Assessment  ................................ ................................ .. 60 \n \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n6 \n  \nA. GUIDELINES  on benefit -risk assessment  for CMR and/or endocrine -\ndisrupting phthalates used in medical devices  \n \nScope  \nThe Regulation  (EU) 2017/745 on m edical devices (MDR), Annex I \u201cGeneral Safety and \nPerformance Requirements\u201d, Chapter II \u201cRequirements regarding design and \nmanufacture\u201d, Section  10.4 deals with the presence of substances that may be released \nfrom a medical device. Annex I Chapter II Section  10.4.1 state s that substances that are \ncarcinogenic, mutagenic, or reprotoxic (CMR) of category 1A and 1B, or substances \nhaving endocrine -disrupting (ED) properties for which there is scientific evidence of \nprobable serious effects on humans, shall only be present in device s, or parts thereof or \nthose materials used therein , above 0.1% weight by weight (w/w) when justified \naccording to a set of criteria listed under Section  10.4.2.  \nThese Guidelines1 describe the methodology on how to perform a BRA for the justification \nof the presence of CMR 1A or 1B and/or ED phthalates (CMR/ED phthalates) in medical \ndevices at percentages above 0.1% by weight (w/w). They also describe the evaluation \nof possible alt ernatives for these phthalates used in medical devices , including  alternative \nmaterials, designs or medical treatments . They are intended to be used by the relevant \nstakeholders e.g. manufacturers, notified bodies and regulatory bodies.  \nThese Guidelines apply to those medical devices and components thereof indicated in \nAnnex I section 10.4.1.of the MDR . They do not provide information for the BRA of the \nuse of a medical device itself . However, the BRA as described can be integrated within \nthe risk management system for individual medical devices. For the BRA of medical \ndevices in general, stakeholders are referred to  section A7.2. of MEDDEV 2.7/1, revision \n4. Additional information may be found elsewhere, for example in the following \ndocuments  FDA 2 016, 2018, EN ISO 14971,  ISO/TR 24971. It should be noted that the \nacceptability of any risk is evaluated in relation to the benefit of the use of the medical \ndevice.  \nWhen the word \u201cpatient\u201d is used in these Guidelines, this also covers  professional users  \nand other persons (e.g. donors in case of blood donation) exposed to the medical device \nas well.  \nAnnex 1 to these Guidelines describes the mandate, Annex 2 describes Annex I Chapter \nII Section  10.4. of the MDR regarding the use of substances  that could be  released from \nthe medical device and pose a risk to patients,  and Annex 3 describes the definitions \nused in these Guidelines.  \n \n \n \n                                                           \n1 It should be noted that, in accordance with Regulation (EC) 2017/745, Annex I, Chapter II Section 10.4.3. \nand 10.4.4., updates of these Guidelines might be available in the future.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n7 \n  \n1. Introduction  \n \nPlacing medical devices  on the market,  making them available on the market and putting \nthem into service are all activities governed by Regulation (EU) 2017/745 that replaces \nDirective s 90/385/EEC and  93/42/EEC . Medical devices are defined in the MDR as \npresented in the text box below:  \nFor the purposes of this Regulation, the following definitions apply  \n(1) \u2018medical device\u2019 means any instrument, apparatus, appliance, software, implant, \nreagent, material or other article intended by the manufacturer to be used, alone \nor in combination, for human beings for one or more of the following specific \nmedical purposes :  \n\u2014 diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of \ndisease,  \n\u2014 diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or \ndisability,  \n\u2014 investigation, replacement or modification of the anat omy or of a physiological or \npathological process or state,  \n\u2014 providing information by means of in vitro examination of specimens derived from \nthe human body, including organ, blood and tissue donations, and which does not \nachieve its principal intended a ction by pharmacological, immunological or metabolic \nmeans, in or on the human body, but which may be assisted in its function by such \nmeans.  \nThe following products shall also be deemed to be medical devices:  \n\u2014 devices for the control or support of conce ption;  \n\u2014 products specifically intended for the cleaning, disinfection or sterilisation of \ndevices as referred to in Article 1(4) and of those referred to in the first paragraph of \nthis point.  \nAs a general requirement , the medical device shall perform acc ording to its intended \npurpose and be safe for professional  users and patients , or where applicable other \npersons (e.g. donor s) on which the device is used. The conformity of medical devices \nshall be evaluated against the requirements of the Regulation (EU) 2017/745. They shall \nbe presumed to be in conformity with this Regulation if they are in conformity with EU -\nharmonised standa rds or the relevant parts of those standards, the references of which \nhave been published in the Official Journal  of the European Union. Although not \nmandatory, these standards provide a route to comply with the MDR.  \nFor medical devices the horizontal standards EN ISO 14971 and EN ISO 10993 -1 are \nespecially relevant. EN ISO 14971 describes the application of a risk management \nprocess for medical devices, whereas EN ISO 10993 -1 deals with the biological evaluation \nand t esting of medical devices within a risk management process. According to EN ISO \n10993 -1, evaluation of the biological safety of a medical device should be a strategy Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n8 \n planned on a case -by-case basis to identify the hazards and estimate the risks of known \nhazards. In Annex A of EN ISO 10993 -1, a series of endpoints is indicated from which a \nselection can be made for the biological evaluation of a medical device. The selection is \nbased on the nature of the device's contact with the body (device category: surfa ce \ndevice, external communicating device, or implant device; type of contact: skin, mucosal \nmembrane, compromised surface, blood, tissues, organs; duration of the contact: limited \n\u226424 h, prolonged >24 h to 30 days, permanent >30 days). A systematic literat ure \nreview is part of the biological evaluation of a medical device in order to avoid \nunnecessary testing  (EN ISO 10993 -1). This systemic literature review should also be \nperformed for a CMR/ED phthalate or potential relevant alternatives identified for a given  \nin a medical device.  \nIn addition to EN ISO 10993 -1, a series of EN ISO 10993 standards has been published \ndescribing various assays and approaches for the evaluation of the endpoints identified in \nEN ISO 10993 -1 for the biological evaluation of medic al devices. Assays described in the \nvarious standards include cytotoxicity, sensitisation, irritation, systemic toxicity, \nimplantation, haemocompatibility, genotoxicity, and carcinogenicity endpoints.  \nAdditionally immunotoxicity and organ -specific toxiciti es need to be considered, if \nappropriate.  In addition, reproductive and developmental toxicity should be addressed for \nnovel materials, materials containing substances with a known reproductive or \ndevelopmental toxicity, medical devices with relevant targe t populations (e.g. pregnant \nwomen), and/or medical devices where there is the potential for local presence of device \nmaterials in the reproductive organs (EN ISO 10993 -1:2018). For the risk assessment EN \nISO 10993 -17 describes determination of allowable l imits for leachable substances, \nwhereas EN ISO 10993 -18 describes methods for chemical characterization of materials \nused in medical devices. In addition to the horizontal standards, vertical i.e. device \nspecific standards and standards for clinical investigation are available ( e.g. EN ISO \n14155).  \nFurthermore, the EU also provides guidance in MEDDEV documents (e.g. MEDDEV 2.7/1 \nrev.4 for clinical evaluation of medical devices).  \nThe MDR states that substances that are classified as carcinogenic, muta genic, or toxic to \nreproduction (CMR) of category 1A or 1B, or substances identified at EU level as having \nendocrine -disrupting (ED) properties for which there is scientific evidence of probable \nserious effects on humans  (CMR/ED substances, in this text) , shall only be present in a \ndevice s or parts thereof or those materials used therein  above 0.1% weight  by weight \n(w/w) when justified. Annex 4 provides further information on the classification of CMR \nand on identification of ED substances. The justificatio n for the use of CMR/ED \nsubstances in a medical device above 0.1% w/w, shall be based on an analysis of \npotential patient and user exposure, availability of possible alternatives, an \nargumentation why possible alternatives are appropriate or inappropriate,  and on the \nmost recent Guidelines of this Scientific Committee.  \nPhthalates are a group of substances widely used in medical devices. When  used as  \nplastici sers they may comprise a substantial part of the medical device. A typical \nconcentration of Bis(2 -ethylhexyl) phthalate (DEHP; CAS 117 -81-7) in plastici sed \npolyvinyl chloride (PVC) can be 30% based on weight (ECB 2008, SCENIHR 201 5). For \nmany years the reproductive toxicity and the possible endocrine disrupting activity of \ncertain phthalates has been a source for debate.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n9 \n Phthalates currently classified as reproductive toxicants category 1B under the \nClassification, Labelling and Pa ckaging (CLP) regulation (EC 1272/2008) and identified as \nsubstances of very high concern (SVHC)  under Article 57 (c) of REACH Regulation (EC) \n1907/2006 are listed in Annex 5  of this document . This list may be updated, so it is \nrecommended to consult the An nex VI of the CLP Regulation.  \nIn addition, the Commission Implementing Decision (EU) 2017/1210 and Commission \nImplementing Decision (EU) 2018/636 identified some phthalates as substances of very \nhigh concern (SVHC) according to Article 57(f) of REACH Regu lation (EC) 1907/2006,  \ndue to their endocrine disrupting properties with probabl e serious effects to humans, \nnamely Bis(2 -ethylhexyl) phthalate (DEHP), Benzyl butyl phthalate (BBP), Dibutyl \nphthalate (DBP) , Diisobutyl phthalate (DIBP) , and Dicyclohexylphthalate  (DCHP) . Bis(2-\nethylhexyl) phthalate (DEHP), was also identified in 2014 as a substance of very high \nconcern in  accordance with Article 57(f) of Regulation (EC) 1907/2006 (REACH) because \nit is a substance with endocrine disrupting prop erties for which there is scientific evidence \nof probable serious effects to the environment which give rise to an equivalent level of \nconcern to those of other substances listed in points (a) to (e) of Article 57 REACH. \nhttps://echa.europa.eu/documents/10162/21837b30 -0318-8b45-92db-9e8c39f89dee  \nSCENIHR adopted an Opinion on the safety of medical devices containing DEHP -\nplasticised PVC in 2008, and a revision of this  Opinion in 201 5 (SCENIHR 2008, 201 5). \nThe main source for DEHP exposure of the general population was determined to be food. \nIn addition, the use of medical devices can increase the exposure considerably in the \ncourse of specific medical treatments, for e xample during massive blood transfusions, \nhaemodialysis, and in neonatal intensive care units (NICU) for prematurely born \nneonates (SCENIHR 201 5). Although quite a number of alternative substances were \navailable for DEHP, for some of them serious data gaps were observed regarding hazard \nidentification and exposure estimation (Bui et al., 2016, SCENIHR 201 5). The Danish EPA \nassessed different alternatives and concluded that to various degrees some substances \ncan be considered to be relevant alternatives to DEHP in terms of human health hazards, \nespecially regarding the endpoints reproductive and developmental toxicity (Nielsen et al. \n2014). However, for a number of possible alternatives the data set was limited. Some \nalternatives showed a low  migration rate and some of them are already used as \nsubstitutes in medical devices for traditional DEHP -applications. For example, four \nadditional plasticisers for PVC (BTHC, DEHT, DINCH, and TOTM) used in medical devices \nhave recently been included in th e updated chapters of the European Pharmacopoeia \n(Council of Europe, EDQM 2018).  \nPhthalates classified as CMR of category 1A or 1B according to the procedure described in \nAnnex 4 are listed in Annex VI of the CLP regulation (CLP -Regulation (EC) No 1272/200 8, \nOJ L353). According to  article 57 (f) of REACH (Regulation (EC) 1907/2006) or the \nBiocides Regulation ( Regulation (EC)  528/2012) phthalates can be identified as having \nED-properties when  there is scientific evidence of probable serious effects to human \nhealth .  \nThese Guidelines provide a framework of how to perform a BRA for the presence of such \nCMR and/or ED phthalates in medical devices or parts or materials used therein at \npercentages above 0.1% weight by weight (w/w) , and shall be used by all relevant \nstakeholders, e.g. manufacturers and notified bodies, and regulatory bodies for the \njustification of the presence of CMR/ED phthalates . The evaluation according to the Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n10 \n Guidelines should be performed by a multidisciplinary team including amongst others  e.g. \na material scientist, medical device specialist, toxicologist and clinician.  \nA justification for the use of a CMR/ED phthalate can also be based on an already \navailabl e justification relating to a medical device for which equivalence with the device \nin question can be demonstrated according to the MDR Annex XIV Section 3. The existing \njustification can be used as a reference, and the data used for this justification sho uld be \navailable . \nThe approach of these Guidelines can also be u sed for a BRA of other CMR/ED substances \npresent in medical devices.  \nOther descriptions for BRA may be \u201cbenefit -risk analysis\u201d or \u201cbenefit -risk determination\u201d \nas defined in the MDR. As Annex I Section 10.4.3 indicates a benefit -risk assessment this \nterminology is used in these Guidelines.  \n \n \n2. Framework for Benefit -Risk A ssessment   \n \nThe MDR allows the use of CMR 1A/1B and/or ED substances in medical devices above a \nconcentration of 0.1% w/w when a proper justification can be provided ( MDR Annex I, \nChapter II  Section  10.4). For such a justification several steps need to be considered \nincluding the availability  of alternative substances, materials, designs, and medical \ntreatments. In addition, the r isk associated with such alternatives shall be weighed \nagainst the risk of the use of CMR 1A/1B and/or ED identified phthalates covered  under \nMDR Annex I Chapter II Section  10.4.1. However, the risk is not the only parameter to \nconsider . The impact of the possible alternatives on the functionality, performance and \nthe overall benefit -risk ratio of the medical device should also be evaluated.   \nThe justification for the presence of CMR 1A or 1B and/or ED phthalates for which there \nis scientific evidence of probable  serious effects on humans should be based on a number \nof considerations as described below and in Figure 1 .  \nIn order to perform the BRA as indicated above , it is important to describe the \nterminology to compare the risk s of the presence of the phthalates  to be evaluated (see \ntext box below). Annex 3  provides  a selection of definitions as present in the MDR and/or \nthe OECD Substitution and Alternatives Assessment Toolbox. (http://www.oecdsaatoolbox.org/ ) \nFor the purpose of these Guidelines the following definition for \"alternatives\" is used:  \n\u201calternatives  are defined as substances, materials, designs  and medical treatments  that \ncan be used to replace the use of CMR and/or ED  substances in medical devices\u201d  \nThe alternative therefore is not limited to a possible substitute substance or material but \ncould also be another device design (e.g. coating/production process/ techniques /lower \nconcentration  of substances)  or medical treatment (e.g. procedure, device) or a \ncombination of technical and substance alternatives that can substitute or eliminate the \nuse of the CMR/ED phthalate (modified from the ECHA REACH guidance on the \npreparation of an application for authori sation).  \nThe functionality and performance of the alternative should  be comparable to the extent \nthat there would be no clinical ly relevant  difference foreseen in the performance of the Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n11 \n device or in the outcome of the alternative medical procedure. Conside rations of \nfunctionality and performance shall be based on proper scientific justification. In order to \njustify the use of a CMR 1A or 1B and/or ED phthalate, the manufacturer shall clearly \ndemonstrate that the identified alternative(s) are not appropriate  to maintain the \nfunctionality, performance and benefit -risk ratios of the medical device.  \nA number of aspects need to be considered for the justification of the presence of a \nphthalate classified as CMR category 1A or 1B and/or identified as ED above  content > \n0.1% w/w in a medical device , or parts thereof or those materials used therein, as \nintended to be used.   \nIn summary, these aspects can be considered by a stepwise approach given below and \npresented in Figure 1. Further details and examples on the steps used in the Guidelines \nare given in the following chapters.  \nAssessment of the CMR/ED phthalate  (CMR/ED scenario)  \nStep 1:  \nDescription and characterisation of the composition of the medical device  (or parts \nor materials thereof) . Identif ication  of the  presence and concentration of CMR/ED \nphthalate (s) in weight by weight percentage (% w/w) . \n \nStep 2:  \nDescription of the use and function of the CMR/ED phthalate used in medical \ndevice.  \n2a. Description of functionality/performance provided by the presence of the \nCMR/ED phthalate.  \n2b. Description of the benefit (material and/or clinical) of the presence  of CMR/ED \nphthalate in the medical device.  \n \nStep 3:  \nAssessment of the risks of the CMR/ED phthalate.  \n3a. Determin ation of  the patient exposure based on realistic worst -case2 use \nscenario  in the intended use . \n3b. Identif ication of  biocompatibility, general toxicological and specific CMR/ED \nhazards associated with the phthalate.  \n3c. Determin ation of  the maxim um tolerable/ acceptable exposure for the patient,  \nbased on pre -clinical and clinical information (if available).  \n3d. Determination of the risks for various intended  use scenarios and patient \ngroups.  \n \nAssessment of possible alternative (s) (non CMR/ED  phthalate scenario)  \nStep 4:  \nInventory of possible alternative (s).  \n4a. Substances.  \n4b. Materials.  \n                                                           \n2 Realistic worst case is the situation where the exposure is estimated us ing a range of factors (i.e. duration, \namount, exposure controls), where applicable, the ones that would be expected to lead to maximum amount of \nexposure (e.g. exposure might be assessed under realistic simulated -use scenarios by EN ISO 10993 -12 and \nEN IS O 10993 -18 or a non-volatile  residue test (USP <661>)). The realistic worst case does not include \ndeliberate misuse. (EU Biocides Regulation 528/2012).  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n12 \n 4c. Designs and/or medical treatments3. \n \nStep 5:  \nIdentification of the potential relevant candidates for assessment as alternatives \nto CMR/ED  phthalates and justification for the selection and exclusion of possible \nalternatives.  This also includes assessment of the availability of the potential \nalternative (s). \n \nStep 6:  \nDescription of identified potential relevant alternative(s).  \n6a. Description of functionality and performance  of the potential alternative(s).  \n6b. Description of the benefit (material and/or clinical) of the use o f the potential \nalternative(s).  \n \nStep 7:  \nAssessment of the risk of identified potential relevant alternative (s). \n7a. Determination of patient exposure o f the alternative based on a realistic \nworst -case use scenario in the intended use.  \n7b. Identification, where available, of biocompatibility, toxicological and CMR/ED \nhazards associated with the alternative.  \n7c. Determination of maximum tolerable/acceptabl e exposure of the alternative \nfor patient (if available).  \n7d. Determination of risk of potential alternatives for various use scenarios and \npatient groups.  \n \nAssessment of potential relevant alternative (s) versus CMR/ED phthalate  \nStep 8:  \nComparison of functionality and performance of CMR/ED phthalate as used in the \nmedical device with functionality and performance of identified potential relevant \nalternative (s). \n \nStep 9:  \nComparison of hazard (s) of original CMR/ED phthalate as used in the medical \ndevice with hazard (s) of identified potential relevant alternative (s). \n \nStep 10:  \nComparison of benefit and risk of CMR/ED phthalate used in the medical device \nwith identified potential relevant alternatives.  \n \nIn addition to patients, the same  approach shall be used for the justification of the \npresence of CMR/ED phthalate in medical devices to evaluate the risk for professional \nusers and for other persons (e.g. donors) exposed to the CMR/ED phthalates. When \nalternative designs or medical treat ments were identified as potential alternatives in step \n5, adequately adopted endpoints for risks and benefits shall be chosen.  \nIt should be noted that scientific developments may be available after the initial \nassessment regarding the use of alternatives for CMR/ED phthalates . Therefore, a \n                                                           \n3 It should be noted that for alternative designs and/or medical treatments, appropriate endpoints for r isks and \nbenefits shall be selected.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n13 \n revision of the BRA of the presence of the CMR and/or ED phthalate may be necessary. \nRevisions of the above indicated BRA shall occur as indicated in the relevant sections of \nMDR for the general risk assessment of the me dical device.   \nFigure 1 illustrates the BRA and is based on Eliason and Morose (2011), EMA (2014), FDA \n(2016) and a critical selection from the OECD Substitution and Alternatives Assessment \nToolbox ( http://www.oecdsaatoolbox.org ). It presents the stepwise approach described \nabove including a general description of factors to consider when performing a BRA.  \nFigure 1 presents a use scenario in which the CMR/ED is used in a medical device versus \na non -use scenario in which a proper potential alternative is evaluated.  \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n14 \n Figure 1 . BRA for evaluation of presence  of CMR/ED phthalates and their  \npotential alternatives in medical devices  (relevant sections between brackets) . \nStep 3 (3)\nUse scenario\nAssessment of the risks of phthalate\n3a. Exposure assessment patient\n3b. Biocompatibility, hazard assessment\n3c. Maximum tolerable /acceptable dose\n3d. Risk characterisation Step 4 (4)\nInventory of possible alternatives\n4a. Substitute substances\n4b. Substitute materials\n4c. Alternative designs/treatmentsDefine aim and \nscope\nStep 1 (3)\nDescription and characterisation of \ncomposition of medical device, \nIdentifIcation of presence and \namount of CMR/ED phthalate\nStep 2\nDescription of phthalate \n2a. Use, functionality and performance of \nphthalate (3)\n2b. Benefit (7)Step 5 (4) \nIdentification of  potential candidates for \nalternatives and justification for the \nselection and exclusion\nStep 6\nDescription of identified potential \nrelevant alternatives\n6a. Functionality, performance (4)\n6b. Material and clinical benefit of the \nuse (7)\nStep 7 (4)\nAssessment of the risks of Identified \npotential relevant alternative(s)\n7a. Exposure assessment patient or user\n7b. Biocompatibility, hazard assessment\n7c. Maximum tolerable /acceptable dose\n7d. Risk characterisation\nStep 8 (5)\nComparIson of  functionality,  \nperformance of use and non- \nuse scenario\nOverall summary report\nJustification for continued use of \nCMR/ED phthalate (6)Step 9 (5)\nComparison of hazard(s) of use \nand non-use scenario\nStep 10 (5,7, 8)\nComparison of benefit and risk \nof  use and non-use scenario\nUncertainty analysis (9)Non-CMR/ED \nphthalate \nscenarioCMR/ED \nphthalate \nscenario\n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n15 \n  \n3. Assessment of the presence of phthalates in a medical device4 \n \nIt is already necessary to provide most of the information as indicated for the use of \nCMR/ED phthalates in order to prove compliance with the general safety and \nperformance requirements for the phthalate containing medical device.  \n \nWhen more than one CMR/ED phthalate is used simultaneously in the medical device, a \njustification shall be provided for each of the phthalates and their combination.  Some risk \nassessment data regarding the combinat ion of phthalates are available, as EFSA has \nrecently proposed a Group TDI for some of them, having a similar Mode of Action (MOA) \nin vivo  (EFSA 2019, see Annex 5). Information on assessment of combined exposures to \nphthalates can be found for example at the report by the National Research Council \nCommittee on the Health Risk of Phthalates (2008) and the ECHA website on the  \nrestriction of f our phthalates ( https://echa.europa.eu/registry -of-restriction -intentions/ -\n/dislist/details/0b0236e180d73895 ) and EFSA guidance on cumulative expos ure (EFSA, \n2019 https://doi.org/10.2903/j.efsa.2019.5634 )  \n \nStep 1: Description and characterisation of the composition of the medical device.  \nProvide a description of the medical device and its composition including identification \nand the concentration of each CMR/ED phthalate in the device , and the type of chemical \n/physical binding of the phthalate in the formulation/device, when there is an impact on \nleakage.  Use available chemical information  for identifying target phthalates (e.g. CAS \nN\u00ba; EINECS N\u00ba; IUPAC name).  The chemical composition of a medical device can be \nevaluated by using e.g. EN ISO 10993 -18 (FDIS published in 2019) . \n \nStep 2: Use and function of CMR/ED phthalates in the medical dev ice.  \nCharacterise the function and use of the CMR/ED phthalates in the medical device and \nthe properties it imparts to the device. Provide a description of the intended use, \nfunctionality and performance of the medical device containing the CMR/ED phthala te \nand how the use of the phthalate is critical for its functionality and performance . For \nexample, for PVC consider, with regard to the performance of the medical device, \nmaintenance, flexibility, durability and for the phthalate viscosity and PVC compatibility. \nProvide a description of the patients targeted (e.g. with respect to sex, age, probable \nvulnerable groups5). Provide a description of use types of the medical device for which it \nis intended (e.g. single  vs repeated exposure ). Other aspects that can be relevant include \nthe critical properties (e.g., flexibility), the conditions of use, critical quality criteria, \nprocess/treatment and performance constraints (e.g., sterilization, device/drug \ninteractions), regulatory or clinical or other requi rements that the CMR/ED phthalates \nand the phthalate -containing device need to deliver. Key criteria for the function,  \n                                                           \n4 The analysis presented in section 3 (steps 1 -3) describes the current use scenario of the CMR/ED phthalate, \ni.e., the scenario that would continue in the future if no additional action (other than, e.g., a planned regulatory \naction entering into force) is taken to limit, substitute or eliminate the presence of the CMR/ED phthalate in the \nmedical device. The current scenario can also be referred to as baseline, business as usual or continued use \nscenario.  \n5 Vulnerabl e Groups (in these Guidelines): vulnerable groups of the population such as children and individuals \nwith increased susceptibility due to pre -existing disease, medication, compromised immunity, pregnancy or \nbreastfeeding, women and men in reproductive age.  These vulnerable groups also include infants, elderly \npeople or people with poor health conditions.  \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n16 \n performance and overall use should be outlined and applied as the basis for an \nidentification and screening of possible alternatives and a more detailed assessment of \npotential alternatives. Justification for the selection of these criteria should be provided.  \n \nBenefits of the device with CMR/ED phthalates should also be considered  e.g. treatment \nof specific patients groups due to tuning of  flexibility of the medical device . Present an \ninventory of the benefits of the CMR/ED phthalates in the medical device for the patients \n(separately for vulnerable groups). More detailed information on the benefit assessment \nis presented in section 7.  \n \nStep 3: Assessment of the risks of the CMR/ED phthalate.  \nPerform a risk assessment of the CMR/ED phthalate present in the medical device. The \nrisk assessment should contain a description of the potential phthalate exposure of \nvarious patient groups for which  the medical device is intended (e.g. single  vs repeated \nexposure ). This should separately include vulnerable groups. EN ISO 10993 -1 provides \ninformation on use type in terms of exposure potential (e.g.  limited ( \u226424h), prolonged \n(>24h to 30d) and permanen t (>30d))  that slightly differs from the duration of use as \ndefined in the MDR (Annex VIII, 1, transient <60 minutes, short term 60 minutes to 30 \ndays, long term >30 days).  \n \nExposure estimation  \n \nProvide information , preferably based on data from direct measurement or, when not \navailable, an estimation based on worst -case scenario or from scientific literature , on the \nrelease of the CMR/ED phthalate from the medical device when used in various clinical \nmodalities. For  data generation , analytical contact conditions for the evaluation of \nleaching of substances from medical device s, should consider fo r example temperature, \ncontact duration and frequency, polarity of contact liquids, flow rates, contact surface, \nand volume  of contact liquids (EN ISO 10993 -1, EN ISO 10993 -12, EN ISO 10993 -18,  USP \n661). The contact conditions should be set to represent realistic worst -case conditions \ntaking into account the intended use of the medical device.  \n \nEstimate exposure to the phtha late(s) considering data on the release of the substance \nfrom the device. Consider repeated use scenarios (e.g. dialysis, apheresis donation, \nchronic treatment)  and different population groups. The combined exposure to different  \nCMR/ED  phthalates also needs to be considered  when present in a medical device. More \ndetails on the use of phthalates in medical devices  are presented in Annex 6.  Risk \nmanagement measures in place and their effectiveness should be described and taken \ninto account in the assessme nt (EN ISO 14971, EN ISO 10993 -1). In addition, data from \nbiomonitoring programs may become available that could also provide information on \nexposure levels of phthalates in the general population and more specifically during \nmedical treatment.   \n \nHazard id entification  \n \nDescribe hazards associated with the CMR/ED phthalate by considering all relevant \ntoxicological endpoints for acute as well as for repeated dose toxicity. EN ISO 10993 -1 \nprovides information on hazard endpoints to be considered depending on the exposure \nand use category of a medical device, whereas allowable limits can be determined \naccording to EN ISO 10993 -17.  Possible hazardous effects of combined exposure  should Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n17 \n also be assessed.  Identify  an adequate point of departure (PoD) for risk ass essment. In \ncase of a threshold Mode of Action, such a PoD could be the most sensitive no-observed -\nadverse -effect -level (NOAEL ) or lowest -observ ed-adverse -effect -levels (LOAEL ), or a \ndose that causes a predefined response (Benchmark dose \u2013 BMD) obtained by  \nBenchmark dose modelling. In case of non -threshold effects (e.g. in the case of \ngenotoxic carcinogens or for certain substances acting via an ED -mediated MoA), such a \ndose descriptor could be a T256 value or the benchmark dose associated with a 10% \nresponse (BMD10) (ECHA, 2012).  \n \nWhere a reference DNEL and /or a reference DMEL have already been derived in the \ncontext of other EU legislations, the analysis could refer to these derived figures without \nreferring to detailed assessment how these data have been derived (e.g. under REACH \nlegislation, Food Contact Material legislation). However, as some of these data may have \nbeen derived in the past, relevant up -to-date scientific evidence (based upon a \nsystematic li terature review) and up -to-date risk assessment methodology for all \nrelevant toxicological endpoints needs to be considered . If such DNEL/DMELs are not \nused in the assessment, a justification should be presented (e.g. new \ninformation /studies). Some of thes e other legislations  are defined under Annex 4. In \naddition, information can also be obtained in the SCENIHR 201 5 Opinion on DEHP.  \n \nThe ED property of the phthalate can be described according to the recently published \nEFSA/ECHA guidance document . \nhttps://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2018.5311   \nThis includes impacts on fertility, birth defects (e.g., cryptorchidism, hypospadias), \ndevelopmental effects, and other effects associated with the CMR/ED phthalates.   \n \nDescribe risk (risk characterisation)  \n \nThe risk can be described by comparing exposure levels that are considered safe with the \nexpected exposure (worst -case scenario) to obtain a risk characterisation ratio (RCR). \nStarting points (points of departure, PoD) for exposure levels that are considered safe \ncould be the most sensitive no -observed -adverse -effect -level (NOAEL) or lowest -\nobserved -adverse -effect -levels (LOAEL), or a dose that causes a predefined response \n(Benchmark dose \u2013 BMD) for threshold substances. For non -threshold substances, a T25 \nvalue or the benchmark dose associated with a 10% response (BMD10) could be used. \nFrom these PoDs, acceptable expo sure values can be derived such as \u201cDer ived No -Effect \nLevel \u201d (DNEL), \u201cDerived Minimum Effect Level\u201d (DMEL) or intakes over lifetime without \npresenting an appreciable risk to health (ADI or TDI/TWI or TE).  As such data are often \nobtained in rat studies, th e use of the TDI seems more appropriate in view of the critical \neffect window for androgenic reproductive toxicity in rats has been reported to be a few \ndays (Welsh et al. , 2008). In addition, patients may be exposed to medical devices only \nfor a limited p eriod of time.  EN ISO 10993 -17:2002 7 calculates for medical devices a \nTolerable Exposure (TE), which is based on a product of the tolerable intake, the body \nmass and the utilization factor.  When necessary, acceptable exposure levels  can be \nderived by dividing the point of departure for risk assessment by appropriate assessment \nor uncertainty factors . Specifically for ED effects additional assessment factors might be \nconsidered as proposed recently (Hass et al.,  2019).  \n                                                           \n6 Animal dose -descriptor; chronic dose rate that will give 25% of the animal's tumours at a specific tissue site \nafter correction for spontaneous incidenc e (Dybing et al.,  1997)  \n7 EN ISO 10993 -17:2002 is currently under revision. It is discussed to replace in the updated version TE by TI.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n18 \n  \nThe risks can also be described by calculation of the Margin of Safety (MoS), which is the \nratio between the lowest PoD and the expected exposure (worst case scenario) and \ncomparison with a reference MoS (see SCCS Notes of Guidance \u2013 SCCS/1602/18).  \nPerform this evaluation for e very group (patients/donors) for which the device is \nintended to be used.  \n \nDetermine and describe in which situation the risk can be acceptable for the use of the \nCMR/ED phthalate in the medical device. The benefit -risk assessment for the use of the \nCMR/ED  phthalate can be performed using for example MEDDEV 2.7/1rev4 and EN ISO \n14971 (see also Section 8).  The MDR considers a risk acceptable when outweighed by \nthe benefit of using the device in patients (Chapter I of MDR , Chapter VI Article 62 ). \n \nIn addition to potential CMR/ED effects, discuss any other potential hazards associated \nwith the composition of the device (e.g. by using the EN ISO 10993 series of standards).  \nEvaluate if such effects are associated with the use of the CMR/ED phthalates i n the \ndevice.  \n \nNote: It should be noted that for some genotoxic carcinogens a no effect level is \nassumed not to exist.  Similarly, a scientific debate is ongoing about whether this also \napplies to ED activity.  \n \nThe assessment of the risk should be accompan ied by an estimation of the impact of \nuncertainties in the described outcomes  (see section  9). \n \n \n4. Assessment of possible alternative substances, materials, designs or \nmedical treatments8 \n \nIn general a similar risk assessment as presented in step 3 above has to be performed \nfor the alternative (substance s, material s, designs or medical treatment ). An inventory \nshould be prepared  in order to be able to evaluate possible alternative s. An alternative \ncould be another substance/material or device design modifi cation or it could be a clinical \nprocedure (e.g. a process, technique, treatment or modification) or a combination of \ntechnical and substance alternatives.  \n \nStep 4: Inventory of possible alternatives  \nPrepare a list of possible alternatives ( such as  substances, materials, designs or medical \ntreatments)9.  \nA description of the alternative scenario (CMR/ED phthalate \"non -use scenario\u201d) needs to \nbe presented including identification of alternative substances , materials, designs or \nmedical treatment , e.g.  by includ ing consideration of all available information, such as \nalternative medical devices available on the market, information about independent \nresearch, published peer-reviewed studies, systematic literature reviews, risk assessment \nreports or scient ific opinions from relevant scientific committees and the results of in -\n                                                           \n8 The analysis presented in section 4 constitutes the non -use scenario or the scenario that would transpire if the \nCMR/ED phthalates would no longer be used in the medical device.  \n9 Information source for alternatives might be the European Pharmacopoeia.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n19 \n house research and development.  The identif ication of  possible  alternatives should be \nproperly documented.  \nStep 5: Identification of the candidates for assessment as potential relevant  alternatives \nfor phthalates  \nThe MDR indicates that an analysis of all possible alternatives shall be performed. \nHowever, when many alternatives are available it would not be feasible to do an \nextensive evaluation of all alternatives. It is therefo re recommended to select a number \nof potential relevant  alternatives  based on screening against key criteria for function, \nperformance, toxicity, and overall use in the medical device in question  (see below). In \naddition, analysis of availability and technical feasibility might affect choices for \nalternatives as well.   \nA preliminary analysis of possible alternative substances, materials or designs or medical \ntreatments should be performed . This preliminary analysis  should include a description of \ntheir possible use as alternative substance , material , designs or medical treatment s. \nJustification on how and why alternatives are rejected for further assessment by defining \ninclusion and exclusion criteria should be provided.  \nInformation/data on functionalit y (e.g. level of flexibility in tubes) as well as performance \nand/or chemical safety assessment (e.g. hazard profile) may be used for rejection of the \nless likely alternatives (see below ) and no further risk assessment for the alternative is \nrequired. The rejection of the less likely alternatives requires justification and \ndocumentation.  The chemical safety assessment should be done after assessment of the \nfunctionality and performance.  \nIn addition to the comparison in terms of functionality, technical per formance and risks \nto patients and users, which are critical elements for the benefit -risk assessment, Annex \nI Section 10.4.2 of the MDR states that the justification for the presence of CMR/ED \nsubstances should also be based on an analysis of the availabi lity of possible alternatives. \nAvailability has several aspects, including for example the availability of necessary \nquantity (volumes) of the alternative on the market within a required timeframe and the \nability to gain access to alternatives that may be proprietary (e.g., via licensing).   \nIf potential alternatives can be identified, a shortlist of the potential alternatives can be \nestablished  for further detailed assessment with regard to technical feasibility, health \nbenefits, comparison of risks, exist ing legal requirements, availability (e.g. sufficient \navailability or accessible to the manufacturer), and technical performance.  In the event \nthat no alternative  is identified, i nformation should be presented on the actions \nundertaken  to identify alternat ives. \n \nA compilation of resources and elements in support of chemical substitution and an \nassessment of alternatives can be found on the OECD webpage : \nhttp://www.oecdsaatoolbox.org/  \nStep 6: Description of identified potential relevant  alternative(s)  and conclusion on their \ntechnical feasibility  \nCMR/ED phthalates are present in medical devices for a specific purpose depending on \nthe intended use of the medical device. For example, phthalates offer the possibility for \nfine tuning the flexibility  (e.g. optimal flexibility without kinking)  of a PVC -based medical Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n20 \n device. In addition, DEHP has a stabilising effect on red blood cells in blood bags \n(SCENIHR 201 5). Technical feasibility of an alternative is based on the alternative \nfulfilling the function of the CMR/ED phthalate. Therefore, the assessment of the \nfunctional properties in relation to the intended use of the medical device is essential. \nBesides functionality, performance under intended use conditi ons should also be \nconsidered.  \n \nArgumentation shall be provided for justifying why possible substances and/or material \nsubstitutes, if available, or design or medical treatment changes, if feasible, are \ninappropriate in relation to main taining the functionality and/or performance of the \nmedical device. For example, it might be the case that replacement is possible for one \nspecific functional use whereas for another functionality the use of the CMR/ED phthalate \nremains necessary . Also oth er aspects related to performance of the alternatives need to \nbe considered like material processing conditions (Crespo et al.,  2007), material quality \nafter sterilisation (Burgos and Jim\u00e9nez 2009), and possible interaction with drugs in \ntherapeutic infusi on systems (Treleano et al. , 2009, Salloum et al. , 2015, Tortolano et \nal., 2018).  \n \nThe benefit(s) should also be considered. An inventory of the benefit(s) of the potential \nalternative substances, materials, designs or medical treatments for patient populations \n(separately for vulnerable patient groups) should be presented (see section 7 ).  \n \nThe evaluation of the identified potential relevant alternatives can be done in a tiered \nway to avoid full assessments for each candidate alternative. For example, based on the \noutcome of the functionality evaluation, the choice of the potential relev ant candidates \nmight be reconsidered and some might be discarded before performing the risk \nassessment (see Step 7).  \n \nThe ECHA guidance on the preparation of an application for authorisation  and ECHA \nformats for Analysis of Alternatives  provide more detailed information on how to conduct \nan initial screening of possible alternatives and to assess the technical feasibility of \npotential alternatives. Submitted applications for authorisations contain a number of  \nexamples (https://echa.europa.eu/applying -for-authorisation/preparing -applications -for-\nauthorisation ) of technical feasibility assessment for uses of substances of very high \nconcern. \nStep 7:  Assessment of the risk of identified potential relevant  alternatives  \nThe risk assessment of alternatives is comparative in nature. Its aim is to assist in the \nconclusion in section 5 whether the transition to the alternatives would lead to lower \nbenefit and/or risk to human health for patients when compared to the current u se of the \nCMR/ED phthalates in the medical device. Th e methodology of the assessment in this  \nstep is similar to that in step 3 as performed for the phthalate to be evaluated with \nreference to the alternative.  \n \nIf potential relevant alternative s were identified under Steps 1 -6, a risk  assessment of \nthese potential relevant  alternative substance/material or designs or medical treatments \nshould be performed. The risk assessment should contain a description of the potential \nsubstance/material (alternative  medical procedure) exposure of various person groups \n(e.g. including patients, donors, professional users)  for which the medical device is \nintended to be used (considering single or repeated use). This should include separately Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n21 \n vulnerable groups . For each  subgroup a different level of risk may be accepted based on \nthe potential benefit of the medical device for that particular group . Risk management \nmeasures (EN ISO 14971, EN ISO 10993 -1) and their effectiveness to reduce exposure \nshould be described and t aken into account in the assessment.  \n \nExposure estimation  \n \nEstimate the potential release of the alternative substance(s) when used in various \ntreatment modalities. Consider also the rate of leaching to estimate the potential \nexposure to the alternative substance. Multiple use scenarios (including various types of \npossible contact) should be considered for the exposure estimation of the alternative \nsubstance (e.g. frequent use of dialyzer) and different population groups.  \n \nHazard identification  \n \nIdentify hazards based on literature, supplier documentation and other information (such \nas risk assessments performed by regulatory bodies). Describe hazards associated with \nthe alternative substance/material by considering all relevant toxicological endpoints for  \nacute as well as for repeated dose toxicity including human data. Identify an adequate \npoint of departure (PoD) for risk assessment. In case of a threshold Mode of Action, such \na PoD could be the most sensitive no -observed -adverse -effect -level (NOAEL) or lowest -\nobserved -adverse -effect -levels (LOAEL), or a dose that causes a predefined response \n(Benchmark dose \u2013 BMD) obtained by Benchmark dose modelling. In case of non -\nthreshold effects (e.g. in the case of genotoxic carcinogens or for substances acting via  \nan ED -mediated MoA), such a dose descriptor could be a T25 value or the benchmark \ndose associated with a 10% response (BMD10) (ECHA, 2012).  Hazards should preferably \nbe evaluated by a relevant exposure route for the intended use of the assessed medical \ndevice. \n \nFor the hazard identification  special attention should be on the determination of any \npotential CMR and/or ED property of the alternative substance used . For further \ninformation purposes, a procedure is described in ECHA Guidance on the application of \nthe CLP criteria  \nhttps://echa.europa.eu/documents/10162/23036412/clp_en.pdf/58b5dc6d -ac2a-4910-\n9702-e9e1f5051cc5   \nor by searching Annex VI of  CLP regulation. ED propert ies of the alternative \nsubstance/material can be described according to the recently published EFSA/ECHA \nguidance document . \nhttps://echa.europa.eu/documents/10162/23036412/bpr_guidance_identif_ed_en.pdf/1a\n4d2811 -3faa-fe61-1de2-3cbce8fd4d95   \nThese effects include impacts on fertility, birth defects (e.g., cryptorchidism, \nhypospadias), developmental eff ects, and other potential toxic effects associated with \nphthalates with ED properties and reprotoxic effects category 1A/B.  It needs also to be \nconsidered that the potential alternative (substances, materials, designs or medical \ntreatments) could also have  other hazards than those of the CMR/ED activity. These \nother hazards and their possible associated risks should be discussed for example by \nusing the EN ISO 14971 and the EN ISO 10993 series. See also Table 1.  \n \nDescri ption of  risk (risk characteri sation)  \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n22 \n The risk can be described by comparing exposure levels that are considered safe with the \nexpected exposure (realistic worst case use scenario). Exposure levels that are \nconsidered safe could be \u201cDerived  No Effect-Levels\u201d (DNEL s) for threshold substances, \n\u201cDerived Minim um Effect Levels\u201d (DMEL s) for non -threshold substances or intakes over \nlifetime without presenting an appreciable risk to health (ADI or TDI/TWI or TE ). As such \ndata are often obtained in rat studies, the use of the TDI seems more appropriate in view \nof the critical effect window for androgenic reproductive toxicity in rats has been reported \nto be a few days (Welsh et al. , 2008). In addition, patients may be exposed to medical \ndevices only for a limited period of time. EN ISO 10993 -17:2002 calculates for medical \ndevices a Tolerable Exposure (TE), which is based on a product of the tolerable intake, \nthe body mass and the utilization factor. When necessary, a cceptable exposure levels   \ncan be derived by dividing the point of departure for risk assessment by appropriate \nassessment or uncertainty factors.  For medical devices allowable limits of their chemical \nconstituents can be determined by EN ISO 10993 -17. \n \nThe risks can also be described by calculation of the Margin of Exposure (MoE) or the \nMargin of Safety (MoS)  due to the substances present in a medical device , which  is the \nratio between the lowest PoD and the expected exposure (e.g. realistic worst case  use \nscenario) and comparison with a reference MoS (see SCCS Notes of Guidance \u2013 \nSCCS/1602/18 ). \nPerform this evaluation for every patient group for which the device is intended to be \nused.  \n \nWhere a reference DNEL and /or a reference DMEL have already been derived in the \ncontext of other EU legislations, the assessment  could refer to these derived figures \nwithout referring to a detailed assessment of how these data have been derived (e.g. \nunder REACH legislation, Food Contact Material legislation). Data on the relevant \nexposure route of the medical device application (e.g. intravenously) are preferred (see \nalso Table 1A, EN ISO 10993 -1). The risk can be described by the so -called risk \ncharacterisation ratio (RCR), being a ratio between the exposure and the DNEL /DMEL . If \nsuch DNEL/DMELs are not used in the assessment, a justification should be stated (e.g. \nnew information /studies).  \n \nDetermine and describe acceptability of the risk for the use of the potential alternative s. \nRisks may be acceptable when they are outweighed by the benefits for the patient.   \n \nConsider any known adverse events associated with the operation of the device using the \nphthalate, and whether the potential alternatives might affect these adverse event s. \nThese considerations can be based upon a systematic literature review  (see MEDDEV \n2.7/1rev4) . \n \nThis exercise has to be performed for each potential relevant  alternative substance  \nand/or materials .  \nA large number of phthalates exist and some may be potential relevant alternatives  for \nthe CMR/ED phthalate used in the medical device. However, a number of these  \nphthalates are also classified as CMR and/or designated ED (see above  and Table 1 \nAnnex 5 ). Such phthalates might be identified as alternatives when the CMR/ED risk is \nreduced compared to the phthalate intended to be  used.  In addition, different \nsubstances , have also been proposed as alternative plastici sers. In 201 5 SCENIHR \npublished an updated Opinion of potential alternative plastici sers for DEHP (SCENIHR Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n23 \n 2015). Although many alternatives were potentially available, it was also observed that \nfor many of them the information on potential risks and the necessary risk assessment \nwas rather limited precluding their use as alternative s. For DEHP an extensive amount of \nliterature is available, allowing a very careful evaluation of the risk associated to its use .  \n \nIn the event that the risk assessment of a potential relevant alternative cannot be \nperformed due to lack of information, document ation should be presented on the actions \nundertaken to obtain information to characterise the risk, including the outcome (for \nexample, QSAR /read across could be performed).  \n \nNote shall be taken that alternative designs or medical treatments might lead to  \nadaptation of  endpoints for the benefit -risk assessme nt when compared to the \ntoxicological endpoints of CMR/ED phthalates.  \n \nThe assessment of the risk should be accompanied by an estimation of the uncertainties \nin the described outcomes which might be qua ntitative (e.g. confidence interval, \nstandard deviation) or qualitative (see section 9).  \nConclude the analysis of the potential  relevant alternative(s) with a summary describing \nthe possible  scenario(s) ( see Fig ure 1).  \n \n \n5. Assessment of potential relevant  alternative substances, materials, \ndesigns or medical treatments versus CMR/ED phthalates  \n \nBased on the information obtained above a decision can be made on the appropriateness \nof potential relevant alternative s (substance, material , design or medical treatment ). In \nthis evaluation several factors need to be included such as weighing of technical \nfeasibility, benefits and risks . And, if possible, quantification of benefits and risks. These \nsteps entail a comparison of the CMR/ED phthalate  \u201cuse-scenario\u201d  (summarised in step \n3) with the \u201cNon-use scenario \u201d (summarised in step 4)  as shown in Figure 1.  \n \nStep 8: Comparison of functionality and performance of CMR/ED phthalate as used in the \nmedical device with functionality and performance of identified potential relevant \nalternative (s). \n \nCompare the functionality and performance of CMR/ED phthalate in the medical device \nand the potential relevant alternative substance/material (or designs or medical \ntreatments by choosing adequate endpoints).  \nPerform step 8 for each candidate identified as the potential relevant alternative in \nsection 4.  \nIf several potential relevant alternatives have a similar functionality and hazard profile, \nexposure conditions and possibilities for Risk Management Measures (RMM) res ulting in \nrisk reduction should be considered (see below).  Risk management is described in EN \nISO 14971.  \nIn this comparison also additional issues not directly related to the functionality and \nperformance of the alternative itself, like technical possibili ties, sterilisation effects and Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n24 \n interactions with infusion liquids, are important for the application of the alternative and \nthe comparison with the CMR/ED phthalates, and thus should be considered.  \nStep 9:  Comparison of risk(s) of CMR/ED phthalate as used in the medical device with \nrisk(s) of identified potential relevant alternatives.  \n \nCompare the risk of both CMR/ED phthalate and alternative substance/material (or \ndesigns or medical treatments by choosing adequate endpoints).  \nPerform step 9 for each potential relevant alternative.  \n \nThere may be difficulties in comparing the risks of a substance e.g. a phthalate, and the \nrisks of a technical alternative such as medical design or medical treatment. For example, \nthere may be risks as sociated with alternative technologies but these may not be of the \nsame nature of the risk of the phthalate. However, the potential relevant alternative \nmust represent a reduction in the overall risks to human health  (Step 10) . Therefore, a \ncomparison of risks must be conducted and the applicant will need to consider how these \ndifferent risks might be compared in terms of risks to human health. Note that an \nalternative medical design or medical treatment may also result in expo sure to other \nrisks previously not present  in the treatment modality. Possible risks of these substances \nwill also need to be considered in the assessment. The comparison with technological \nalternatives such as a medical design or medical treatment can nor mally not be fully \nquantitative (i.e. with directly comparable numeric values), as the hazards and \nassociated risks will not be expressed in similar terms, but will in most cases be \nqualitative or semi -quantitative.  Nevertheless, a clear and transparent de scription can \ngive a good basis to conclude whether overall risks are reduced  or not  (Step 10) .  \nStep 10: Comparison of benefit and risk of CMR/ED phthalate used in the medical device \nwith identified potential relevant alternatives.  \n \nPresent summary/overvi ew of comparison of benefit and risk of CMR/ED phthalate used \nin the medical device with the potential relevant alternatives, including uncertainties  \nabout the estimates or reliability of the data, assumptions, etc. for the parameters \npresented. The summary should contain various aspects of functionality, performance, \nrisk and benefit of the use of the original CMR/ED phthalate used in the medical devic e \nand the potential relevant  alternative (s). In section  6 below the justification of the use of \na CMR/ED phthalate is described based on the summary table comparing an alternative \nwith the CMR/ED phthalate.  \nPerform step 10 for every potential relevant alternative.  \n \nEach of the assessments performed in steps 1 to 1 0 is associated with uncertainties. \nCertain uncertainties can be described by the use of measures  like the standard deviation \nor confidence interval. For other uncertainties , a description may be necessary to explain \nthe extent of the uncertainty  and its impact on the final outcome . \n \nBenefit and risks should be described and weighted against each other in the use of the \npotential alternative substance /material  in the medical device (or designs or medical \ntreatments  by choosing adequate endpoints)  similar to the procedure for the CMR/ED \nphthalate (see step 2).  \n \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n25 \n  \n6. Justification for the u se of CMR/ED phthalate  \n \nBased on the comparison of functionality, performance, availability, risk and benefit, an \nargumentation can be built as to why a possible substance and/or material alternative, if \navailable, or changes in designs or medical treatment, if feasible, are inap propriate in \nrelation to maintaining the functionality, performance and the benefit -risk ratio or profile \n(quantitative/semi -quantitative or qualitative) of the medical device containing a CMR/ED \nphthalate.  \n \nExplain the importance of any difference in ter ms of benefits and risks between the \nCMR/ED phthalate to be used in the medical device and potential relevant alternatives \nusing value judg ements and explain how  the use of the CMR/ED phthalate can be \njustified over the alternatives by describing the accep tability of trade -offs in the \nachievement of some criteria against others.  Any advantage in benefits needs to be \nweighed against possible disadvantages in terms of functionality and risks. Both \ndifferences in benefits and risks need to be considered jointly.  \n  \nIn building the argumentation for the use of a CMR/ED phthalate, note can be taken of \nthe Memorandum on weight of evidence and uncertainties of SCHEER (SCHEER 2018). \nThis Memorandum describes a  methodology  that classifies the strength of evidenc e in the \nhuman health risk assessment  based on integration of different lines of evidence  into \nstrong, moderate, weak, uncertain and inconclusive (no suitable evidence available).  Any \nweight of evidence evaluation needs to show the overall confidence in t he assessment.   \n \nThe argumentation should specifically take into account the intended use of such devices. \nThis should include consideration and discussion of possible high risk groups such as \nchildren or pregnant or breastfeeding women, and other patient groups considered \nparticularly vulnerable to such substances and/or materials. In addition, where applicable \nand available, any future update of these Guidelines shall be considered. A Table with the \nmost relevant information and values should be used to p resent an overview of the \nperformed assessment comparing the CMR/ED phthalate with potential alternative(s). A \nnon-exhaustive example of such Table is presented below. The Table should  be extended \ndepending on the number of criteria evaluated and the numbe r of potential alternatives \nidentified.  \n \nTable 1:  Example for a comparison of CMR/ED phthalate with potential relevant \nalternative(s).  \n  \nAssessment criteria  Description \n(examples)  Reference \nphthalate  Alternative I  Alternative \nII etc.  \nIdentification of \nsubstances/material etc  \nName and CAS number  Chemical \ninformation  CAS \n117-81-7  \n   \nFunctionality/performance  Used as \nplasticiser  e.g. DEHP    \nClinical \nbenefit/performance  Treatment \npossibility  e.g. Flexibility \nof tubing / \nred blood   Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n26 \n cells storage  \nMaterial benefit      \nConcentration (% w/w)      \nLeaching  from medical \ndevice for relevant \nconditions e.g. media, \ntemperature, etc  \n(mg per hour/day)      \nExposure estimation \n(realistic worst case use \nscenario ) for relevant \nroute of exposure      \nHazard identification  Local and \nsystemic \nacute and \nrepeat -dose \ntoxicity, ED -\nproperties, \norgan \ntoxicity, CMR \nproperties, \nbiocompatibili\nty, and \nothers     \nIdentification of a point of \ndeparture for risk \nassessment ( LOAEL, \nNOAEL, BMD, T25, \nBMD10)  \n     \nIdentification of dose \nlevels associated with \nminimal or negligible risk  \n(e.g. DNEL, DMEL, TDI , \nTE, TI)     \nRisk characterisation \n(MoE, MoS, RCR)      \nConfidence  estimation \n(see Table 2)      \nTechnical feasibility       \nOther      \n \nThis Table shall be completed for every component of the medical device that contains \nCMR/ED phthalate(s ) above the 0.1% w/w level. For some medical devices used as a \nsystem (e.g. blood bag system) the whole system might be evaluated.  Note that in case \nof alternative designs or medical treatments adequate endpoints for the comparison shall \nbe chosen. These endpoints may represent risks that may be of a different nature than \nthat of the risk of the phthalate.  \nWhen the outcome of the comp arison shows that the alternative fulfils a comparable or \nbetter intended functionality as well as performance and shows a reduced risk, the use of \na CMR/ED phthalate is not possible. The risk assessment should also indicate whether \nthere would be a reduce d hazard concerning CMR and/or ED properties, and/or reduced \nexposure overall resulting in reduced risk. In this evaluation, other toxicities (e.g. for any Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n27 \n other organ  or system ) of the potential relevant alternatives shall also be considered. So, \nthe full  toxicological profile of the potential relevant alternatives shall be taken into \naccount.  \nA balanced weighing of the benefit  versus the risk has to be performed . For example it is \npossible to use a combination of a CMR/ED phthalate and PVC/material with h igh intrinsic \ntoxicological hazards, thus accepting a risk from a toxicological perspective, in case the \nclinical benefit is very high . In contrast, a minor loss in medical  functionality might be \nacceptable if there is a large reduction  or even absence of risk. Each comparison of a \npotential alternative for the use of a phthalate should be based on the combination of \nfunctionality , risk and benefits for patients.  \nIn this final evaluation , the assessment  of uncertainties associated with the alternatives \n(e.g. on the nature of the risks; assumptions made) should also be considered (see Table \n2 below section 9). Therefore, where possible, quantitative results should be collected \nand compared (e.g. NOAEL, estimated exposure in mg/kg) and their uncertainties should \nbe reported. Also a qualitative description of the uncertainties may be useful (see Table 2 \nbelow sec tion 9). Their impact on the conclusions should also be discussed.  \nAlthough not the main subject of these Guidelines, it should be realised that availability \nand accessibility on the market  might be a limitation for the introduction of an alternative \nsubst ance/material. Some chemicals proposed as alternatives are widely available (e.g. \nBTHC, DEHT, DINCH, and TOTM) however, this may not be the case for other alternatives \nidentified . The lack of the availability of a potential alternative for a medical device might \nresult in the conclusion that replacement is not feasible and that the use of a phthalate \nwith CMR and/or ED property continues in order to keep the device available for pat ients. \nSo, besides technical feasibility in terms of functionality and risk reduction (risk \nassessment of the phthalate versus the alternative), also availability and accessibility on \nthe market needs to be considered.  \nThe BRA of the CMR/ED phthalate shoul d be updated when new scientific information \nbecomes available on alternatives for the use of phthalates, when new Guidelines are \nreleased, or as the \"overall\" benefit -risk determination of the medical device is updated.  \nA plan to perform an update of the relevant part of the technical file of the device needs \nto be submitted during the certification process (post -market surveillance plan referred \nto in Article 84, the requirements are set out in  Section 1.1 of Annex III MDR) and this \nshould also cover upd ates needed on the justification for the presence of CMR/ED \nphthalates .  \n \n7. Benefit assessment  \n \nThese Guidelines do not provide information for the benefit -risk assessment of the use of \na medical device itself but are limited to the methodology on how to perform a BRA for \nthe justification of the  presence  of CMR 1A or 1B and/or ED phthalates in a medical \ndevice  above 0.1% (w/w).  \nThe evaluation of the overall benefit -risk assessment of a medical device is  presented in \nother documents (e.g. MEDDEV 2.7/1 rev4, EN ISO 14971).   \nThe benefits of the CMR/ED phthalate use in a medical device need to be compared to \nthe benefits of the potential relevant alternatives, with the focus of the analysis being on Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n28 \n the net or incremental benefits of use of the CMR/ED phthalate in comparison to the \nalternatives. These benefits may include material or clinical benefits. Uncertainties about \nthe estimates or reliability of the data, assumptions, etc. for the parameters need to b e \npresented.  \n \n7.1 Material benefit  \n \nA medical device does not achieve its principal intended action by pharmacological, \nimmunological or metabolic means, in or on the human body, but may be assisted in its \nfunction by such means.  For the use of phthalates in medical devices, additional \nfunctionalit ies need to be considered. One of the functionalit ies is the fine -tuning of the \nflexibility of PVC when  used as plasticiser s e.g. in intubation devices. For blood bag \nmaterials other requirements are , for example,  resistance to heat and chemicals, \nespecially during sterili sation, and permeability of gases to assure that pH and oxygen \nlevels remain stable .  In addition, DEHP has an additional property namely the stabilising \neffect on red blood cells (RBCs) (SCENIHR 2015). A number of alternatives were \nevaluated as alternative for DEHP in blood bags (Simmchen et al., 2012, SCHENIR \n2015).  \nPlatelets are extremely sensitive to changes in the pH of the medium in which they are \nsuspended, so sufficient gas permeability to O2 and CO 2 has to be assured in the \ncontainers devoted to their storage (Simmchen et al. , 2012). For this reason, DEHP has \nbeen almost fully replaced with  BTHC, DINCH, and/or Trioctyltrimellitate (TOTM or  Tri( 2 -\nethyl hexyl)trimellitate (TEHTM) ) (Simmchen et al.  2012, Prowse et al.  2014).  A better \ngas exchange has been found in bags plasticised with these chemicals . Also other \nmaterials, like polyolefins, are currently used for platelet storage bags (Prowse et al.  \n2014).  This potentially will allow  the stor age of platelet concentrates for up to 7 days, if \nmeasures to prevent bacterial contamination can be safely implemented.  \nIt should be noted that the benefit of phthalates in terms of material  functionality and \nperformance may differ from device to device. An alternative may be available  for one \napplication while this may not be available  for another in view of added or specific \ndemands on the functionality  of the p hthalate .  \n \n \n7.2 Clinical benefits  \n \nClinical benefit of medical devices is defined in the MDR as follows:  \n\u2018clinical benefit\u2019 means the positive impact of a device on the health of an individual, \nexpressed in terms of a meaningful, measurable, patient -relevant clinical outcome(s), \nincluding outcome(s) related to diagnos is, or a positive impact on patient management or \npublic health; (Regulation (EU)2017/745: Article 2 Definitions: (53)):  \nThis \u201cclinical benefit\u201d has to  be substantiated by the manufacturers in the \u201cclinical \nevaluation\u201d of the medical device, which includes a number of considerations. These  \ninclude a discussion and overall conclusions covering safety and performance results, \nassessment  of risks and clinic al benefits, discussion of clinical relevance in accordance Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n29 \n with clinical state of the art, any specific precautions for specific patient populations, \nimplications for the investigational device  and limitations of the investigation.  \nA \u201dclinical benefit \u201d could include any meaningful, measurable, patient -relevant outcome \nas presented below. SCHEER identified the following examples  that may be relevant for \nthe use of phthalates (list not exclusive):  \n\uf0b7 Improved survival rates  \n\uf0b7 Improved length of hospital stay  \n\uf0b7 Improved time of intervention  \n\uf0b7 Improved time of placing ( among others  in tubes and catheters)  \n\uf0b7 Improved product quality/ clinical performance ( among others in tubes and \ncatheters) in terms of:  \no Improved leakage rates  \no Improved breakage rates  \no Improved knotting rates  \no Improved blockage rates  \no Improved bending performance rates  \no Improved release rates of toxic substances  \no Improved release rates of (nano -)particles  \n\uf0b7 Improved displacement  rates \n\uf0b7 Improved possibilities for sterili sation \n\uf0b7 Reduction of diameters in relation to performance  \n\uf0b7 Possibility to produce \u201cmultiple -purpose\u201d devices, (e.g. inclusion of additional \nsensors), and therefore reduction of over -all patient -stress and patient -impact  \n\uf0b7 Improved observability (safety) in terms of translucence, printability, radiopaque \nlines included, identifiab ility, traceability, etc. ( among others  in tubes and \ncatheters)  \n\uf0b7 Fewer  adverse events , e.g. r educed mucosal or endothelial irritation or injury \nrates ( among others  in tubes and catheters)  \n\uf0b7 Fewer serious adve rse events  and serious incidents  \nThe benefit of the use of the CMR/ED phthalate should always be judged with respect to \nthe \u201cintended use\u201d of the medical device and the exposed patient -group to the medical \ndevice and weighed in its clinical impact (\u201cclinically relevant difference\u201d). These aspects \nshould be judged by clinical experts.  \nQuantitative information on the benefits should be provided where possible or at a \nminimum qualitative description of their magnitude. Information on the probability of  the \nbenefit to occur and/or the duration of the benefit should also be included.  \n \n \n8. Methodologies for Benefit \u2013Risk A ssessment  \n \nIn general, a Benefit - Risk A ssessment  (BRA) aims to evaluate the desired effects of \ntherapeutic mean s, medicine s or device s, against their undesired effects, i.e., risks for \nhuman health. An appropriate BRA can contribute to a more objective analysis and help  \nconformity verification bodies and  authorities towards a more objective and transparent \ndecision -making process. Weighi ng the benefits and risks can be a complex task. It may \ninvolve the evaluation of a large amount of data that should be as accurate  as possible , Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n30 \n without methodological weaknesses  and biases. There is always some uncertainty around \nthe actual benefits and r isks, because they can only be determined by looking at the \ninformation that is available at a given point in time  which may contain various sources \nof uncertainty.  \nFor the BRA of medical devices in general, guidance is available in section A7.2. of  \nMEDDEV 2.7/1, revision 4   \u201cClinical evaluation: A guide for manufacturers and notified \nbodies under directives 93/42/EEC and 90/385/EEC\u201d . EN ISO 14971  (FDIS published in \n2019)  and the accompanying  ISO/TR 24971 provide information on the risk benefit \nanalys is to be performed within a risk management process. Additional information may \nbe found elsewhere, for example in the documents  of the FDA 2016,  2018,. It should be \nnoted that the acceptability of any risk is weighted against the benefit of the use of the \nmedical device.   \nSeveral methodologies for BRA have been proposed (Guo et al, 2010 , Mt-Isa et al.  \n2014), of which most methodologies  are so far , mainly used for pharmaceutical products. \nHowever, it should be underlined that f or medical devices the quantitative determination \nof a benefit -risk ratio may be rather difficult to be made  and expressed in a figure. In \nsuch cases a qualitative approach of weighing the benefit based on expert judgement \nmight be used.  One methodology, namely the multi criteria decision analysis (MCDA), \ncan be generally applied to various areas of BRA. Therefore, this methodology might also \nbe suitable for performing the BRA of medical devices (see Annex 7).  The MCDA \nmethodology has its origins in decisi on theory aiming to evaluate multiple conflicting \ncriteria in decision making. These criteria can include the benefits and risks of the use of \na medical device on human health.   \nThe final BRA of both the used CMR/ED  phthalate and potential relevant alterna tives \nshould contain all aspects as indicated in the framework above. A quantitative or semi -\nquantitative description of the risks (e.g. MoS, RCR) and of the benefits of a medical \ndevice containing a CMR/ED phthalate or alternative should  be the basis for a BRA. \nHowever, a lthough quantitative approaches for a BRA are preferable, a qualitative \ndescription of the value judgements about the balance of benefits and risks might also be \nan acceptable approach when justified (see step 10).  \n \n \n9. Uncertainty analysis  \n \nUncertainty plays an important role in medical decision making. It is widely accepted \nthat, despite the methodological and technological improvements that were achieved in \nthe past decades, there is never absolute certainty regarding the safety, effective ness, or \nperformance  of a medical treatment or use of a device. Therefore, the degree of certainty \nand thus uncertainty of the benefits and risks of a medical device is a factor that should \nalways be considered when making BRA.  \nThere are various sources of uncertainty in bio -medical studies; a major source of \nuncertainty is the biological differences among individuals. Another source of uncertainty \nis the intra - and inter - variability of the laboratories, with respect to equipmen t, \nreagents, and methods used. It is also accepted that diagnostic tools which evaluate \nbenefit and risk share several limitations , giving false negative and false positive results \nin a variety of cases. Observer variation occurs quite often  and should alw ays be taken Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n31 \n into account. Other factors that may influence the degree of uncertainty include: the type \nof clinical information available (e.g., clinical investigation  data, observational studies, \nevidence derived from registries or use experience), the re presentativeness of the \ninformation (e.g., sample size, relevance  of the sample to the referent population \nexposed to the device), as well as the statistical inferences derived from the information.  \nA number of techniques for uncertainty analysis are descr ibed in t he Guidance for Socio -\nEconomic Analysis of ECHA (ECHA 2011). The aim is to determine whether uncertainties \nin the estimation of impacts could affect the overall conclusions. More accurately , the \ntechniques shown can be used to either reduce the va riability of estimates, or to help \ntest whether uncertainties affect the conclusions drawn. The only way to actually reduce \nuncertainty is through better data, better understanding and knowledge of the \nuncertainties and through further analysis. However, i n most cases residual uncertainties \nwill remain.  \nRecently EFSA published a guidance on uncertainty analysis (EFSA 2018 a) and a \ndescription of the principles and methods behind the guidance for uncertainty analysis \n(EFSA 2018 b). The EFSA Guidance recogni ses that the form and extent of uncertainty \nanalysis, and how the conclusions should be reported, vary widely depending on the \nnature and context of each analysis and the degree of uncertainty that is present. \nTherefore it is important to identify appropriat e options for each BRA. The EFSA \ndocuments provide a flexible framework for uncertainty analysis within which different  \nmethods may be selected, according to the needs of each BRA. It seems likely that also \nfor medical devices a similar flexibility is need ed in view of the broad range of medical \ndevices used.  \nEFSA describes a number of main elements of uncertainty that need to be considered in \nthe uncertainty analysis:  \nEFSA: Main elements of uncertainty analysis  \n\uf0b7 Identifying uncertainties affecting the assessment. This is necessary in every \nassessment and should be done in a structured way to minimise the chance of \noverlooking relevant uncertainties. In assessments that follow standardised \nprocedures, it is only necessary to identify nonstandard uncertai nties.  \n\uf0b7 Prioritising uncertainties within the assessment plays an important role in planning \nthe uncertainty analysis, enabling the assessor to focus detailed analysis on the \nmost important uncertainties and address others collectively when evaluating \novera ll uncertainty. Often prioritisation will be done by expert judgement during \nthe planning process, but in more complex assessments it may be done explicitly \nusing influence analysis or sensitivity analysis.  \n\uf0b7 Dividing the uncertainty analysis into parts. In some assessments, it may be \nsufficient to characterise overall uncertainty for the whole assessment directly, by \nexpert judgement. In other cases, it may be preferable to evaluate uncertainty for \nsome or all parts of the assessment separately and then comb ine them, either by \ncalculation or expert judgement.  \n\uf0b7 Ensuring the questions or quantities of interest are well -defined. Each question or \nquantity of interest must be well -defined so that the true answer or value could be \ndetermined, at least in principle.  This is necessary to make the question or \nquantity a proper subject for scientific assessment, and to make it possible to \nexpress uncertainty about the true answer or value clearly and unambiguously. Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n32 \n Some assessments follow standardised procedures, within  which the questions \nand/or quantities of interest should be predefined. In other assessments, the \nassessors will need to identify and define the questions and/or quantities of \ninterest case by case.  \n\uf0b7 Characterising uncertainty for parts of the uncertainty analysis. This is needed for \nassessments where assessors choose to divide the uncertainty analysis into parts \nbut may only be done for some of the parts, with the other parts being considered \nwhen characterising overall uncertainty.  \n\uf0b7 Combining uncertainty f rom different parts of the uncertainty analysis. This is \nneeded for assessments where the assessors quantify uncertainty separately for \ntwo or more parts of the uncertainty analysis.  \n\uf0b7 Characterising overall uncertainty. Expressing quantitatively the overall  impact of \nas many as possible of the identified uncertainties, and describing qualitatively \nany that remain unquantified. This is necessary in all assessments except those \nstandardised assessments where only standard uncertainties are identified  (e.g. \ninter-and intra -species uncertainty factors).  \n\uf0b7 Prioritising uncertainties for future investigation. This is implicit or explicit in any \nassessment where recommendations are made for future data collection or \nresearch, and may be informed by influence or sensit ivity analysis.  \n\uf0b7 Reporting uncertainty analysis. Required for all assessments, but extremely brief \nin standardised assessments where only standard  uncertainties  are identified.  \nA number of methods that can be used in the uncertainty analysis include:  \n\uf0b7 Sensitivity analysis  \n\uf0b7 Scenario analysis  \n\uf0b7 Expert judgement  \n\uf0b7 Monte Carlo Simulations  \nSome of these techniques can be used in combination (e.g. scenario analysis together \nwith expert judgement to establish ranges for key variables) but also together with less  \ncommonly used techniques such as risk -risk analysis, Delphi techniques and portfolio \nanalysis, which can be used to help reduce the variability of estimates but are not \ndiscussed in these Guidelines.  \nAfter performing the uncertainty analysis , the observed overall confidence associated \nwith a BRA can be expressed as a probability score. This score gives the risk assessor an \nindication what the uncertainty is in the BRA. \nIn situations where sufficient data are available, a quantitative categori sation of \nprobability levels is preferred. If this is not possible, the manufacturer should give a \nqualitative description. A good qualitative description is preferable to an inaccurate \nquantitative description ( EN ISO  14971).  \nEFSA (EFSA, 2018 b) and SCHEER (2018) use a rather detailed probability scale  of 9 and \n7 probab ility levels, respectively. EFSA stresses that this scale may be used as an aid to \nsupport the development of judgements and that other ranges or qualitative descriptions \ncan be used as well. EFSA (2018 b) also argues that presenting the numerical \nprobabilities alongside verbal expressions of probability, e.g. \u2018Likely (> 66% probability)\u2019, \nincreases the consistency of interpretation.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n33 \n A detailed scale does not seem to be applicable for the uncertainties that can be obtained \nduring a  BRA evaluation of medical devices. For medical devices, a probability scale as \nindicated in Table 2  may b e used  EN ISO showing a 5-level scale recommended by ISO \nfor semi -quantitative assessments ( EN ISO  14971, Table D4 ). Table 2 further show s the \nverbal terms and subjective probability ranges that are based on a simplification of the \nEFSA/SCHEER scales.  \n \nTable 2: Probability scale for (semi -)quantitative  description of the overall \nconfidence  \nISO probabil ity term  \n Subjective  probability range  Probability term  \n \nFrequent  \n \nProbable  \n \nOccasional  \n \nRemote  \n \nImprobable  \n  \n> 90% \n \n66-90% \n \n33-66% \n \n10-33% \n \n<10%  \nvery l ikely \n \nlikely \n \nas likely as not  \n \nunlikely  \n \nvery unlikely  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n34 \n  \n10.  Conclusions  \n \nThese G uidelines are intended to be used for  a BRA of the presence of phthalates in \ncertain medical devices  covering phthalates which are carcinogenic, mutagenic, toxic to \nreproduction (CMR) or have endocrine -disrupting (ED) properties . The Guidelines can be \nused for the justification of the use of CMR/ED phthalates in a medical device according \nto the Regulation (EU) 2017/745 on medical devices. They also provide a framework on \nhow to assess  and compare possible alternative substances, materials , designs  or \nmedic al treatments  to the use of CMR/ED phthalates in medical devices. Major aspects \ninclude the functionality of phthalates, the performance  of the medical device using  the \nphthalate or the potential  relevant alternative for the phthalate, as well as the risk \nassessment of the phthalate or the alternative s. In the end , the benefit (s) shall be \nweighed against the possible risk s of the use of the CMR/ED phthalate and of the \nalternative substance, materials , desig ns or medical treatments . This overall analysis  will \ndetermine whether it is justified  or not  to use  a CMR/ED phthalat e in a medical device.  \nIn view of the concern of the CMR/ED properties of phthalates, further research to \npossibilities to replace these p hthalates in medical devices is highly encouraged  by the \nSCHEER .  \nDuring the preparation of these Guidelines for BRA of the use of CMR/ED phthalates in \nmedical devices , SCHEER noticed that a number of BRA methodologies are theoretically \navailable. However , there is a considerable lack of data for the BRA for potential  relevant \nalternatives to be used in medical devices. Therefore, SCHEER encourages manufacturers \nto generate data of high quality on such alternatives for CMR/ED phthalates in medical \ndevices . As the BRA of the presence of phthalates may have an impact on the \nconclusions of the \"overall\" benefit -risk determination of the medical device, a  periodic  \nupdate of the BRA of the medical device may be needed. The BRA of the presence of the \nCMR/ ED phtha late should be updated when new scientific information becomes available \non alternatives for the use of phthalates, when new Guidelines are released, or as the \n\"overall\" benefit -risk determination of the medical device is updated . A plan to perform \nan update of the general BRA for the medical device should be included in the dossier \nbefore marketing the device, and this should also include a plan regarding the necessary \nupdates on the evaluation of alternatives for CMR/ED phthalate s.  \nPending on new scientific evidence, i t is recommended to evaluate the use and \nusefulness of these Guidelines after an application  period of three years.  \n \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n35 \n  \n11.  Consideration of the responses received during the public \nconsultation process   \n \nA public consultation on these Guidelines was opened on the website of the non -food \nscientific committees from 18 March to 29 April 2019 . Information about the public \nconsultation was broadly communicated to national authorities, international \norganisation s and other stakeholders. A to tal of 197 submissions from 19  contributors \n(providing 378 comments  and additional references ) provided input to different chapters \nand subchapters of the document.  The vast majority of comments came from industry  \nand were requesting clarifications .  Each submission was carefully considered by the \nSCHEER and the scientific opinion has been revised to take account of relevant \ncomments. The literature has been accordingly updated with relevant publications. The \nSCHEE R expresses their thanks to all contributors for their comments and for the \nliterature references provided during the public consultation. The text of the comments \nreceived and the response provided by the SCHEER is available at:   \nhttps://ec.europa.eu/health/scientific_committees/consultations/public_consultations/sch\neer_consultation_08_en   \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n36 \n  \nB. REFERENCES  \n \n\uf0b7 Bui TT, Giovanoulis G, Cousins AP, Magn\u00e9r J, Cousins IT, de Wit CA. Human \nexposure, hazard and risk of alternative plasticizers to phthalate esters.  Sci Total \nEnviron. 2016 Jan 15;541:451 -467. do i: 10.1016/j.scitotenv.2015.09.036 . \n \n\uf0b7 Burgos N, Jim\u00e9nez A.Degradation of poly(vinyl chloride) plasticized with non -\nphthalate plasticizers under sterilization conditions. Polymer Degradation and \nStability 94 (2009) 1473 \u20131478.  \n \n\uf0b7 Crespo JR, Balart R, Sanchez L,  L\u00f3pez J. Substitution of Di(2 -ethylhexyl) Phthalate \nby Di(isononyl) Cyclohexane -1,2-Dicarboxylate as a Plasticizer for Industrial Vinyl \nPlastisol Formulations. Journal of Applied Polymer Science, 104, 1215 \u20131220, \n2007.  \n \n\uf0b7 Dybing E, Sanner T, Roelfzema H, Kroese D, Tennant RW. T25: a simplified \ncarcinogenic potency index: description of the system and study of correlations \nbetween carcinogenic potency and species/site specificity and mutagenicity.  \nPharmacol Toxicol. 80 , 272-279, 1997 . \n \n\uf0b7 ECB (European Chemical Bureau). European Union Risk Assessment Report for \nBis(2-ethylhexyl) phthalate (Consolidated Final Report) 2008.  \n \n\uf0b7 ECHA, 2011. Annex XV Restriction Report, Proposal for a Restriction Substance \nname: Bis(2 -ethylhexyl)phthal ate (DEHP), Benzyl butyl phthalate (BBP), Dibutyl \nphthalate (DBP), Diisobutylphthalate (DIBP). European Chemicals Agency 2011.  \n \n\uf0b7 ECHA 2011 Guidance on the preparation of socio -economic analysis as part of an \napplication for authorisation, European Chemicals  Agency 2011.  \n \n\uf0b7 ECHA 2011 Guidance on the preparation of an application for authorisation, \nEuropean Chemicals Agency 2011.  \n \n\uf0b7 EFSA (European Food Safety Authority) Scientific Committee, Benford D,  \nHalldorsson T, Jeger MJ, Knutsen HK, More S, Naegeli H, Notebo rn H, Ockleford C, \nRicci A, Rychen G, Schlatter JR, Silano V, Solecki R, Turck D, Younes M, Craig P, \nHart A, Von Goetz N, Koutsoumanis K, Mortensen A, Ossendorp B, Martino L, \nMerten C, Mosbach -Schulz O and Hardy A, 2018. Guidance on Uncertainty \nAnalysis in  Scientific Assessments. EFSA Journal 2018;16(1):5123, 39 pp. \n(https://doi.org/10.2903/j.efsa.2018.5123 .) \n \n\uf0b7 EFSA Scientific Committee, Benford D, Halldorsson T, Jeger MJ, Knutsen HK,More \nS, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Schlatter JR, Silano V, \nSolecki R, Turck D, Younes M, Craig P, Hart A, Von Goetz N, Koutsoumanis K, \nMortensen A, Ossend orp B, Germini A, Martino L, Merten C, Mosbach -Schulz O, \nSmith A and Hardy A, 2018. Scientific Opinion on the principles and methods Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n37 \n behind EFSA\u2019s Guidance on Uncertainty Analysis in Scientific Assessment. EFSA \nJournal 2018;16(1):5122,235 pp. https://doi.org/10.2903/j.efsa.2018.5122  \n \n\uf0b7 EFSA Scienti\ufb01c Com mittee, More SJ, Bampidis V, Benford D, Bennekou \n-Jerez AF, Koutsoumanis K, Naegeli H, \nSchlatter JR, Silano V,N ielsen SS, Schrenk D, Turck D, Younes M, Benfenati E, \nCastle L, Cedergreen N, Hardy A, Laskowski R,Leblanc JC, Kortenkamp A, Ragas \nA, Posthuma L, Svendsen C, Solecki R, Testai E, Dujardin B, Kass GEN,Manini P, \nJeddi MZ , Dorne J -LCM and Hogstrand C, 2019. Guidance on harmonised method \nologies forhuman health, animal health and ecological risk assessment of \ncombined exposure to multiple chemicals.EFSA Journal 2019;17(3):5634, 77 pp. \nhttps://doi.org/10. 2903/j.efsa.2019.5634  \n \n\uf0b7 Eliason P, Morose G Safer alternatives assessment: the Massachusetts process as \na model for state governments. Journal of Cleaner Production 2011 , 19, 517-526 \n \n\uf0b7 European Commission 2017 COMMISSION IMPLEMENTING DECISION (EU) \n2017/1210 of 4 July 2017 on the identification of bis(2 -ethylhexyl) phthalate \n(DEHP), dibutyl phthalate (DBP), benzyl butyl phthalate (BBP) and diisobutyl \nphthalate (DIBP) as substances of very high concern according to Article 57(f) of \nRegulation (EC) No 1907/2006 of the European Parliament and of the Council. \nOfficial Journal of the European Commission,  L173/35,  6.7.2017.  \n \n\uf0b7 European Directorate for the Quality of Medicines and Healthcare (EDQM), \nEuropean Pharmacopoeia (Ph. Eur.) 9th Edition 2019, Council of Europe, \nStrasbourg, France.   \n \n\uf0b7 European Medicines Agency (2014)  Benefit -risk methodology project \n(https://www.ema.europa.eu/documents/report/benefit -risk-methodology -\nproject -update -work-package -5-effects -table-pilot-phase -i_en.pdf ) \n \n\uf0b7 FDA. US Food and Drug Administration.  Benefit -Risk Factors to Consider When \nDetermining Substantial Equivalence in Premarket Notifications (510(k)) with \nDifferent Technological Characteristics.  Guidance for Industry and Food and Drug \nAdministration Staff. September 25, 2018. Washington , USA. \nhttps://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/G\nuidanceDocuments/UCM404773.pdf  \n \n\uf0b7 FDA. US Food and Drug Administration.  Factors to Consider Regarding Benefit -\nRisk in Medical Device Product Availability, Compliance, and Enforcement \nDecisions.  Guidance for Industry and Food and Drug Administration Staff. \nDecember 27, 2016. Washington, USA.  \nhttps://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/G\nuidanceDocuments/UCM506679.pdf  \n \n\uf0b7 Guo JJ, Pandey S, Doyle J, Bian B, Lis Y, Raisch DW. A review of quantitative risk -\nbenefit methodologies for assessing drug safety and efficacy -report of the ISPOR \nrisk-benefit management working group. Value Health. 2010;13(5):657 -66 \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n38 \n \uf0b7 Hass U, Christiansen S, Andersson A -M, Holbech H, Bjerregaard P. Report on \ninterpretation of knowledge on endocr ine disrupting substances (EDs) \u2013 what is \nthe risk? Danish Centre on Endocrine Disruptors, Denmark . \n(http://www.cend.dk/files/ED_Risk_report -final-2019.pdf)  \n \n\uf0b7 Katsikantami I, Sifakis S, Tzatzarakis MN, Vakonaki E, Kalantzi OI, Tsatsakis AM, \nRizos AK. A global assessment of phthalates burden and related links to health \neffects.  Environ Int. 2016;97:212 -236. doi: 10.1016/j.envint.2016.09.013  \n \n\uf0b7 Mariana M, Feiteiro J, Verde I, Cairrao E. The effects of phthalates in the \ncardiovascular and reproductive systems: A review.  Environ Int. 2016;94:758 -\n776. doi: 10.1016 /j.envint.2016.07.004.  \n \n\uf0b7 Mt-Isa S, Hallgreen C.E., Wang N., Callr\u00e9us T.,  Genov G., Hirsch I., Hobbiger S., \nHockley .S., Luciani D., Phillips L.D., Quartey G., Sarac S.B., Stoeckert I., Tzoulaki \nI., Micaleff A., Ashby D. , IMI-PROTECT benefit -risk participants.  Balancing benefit \nand risk of medicines a systematic review and clas sification of available \nmethodologies, Pharmacoepidemiol Drug Saf. 23(7):667 -78, 2014. doi: \n10.1002/pds.3636.  \n \n\uf0b7 Nielsen BS, Andersen BN, Giovalle E, Bjergstrom M, Larsen PB. Alternatives to \nclassified phthalates in medical devices. The Danish Environmental Protection \nAgency 2014, Copenhagen, Denmark  \n \n\uf0b7 Prowse CV, de Korte D, Hess JR, van der Meer PF; Biomedical Excellence for Safer \nTransfusion (BEST) Collaborative.Commercially available blood storage containers.  \nVox Sang. 106(1):1 -13, 2014. doi: 10.1111/vox.12 084.  \n \n\uf0b7 Salloum HA, Saunier J, Aymes -Chodur C, Barakat H, Yagoubi N. Impact of the \nnature and concentration of plasticizers on the ability of PVC to sorb drug. \nInternational Journal of Pharmaceutics 496, 664 \u2013675, 2015.  \n \n\uf0b7 SCHEER 2018 Memorandum on weight of evidence and  uncertainties. Revision \n2018. \nhttps://ec.europa.eu/health/sites/health/files/scientific_committees/scheer/docs/s\ncheer_o_014.pdf  \n \n\uf0b7 SCENIHR Opinion on The safety of medical devices containing DEHP  plasticized   \nPVC or other plasticizers on neonates and other groups possibly at risk (2015 \nupdate).  2015 \nhttps://ec.europa.eu/health/scientific_committees/emerging/docs/scenihr_o_047.\npdf \n \n\uf0b7 Simmchen J , Ventura R , Segura J . Progress in the removal of di -[2-ethylhexyl] -\nphthalate as plasticizer in blood bags. Transfus Med Rev. 2012; 26(1):27 -37. doi: \n10.1016/j.tmrv.2011.06.001. Epub 2011 Aug 5.  \n \n\uf0b7 Tortolano L, Matmati H, Bourhis M,Manerlax K, Lemare F, Saunier J,Yagoubi N. \nDinCH and ESBO actual migration from PVC infusion tubings used in an \noncopediatric unit. J. Appl. Polym.  Sci. 135, 46649, 2018.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n39 \n  \n\uf0b7 Treleano A,Wolz  G,Brandsch  R, Welle  F. Investigation into the sorption of \nnitroglycerin and diazepam intoPVC tubes and alternative tube materials during \napplication . Intl JPharmac 369, 30 \u201337, 2009.  \n \n\uf0b7 Welsh M, Saunders PT, Fisken M, Scott HM, Hutchison GR, Smith LB, Sharpe RM.  \nIdentification in rats of a programming window for reproductive tract \nmasculinization, disruption of which leads to hypospadias and cryptorchidism. J \nClin Invest. 2008 ; 118(4):1479 -90. doi: 10.1172/JCI34241.  \n \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n40 \n  \nC. ANNEXES  \n \nAnnex   1: SCHEER mandate on benefit -risk assessment on the use of CMR/ED phthalates  \n \n1. Background  \n \nWhat are phthalates?  \nPhthalates are the esters of 1,2 -benzenedicarboxylic acid (o -phthalic acid) and their \nchemical structure consists of one benzene  ring and two ester functional groups linked \nwith two consecutive carbons on the ring10. The hydrocarbon chains of the ester groups \nare either straight or branching; they give each substance its name and they are \nresponsible for the different properties amo ng phthalates. Phthalate esters (PEs) may be \ncategori sed into three distinct groups according to the length of their carbon chain. High \nmolecular weight (HMW) phthalates include those with 7 \u201313 carbon atoms in their carbon \nchain and low molecular weight (L MW) those with 3 \u20136 carbon atoms in their backbone. \nDEHP is classified as a LMW phthalate. A third group includes dimethyl phthalate (DMP) \nand diethyl phthalate (DEP)11. \n \nWhat are they used for?  \nPhthalates are widely used in industry as plastici sers of polym ers such as polyvinyl \nchloride (PVC). HMW phthalates are used in a variety of applications such as coated \nfabrics and roofing membranes.  LMW phthalates are used in medical devices, adhesives, \npaints, inks and enteric -coated tablets. DEHP is the most widel y used phthalate in \nmedical devices. DMP and DEP are not used as plastici sers but e.g. as  additives in \ncosmetics, medical devices, and household products.  \n \nPotential CMR  or endocrine -disrupting properties  \nThe interaction of phthalates with the polymers the y are embedded in is weak, so they \nmay migrate from the plastic product into the environment and into the human body if \nthe product is in contact with it.  \nCorrelation between exposure to a range of phthalates and adverse health effects has \nbeen documented in animals and humans (see for example tables in Mariana et al. 2016 \nand Katsikantami et al.  2016). A number of phthalates are suspected of and/or have \nbeen classified or identified as having CMR or endocrine -disrupting properties.  \n                                                           \n10 A global assessment of phthalates burden and related links to health effects. Katsikantami et al., Environ Int. \n2016 Dec;97:212 -236. https://www.ncbi.nlm.nih.gov/pubmed/?term=katsikantami   \n11 Footnote added by SCHEER. It should be noted that there are hundreds of phthalates of which only a limited \nnumber is used as plasticiser in polymers. Phthalates can be categorised according to the length of the carbon \nchain and one of these categorisations is mentioned in the mandate of DG GROW.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n41 \n  \nPrevious work of Commission Scientific Committees on phthalates  \nPrevious opinions on the most commonly used phthalate DEHP [di -(2-(ethylhexyl) \nphthalate] in medical devices were issued by EU Scientific Committees in 2002 \n(SCMPMD), 2008 and 2015 (SCENIHR). The 2008 Opinion concluded that \"So far, there is \nno conclusive scientific evidence that DEHP exposure via medical treatments has harmful \neffects in humans\",  but noted that \"newborn and pre -term born male infants are of \nspecial concern\" . In the 2015 Opinion, SCENIHR additi onally identified that \"patients \nsubject to haemodialysis procedure may be at risk of DEHP induced effects\" . The \nCommittee noted that \"Food is the primary source of exposure to DEHP for the general \npopulation.\"  \nIn both opinions, the Committee emphasised th at \"the benefit of the medical devices \nmust also be considered\"  and in the 2008 Opinion the Committee states that \"each \nalternative to DEHP, however, must also be evaluated with regard to their functionality in \nrespect to medical devices. The risk and bene fits of using alternative plasti cizers should \nbe evaluated case by case.\"  In the 2015 opinion, the Committee states that \u201cThe \npotential for replacement of DEHP in these products should be considered against their \nefficiency in the treatment, as well as the  toxicological profile and leaching properties of \nthe alternative materials.\u201d  \n \nThe legal obligation  \nArticle 5 paragraph 2 of the Regulation 2017/745 on medical devices stipulates: \"A \ndevice shall meet the general safety and performance requirements set out  in Annex I \nwhich apply to it, taking into account its intended purpose.\"   \nAccordingly, Section 10.4 of Annex I, which deals with substances in medical devices, \nstates that \"Devices shall be designed and manufactured in such a way as to reduce as \nfar as possible the risks posed by substances or particles, including wear debris, \ndegradation products and  processing residues, that may be released from the device.\"  \nParticular substances of concern are those which (a) are carcinogenic, mutagenic or toxic \nto reproduction (CMR),  of category 1A or 1B,12 or (b) have endocrine -disrupting \nproperties (ED)13. The Regulation states that:  \n \n\"Devices, or those parts thereof or those materials used therein that:  \n\uf02d are invasive and come into direct contact with the human body,   \n\uf02d (re)administer medicines, body liquids or other substances, including gases, \nto/from the body, or  \n\uf02d transport or store such medicines, body fluids or substances, including gases, to \nbe (re)administered to the body\"  \n \n                                                           \n12 in accordance with Part 3 of Annex VI to Regulation (EC) No 1272/2008  \n13 identified as such in accordance with the relevant provisions of Regulation (EC) No 1907/2006 or respectively \nof Regulation (EU) No 528/2012  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n42 \n shall only contain any such substance ab ove the concentration of 0.1% weight by weight \nwhere justified pursuant to Section 10.4.2. The justification shall be based on several \nelements, including the latest relevant scientific committee guidelines on benefit -risk \nassessment of the presence of suc h substance in devices.  \nAccording to Section 10.4.3, the Commission shall provide a mandate to the relevant \nscientific committee to prepare such guidelines for phthalates which are subject to these \nprovisions. These guidelines are explicitly requested by t he Regulation to be available at \nthe latest on the date of application of the Regulation, and are to be updated whenever \nappropriate on the basis of the latest scientific evidence, or at least every five years.  \n \n2. Terms of reference  \n \nThe Scientific Committee  is requested to provide guidelines on the benefit -risk \nassessment of the presence, in the medical devices specified below, of phthalates which \nhave one or more of the following properties: carcinogenic, mutagenic, toxic to \nreproduction or endocrine -disrup ting, according to the criteria outlined in the previous \nsection.  \nThe devices covered, or those parts thereof of those materials used therein, are those \nwhich:  \n\uf0b7 are invasive and come into direct contact with the human body,  \n\uf0b7 (re)administer medicines, body l iquids or other substances, including gases, \nto/from the body, or  \n\uf0b7 transport or store such medicines, body fluids or substances, including gases, to \nbe (re)administered  to the body.  \n \nThe guidelines shall include guidance on how, for an individual device, to: \n\uf0b7 analyse and estimate potential patient or user exposure to the substance,  \n\uf0b7 analyse possible alternative substances, materials, designs, or medical \ntreatments,  \n\uf0b7 to justify why possible substance and/or material substitutes, if available, or \ndesign change s, if feasible, are inappropriate in relation to maintaining the \nfunctionality, performance and the benefit -risk ratios of the product, including \ntaking into account if the intended use of such devices includes treatment of \nchildren or treatment of pregnan t or breastfeeding women or treatment of other \npatient groups considered particularly vulnerable to such substances and/or \nmaterials.  \n \nIn addition, the Scientific Committee is requested to : \n\uf0b7 identify any relevant knowledge gap , and \n\uf0b7 to give consideration to what extent of new evidence would be deemed \nappropriate to justify an update of these guidelines before the maximum period of \nfive years.  \n \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n43 \n  \nIn order to ensure the appropriateness of this guidance the Scientific Committee should \ninter alia : \n\uf0b7 involve at the appropriate level the notified bodies active in the field of medical \ndevices, or other relevant stakeholders such as Competent Authorities, \nprofessional and patient associations, industry associations, while maintaining \nscientific independence , \n\uf0b7 involve to the necessary extent the relevant EU Agencies  and Scientific \nCommittees.  \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n44 \n  \nAnnex  2: Medical Device Regulation (Regulation 2017/745) on CMR and/or ED \nsubstances  \n \nThe requirement for justification of the presence  of CMR 1A or 1B and/or ED hazardous \nsubstances is described in Annex I 10.4.2 as presented in the text box below.  \n \n \n \n10.4. Substances  \n \n10.4.1. Design and manufacture of devices  \n \nDevices shall be designed and manufactured in such a way as to reduce as fa r as possible the \nrisks posed by substances or particles, including wear debris, degradation products and \nprocessing residues that  may be released from the device.  \nDevices, or those parts thereof or those materials used therein that:  \n \n\u2014 are invasive and come into direct contact with the human body,  \n \n\u2014 (re)administer medicines, body liquids or other substances, including gases, to/from the \nbody, or  \n \n\u2014 transport or store such medicines, body fluids or substances, including gases, to be \n(re)administered to the body,  \n  \nshall only contain the following substances in a concentration that is above 0,1 % weight by \nweight (w/w) where justified pursuant to Section 10.4.2:  \n  \n(a) substances which are carcinogenic, mutagenic or toxic to reproduction (\u2018CMR\u2019), of category \n1A or 1B, in accordance with Part 3 of Annex VI to Regulation (EC) No 1272/2008 of the \nEuropean Parliament and of the Council (1), or  \n  \n(b) substances having endocrine -disrupting properties for which there is scientific ev idence of \nprobable serious effects to human health and which are identified either in accordance with the \nprocedure set out in Article 59 of Regulation (EC) No 1907/2006 of the European Parliament \nand of the Council (2) or, once a delegated act has been ad opted by the Commission pursuant \nto the first subparagraph of Article 5(3) of Regulation (EU) No 528/2012 of the European \nParliament and the Council (3), in accordance with the criteria that are relevant to human \nhealth amongst the criteria established the rein.  \n \n10.4.2. Justification regarding the presence of CMR and/or endocrine -disrupting substances  \n \nThe justification for the presence of such substances shall be based upon:  \n(a) an analysis and estimation of potential patient or user exposure to the subs tance;  \n(b) an analysis of possible alternative substances, materials or designs, including, where \navailable, information about independent research, peer -reviewed studies, scientific opinions \nfrom relevant scientific committees and an analysis of the avail ability of such alternatives;  \n(c) argumentation as to why possible substance and/ or material substitutes, if available, or \ndesign changes, if feasible, are inappropriate in relation to maintaining the functionality, \nperformance and the benefit -risk ratio s of the product; including taking into account if the \nintended use of such devices includes treatment of children or treatment of pregnant or \nbreastfeeding women or treatment of other patient groups considered particularly vulnerable to \nsuch substances an d/or materials; and  \n(d) where applicable and available, the latest relevant scientific committee guidelines in \naccordance with Sections 10.4.3 and 10.4.4.  \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n45 \n  \nAnnex 3:  Definitions/descriptions \u2013 References - Glossary  \n \nDefinitions ( Regulation  (EU) 2017/745 ) \n \nBenefit -risk determination:  means the analysis of all assessments of benefit and risk \nof possible relevance for the use of the device for the intended purpose, when used in \naccordance with the intended purpose given by the manufacturer.  \n \nPerformance:  means the ability of a device to achieve its intended purpose as stated by \nthe manufacturer.  \n \nClinical performance:  means the ability of a device, resulting from any direct or \nindirect medical effects which stem from its technical or functional characteri stics, \nincluding diagnostic characteristics, to achieve its intended purpose as claimed by the \nmanufacturer, thereby leading to a clinical benefit for patients, when used as intended by \nthe manufacturer.  \n \nClinical benefit:  means the positive impact of a de vice on the health of an individual, \nexpressed in terms of a meaningful, measurable, patient -relevant clinical outcome(s), \nincluding outcome(s) related to diagnosis, or a positive impact on patient management or \npublic health.  \n \nRisk: means the combination of the probability of occurrence of harm and the severity of \nthat harm.  \n \nAdverse event:  means any untoward medical occurrence, unintended disease or injury \nor any untoward clinical signs, including an abnormal laboratory finding, in subjects, \nusers or othe r persons, in the context of a clinical investigation, whether or not related to \nthe investigational device.  \n  \nSerious adverse event:  means any adverse event that led to any of the following: (a) \ndeath, (b) serious deterioration in the health of the subjec t, that resulted in any of the \nfollowing: (i) life -threatening illness or injury, (ii) permanent impairment of a body \nstructure or a body function, (iii) hospitali sation or prolongation of patient hospitali sation, \n(iv) medical or surgical intervention to p revent life -threatening illness or injury or \npermanent impairment to a body structure or a body function, (v) chronic disease, (c) \nfetal distress, fetal death or a congenital physical or mental impairment or birth defect.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n46 \n   \nIncident:  means any malfunction or deterioration in the characteristics or performance \nof a device made available on the market, including use -error due to ergonomic features, \nas well as any inadequacy in the information supplied by the manufacturer and any \nundesir able side -effect.  \n \nSerious incident:  means any incident that directly or indirectly led, might have led or \nmight lead to any of the following: (a) the death of a patient, user or other person, (b) \nthe temporary or permanent serious deterioration of a pati ent's, user's or other person's \nstate of health, (c) a serious public health threat.  \n \nSerious public health threat : means an event which could result in imminent risk of \ndeath, serious deterioration in a person's state of health, or serious illness, that may \nrequire prompt remedial action, and that may cause significant morbidity or mortality in \nhumans, or that is unusual or unexpected for the given place and time.  \n \nDevice deficiency:  means any inadequacy in the identity, quality, durability, reliability,  \nsafety or performance of an investigational device, including malfunction, use errors or \ninadequacy in information supplied by the manufacturer.  \n \nRegulation (EU) 2017/745 Annex XIV Clinical evaluation and post -market \nclinical follow -up. Part A \u201cClinical evaluation\u201d Section 3 describes the \ncharacteristics that shall be considered for demonstration of equivalence .  \n\u201cA clinical evaluation may be based on clinical data relating to a device for which \nequivalence to the device in question can be demonstrated. T he following technical, \nbiological and clinical characteristics shall be taken into consideration for the \ndemonstration of equivalence:  \n \nTechnical : the device is of similar design; is used under similar conditions of use; has \nsimilar specifications and pr operties including physicochemical properties such as \nintensity of energy, tensile strength, viscosity, surface characteristics, wavelength and \nsoftware algorithms; uses similar deployment methods, where relevant; has similar \nprinciples of operation and cr itical performance requirements;  \n  \nBiological : the device uses the same materials or substances in contact with the same \nhuman tissues or body fluids for a similar kind and duration of contact and similar release \ncharacteristics of substances, including de gradation products and leachables;  \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n47 \n  \nClinical : the device is used for the same clinical condition or purpose, including similar \nseverity and stage of disease, at the same site in the body, in a similar population, \nincluding as regards age, anatomy and physiology; has the same kind of user; has \nsimila r relevant critical performance in view of the expected clinical effect for a specific \nintended purpose.  \nThe characteristics shall be similar to the extent that there would be no clinically \nsignificant  difference in the safety and clinical performance of the device. Considerations \nof equivalence shall be based on proper scientific justification. It shall be clearly \ndemonstrated that manufacturers have sufficient levels of access to the data relating  to \ndevices with which they are claiming equivalence in or der to justify their claims of \nequivalence. \u201d \n \nDefinitions on assessment of alternatives (OECD Toolbox Glossary)  \nNote: The term \"chemical\" is used synonymously with \"substance\"  \n \nAlternativ es assessment : A process for identifying and comparing potential chem ical \nand non -chemical alternatives that can be used as substitutes to replace chemicals or \ntechnologies of high concern1 \n \nChemical substitution : The process of replacing a chemical of concern with a safer \nchemical, material or product, or technology/process that eliminates the need to use that \nchemical  \n \nCost/benefits and availability : The negative (cost) and positive (benefit) implications, \ndirect and indirect, resulting from some actio n. This includes both financial and non -\nfinancial information. Availability refers to the production of an alternative and its market \naccessibility3 \n \nFunctional use approach : This approach starts with identifying the function that is \ndesired. The concept is applied in two ways: \ufb01rst and foremost, to characteri se the \npurpose a chemical or mixture serves, or the properties it imparts in a product or process \n(functional use), and second, to eva luate the function of the product and how its use may \nin\ufb02uence the assessment of alternatives4, 5 \n \nMaterial substitution : The process of replacing a material containing a chemical of \nconcern with a safer chemical, material, product or technology/process that eliminates \nthe need to use that chemical  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n48 \n  \nMixture : A composition of at least two chemicals in which they do not react6 \n \nTechnical feasibility : The determination as to whether the performance or functional \nrequirements of a chemical, material or product could be fulfilled or replaced by \neliminating or using an alternative chemical, material, product, process or technology, \nwhile considering any need for process adaptations and changes3 \n \nProcess modification : Changes in manufacturing processes to eliminate, reduce or \nsubstitute chemicals of concern. Such changes may include synthesis pathways, waste \nreduction, and manufacturing procedures where chemicals are used.  \n \nProduct performance : The ability of a product to meet identified performance \nrequirements. The boundaries of performance characteristics are defined by the user3 \n \nProduct substitution : The process of replacing a product containing a chemical of \nconcern with a chemical, material or product or technology/process that eliminates, \nreduces or substitutes the need to use that chemical.  \n \n1 Adapted from Alternatives Assessment Guide, version 1.0 . 2013. Interstate Chemicals \nClearinghouse.  \n2 REACH. Title I, Chapter 2, Article 3.  \n3 Current Landscape of Alternatives Assessment Practice: A Meta -Review. Organisation \nfor Economic Cooperation and Development. 2013.  \n4 U.S. EPA. 2006. National Pollution Prevention and Toxics Advisory Committee (NPPTAC) \nRecommendation to the EPA Administrat or and Deputy Administrator on Incorporating \nthe Functional Use Approach into OPPT Activities.  \n5 Lavoie, E. T., et al.  2010. \"Chemical Alternatives Assessment: Enabling Substitution to \nSafer Chemicals.\" Environmental Science & Technology 44(24): 9244 -9249.  \n6 Adapted from U.N. Global Harmonized System of Classification and Labelling  of \nChemicals . 2003.  \n7 ECHA, 2008. Guidance on Socio -Economic Analysis - Restrictions.  \n8 Adverse event means pre -clinical and clinical occurrences of an effect whereas incident \nindicates a clinical effect occurring during post -market surveillance.  \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n49 \n  \nReference s \n\uf0b7 ECHA (2011) Guidance on the preparation of socio -economic analysis as part of \nan application for authorisation, European Chemicals Agency 2011 . \n\uf0b7 EFSA (2019)  Draft update of the risk assessment of di -butylphthalate 1 (DBP), \nbutyl-benzyl -phthalate (BBP), bis(2 -2 ethylhexyl)phthalate (DEHP), di -\nisononylphthalate (DINP) 3 and di -isodecylphthalate (DIDP) for use in food \ncontact 4 materials  http://www.efsa.europa.eu/en/consultations/call/190221 .  \n\uf0b7 Guo JJ, Pandey S, Doyle J, Bian B, Lis Y, Raisch DW. A review of quantitative risk -\nbenefit methodologies for assessing drug safety and efficacy -report o f the ISPOR \nrisk-benefit management working group. Value Health. 2010;13(5):657 -66. \n \nGlossary  \nBBP   Benzylbutylphthalate  \nBMD  Bench Mark Dose  \nBRA  Benefit -Risk Analysis  \nBTHC   Butyryl -tri-n-hexylcitrate  \nCAS  Chemical Abstracts Service  \nCEN  European Committee for Standardization  \nCLP  Classification Labelling and Packaging regulation (EC No 1272/2008)  \nCMR  Carcinogenic, Mutagenic, toxic to Reproduction (Reprotoxic)  \nDBP   DiButylphthalate,  \nDCHP   Dicyclohexylphthalate  \nDEHP   Diethylhexylphthalate  \nDIBP   Diisobutylphthalate  \nDIDP   Di isodecyl phthalate)  \nDINCH  1,2- cyclohexan edicarboxylic acid, di isononyl ester)  \nDINP   Di isononyl phthalate)  \nDIPP  Diisopentylphthalate  \nDMEP   Bis(2-methoxyethyl)phthalate  \nDNHP   Dihexylphthalate  \nDHNUP  1,2-Benzenedicarboxylic acid, di -C7-11-branched and linear alkyl esters  \nDPP   Dipentyl phthalate  \nDMEL   Derived Minimum Effect Level  \nDNEL   Derived No Effect Level  \nEC  European Commission  \nECB  European Chemicals Bureau (now ECHA)  \nECHA   European Chemicals Ag ency (formerly ECB)  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n50 \n ED  Endocrine Disruptor  \nEEC  European Economic Community  \nEMA  European Medicines Agency  \nEFSA  European Food Safety Authority  \nEN-ISO CEN and ISO combined published document  \nFDA  Food and Drug Administration (USA)  \nFDIS  Final Draft International Standard  \nISO  International Organization  for Standardization  \nLOAEL   Lowest Observed Adverse Effect Level  \nMCDA   Multi Criteria Decision Analysis  \nMDD  Medical Device Directive (Council Directive 93/42/EEC)  \nMDR  Medical Device Regulation (EU 20 17/745)  \nMoA  Mode of Action \nMoE  Margin of Exposure  \nMoS  Margin of Safety  \nNICU  Neonatal Intensive Care Unit  \nNOAEL   No Observed Adverse Effect Level  \nOECD   Organization for Economic Cooperation and Development  \nPoD  Point of departure  \nPVC  Polyvinyl chloride  \nRBC  Red Blood Cell  \nRCR  Risk Characterisation Ratio  \nREACH   Registration, Evaluation, Authorisation and restriction of CHemicals.  \nSCHEER  Scientific Committee on Health, Environmental and Emerging Risks  \nSCENIHR  Scientific Committee on Emerging and Newly Identified Health Risks  \nT25   25 % increase of the tumour rate over controls  \nTDI  Tolerable Daily Intake  \nTE  Tolerable Exposure (EN ISO 10993 -17:2002 in mg/day)  \nTEHTM   Tri( 2 -ethyl hexyl)trimellitate also TOTM Trioctyltrimellitate  \nTI  Tolerable Intake  \nTOTM   Trioctyltrimellitate also TEHTM Tri( 2 -ethyl hexyl)trimellitate  \nTWI    Tolerable Weekly Intake   Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n51 \n  \nAnnex 4:  CMR and/or ED substances  \n \nCMR substances are substances identified and classified as carcinogenic, mutagenic or \ntoxic for reproduction of different categories based on the intrinsic toxic properties of a \nsubstance for which categories 1A and 1B apply to these Guidelines. In Europe, \nclassification for  these endpoints is harmonised through harmonised classification and \nlabelling (CLH). Details  can be found at  \nhttps://echa.europa.eu/regulations/clp/understanding -clp. For a specific substance to be \nclassified as CMR 1A, 1B or 2 a dossier needs to be prepared and if the Commission finds \nthat the proposed classification is appropriate, it submits a draft decision concerning the \ninclusion of that substance in Part 3 of Annex VI to the CL P Regulation (Regulation (EC) \n1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures).  \n\uf0b7 Category 1A means that the substance is a known human carcinogen, mutagen or \nreproductive toxicant based on human evidence.  \n\uf0b7 Category 1B means that the substance is a presumed human carcinogen, \nmutagen or reproductive toxicant based on animal studies.  \n\uf0b7 Category 2 means that a substance is considered as suspected carcinogen, \nmutagen or reproductive toxicant based on limited evidence from ani mal studies \nor humans  (not part of these Guidelines) .  \nDocuments on the classification are publicly available , and  a tutorial to search entries is \ngiven here:  \nhttp://www.chemsafetypro.com/Topics/EU/Annex_VI_to_CLP:_List_of_Harmonised_Class\nification_and_Labelling_for_Certain_Hazardous_Substances.html  \nGuidance for the identification of endocrine disrupto rs (ED) in the context of Regulations \n(EU) No 528/2012 and (EC) No 1107/2009 has been published on 7th June 2018 by \nECHA and EFSA (doi: 10.2903/j.efsa.2018.5311; EFSA Journal 2018;16(6):5311) which \ncan be accessed via:   \nhttps://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2018.5311  \nThis EFSA/ECHA Guidance describes when a substance shall be considered as having \nendocrine disrupting  properties.  \n\u201cA  substance shall be considered as having endocrine disrupting properties  if it meets all \nof the following criteria:  \na) it shows an adverse effect in [an intact organism or its progeny]/[non -target \norganisms], which is a change in the morphology, physiology , growth, \ndevelopment, reproduction or life span of an organism, system or \n(sub)population6 that results in an impairment of functional capacity, an \nimpairment of the capacity to compensate for additional stress or an increase in \nsusceptibility to other in fluences;  \nb) it has an endocrine mode of action, i.e. it alters the function(s) of the endocrine \nsystem;  \nc) the adverse effect is a consequence of the endocrine mode of action.  \nIt should be highlighted that the \u2018endocrine mode of action \u2019 as stated in point  (b) \nshould be interpreted  as \u2018endocrine activity \u2019 while the term \u2018endocrine mode of Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n52 \n action\u2019 in point (c) covers the link between the adverse effect and the endocrine activity \nidentified in points a) and b), respectively.  \nKeeping this in mind point (b) abo ve should be understood as (differences from above in \nitalics ): \nit shows endocrine  activity, i.e. it has the potential to alter the function(s) of the \nendocrine system;  \nConsequently point (c) above should be understood as (differences from above in italics ): \nthe substance has an endocrine disrupting mode of action, i.e. there is a \nbiologically plausible link between the adverse effect and the endocrine activity. \u201d \nEDs identified with the procedure set out in Article 59 of Regulation (EC) No 1907/2006 \nconcern ing the Registration, Evaluation, Authorisation and Restriction of Chemicals \n(REACH),   will finally enter the REACH candidate list of substances of very high concern \nfor potential inclusion in REACH Annex XIV.  The information can be found in the \nrespecti ve decision document accessible via : https://echa.europa.eu/candidate -list-table. \nFor substances having endocrine -disrupting properties as indicated above, there is \ncurrently no information concer ning whether it is foreseen to publish them in central lists \nor annexed to a Regulation.  \nEDs identified by the delegated act pursuant to the first subparagraph of Article 5(3) of \nRegulation (EU) No 528/2012 concerning the making available on the market and  use of \nbiocidal products, can be accessed through the Biocidal Products Committee opinions on \nactive substance approval which can be accessed via ECHA\u2019s website \n(https://echa.europa.eu/regulations/biocidal -products -regulation/approval -of-active -\nsubstances/bpc -opinions -on-active -substance -approval ).  \nSubstances undergoing an ED assessment under the REACH or Biocidal Products \nregulations that have been brought for discussion to ECHA\u2019s ED Expert Group are \nincluded in ECHA\u2019s endocrine disruptor (ED) assessment list: https://echa.europa.eu/ed -\nassessment . For each substance, the table shows the assessing or evaluating Member \nState (submitter), the outcome and the suggested follow -up for the assessment, and the \ndate of the latest update to the list entry.  \nRecently the Commission Implementing Decision (EU) 2017/1210 was published that \nidentified some phthalates (Bis(2 -ethylhexyl) phthalate (DEHP), Benzyl butyl phthalate \n(BBP), Dibutyl phthalate (DBP) and Diisobutyl phthalate (DIBP)) as substances of very \nhigh concern due to their endocrine disrupting properties with probable serious effects to \nhumans (European Commission 2017).  \nhttps://publications.europa.eu/en/publication -detail/ -/publication/357b3d45 -620f-11e7-\n9dbe-01aa75ed71a1/language -en/format -PDF \nFor completeness, even if not relevant for the purpose of this guidelines, Bis(2 -\nethylhexyl) phthalate (DEHP) was also  identified in 2014 as a substance of very high \nconcern due to its endocrine disrupting properties with probable serious effects to the \nenvironment.  \nIn addition, Commission Implementing Decision (EU) 2018/636 identified \nDicyclohexylphthalate (DCHP) as subs tance of very high concern (SVHC) according to \nArticle 57(f) of REACH Regulation (EC) 1907/2006, due to its endocrine disrupting Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n53 \n properties with probable serious effects to humans.  https://eur -lex.europa.eu/legal -\ncontent/EN/TXT/PDF/?uri=CELEX:32018D0636&fr om=EN     Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n54 \n  \nAnnex 5:  Legislation on CMR and/or ED phthalates  \n \nDue to their reprotoxic properties and additionally since 2014 for DEHP due to their \nendocrine disrupting properties for the environment and since 2017 for DEHP, BBP, DBP, \nand DIBP  due to their endocrine disrupting properties  for human health , a considerable \nnumber of phthalates have been identified as substances of very high concern (SVHC) \nand therefore included in the candidate list for the inclusion in Annex XIV of the REACH \nregulation (Annex XIV of REACH EC 1907/2006 , see \nhttps://echa.europa.eu/de/candidate -list-table for the most recent update of the \ncandidate list).  \nEight phthalates are also listed on the Authorisation list (Annex XIV of REACH), namely \nDEHP, BBP, DIBP, DBP, DIPP (diisopentylphthalate), Bis(2 -methoxyethyl) phthalate, \ndipentyl phthalate, and N -pentyl -isopentylphthalate. Since February 2015 DEHP, BBP, \nDIBP, and DBP cannot be used within the European Union withou t authorisation. The \nsame provision would apply to the remaining four phthalates on Annex XIV from July \n2020. To date, applications for authorisation have been submitted for DEHP and DBP \nonly. However, imported articles do not come under the authorisation requirement. For \nthe purpose of evaluating applications for authorisation, the ECHA Committee for Risk \nAssessment (RAC) has developed reference DNELs for several substances, including \nDEHP, BBP, DBP, and DIPP. (See Evaluating Applications table/Ref erence D NELs on \nECHA\u2019s website:  \nhttps://echa.europa.eu/applying -for-authorisation/evaluating -applications .) \nRisks to human health arising from the use of an Annex XIV substan ce in medical devices \nregulated by Directives 90/385/EEC, 93/42/EEC or 98/79/EC are exempted from \nauthorisation requirements under Title VII of the REACH Regulation14. ECHA is currently \npreparing a recommendation on the inclusion of the ED properties for environment for \nDEHP in Annex XIV to REACH .15 If DEHP is included on Annex XIV for environmental \nhazards , applications for authorisations may need to be prepared for uses of the \nsubstance in medical devices in the future.  \nREACH Annex XVII (entry 51) also restricts the placing on the market of articles \ncontaining DEHP, BBP, DBP, and DIBP in concentration greater than 0.1% weight by \nweight of the plasticised material, individually or in combination in a range of articles. \nThese articles include toys16 and childcare articles, as well as other primarily consumer \nand professional use articles whic h lead to dermal or inhalation exposure. (For risk \nassessment conclusions, including derivation of a DNEL for DIBP, see Compiled RAC & \nSEAC opinion and background document on ECHA\u2019s website:  \nhttps://echa.europa.eu/previous -consultations -on-restriction -proposals/ -/substance -\nrev/13919/term .)   \n                                                           \n14 These Regulations will be replaced by:  \n\uf0b7 Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical \ndevices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No \n1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC  \n\u2022Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro  \ndiagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU  \n15 https://echa.europa.eu/draft -recommendation -for-amendment -of-authorisation -list-entries -previous -\nconsultation   \n16 The Toy Safety Directive (2009/48/EC) stipulates that chemicals that are susceptible to cause cancer, change \ngenetic information, harm fertility or harm an unborn child (CMR substances) are no longer allowed in \naccessible parts of toys beyond the concentration limits set in the CLP Regulation ((EC) No 1272/2008).  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n55 \n REACH Annex XVII (entry 52) restricts the placing on the market and the use of DINP, \nDIDP, and DNOP, as a  substance or in mixture, in concentrations greater than 0.1% \nweight by weight of the plasticised material in toys and childcare articles which can be \nplaced in the mouth of children. In 2010, the European Commission requested ECHA to \nreview the scientific  evidence on the risks posed by articles containing these phthalates \nwith the view to conclude on the need or not for further actions under REACH. The report \nand RAC risk assessment conclusions (including information on the derivation of DNELs) \ncan be foun d on ECHA\u2019s website: https://echa.europa.eu/consultations -draft-review -\nreport -previous -consultations/ -/substance -rev/1108/term .  \nEFSA recently launched a consultation on its updated 2005 risk assessments of DBP, \nBBP, DEHP, DINP and DIDP which are authorised for use in plastic FCM, by using the \nsame database as ECHA for its 2017 assessment of certain phthalates. The draft update \nof the ri sk assessment can be found here:  \nhttp://www.efsa.europa.eu/en/consultations/call/190221  \nIn addition to the REACH legislation, there is also product -specific legislation which \nregulates certain phthalates, i.e. the Cosmetic Products\u2019 Regulation (EC/1223/2009) and \nthe Regulation on materials and articles intended to come into contact with food ( Food \nContact Materials,  Regulation EC 1935/2004 , as general framework regulation and \nRegulation EU 10/2011 specific for plastic materials and articles destined to be in contact \nwith foodstuffs , recently amended by Regulation 2018/831 ). Both in the MDD \n(93/42/EEC) and the more recent MDR (2017/745), phthalates are specifically mentioned \nfor their use in medical devices.  \nFor a number of phthalates there is legislation available that might contain information \nrelevant for the use of phthalates in medical devices. Of specific relevance for medical \ndevices may be the Regulation EU 10/ 2011, which also incl udes provisions for the use of \nphthalates in food contact materials and articles with respect to migration limits. This \nmay be a parallel with migration (and thus potential internal exposure) of phthalates as \npresent in polymers used for medical device man ufacturing. In Annex I of the Regulation \nEU 10/2011 all substances are listed, which are authorised for the use as starting \nmaterial or additive for plastic layers in plastic materials and articles. Each substance \nmust not exceed its specific migration lim it (SML). The following phthalates and other \nplastici sers17 are authorised for use as additives:  \n \nDBP (SML) = 0.3 mg/kg food  \nonly to be used as:  \n(a) plasticiser in repeated use materials and articles in contact with  non -fatty foods;   \n(b) technical supp ort agent in polyolefins in concentrations up to 0.05% in the final  \nproduct  \n \nBBP, SML = 30 mg/kg food  \nOnly to be used as:  \n(a) plasticiser in repeated use materials and articles;  \n                                                           \n17 Not exhausti ve examples for other than phthalates  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n56 \n (b) plasticiser in single -use materials and articles in contact with  non -fatty foods, not for \ncontact with infant formulae and follow -on formulae (Directive 2006/141/EC) and \nprocessed cereal -based foods and baby foods for infants and young children (Direc tive \n2006/125/EC);  \n(c) technical support agent in concentrations up to 0.1% in the final product.  \n \nDEHP, SML = 1.5 mg/kg food   \nOnly to be used as:  \n(a) plasticiser in repeated use materials and articles in contact with non -fatty foods;  \n(b) technical su pport agent in concentrations up to 0.1% in the final product.  \n \nDINP SML = 9 mg/kg food (cumulative with DIDP)  \nonly to be used as  \n(a) plasticiser in repeated use materials and articles;  \n(b) plasticiser in single -use materials and articles in contact with  non -fatty foods , not \nfor contact with  infant formulae and follow -on formulae ( Directive 2006/141/EC) and \nprocessed cereal -based foods and baby foods for infants and young children (Di rective \n2006/125/EC)  \n(c) technical support agent in concentrations up to 0.1% in the final product.   \n \nDIDP, SML = 9 mg/kg food ( cumulative with DINP)  \nOnly to be used as  \n(a) plasticiser in repeated use materials and articles;  \n(b) plasticiser in single -use materials and articles in contact with  non -fatty foods , not \nfor contact with infant formulae and follow -on formulae ( Directive 2006/141/EC) and \nprocessed cereal -based foods and baby foods for infants and young children (Directive \n2006/125/EC)  \n(c) te chnical support agent in concentrations up to 0.1% in the final product.   \n \nFurthermore, for certain plasticizers listed in Regulation (EU) 10/2011, including a \nnumber of phthalates, applies a group restriction  (Group restriction number 32),  that is, \nthe sum of these substances must not exceed an SML of 60 mg/kg foodstuff.  \nDEHP, BBP, DBP and DIBP must not be contained in homogenous materials above the \nconcentration of 0.1% w/w from July 2019 on according to the Restriction of Hazardous \nSubstances Directive  in electrical and electronic equipment RoHS2 (2011/65/EC). For \nmedical devices and  in vitro  diagnostic products this restriction takes effect in July 2021.  \n \n \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n57 \n  \nTable 1  CMR Classification*) and ED designation**) of phthalates (status Jan 2019)  \nPhthalate  Abbreviation  CAS \nnumber  CMR \nClassification*  ED \nidentification**  \nbis(2-\nmethoxyethyl)phthalate  DMEP  117-82-\n8 Repr 1B  - \nbis  \n(2-ethylhexyl)phthalate  DEHP  117-81-\n7 Repr 1B  ED \ndibutyl phthalate  DBP 84-74-2 Repr 1B  ED \n1,2-\nbenzenedicarboxylic \nacid, dipentylester, \nbranched and linear   84777 -\n06-0 Repr 1B  - \nn-pentyl -\nisopentylphthalate  PIPP No CAS  \n776297 -\n69-9? Repr 1B  - \ndi-n-pentyl phthalate  DnPP 131-18-\n0 Repr 1B  - \ndiisopentylphthalate  DiPeP  605-50-\n5 Repr 1B  - \nbenzyl butyl phthalate  BBP 85-68-7 Repr 1B - ED \ndiisobutylphthalate  DIBP 85-69-5 Repr 1B  ED \ndihexylphthalate  DHP 84-75-3 Repr 1B   \ndicyclohexylphthalate  DCHP  84-61-7 Repr 1B  ED \n*) as indicated in Annex VI to CLP_ATP10 (in force from 1 December 2018).  \n**) according to the ECHA Candidate List of substances of very high concern for Authorisation  published in \naccordance with Article 59(10) of the REACH Regulation  https://echa.europa.eu/candidate -list-table  \n \nAs substances of concern, knowledge on the exposure to phthalates is important and \nbiomonitoring of populations provides important information.  For some of the phthalates \nalready human biomonitoring assessment values, namely Biomonitoring equi valents (BE) \nor human biomonitoring (HBM) values, have been derived \u2013 these are concentrations of \nbiomarkers (metabolites) in urine, which reflect an acceptable chronic exposure, since \nthe basic assumption is an equilibrium between external exposure and in ternal burden \n(Angerer et al.  2011, Apel et al.  2017). In the course of the work done within the \nHBM4EU project, Human Biomonitoring Guidance Values (HBM -GVs) could be derived for \nDEHP and DINCH (see HBM4EU Deliverable D5.2, https://www.hbm4eu.eu ). In addition, \nHBM-GVs for the following SVHC phthal ates are finalised in September 2019 (Deliverable \nD5.6) and will also be published on the website: BBzP, DiBP, and DnBP.   Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n58 \n  \nAnnex 6:  Use of phthal ates in medical devices  \n \nPhthalates are abundantly used in polyvinyl chloride (PVC) medical devices such as blood \nbags, intravenous bags, nutrition pockets, tubing, catheters, respiratory masks or \ndisposable gloves. More than 40% of all plastic -based disposable medical devices are  \nmade from PVC. Di -2-ethylhexyl phthalate (DEHP) has been for many years the most \ncommonly used phthalate ester plasticiser in medical devices. A survey among the \nDanish Medical Device Industry found that 95% of the products contained DEHP [Huntley \nP, edit or The classified phthalates should be phased out of medical devices. Alternatives \nto Classified Phthalates in PVC Medical Devices Conference; 2014 Mar 27; Copenhagen, \nDenmark].  \n \nSafety concerns have been expressed for several high -risk patients groups, s uch as \nneonates, infants, pregnant and breast -feeding women exposed to DEHP. The SCENIHR \nin its Opinion of 201 5 indicated that \u201ca lack of evidence of causation between DEHP -PVC \nand any disease or adverse effect does not mean that there are no risks\u201d. This lack of \nevidence applies to all phthalates classified as CMR and/or identified as ED. Therefore the \nrequirement of patient subgroup analysis for the target patient groups as defined in the \n\u201cIntended Use\u201d of a medical device is now included in the Regulatio n (EU) 2017/745.  \n \nFor the use of DEHP, high risk groups were identified including patients undergoing \nhaemodialysis, extracorporeal membrane oxygenation (ECMO), and prematurely born \ninfants in Neonatal Intensive Care Units (NICU), (SCENIHR 201 5). The actua l exposure of \nsuch patient groups relative to the toxicity including CMR/ED property needs to be \ndetermined. However, even if the remaining risk is high, the benefit of the treatment \nshould be considered as well. It might be useful to evaluate the patient subgroups \nseparately:  \n \n\uf0b7 Paediatric Population (see subgroups)  \n\uf0b7 Peripubertal males  \n\uf0b7 Pregnant women  \n\uf0b7 Breast -feeding women  \n\uf0b7 any other patient group considered particularly vulnerable or exposed to high \nlevels of phthalates.  \n \nFor purposes of this Guideline, the following ranges of paediatric subpopulations are \nproposed to be used as a guide for manufacturers in medical devices (ref. SCCS Notes of \nGuidance \u2013 SCCS/1602/18, section 3 -6.9.1, page 7818) \n \n \n \n \n \n \n \n \n                                                           \n18 https://ec.europa.eu/health/sites/health/files/scientific_committees/consumer_safety/docs/sccs _o_224.pdf   Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n59 \n  \nDefinition of Paediatric Population Subgroups  \n \nPaediatri c Subgroup  Approximate Age Range  \nFull-term neonate  <1 week  \nNewborn  1 week\u20132 months  \nEarly infant  2\u20136 months   \nCrawlers/toddler  6 months \u20132 years  \nPreadolescent  2\u201312 years   \nAdolescent  12\u201318 years   \n \nIn view of ED activity, a dditional (paediatric ) subpopulations may need to be considered \ninclud ing:  \n \n\uf0b7 very low birth weight describes newborns less than 1.5 Kg  \n\uf0b7 low birth weight describes newborns less than 2.5 Kg  \n\uf0b7 preadolescent age group typically ranges from 11 to 13 years.  \n\uf0b7 peripubertal males  or females  \n \nIt should be realised that the benefit of medical devices including the use of phthalates \nmust also be considered: The survival of prematurely born infants often depends on the \navailability of the same medical devices that result in a relative ly high phthalate content \nexposure due to treatment. Whenever possible, material with low release potential \nshould be used (see SCENIHR opinion 201 5). \n \nBesides the direct patient benefits of the treatment with a medical device containing \nphthalates, other functionalities may also need to be considered.  For example, DEHP has \na stabilising effect on red blood cells (RBCs). RBCs have increased survival rates when \nstored in DEHP containing blood bags. DEHP is incorporated into the cell walls of RBCs \nand stabil ises the membrane integrity of the RBCs. This results in a prolonged shelf life \nand thus patient availability of blood stored in DEHP containing blood bags (SCENIHR \n2015). A maximum limit of extractable DEHP of 15 mg/100 mL for flexible PVC \ncontaining DEHP  is indicated in EN ISO 3826 -1 on containers for the collection of human \nblood and blood components.   \n \nThe plasticiser industry has been investing and developing alternatives to DEHP in \nmedical devices. Today, other plasticisers such as Di -isononyl cyclohe xanoate (DINCH, \nCAS 166412 -78-8), Tri -2-ethylhexyl trimellitate (TEHTM, CAS 3319 -31-1), butyryl tri -n-\nhexyl citrate (BTHC, CAS 102818 -95-1) and Dioctyl Terephthalate (DOTP, CAS \u200e6422-86-\n2) are being proposed in medical applications such as medical tubing and blood bags.  \nhttps://www.plasticisers.org/applications/medical -applications/   \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n60 \n In conclusion, for any BRA on the use of phthalates and the development of alternatives \nin me dical devices, careful consideration should be used to appropriate patient subgroup \nanalysis regarding medical device use and the resulting potential exposure.  \n \nReference  \nHuntley P, Editor . The classified phthalates  should be phased out of medical devices. \nProgram Meeting on Alternatives to Classified Phthalates in PVC Medical Devices \nConference; 2014 Mar 27; Copenhagen, Denmark.  \nhttps://pvc.dk/wp -content/uploads/2016/02/pvc -alternativer -til-klassificerede -ftalater -\nprogram.pdf  \n \n \n   Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n61 \n  \nAnnex 7:  Approaches for Benefit -Risk Assessment  \n \nSeveral approaches for BRA have been proposed especially in the context of medicinal \nproducts. The Innovative Medicines Initiative PROTECT Project (www.imiprotect.eu), \npresented a detailed review of approaches used for BRA (Mt -Isa et al.  2014). In this \nreview, a large number of approaches were identified and classified as descriptive \n(qualitative or semi -qualitative) or quantitative frameworks (relying on quantitative \nmethods of trading risks and benefits following mathematical principles), metrics \n(measure s for benefits and risks that are usually endpoint specific), estimation \ntechniques (i.e., simulation techniques and meta -analysis) , and utility survey techniques \n(to elicit stakeholders\u2019 preferences).  \nConcerning quantitative frameworks, according to the European Medicines Agency (EMA) \nProject Report (EMA/227124/2011), there is no agreement on any one approach to be \nused in regulatory submission on the benefits and risks of medicines. However, EMA has \nencouraged the use of quantitative frameworks in regulatory submissions of applications \nfor marketing authorisation of medicinal products.  \nAlthough there is little experience with quantitative frameworks in the area of medical \ndevices, some of the BRA appro aches used for pharmaceuticals may also be relevant for \nmedical devices and particularly regarding the use of CMR/ED phthalates. In particular, \napproaches based on multicriteria decision analysis ( MCDA) have attracted much \nattention during the past years in the field of medical decisions. For an introduction to \nMCDA see Dodgson et al. (2009).  \nIn brief, MCDA is based on decision theory and belongs to the general class of multi -\ncriteria analysis mode ls that accommodate decision making with multiple objectives. The \nmain purpose of MCDA is to bring together evaluations of options on different criteria into \none overall evaluation.  The starting point for MCDA approaches include s identification of \nthe alte rnatives and the criteria against which the alternatives are appraised.  MCDA \nincludes weighting, which ensures that the units of value on all the criteria are \ncomparable so that benefits and risks can be compared by using a common unit of value. \nIn this wa y, the added value of benefits can be compared to the loss of value from the \nrisks. A number of different weighting methods can be used, ranging from precise \nelicitation of weights, to weights based on qualitative judgements or including \nuncertainty.  \nA generic framework for conducting an MCDA can be based on the steps of the PROACT -\nURL framework (Hammond et al. , 1999), as presented below. A detailed description of \nthe different implementations of MCDA techniques is beyond the scope of this guideline. \nThe c hosen techniques and analyses should be presented and justified among others on \nthe basis of internal consistency, logical soundness and transparency.  \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n62 \n  \nSTEP Description and relation to framework for Benefit -Risk \nAssessment described in section A of the  Guidelines  \nProblem  Describe the medical device, its intended use, and the \ntherapeutic context; frame the decision problem in terms \nof potential alternatives to CMR/ED phthalate. See Step 1: \nDescription and characterisation of the composition of the \nmedic al device; and Step 2: Use and function of the \nphthalates in the medical device.  \nObjectives  Identify the full set of criteria to evaluate different \nalternatives. See Step 2: Use and function of the \nphthalates in the medical device; and Step 3: Assessment  \nof the risks of the CMR/ED phthalate. See 7 Benefit \nassessment . \nAlternatives  Identify alternatives that are being evaluated against each \nother. See Step 4: Inventory of possible alternatives; and \nStep 5: Identification of the candidates for assessment as  \npotential relevant alternatives for phthalates . \nConsequences  Describe how the alternatives perform for each of the \ncriteria, i.e., the magnitudes of all effects in terms of the \ndifferent benefits and risks. See Step 2: Use and function \nof the phthalates in the medical device; Step 3: \nAssessment of the risks of the C MR/ED phthalate; Step 6: \nDescription of identified relevant potential alternative(s); \nStep 7: Assessment of the risk of identified potential \nrelevant alternatives. For a summary table see Table 1. \nExample for a comparison of CMR/ED phthalate with \npotential  alternative(s).  \nTrade -offs Assess the balance between benefits and risks using \njudgements of weights associated with the criteria and the \nvalue associated with the benefits and risks of every \nalternative. MCDA techniques commonly achieve this \nthrough num erical analysis. A number of different \nweighting methods can be used. Conduct sensitivity \nanalyses to explore uncertainties using different scenarios, \nand assess how different weights affect the overall \nordering of the alternatives.  \nSee also Step 8: Compar ison of functionality and \nperformance of CMR/ED phthalate as used in the medical \ndevice with functionality and performance of identified \npotential relevant alternatives; Step 9: Comparison of \nrisk(s) of original CMR/ED phthalate as used in the medical \ndevice with risk(s) of identified potential relevant \nalternatives; and Step 10: Comparison of benefit and risk \nof CMR/ED phthalate used in the medical device with \nidentified potential relevant alternatives.  \nUncertainty  Report the uncertainty associated with the benefits and  \nRisks. Consider how the balance between benefits and \nrisks is affected by uncertainty. A quantitative model will Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n63 \n explore in sensitivity analyses and scenario analyses (or by \nexplicitly incorporating probability distributions in the \nmodel) the effects on the overall benefit -risk balance of all \nsources of uncertainty. See 1.9 Uncertainty analysis.  \nRisk tolerance  Describe any considerations that could or should affect the \ndecision maker\u2019s attitude toward risks (e.g., special \npopulation, unmet  medical need).  \nLinked -decisions  Discuss how the value judgements and data are consistent \nwith similar decisions on medical devices.  \n  \n \nReferences  \n\uf0b7 Dodgson J, Spackman M, Pearman A, Phillips LD. Multi -criteria analysis: A \nmanual. London: Department for Communities and Local Government, First \npublished in 2000 by the Department for Environment, Transport and the \nRegions; 2009.  \n \n\uf0b7 ECHA 2011 Guidance on the preparation of socio -economic analysis as part of an \napplication for authorisation, European Chemicals Agency 2011 . \n \n\uf0b7 Hammond JS, Keeney RL, Raiffa H, Smart Choices: A Practical Guide to making \nBetter Decisions, Boston, MA: Harvard Business School Press; 1999.  \n \n\uf0b7 Mt-Isa S, Hallgreen C.E., Wang N., Callr\u00e9us T., Genov G., Hirsch I., Hobbiger S., \nHockley .S., Luciani D., Phillips L.D., Quartey G., Sarac S.B., Stoeckert I., Tzoulaki \nI., Micaleff A., Ashby D. - Balancing benefit and risk of medicines a systematic \nreview and classification of available methodologies, Pharmacoepidemiology and \nDrug Safety, May 2014 ."}, {"title": "md_transitional-provisions-art-3-and-4_en.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document                          MDCG 2020 -2 rev.1  \n \n \n \n \n     MDCG  2020 -2 rev. 1  \n       Class I Transitional provisions under  Article      \n      120 (3 and 4) \u2013 (MDR)             \n \n             March 2020  \n         July 2020 rev.1  \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group  (MDCG) established by \nArticle 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member \nStates and it is chaired by a representative of the European Commission.  \nThe document is not a European Commission document and it cannot be regarded as reflecting the \nofficial position of the European Commission. Any views expressed in this document are not legally \nbinding and only the Court of Justice of the European Union can give binding interpretations of Union \nlaw. \n \n \n \n  Medical Device       \nMedical Device Coordination Group Document                          MDCG 2020 -2 rev.1  \n \nMDCG 2020 -2 revision 1 changes  \nMDR postponement dates  : from 2020 to 2021  \nHow can a ffected manufacturers of some class I devices1 make efficient \nuse of the transitional provisions in A rticle 120 (3 ) and (4) of Regulation \n(EU) 2017/745 \u2013 Medical Devices Regulation ( MDR )? \nBackground:  \nThe corrected MDR2 Article 120 (3) allows  under certain condition s, some class I devices pursuant to \nDirective 93/42/EEC  \u2013 Medical Devices Directive (MDD) , for which the Declaration of C onformity \nwas drawn up prior to 26 May 2021 and for which the conformity assessment procedure pursuant to \nthe MDR would require the involvement of a notified body,  to be placed on the market3 until 2 6 May \n20244.  \nIn order  to make use of this article , the following conditions must be met:  \n1. The device continues to comply with Directive 93/42/EEC,  \n2. A notified body will need to be involved under the MDR (e.g. re -usable surgical instruments \nor up -classified devices)  \n3. A valid Declaration of C onformity , according to Annex VII  of the MDD , must be drawn up \nbefor e 26 May 2021,  \n4. No significant changes to the design or intended purpose of the device  after 26 May 202 15, \n5. The requirements of the MDR relating to post -market surveillance, market surveillance, \nvigilance, registration of economic operators and of devices shall apply in place of the \ncorresponding  requirements in Directive 93/42/EEC .6 This shall be in place on the 26 May \n2021. \n \nScope  \nThe scope of this document is to provide guidance related to the information to be provided in the \nform of a  Declaration of Conformity by manufacturers of Class I devices  (devices which are non -\n                                                           \n1 Class I devices for which the conformity assessment procedure pursuant to the MDR would require the involvement of a \nnotified body.  \n2 Corrigendum to Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical \ndevices, amending Directive 2001/83/EC, Regulation (EC) No\u202f178/2002 and Regulation (EC) No\u202f1223/2009 and repealing \nCouncil Directives 90/385/E EC and 93/42/EEC (OJ L 117, 5.5.2017), of 27.12.2019.  \n3 Devices which are not placed on the market but put into service may also make use of the transitional provisions .  \n4 Article 120(4) \u2018and may continue to be made available on the market \u2026until 26  May 2025\u2019 . \n5 Guidance on significant changes under Article 120 of the MDR with regard to devices covered by certificates according to \nMDD or AIMDD . \n6 Upcoming guidance on harmonised practices and technical solutions  to facilitate exchange of information in absence of \nEUDAMED .  Medical Device       \nMedical Device Coordination Group Document                          MDCG 2020 -2 rev.1  \n \nsterile or do not have a measuring function) that are required to have certificates after 26 May 2024 \naccording to the MDR.  \nContent of a val id Declaration of Conformity  \nThe manufacturer or his authorised representative established in the European Union is  obliged to \nissue a  Declaration of Conformity  that the  product has undergone  a conformity assessment  procedure \nrequired by the MDD  before being placed on the market.   \n \nWith the Declaration of Conformity, the manufacturer declares that the products concerned meet the \nrelevant provisions of the MDD.  \nMDD Annex II, Annex V, Annex VI set out that a Declaration of Conformity must cover one or more \nmedical devices manufactured  7 clearly identified by means of product name, product code or other \nunambiguous reference for class IIa, IIb and III devices, and also class Im and class Is devices. This is \nhowever not necessary for  other  Class I devices, as it is not required by the MD D (Annex VII) and as \nthere is no certificate from a notified body to which the issued Declaration of Conformity is related.  \nGuidance on  the content of the Declaration of C onformity can be found, inter alia, in the \u201cThe \u2018Blue \nGuide\u2019 on the implementa tion of EU products rules 2016 (2016/C272/01) \u201d8 and the  standard EN \nISO/IEC 17050 -1.9 According to this standard , the declaration may take the form of a document or any \nother suitable medium , and should contain sufficient information to enable all products  covered to be \ntraced back to it.  The model declaration in Annex III of Decision No 768/2008/EC  and the \u2018Blue \nGuide\u2019  on the implementation of EU products rules 2016 (2016/C272/0 1) describe the content of the \nDeclaration of C onformity to be as follows:   \n1.  A number identifying the product. This number does not need to be unique to each product. It \ncould refer to a product, batch, type or a serial number .10 This is left to the discretion of the \nmanufacturer .11   \n2.  The name and address of the manufacturer or  the authorised representative issuing the \ndeclaration.  \n3.  A statement that the declaration is issued under the sole responsibility of the manufacturer.  \n                                                           \n7 MDD Annex II, paragraph 2  \u2018This declaration must cover one or more medical devices manufactured, clearly identified by \nmeans of product name, product code or other unambiguous reference and must be kept by the manufacturer.\u2019  \n8 https://eur -lex.europa.eu/legal -content/GA/TXT/?uri=CELEX:52016XC0726(02) . \n9 EN ISO/IEC 17050 -1 : 2004 Conf ormity assessment \u2013 Supplier\u2019s D eclaration of Conformity \u2013 Part 1: General requirements \n/EN ISO/IEC 17050 -2 : 200 4 Conformity assessment \u2013 Supplier\u2019s Declaration of C onformity \u2013 Part 2: Supporting \ndocumentation . \n10 The \u2018number\u2019 may be an alpha -numerical code  or could also refer to a software version .  \n11 In addition, whether this is expressly envisaged or not by the Union harmonisation legislation,  manufacturers are free to \nadd a number identifying the Declaration of Conformity itself in line with EN ISO/IEC 17050 -2. Medical Device       \nMedical Device Coordination Group Document                          MDCG 2020 -2 rev.1  \n \n4.  The identification of the product allowing traceability. This is any relevant information \nsuppleme ntary to point 1 describing the product and allowing for its traceability . Where relevant \nfor the identification of the product , it may  contain an image, but unless specified as a \nrequirement in the Union harmonisation legislation this is left to the discr etion of the \nmanufacturer.  \n5.  All relevant Union harmonisation legislation complied with; the referenced standards or other \ntechnical specifications (such as national technical standards and specifications) in a precise,  \ncomplete and clearly defined way;  this implies that the version and/or date of the relevant \nstandard is specified.12  \n6.  If applicable, t he name and identification number of the notified body ,13 when it has been \ninvolved in the conformity assessment procedure ,14 15 and the reference to the relevant \ncertificate.  \n7.  If applicable, a ll supplementary information that may be required (for example category) . \n8.  The date of issue of the declaration; signature and title or an equivalent marking of the \nauthorised person16 17 \n\uf0fc This could be any date after the complet ion of the conformity assessment , but must be before \n26 May 202 1 if the manufacturer wants to make use of the transitional period in Article \n120(3) and (4)  of the MDR . \nEvery Declaration of C onformity must be based on proper technical documentation according to \nAnnex VII para graph  3 of the MDD.  The technical documentation and the D eclaration of Conformity \nshould be subject to appropriate  measures of document and record control. The Declaration  of \nConformity is to be kept by the manufacturer and shall be at the  disposal of the competent  authorities \nfor a period ending at least five years after the last product  has been manufactured.  \nNecessary amendm ents/updates to the t echnical documentation should be done in a transparent \nmanner. Both t he changes and the dates of when the changes were  made should be recorded. On the \nbasis of the Declaration of Conformity and the corresponding technical documentation, the \nmanufacturer should be able to demonstrate that the Declaration of Conformity was lawfully18 issued \nbefore 26 May 202 1 and that, subsequently, there are no significant changes  in the design or intended \n                                                           \n12 According to the MDD , referencing st andards or technical specifications complied with is voluntary .  \n13 For class I devices in scope of this guidance document, the involvement of a notified body is not required.  \n14 Not all Union harmonisation legislation requires the intervention of a notified  body (e.g. the Low Voltage Directive and the \nToys D irective . \n15 The name and address of the person who keeps the technical documentation may also be required by some pieces of Union \nharmonisation legislation since according to those, not only the manufactu rer shall keep the technical documentation.  \n16 This could be the m anaging director of the company or another representative of the company to whom this responsibility \nhas been delegated.  \n17 It is not necessary for the signatory to be domiciled in the Europea n Union. A manufacturer established outside the Union \nis entitled to carry out all the conformity assessment procedures at his premises and, to sign the Declaration of Conformity . \n18 Lawfully according to the Directive and to any relevant national provisions which apply.  Medical Device       \nMedical Device Coordination Group Document                          MDCG 2020 -2 rev.1  \n \npurpose19 in the meaning of Article 120(3) MDR. Taking into account Article 123(3) and 123 (3)(d), \nand a s EUDAMED will not be fully functional in May 202 1, it is required that the manufacturer keep \nthe Declaration of Conformity together with the  technical documentation available to the Competent \nAuthorities . This would also include details o f all device registrations and economic operator \nregistrations completed pursuant to national provisions implementing the requirements of Articles 14 \n(1) and (2) of Directive 93/42/EEC.  \n \n \n                                                           \n19 Guidance on significant changes under Article 120 of the MDR with regard to devices covered by certificates according to \nMDD or AIMDD ."}, {"title": "09 MDCG 2020-9 Regulatory Requirements for Ventilators and Reated Accessories.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document   MDCG  2020-9  \n \n  \n  \n \n \n \nMDCG 2020-9 \n  \n         REGULATORY REQUIREMENTS    \n      FOR VENTILATORS AND \n      RELATED ACCESSORIES    \n           \n \n April 2020 \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.The document is not a European \nCommission document and it cannot be regarded as reflecting the official \nposition of the European Commission. Any views expressed in this document are \nnot legally binding and only the Court of Justice of the European Union can give \nbinding interpretations of Union law. \n \n   \n2 REGULATORY REQUIREMENTS FOR VENTILATORS AND \nRELATED ACCESSORIES  \nOptions for supporting production and/or placing on the market of \nventilators in the context of COVID-19 pandemic \n1. INTRODUCTION AND SCOPE  \nThe World Health Organization (WHO) declared the COVID-19 outbreak a pandemic on \nMarch the 12th 2020. Patients infected by SARS-CoV-2 virus and developing the \nCOVID-19 disease with acute and severe respiratory symptoms have to be treated with \nmechanical ventilators to assure possibilities of survival.  \nThis guidance document focuses on ventilators and related accessories that are currently \nregulated under the Council Directive 93/42/EEC (MDD)1. According to the MDD, \ndevices may be placed on the market and/or put into service only if they comply with the \nrequirements laid down in this Directive when duly supplied and properly installed, \nmaintained and used in accordance with their intended purpose2. \nThe devices must meet the essential requirements set out in Annex I of the MDD, which \napply to them, taking account of the intended purpose of the devices concerned. In \naddition, devices may be placed and circulate on the European single market if they have \nbeen subject to a conformity assessment in accordance with the provisions of Article 11 \nof the MDD.  \nUnder the current COVID-19 context, the demand for ventilators and related accessories \nhas rapidly increased. Therefore, this document intends to outline the different regulatory \noptions for placing these devices on the EU market indicating their feasibility to allow \nshort-term supply. \n2. TYPES OF MEDICAL DEVICES AND THEIR PARTS /COMPONENTS  \n2.1. Ventilators \nVentilators are breathing support devices and can fall into different types according to \ntheir intended use and characteristics3: \n                                                \n1 However, placing on the market of devices which comply with MDD is limited to 27 May 2024. After \nthis date every device placed on the market has to comply with the requirements of Regulation (EU) \n2017/745 (MDR). According to the Article 120 section 5 and 6 of the MDR devices which comply \nwith MDR may be placed on the market before its application and notified bodies which are \ndesignated and notified in accordance with MDR may carry out the conformity assessment procedures \nlaid down in MDR and issue certificates in accordance with MDR. \n2 According to Article 1(g) of the MDD, intended purpose is the use for which the device is intended \naccording to the data supplied by the manufacturer on the labelling, in the instructions and/or in \npromotional materials. \n3 This list of ventilators includes some standards applicable to the specific ventilator. However, it should be \nnoted that this is not an exhaustive list and other standards also apply to these devices and should be \ntaken into account (e.g. EN 60601-1-2, EN 60601-1-6, EN 60601-1-8, EN 60601-1-11, EN 62304, EN \n62366). In addition, the current state of the art should be considered. This applies also to accessories.   \n3 - Ventilator for critical care:   automatic equipment that is intended to augment or \nprovide ventilation of the lungs of the patient when connected to the airway of the \npatient: \no intended for use in an environment that provides specialized care for \npatients whose conditions can be life threatening and who can require \ncomprehensive care and constant monitoring in a professional healthcare \nfacility; \no intended to be operated by a healthcare professional operator; and \no intended for those patients who need differing levels of support from \nartificial ventilation including for ventilator-dependent patients. \n(See e.g. EN ISO/IEC 80601-2-12:2011 + Cor.:2011).   \n- Home healthcare environment ventilators for ventilator-dependent patients: \nintended for use in the home healthcare environment; intended for use by a lay \noperator; intended for use with patients who are dependent on mechanical \nventilation for their life support. Depending on the intended purpose can be also \nused in the clinical setting (See e.g. EN ISO 80601-2-72:2015). \n- Ventilators for emergency and transport : these ventilators are used in \nEmergency Medical Service environment, e.g. in ambulances, transport of \npatients to the hospital, patient transport from hospital to hospital or transport \nwithin the hospital. The alarm and safety concept of emergency and transport \nventilators in general is designed for a permanent presence of the user. This \nfacilitates fast recognition and response in the event of an alarm or in the event of \nany malfunction (See e.g. EN 794-3:1998+A2:2009).  \n- Anaesthetic ventilator:  are designed for use during anaesthesia with an \nanaesthetic breathing system (See e.g. EN ISO 80601-2-13:2012). \nVentilators for critical care are usually invasive, which enables the ventilator machine to \nprovide lung support for inspiration and expiration through tracheal intubation. However, \nmost critical care ventilators allow non-invasive ventilation modes for critical care \npatients as well. Ventilators for non-critical care are usually non-invasive and therefore \nprovide air pressure support to natural breathing through e.g. a facemask. \nVentilators may offer different types of additional complementary functions that include: \n\uf0b7 High flow oxygen supply (nasal high flow therapy); \n\uf0b7 Monitoring systems; \n\uf0b7 Nebulisation systems. \n \n2.2. Accessories \nVentilators need to be \u201cconnected\u201d to the patients through dedicated accessories4 to the \nventilator that allow the machine to support the patient\u2019s breathing; therefore, it is \nimportant to proof compatibility with the ventilator(s). These accessories can be placed \non the market individually and usually fall into one of the following categories: \n                                                \n4 See MEDDEV 2.1/1  Definitions of 'medical devices', 'accessory' and 'manufacturer' \n(https://ec.europa.eu/docsroom/documents/10278/attachments/1/translations ).  \n4 \uf0b7 Breathing systems and circuits, such as: \no Circuits; \no Connections/Adapters; \no Tubes; \no Nasal cannulas for O 2; \no Masks or helmets for non-invasive ventilation; \no Air compressors; \n\uf0b7 Nebulizers; \n\uf0b7 Humidifiers and filters; \n\uf0b7 Monitoring accessories, including alarms, in-built safety features. \nAccessories are provided either disposable or reusable and are treated as medical devices \nin their own right5. \n2.3. Parts or components \nParts or components of medical devices that do not qualify as accessories are generally \nnot considered medical devices and thus not requiring themselves to be CE marked \naccording to the MDD (e.g. expiratory valves or flow sensors).  \n3. CLASSIFICATION  \n3.1. Ventilators \nThere are different types of ventilators depending on the degree of invasiveness and the \nsetting in which they are used in (e.g. Intensive Care Unit - ICU). Ventilators fall under \ntwo different classes in accordance with rule 11 (or rule 9) of Annex IX6,7 to the MDD: \n- Class IIa: only applicable to non-invasive devices, e.g. continuous positive airway \npressure \u2013 CPAP non-intended for critical care, or devices that only support \nspontaneous breathing. \n- Class IIb: applicable to most ventilators.  \nThe classification depends on the intended purpose of the ventilator and has important \nimplications in the selection of appropriate conformity assessment procedure(s) for the \ndevice including timing and complexity (see section 4 for details).  \n3.2. Accessories \nAccessories are classified in their own right usually in accordance with rule 2 or 5 of \nAnnex IX to the MDD, under Class I, IIa or IIb.  \n                                                \n5 Art. 1(1) of the MDD \n6 See MEDDEV 2.4/1 rev.9 Classification of Medical Devices -  \n(https://ec.europa.eu/docsroom/documents/10337/attachments/1/translations).  \n7 Please note that if a conformity assessment under the MDR is followed, the rules of classification \nspecified in Annex VIII to the MDR apply. Breathing support devices may be classified to class IIa or \nIIb (rule 12) or class III (rule 22) if they integrate or incorporate diagnostic functions which \nsignificantly determine the patient management by the device, such as closed loop systems.  \n5 3.3. Impact of classification on conformity assessment \nGiven that ventilators are classified as Class IIa or Class IIb, and accessories (except for \nClass I non-sterile and without measuring function), will in principle need the \ninvolvement of a notified body prior to their placing on the market.  Other options for the \nplacing on the market are provided in section 4 for both ventilators and accessories. \n4. REGULATORY OPTIONS FOR PLACING VENTILATORS ON THE MARKET  \nIn the context of the COVID-19 outbreak, several industries have expressed their \nwillingness to support and scale up the production of ventilators8. There are different \nregulatory options9 available for supporting production or placing on the market of \nventilators. These options are presented below, ordered by feasibility, to allow a swift \nsupply in the current context. \n4.1. Supplying parts, components or the finished devices to medical devices \nmanufacturers currently placing on the market ventilators  \nWhen the legal manufacturer10 has already undergone a conformity assessment for the \nventilator, has obtained a certificate and is lawfully placing ventilators on the market \nunder its own name, other producers (e.g. not currently working in the medical devices \nfield) can support its production. Such producers can provide parts or components, or the \nfinished device, therefore becoming suppliers or subcontractors of this manufacturer. \nGiven that the medical devices sector is highly regulated and complex, leveraging the \nknowledge and responsibilities of an already established manufacturer of ventilators \ncould be the least burdensome and fastest option to scale up the production of \nventilators.   \n4.1.1. Producers supplying parts or components to medical devices manufacturers \ncurrently placing on the market ventilators \nManufacturers of medical devices can have many suppliers, which in case of quality \nsystem certification are qualified, approved and controlled by the manufacturer. These \nsuppliers may need to be assessed by a notified body as part of the conformity \nassessment procedure on the basis of their criticality and the manufacturer\u2019s process in \nplace to control suppliers and the verification of purchased products11. When the \nmanufacturer wishes to use an additional supplier, this might need to be communicated in \nadvance to the notified body.  \n                                                \n8 Scaling up of production might also be needed for accessories. These medical devices can follow the \nsame options explained in section 4 but small differences can be applicable in case they have a \ndifferent classification (e.g. class Is).   \n9 This document mainly focuses on regulatory options provided by the MDD. If a conformity assessment \nunder the MDR is followed, similar procedures will apply under Annex IX, X or XI of the MDR \ndepending on the classification of the product.  \n10 Legal manufacturer refers to the definition of manufacturer established in Art. 1(f) of the MDD.  \n11 See Guidance for Notified Bodies auditing suppliers to medical device manufacturers \u2013 \n(http://www.doks.nbog.eu/Doks/NBOG_BPG_2010_1.pdf)   \n6 4.1.2. Producers manufacturing the ventilator itself for the medical device \nmanufacturer currently placing on the market ventilators \nManufacturers of medical devices producing ventilators may provide the specifications \nof a ventilator (e.g. current or older/simpler design) including parts of the technical \ndocumentation to a producer that becomes its subcontractor. The producer will \nmanufacture the ventilator but the medical device manufacturer will keep its role of legal \nmanufacturer according to the MDD.  \nThe legal manufacturer of the ventilator, which holds a quality system certification, \nqualifies, approves and controls the subcontractor that will need to be assessed by a \nnotified body as part of the conformity assessment procedure. When the manufacturer \nwishes to use an additional subcontractor, this will need to be communicated in advance \nto the notified body (i.e. as the subcontractor is considered critical11) that will assess the \navailable information and will decide the actions to be put in place e.g. whether or not it \nis necessary to carry out an (on-site12) audit. \nAlternatively, the manufacturer of medical devices could also follow other conformity \nassessment routes such as the EC type-examination, as established in Annex III to the \nMDD, and/or EC verification, as established in Annex IV to the MDD (these routes are \nelaborated in 4.3.2).     \n4.2. Derogation procedure \u2013 placing on the market authorised by the \nrelevant authorities of one Member State in the interest of public health \nThe relevant authority of one Member State may decide to authorise the placing on the \nmarket of devices in the interest of protection of health, even if the applicable conformity \nassessment procedures have not been finalised or initiated ('national derogation'). \nIn view of the epidemiological context as well as the exponential growth in demand for \nmedical devices, the Commission has published a Guidance on medical devices, active \nimplantable medical devices and in vitro diagnostic medical devices in the Covid-19 \ncontext.  \nQuestion 5 of this guidance provides information on the derogation procedures for \nmedical devices which is established in Article 11(13) of the MDD. In particular, the \nguidance specifies that the Covid-19 context warrants the application of such \nderogations.  \nBy amendment of 23 April 202013, Article 59(1) of Medical Devices Regulation (EU) \n2017/745 (MDR) empowers Member States to adopt national derogations under both the \nMDD and the MDR from the date of entry into force of that amendment. \nThe relevant competent authority of the Member State in this case authorises the placing \non the market within its territory and can also organise the purchase.  \n                                                \n12 See MDCG 2020-4 Guidance on temporary extraordinary measures related to medical device Notified \nBody audits during COVID-19 quarantine orders and travel restrictions \n(https://ec.europa.eu/docsroom/documents/40705).   \n13 Regulation 2020/561  amending Regulation (EU) 2017/745 on medical devices as regards the dates of \napplication of certain of its provisions.  \n7 In practice, this implies that each competent authority would need to assess whether the \nproducts produced by the manufacture provides an adequate level of safety in respect to \nthe applicable legal requirements. The assessment procedures can vary among Member \nStates and in some cases will involve the support of third parties (e.g. testing \nlaboratories).   \nIn the exceptional COVID-19 context, the assessment procedures will ensure a short-\nterm supply while guaranteeing patient safety14. The Member State will evaluate the \navailable technical documentation to find evidence that essential performance and safety \nrequirements are guaranteed in the context of use. In particular, the role of healthcare \nteams and health facilities is essential to allow a rational use and a continuous assessment \nof these crisis solutions. \nOnce this assessment is performed, the authority has to take a decision, whether or not \nthe respective device produced by the manufacturer may enter the national territory of the \nMember State. Competent authorities should inform the Commission and their \ncounterparts in other Member States of any temporary agreement they have granted to \nspecific devices.  \nIn addition, Article 59(3) of the MDR empowers the Commission to extend, in \nexceptional cases relating to public health or patient safety or health, by means of \nimplementing acts, for a limited period of time the validity of a national derogation, \ngranted by a Member State under the MDD or the MDR, to the territory of the Union and \nset the conditions under which a device may be placed on the market or put into service. \nThis allows the Commission and the Member States to address potential shortages Union \nwide of vitally important medical devices in an effective manner. \nTiming to obtain a national derogation by a competent authority will greatly depend on \nthe quality and adequacy of the evidence provided by the manufacturer.  When technical \ndocumentation and evidence of safety of performance is adequate, this can be a feasible \noption to ensure short-term supply.  \n \n4.3. Manufacturing of the finished device by a producer that was not \npreviously placing on the market ventilators  \nIf the ventilator is entirely manufactured by a producer that decides to place it on the \nmarket under its name, such producer will become the legal manufacturer in its own \nright. This means that the manufacturer will need to fulfil all requirements of the MDD \n(e.g. including the need to draw up the technical documentation and clinical evaluation \nrelated to the ventilator, and to establish and keep up to date a systematic procedure to \nreview experience gained from devices in the post-production phase).  \nThe manufacturer who places the finished CE marked ventilator on the market under its \nown name needs to ensure that the device complies with the essential requirements \n(established in Annex I of the MDD) and provide relevant evidence. A notified body will \nbe involved in the conformity assessment in all cases.  \n                                                \n14 Some Member States have published guidance on their respective websites to support this assessment \ne.g. in case of implementation of innovative manufacturing processes such as 3D printing.   \n8 Given that the medical devices sector is highly regulated and complex, the scenarios \npresented below will be the most burdensome and therefore only applicable to increase \nsupply in the medium-long term.  \n4.3.1. Medical devices manufacturers\u2019 not currently producing ventilators request \nan extension of their product range. \nThis option is available for medical devices manufacturers currently certified. It includes, \nfor instance, medical devices manufacturers already holding a full quality management \nsystem certificate under Annex II to the MDD for other devices and wishing to add \nventilators to their certification. They could seek the support from (non-medical devices) \nproducers to act as subcontractors and extend the scope of their certificate.   \nFrom a procedural point of view, the medical devices manufacturer may produce the \nventilator itself or may utilise a subcontractor (i.e. producer linked or not to the medical \ndevices field). In the latter case, the manufacturer will qualify, approve and control the \nsubcontractor that will be assessed by the notified body as part of the conformity \nassessment procedure. When the manufacturer wishes to use an additional subcontractor, \nthis will need to be communicated in advance to the notified body (i.e. as the \nsubcontractor is considered critical11) that will assess the available information and will \ndecide the actions to be put in place e.g. whether or not it is necessary to carry out an (on-\nsite12) audit. \nMost importantly, the manufacturer will need to request an extension of the product \nrange from its notified body. The notified body will assess the available information in \nrelation to the new product (that include an assessment of the technical documentation \nand clinical evaluation) and update the certificate. \nThe manufacturer of medical devices could also use other conformity assessment routes \nsuch as the EC Type-Examination and EC Verification and testing of every product \nunder Annex III and IV respectively (these routes are elaborated in section 4.3.2).   \n \n4.3.2. Ventilator manufactured entirely by a producer that is not currently a legal \nmanufacturer under the MDD \nProducers that do not currently qualify as legal manufacturers under the MDD and decide \nto place ventilators on the market under their own name need to be aware of all the legal \nrequirements for manufactures under the MDD. It is important to mention that in the field \nof medical devices some Member States could have additional requirements, for instance, \nthe need to authorise the facility of the medical device manufacturer prior to starting \nproduction.  \nIn addition to this, the involvement of a notified body will depend on the classification. \nIn particular: \n1. Class IIa ventilators can follow the following routes established in the relevant \nAnnexes of the MDD: \na. Annex II (excluding point 4) \u2013 which involves the assessment of the full \nmanufacturer\u2019s quality management system. This will require an on-site \naudit (which may be performed remotely in the current context) and  \n9 regular surveillance audits at least annually. In addition, the notified body \nwill assess the technical documentation and the clinical evaluation of the \nproduct to be certified prior to certification on a sampling basis15.   \nb. Declaration of conformity (Annex VII) combined with either an \nassessment of the quality assurance of the production or of the product \n(Annex V or VI) or a EC verification (set out in Annex IV): \n\uf0a7 The assessment of the quality system performed by the notified \nbody will be similar to the one outlined in section 1.a above. \n\uf0a7 The verification by testing of products by the notified body will be \nperformed by examination and testing of every product.   \n \n2. Class IIb ventilators can follow the following routes: \na. Annex II (excluding point 4) \u2013 which involves the assessment of the full \nmanufacturer\u2019s quality management system. This will require an on-site \naudit (which may be performed remotely in the current context) and \nregular surveillance audits at least annually. In addition, the notified body \nwill assess the technical documentation and the clinical evaluation of the \nproducts to be certified prior to certification on a sampling basis15.   \nb. EC type-examination (Annex III) combined with either an assessment of \nthe quality assurance either of the production or of the product (Annex V \nor VI) or EC verification by testing of products (set out in Annex IV). EC \nType-examination consists in the assessment of the technical \ndocumentation and testing of a number of features of the device type to \nensure it conforms to the requirements. The additional procedures (Annex \nIV, V or VI) are the same as the ones described in 1.b above. \nThe assessment of the quality management system of the manufacturer (Annex II, V and \nVI) can be partly fulfilled by compliance with a harmonised standard (EN ISO 13485) \nbut this route will unlikely be fast enough to ensure short-term supply. This is due to the \ntimelines and experience required to get a certificate under these annexes of the MDD \nand taking into account the current circumstances where auditing capacity is restricted by \nthe Covid19 situation. \nA faster route but also time-consuming route will probably be the performance of tests on \nthe products that might be combined with the assessment of the technical documentation, \nnamely:  \n- declaration of conformity (Annex VII) + verification of products (Annex IV) for \nClass IIa; or \n- EC type-examination (Annex III) + verification of products (Annex IV) for \nClass IIb. \nThrough this route, the device type or device samples are tested and there is no obligation \nto have a certified quality management system in place and subject to regular \nsurveillance audits. However, quality management processes are important and critical to \nthe production of safe and functional medical devices. The conformity assessment will be \n                                                \n15 See Annex II, section 3.3 to the MDD  \n10 based on the manufacturers testing strategy that must ensure compliance with the safety \nand performance requirements.  \nIt should be noted that this option is burdensome and will take several months, especially \nto draw up an adequate technical documentation. In addition, there is only a limited \nnumber of notified bodies designated to perform EC type-examination and/or EC \nverification in ventilators (according to NANDO16 18 notified bodies out of 56 are \nauthorised to perform these tests at the moment).  \n                                                \n16 This information can be found in NANDO, by searching notified bodies under the MDD that are \ndesignated under Annex III and IV for code MD 1102 - Respiratory devices, devices including \nhyperbaric chambers for oxygen therapy, inhalation anaesthesia -   \nhttps://ec.europa.eu/growth/tools-databases/nando/index.cfm?fuseaction=directive.notifiedbody&dir_id=13"}, {"title": "Mdr.Html.txt", "text": "L_2017117EN.01000101.xml\n\n\n\n\n\n\n\n\n\n\n\n5.5.2017\u00a0\u00a0\u00a0\n\n\nEN\n\n\nOfficial Journal of the European Union\n\n\nL 117/1\n\n\n\n\n\n\n\n\n            REGULATION (EU) 2017/745 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL\n         \nof 5 April 2017\n         \non medical devices, amending Directive\u00a02001/83/EC, Regulation\u00a0(EC)\u00a0No\u00a0178/2002 and Regulation\u00a0(EC)\u00a0No\u00a01223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC\n(Text with EEA relevance)\n\n\nTHE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION,\n\nHaving regard to the Treaty on the Functioning of the European Union, and in particular Article\u00a0114 and Article\u00a0168(4)(c) thereof,\n\n\nHaving regard to the proposal from the European Commission,\n\n\nAfter transmission of the draft legislative act to the national parliaments,\n\n\nHaving regard to the opinion of the European Economic and Social Committee\u00a0(1),\n\n\nAfter consulting the Committee of the Regions,\n\n\nActing in accordance with the ordinary legislative procedure\u00a0(2),\n\nWhereas:\n\n\n\n\n\n\n\n(1)\n\n\nCouncil Directive\u00a090/385/EEC\u00a0(3) and Council Directive\u00a093/42/EEC\u00a0(4) constitute the Union regulatory framework for medical devices, other than in vitro diagnostic medical devices. However, a fundamental revision of those Directives is needed to establish a robust, transparent, predictable and sustainable regulatory framework for medical devices which ensures a high level of safety and health whilst supporting innovation.\n\n\n\n\n\n\n\n\n\n\n\n\n(2)\n\n\nThis Regulation aims to ensure the smooth functioning of the internal market as regards medical devices, taking as a base a high level of protection of health for patients and users, and taking into account the small- and medium-sized enterprises that are active in this sector. At the same time, this Regulation sets high standards of quality and safety for medical devices in order to meet common safety concerns as regards such products. Both objectives are being pursued simultaneously and are inseparably linked whilst one not being secondary to the other. As regards Article\u00a0114 of the Treaty on the Functioning of the European Union (TFEU), this Regulation harmonises the rules for the placing on the market and putting into service of medical devices and their accessories on the Union market thus allowing them to benefit from the principle of free movement of goods. As regards Article\u00a0168(4)(c)\u00a0TFEU, this Regulation sets high standards of quality and safety for medical devices by ensuring, among other things, that data generated in clinical investigations are reliable and robust and that the safety of the subjects participating in a clinical investigation is protected.\n\n\n\n\n\n\n\n\n\n\n\n\n(3)\n\n\nThis Regulation does not seek to harmonise rules relating to the further making available on the market of medical devices after they have already been put into service such as in the context of second-hand sales.\n\n\n\n\n\n\n\n\n\n\n\n\n(4)\n\n\nKey elements of the existing regulatory approach, such as the supervision of notified bodies, conformity assessment procedures, clinical investigations and clinical evaluation, vigilance and market surveillance should be significantly reinforced, whilst provisions ensuring transparency and traceability regarding medical devices should be introduced, to improve health and safety.\n\n\n\n\n\n\n\n\n\n\n\n\n(5)\n\n\nTo the extent possible, guidance developed for medical devices at international level, in particular in the context of the Global Harmonization Task Force (GHTF) and its follow-up initiative, the International Medical Devices Regulators Forum (IMDRF), should be taken into account to promote the global convergence of regulations which contributes to a high level of safety protection worldwide, and to facilitate trade, in particular in the provisions on Unique Device Identification, general safety and performance requirements, technical documentation, classification rules, conformity assessment procedures and clinical investigations.\n\n\n\n\n\n\n\n\n\n\n\n\n(6)\n\n\nFor historical reasons, active implantable medical devices, covered by Directive\u00a090/385/EEC, and other medical devices, covered by Directive\u00a093/42/EEC, were regulated in two separate legal instruments. In the interest of simplification, both directives, which have been amended several times, should be replaced by a single legislative act applicable to all medical devices other than in vitro diagnostic medical devices.\n\n\n\n\n\n\n\n\n\n\n\n\n(7)\n\n\nThe scope of application of this Regulation should be clearly delimited from other Union harmonisation legislation concerning products, such as in vitro diagnostic medical devices, medicinal products, cosmetics and food. Therefore, Regulation\u00a0(EC)\u00a0No\u00a0178/2002 of the European Parliament and of the Council\u00a0(5) should be amended to exclude medical devices from its scope.\n\n\n\n\n\n\n\n\n\n\n\n\n(8)\n\n\nIt should be the responsibility of the Member\u00a0States to decide on a case-by-case basis whether or not a product falls within the scope of this Regulation. In order to ensure consistent qualification decisions in that regard across all Member\u00a0States, particularly with regard to borderline cases, the Commission should be allowed to, on its own initiative or at the duly substantiated request of a Member\u00a0State, having consulted the Medical Device Coordination Group (\u2018MDCG\u2019), decide on a case-by-case basis whether or not a specific product, category or group of products falls within the scope of this Regulation. When deliberating on the regulatory status of products in borderline cases involving medicinal products, human tissues and cells, biocidal products or food products, the Commission should ensure an appropriate level of consultation of the European Medicines Agency\u00a0(EMA), the European Chemicals Agency and the European Food Safety Authority, as relevant.\n\n\n\n\n\n\n\n\n\n\n\n\n(9)\n\n\nSince in some cases it is difficult to distinguish between medical devices and cosmetic products, the possibility of taking a Union-wide decision regarding the regulatory status of a product should also be introduced in Regulation\u00a0(EC)\u00a0No\u00a01223/2009 of the European Parliament and of the Council\u00a0(6).\n\n\n\n\n\n\n\n\n\n\n\n\n(10)\n\n\nProducts which combine a medicinal product or substance and a medical device are regulated either under this Regulation or under Directive\u00a02001/83/EC of the European Parliament and of the Council.\u00a0(7) The two legislative acts should ensure appropriate interaction in terms of consultations during pre-market assessment, and of exchange of information in the context of vigilance activities involving such combination products. For medicinal products that integrate a medical device part, compliance with the general safety and performance requirements laid down in this Regulation for the device part should be adequately assessed in the context of the marketing authorisation for such medicinal products. Directive\u00a02001/83/EC should therefore be amended.\n\n\n\n\n\n\n\n\n\n\n\n\n(11)\n\n\nUnion legislation, in particular Regulation\u00a0(EC)\u00a0No\u00a01394/2007 of the European Parliament and of the Council\u00a0(8) and Directive\u00a02004/23/EC of the European Parliament and of the Council\u00a0(9), is incomplete in respect of certain products manufactured utilising derivatives of tissues or cells of human origin that are non-viable or are rendered non-viable. Such products should come under the scope of this Regulation, provided they comply with the definition of a medical device or are covered by this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(12)\n\n\nCertain groups of products for which a manufacturer claims only an aesthetic or another non-medical purpose but which are similar to medical devices in terms of functioning and risks profile should be covered by this Regulation. In order for manufacturers to be able to demonstrate the conformity of such products, the Commission should adopt common specifications at least with regard to application of risk management and, where necessary, clinical evaluation regarding safety. Such common specifications should be developed specifically for a group of products without an intended medical purpose and should not be used for conformity assessment of the analogous devices with a medical purpose. Devices with both a medical and a non-medical intended purpose should fulfil both the requirements applicable to devices with, and to devices without, an intended medical purpose.\n\n\n\n\n\n\n\n\n\n\n\n\n(13)\n\n\nAs is the case for products that contain viable tissues or cells of human or animal origin, that are explicitly excluded from Directives\u00a090/385/EEC and 93/42/EEC and hence from this Regulation, it should be clarified that products that contain or consist of viable biological materials or viable organisms of another origin in order to achieve or support the intended purpose of those products are not covered by this Regulation either.\n\n\n\n\n\n\n\n\n\n\n\n\n(14)\n\n\nThe requirements laid down in Directive\u00a02002/98/EC of the European Parliament and of the Council\u00a0(10) should continue to apply.\n\n\n\n\n\n\n\n\n\n\n\n\n(15)\n\n\nThere is scientific uncertainty about the risks and benefits of nanomaterials used for devices. In order to ensure a high level of health protection, free movement of goods and legal certainty for manufacturers, it is necessary to introduce a uniform definition for nanomaterials based on Commission Recommendation\u00a02011/696/EU\u00a0(11), with the necessary flexibility to adapt that definition to scientific and technical progress and subsequent regulatory development at Union and international level. In the design and manufacture of devices, manufacturers should take special care when using nanoparticles for which there is a high or medium potential for internal exposure. Such devices should be subject to the most stringent conformity assessment procedures. In preparation of implementing acts regulating the practical and uniform application of the corresponding requirements laid down in this Regulation, the relevant scientific opinions of the relevant scientific committees should be taken into account.\n\n\n\n\n\n\n\n\n\n\n\n\n(16)\n\n\nSafety aspects addressed by Directive\u00a02014/30/EU of the European Parliament and of the Council\u00a0(12) are an integral part of the general safety and performance requirements laid down in this Regulation for devices. Consequently, this Regulation should be considered a lex\u00a0specialis in relation to that Directive.\n\n\n\n\n\n\n\n\n\n\n\n\n(17)\n\n\nThis Regulation should include requirements regarding the design and manufacture of devices emitting ionizing radiation without affecting the application of Council Directive\u00a02013/59/Euratom\u00a0(13) which pursues other objectives.\n\n\n\n\n\n\n\n\n\n\n\n\n(18)\n\n\nThis Regulation should include requirements for devices' design, safety and performance characteristics which are developed in such a way as to prevent occupational injuries, including protection from radiation.\n\n\n\n\n\n\n\n\n\n\n\n\n(19)\n\n\nIt is necessary to clarify that software in its own right, when specifically intended by the manufacturer to be used for one or more of the medical purposes set out in the definition of a medical device, qualifies as a medical device, while software for general purposes, even when used in a healthcare setting, or software intended for life-style and well-being purposes is not a medical device. The qualification of software, either as a device or an accessory, is independent of the software's location or the type of interconnection between the software and a device.\n\n\n\n\n\n\n\n\n\n\n\n\n(20)\n\n\nThe definitions in this Regulation, regarding devices themselves, the making available of devices, economic operators, users and specific processes, the conformity assessment, clinical investigations and clinical evaluations, post-market surveillance, vigilance and market surveillance, standards and other technical specifications, should be aligned with well-established practice in the field at Union and international level in order to enhance legal certainty.\n\n\n\n\n\n\n\n\n\n\n\n\n(21)\n\n\nIt should be made clear that it is essential that devices offered to persons in the Union by means of information society services within the meaning of Directive\u00a0(EU)\u00a02015/1535 of the European Parliament and of the Council\u00a0(14) and devices used in the context of a commercial activity to provide a diagnostic or therapeutic service to persons within the Union comply with the requirements of this Regulation, where the product in question is placed on the market or the service is provided in the Union.\n\n\n\n\n\n\n\n\n\n\n\n\n(22)\n\n\nTo recognise the important role of standardisation in the field of medical devices, compliance with harmonised standards as defined in Regulation (EU)\u00a0No\u00a01025/2012 of the European Parliament and of the Council\u00a0(15) should be a means for manufacturers to demonstrate conformity with the general safety and performance requirements and other legal requirements, such as those relating to quality and risk management, laid down in this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(23)\n\n\nDirective\u00a098/79/EC of the European Parliament and of the Council\u00a0(16) allows the Commission to adopt common technical specifications for specific categories of in vitro diagnostic medical devices. In areas where no harmonised standards exist or where they are insufficient, the Commission should be empowered to lay down common specifications which provide a means of complying with the general safety and performance requirements, and the requirements for clinical investigations and clinical evaluation and/or post-market clinical follow-up, laid down in this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(24)\n\n\nCommon specifications (\u2018CS\u2019) should be developed after consulting the relevant stakeholders and taking account of European and international standards.\n\n\n\n\n\n\n\n\n\n\n\n\n(25)\n\n\nThe rules applicable to devices should be aligned, where appropriate, with the New Legislative Framework for the Marketing of Products, which consists of Regulation\u00a0(EC)\u00a0No\u00a0765/2008 of the European Parliament and of the Council\u00a0(17) and Decision\u00a0No\u00a0768/2008/EC of the European Parliament and of the Council\u00a0(18).\n\n\n\n\n\n\n\n\n\n\n\n\n(26)\n\n\nThe rules on Union market surveillance and control of products entering the Union market laid down in Regulation\u00a0(EC)\u00a0No\u00a0765/2008 apply to devices covered by this Regulation which does not prevent Member\u00a0States from choosing the competent authorities to carry out those tasks.\n\n\n\n\n\n\n\n\n\n\n\n\n(27)\n\n\nIt is appropriate to set out clearly the general obligations of the different economic operators, including importers and distributors, building on the New Legislative Framework for the Marketing of Products, without prejudice to the specific obligations laid down in the various parts of this Regulation, to enhance understanding of the requirements laid down in this Regulation and thus to improve regulatory compliance by the relevant operators.\n\n\n\n\n\n\n\n\n\n\n\n\n(28)\n\n\nFor the purpose of this Regulation, the activities of distributors should be deemed to include acquisition, holding and supplying of devices.\n\n\n\n\n\n\n\n\n\n\n\n\n(29)\n\n\nSeveral of the obligations on manufacturers, such as clinical evaluation or vigilance reporting, that were set out only in the Annexes\u00a0to Directives\u00a090/385/EEC and\u00a093/42/EEC, should be incorporated into the enacting provisions of this Regulation to facilitate its application.\n\n\n\n\n\n\n\n\n\n\n\n\n(30)\n\n\nHealth institutions should have the possibility of manufacturing, modifying and using devices in-house and thereby address, on a non-industrial scale, the specific needs of target patient groups which cannot be met at the appropriate level of performance by an equivalent device available on the market. In that context, it is appropriate to provide that certain rules of this Regulation, as regards medical devices manufactured and used only within health institutions, including hospitals as well as institutions, such as laboratories and public health institutes that support the healthcare system and/or address patient needs, but which do not treat or care for patients directly, should not apply, since the aims of this Regulation would still be met in a proportionate manner. It should be noted that the concept of \u2018health institution\u2019 does not cover establishments primarily claiming to pursue health interests or healthy lifestyles, such as gyms, spas, wellness and fitness centres. As a result, the exemption applicable to health institutions does not apply to such establishments.\n\n\n\n\n\n\n\n\n\n\n\n\n(31)\n\n\nIn view of the fact that natural or legal persons can claim compensation for damage caused by a defective device in accordance with applicable Union and national law, it is appropriate to require manufacturers to have measures in place to provide sufficient financial coverage in respect of their potential liability under Council Directive\u00a085/374/EEC\u00a0(19). Such measures should be proportionate to the risk class, type of device and the size of the enterprise. In this context, it is also appropriate to lay down rules concerning the facilitation, by a competent authority, of the provision of information to persons who may have been injured by a defective device.\n\n\n\n\n\n\n\n\n\n\n\n\n(32)\n\n\nTo ensure that devices manufactured in series production continue to be in conformity with the requirements of this Regulation and that experience from the use of the devices they manufacture is taken into account for the production process, all manufacturers should have a quality management system and a post-market surveillance system in place which should be proportionate to the risk class and the type of the device in question. In addition, in order to minimize risks or prevent incidents related to devices, manufacturers should establish a system for risk management and a system for reporting of incidents and field safety corrective actions.\n\n\n\n\n\n\n\n\n\n\n\n\n(33)\n\n\nThe risk management system should be carefully aligned with and reflected in the clinical evaluation for the device, including the clinical risks to be addressed as part of clinical investigations, clinical evaluation and post-market clinical follow up. The risk management and clinical evaluation processes should be inter-dependent and should be regularly updated.\n\n\n\n\n\n\n\n\n\n\n\n\n(34)\n\n\nIt should be ensured that supervision and control of the manufacture of devices, and the post-market surveillance and vigilance activities concerning them, are carried out within the manufacturer's organisation by a person responsible for regulatory compliance who fulfils minimum conditions of qualification.\n\n\n\n\n\n\n\n\n\n\n\n\n(35)\n\n\nFor manufacturers who are not established in the Union, the authorised representative plays a pivotal role in ensuring the compliance of the devices produced by those manufacturers and in serving as their contact person established in the Union. Given that pivotal role, for the purposes of enforcement it is appropriate to make the authorised representative legally liable for defective devices in the event that a manufacturer established outside the Union has not complied with its general obligations. The liability of the authorised representative provided for in this Regulation is without prejudice to the provisions of Directive\u00a085/374/EEC, and accordingly the authorised representative should be jointly and severally liable with the importer and the manufacturer. The tasks of an authorised representative should be defined in a written mandate. Considering the role of authorised representatives, the minimum requirements they should meet should be clearly defined, including the requirement of having available a person who fulfils minimum conditions of qualification which should be similar to those for a manufacturer's person responsible for regulatory compliance.\n\n\n\n\n\n\n\n\n\n\n\n\n(36)\n\n\nTo ensure legal certainty in respect of the obligations incumbent on economic operators, it is necessary to clarify when a distributor, importer or other person is to be considered the manufacturer of a device.\n\n\n\n\n\n\n\n\n\n\n\n\n(37)\n\n\nParallel trade in products already placed on the market is a lawful form of trade within the internal market on the basis of Article\u00a034 TFEU subject to the limitations arising from the need for protection of health and safety and from the need for protection of intellectual property rights provided for under Article\u00a036 TFEU. Application of the principle of parallel trade is, however, subject to different interpretations in the Member\u00a0States. The conditions, in particular the requirements for relabelling and repackaging, should therefore be specified in this Regulation, taking into account the case-law of the Court of Justice\u00a0(20) in other relevant sectors and existing good practice in the field of medical devices.\n\n\n\n\n\n\n\n\n\n\n\n\n(38)\n\n\nThe reprocessing and further use of single-use devices should only take place where permitted by national law and while complying with the requirements laid down in this Regulation. The reprocessor of a single-use device should be considered to be the manufacturer of the reprocessed device and should assume the obligations incumbent on manufacturers under this Regulation. Nevertheless, Member\u00a0States should have the possibility of deciding that the obligations relating to reprocessing and re-use of single-use devices within a health institution or by an external reprocessor acting on its behalf may differ from the obligations on a manufacturer described in this Regulation. In principle, such divergence should only be permitted where reprocessing and reuse of single-use devices within a health institution or by an external reprocessor are compliant with CS that have been adopted, or, in the absence of such CS, with relevant harmonised standards and national provisions. The reprocessing of such devices should ensure an equivalent level of safety and performance to that of the corresponding initial single-use device.\n\n\n\n\n\n\n\n\n\n\n\n\n(39)\n\n\nPatients who are implanted with a device should be given clear and easily accessible essential information allowing the implanted device to be identified and other relevant information about the device, including any necessary health risk warnings or precautions to be taken, for example indications as to whether or not it is compatible with certain diagnostic devices or with scanners used for security controls.\n\n\n\n\n\n\n\n\n\n\n\n\n(40)\n\n\nDevices should, as a general rule, bear the CE marking to indicate their conformity with this Regulation so that they can move freely within the Union and be put into service in accordance with their intended purpose. Member\u00a0States should not create obstacles to the placing on the market or putting into service of devices that comply with the requirements laid down in this Regulation. However, Member\u00a0States should be allowed to decide whether to restrict the use of any specific type of device in relation to aspects that are not covered by this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(41)\n\n\nThe traceability of devices by means of a Unique Device Identification system\u00a0(UDI\u00a0system) based on international guidance should significantly enhance the effectiveness of the post-market safety-related activities for devices, which is owing to improved incident reporting, targeted field safety corrective actions and better monitoring by competent authorities. It should also help to reduce medical errors and to fight against falsified devices. Use of the UDI system should also improve purchasing and waste disposal policies and stock-management by health institutions and other economic operators and, where possible, be compatible with other authentication systems already in place in those settings.\n\n\n\n\n\n\n\n\n\n\n\n\n(42)\n\n\nThe UDI system should apply to all devices placed on the market except custom-made devices, and be based on internationally recognised principles including definitions that are compatible with those used by major trade partners. In order for the UDI system to become functional in time for the application of this Regulation, detailed rules should be laid down in this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(43)\n\n\nTransparency and adequate access to information, appropriately presented for the intended user, are essential in the public interest, to protect public health, to empower patients and healthcare professionals and to enable them to make informed decisions, to provide a sound basis for regulatory decision-making and to build confidence in the regulatory system.\n\n\n\n\n\n\n\n\n\n\n\n\n(44)\n\n\nOne key aspect in fulfilling the objectives of this Regulation is the creation of a European database on medical devices (Eudamed) that should integrate different electronic systems to collate and process information regarding devices on the market and the relevant economic operators, certain aspects of conformity assessment, notified bodies, certificates, clinical investigations, vigilance and market surveillance. The objectives of the database are to enhance overall transparency, including through better access to information for the public and healthcare professionals, to avoid multiple reporting requirements, to enhance coordination between Member\u00a0States and to streamline and facilitate the flow of information between economic operators, notified bodies or sponsors and Member\u00a0States as well as between Member\u00a0States among themselves and with the Commission. Within the internal market, this can be ensured effectively only at Union level and the Commission should therefore further\u00a0develop and manage the European databank on medical devices set up by Commission Decision\u00a02010/227/EU\u00a0(21).\n\n\n\n\n\n\n\n\n\n\n\n\n(45)\n\n\nTo facilitate the functioning of Eudamed, an internationally recognised medical device nomenclature should be available free of charge to manufacturers and other natural or legal persons required by this Regulation to use that nomenclature. Furthermore, that nomenclature should be available, where reasonably practicable, free of charge also to other stakeholders.\n\n\n\n\n\n\n\n\n\n\n\n\n(46)\n\n\nEudamed's electronic systems regarding devices on the market, the relevant economic operators and certificates should enable the public to be adequately informed about devices on the Union market. The electronic system on clinical investigations should serve as a tool for the cooperation between Member\u00a0States and for enabling sponsors to submit, on a voluntary basis, a single application for several Member\u00a0States and to report serious adverse events, device deficiencies and related updates. The electronic system on vigilance should enable manufacturers to report serious incidents and other reportable events and to support the coordination of the evaluation of such incidents and events by competent authorities. The electronic system regarding market surveillance should be a tool for the exchange of information between competent authorities.\n\n\n\n\n\n\n\n\n\n\n\n\n(47)\n\n\nIn respect of data collated and processed through the electronic systems of Eudamed, Directive\u00a095/46/EC of the European Parliament and of the Council\u00a0(22) applies to the processing of personal data carried out in the Member\u00a0States, under the supervision of the Member\u00a0States' competent authorities, in particular the public independent authorities designated by the Member\u00a0States. Regulation\u00a0(EC)\u00a0No\u00a045/2001 of the European Parliament and of the Council\u00a0(23) applies to the processing of personal data carried out by the Commission within the framework of this Regulation, under the supervision of the European Data Protection Supervisor. In accordance with Regulation\u00a0(EC)\u00a0No\u00a045/2001, the Commission should be designated as the controller of Eudamed and its electronic systems.\n\n\n\n\n\n\n\n\n\n\n\n\n(48)\n\n\nFor implantable devices and for class III devices, manufacturers should summarise the main safety and performance aspects of the device and the outcome of the clinical evaluation in a document that should be publicly available.\n\n\n\n\n\n\n\n\n\n\n\n\n(49)\n\n\nThe summary of safety and clinical performance for a device should include in particular the place of the device in the context of diagnostic or therapeutic options taking into account the clinical evaluation of that device when compared to the diagnostic or therapeutic alternatives and the specific conditions under which that device and its alternatives can be considered.\n\n\n\n\n\n\n\n\n\n\n\n\n(50)\n\n\nThe proper functioning of notified bodies is crucial for ensuring a high level of health and safety protection and citizens' confidence in the system. Designation and monitoring of notified bodies by the Member\u00a0States, in accordance with detailed and strict criteria, should therefore be subject to controls at Union level.\n\n\n\n\n\n\n\n\n\n\n\n\n(51)\n\n\nNotified bodies' assessments of manufacturers' technical documentation, in particular documentation on clinical evaluation, should be critically evaluated by the authority responsible for notified bodies. That evaluation should be part of the risk-based approach to the oversight and monitoring activities of notified bodies and should be based on sampling of the relevant documentation.\n\n\n\n\n\n\n\n\n\n\n\n\n(52)\n\n\nThe position of notified bodies vis-\u00e0-vis manufacturers should be strengthened, including with regard to their right and duty to carry out unannounced on-site audits and to conduct physical or laboratory tests on devices to ensure continuous compliance by manufacturers after receipt of the original certification.\n\n\n\n\n\n\n\n\n\n\n\n\n(53)\n\n\nTo increase transparency with regard to the oversight of notified bodies by national authorities, the authorities responsible for notified bodies should publish information on the national measures governing the assessment, designation and monitoring of notified bodies. In accordance with good administrative practice, this information should be kept up to date by those authorities in particular to reflect relevant, significant or substantive changes to the procedures in question.\n\n\n\n\n\n\n\n\n\n\n\n\n(54)\n\n\nThe Member\u00a0State in which a notified body is established should be responsible for enforcing the requirements of this Regulation with regard to that notified body.\n\n\n\n\n\n\n\n\n\n\n\n\n(55)\n\n\nIn view, in particular, of the responsibility of Member\u00a0States for the organisation and delivery of health services and medical care, they should be allowed to lay down additional requirements on notified bodies designated for the conformity assessment of devices and established on their territory as far as issues that are not regulated in this Regulation are concerned. Any such additional requirements laid down should not affect more specific horizontal Union legislation on notified bodies and equal treatment of notified bodies.\n\n\n\n\n\n\n\n\n\n\n\n\n(56)\n\n\nFor class III implantable devices and class IIb active devices intended to administer and/or remove a medicinal product, notified bodies should, except in certain cases, be obliged to request expert panels to scrutinise their clinical evaluation assessment report. Competent authorities should be informed about devices that have been granted a certificate following a conformity assessment procedure involving an expert panel. The consultation of expert panels in relation to the clinical evaluation should lead to a harmonised evaluation of high-risk medical devices by sharing expertise on clinical aspects and developing CS on categories of devices that have undergone that consultation process.\n\n\n\n\n\n\n\n\n\n\n\n\n(57)\n\n\nFor class\u00a0III devices and for certain class\u00a0IIb devices, a manufacturer should be able to consult voluntarily an expert panel, prior to that manufacturer's clinical evaluation and/or investigation, on its clinical development strategy and on proposals for clinical investigations.\n\n\n\n\n\n\n\n\n\n\n\n\n(58)\n\n\nIt is necessary, in particular for the purpose of the conformity assessment procedures, to maintain the division of devices into four product classes in line with international practice. The classification rules, which are based on the vulnerability of the human body, should take into account the potential risks associated with the technical design and manufacture of the devices. To maintain the same level of safety as provided by Directive\u00a090/385/EEC, active implantable devices should be in the highest risk class.\n\n\n\n\n\n\n\n\n\n\n\n\n(59)\n\n\nRules under the old regime applied to invasive devices do not sufficiently take account of the level of invasiveness and potential toxicity of certain devices which are introduced into the human body. In order to obtain a suitable risk-based classification of devices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body, it is necessary to introduce specific classification rules for such devices. The classification rules should take into account the place where the device performs its action in or on the human body, where it is introduced or applied, and whether a systemic absorption of the substances of which the device is composed, or of the products of metabolism in the human body of those substances occurs.\n\n\n\n\n\n\n\n\n\n\n\n\n(60)\n\n\nThe conformity assessment procedure for class I devices should be carried out, as a general rule, under the sole responsibility of manufacturers in view of the low level of vulnerability associated with such devices. For class\u00a0IIa, class\u00a0IIb and class\u00a0III devices, an appropriate level of involvement of a notified body should be compulsory.\n\n\n\n\n\n\n\n\n\n\n\n\n(61)\n\n\nThe conformity assessment procedures for devices should be further strengthened and streamlined whilst the requirements for notified bodies as regards the performance of their assessments should be clearly specified to ensure a level playing field.\n\n\n\n\n\n\n\n\n\n\n\n\n(62)\n\n\nIt is appropriate that certificates of free sale contain information that makes it possible to use Eudamed in order to obtain information on the device, in particular with regard to whether it is on the market, withdrawn from the market or recalled, and on any certificate on its conformity.\n\n\n\n\n\n\n\n\n\n\n\n\n(63)\n\n\nTo ensure a high level of safety and performance, demonstration of compliance with the general safety and performance requirements laid down in this Regulation should be based on clinical data that, for class\u00a0III\u00a0devices and implantable devices should, as a general rule, be sourced from clinical investigations that have been carried out under the responsibility of a sponsor. It should be possible both for the manufacturer and for another natural or legal person to be the sponsor taking responsibility for the clinical investigation.\n\n\n\n\n\n\n\n\n\n\n\n\n(64)\n\n\nThe rules on clinical investigations should be in line with well-established international guidance in this field, such as the international standard ISO\u00a014155:2011 on good clinical practice for clinical investigations of medical devices for human subjects, so as to make it easier for the results of clinical investigations conducted in the Union to be accepted as documentation outside the Union and to make it easier for the results of clinical investigations conducted outside the Union in accordance with international guidelines to be accepted within the Union. In addition, the rules should be in line with the most recent version of the World Medical Association Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects.\n\n\n\n\n\n\n\n\n\n\n\n\n(65)\n\n\nIt should be left to the Member\u00a0State where a clinical investigation is to be conducted to determine the appropriate authority to be involved in the assessment of the application to conduct a clinical investigation and to organise the involvement of ethics committees within the timelines for the authorisation of that clinical investigation as set out in this Regulation. Such decisions are a matter of internal organisation for each Member\u00a0State. In that context, Member\u00a0States should ensure the involvement of laypersons, in particular patients or patients' organisations. They should also ensure that the necessary expertise is available.\n\n\n\n\n\n\n\n\n\n\n\n\n(66)\n\n\nWhere, in the course of a clinical investigation, harm caused to a subject leads to the civil or criminal liability of the investigator or the sponsor being invoked, the conditions for liability in such cases, including issues of causality and the level of damages and sanctions, should remain governed by national law.\n\n\n\n\n\n\n\n\n\n\n\n\n(67)\n\n\nAn electronic system should be set up at Union level to ensure that every clinical investigation is recorded and reported in a publicly accessible database. To protect the right to the protection of personal data, recognised by Article\u00a08 of the Charter of Fundamental Rights of the European Union (\u2018the Charter\u2019), no personal data of subjects participating in a clinical investigation should be recorded in the electronic system. To ensure synergies with the area of clinical trials on medicinal products, the electronic system on clinical investigations should be interoperable with the EU database to be set up for clinical trials on medicinal products for human use.\n\n\n\n\n\n\n\n\n\n\n\n\n(68)\n\n\nWhere a clinical investigation is to be conducted in more than one Member\u00a0State, the sponsor should have the possibility of submitting a single application in order to reduce administrative burden. In order to allow for resource-sharing and to ensure consistency regarding the assessment of the health and safety-related aspects of the investigational device and of the scientific design of that clinical investigation, the procedure for the assessment of such single application should be coordinated between the Member\u00a0States under the direction of a coordinating Member\u00a0State. Such coordinated assessment should not include the assessment of intrinsically national, local and ethical aspects of a clinical investigation, including informed consent. For an initial period of seven years from the date of application of this Regulation, Member\u00a0States should be able to participate on a voluntary basis in the coordinated assessment. After that period, all Member\u00a0States should be obliged to participate in the coordinated assessment. The Commission, based on the experience gained from the voluntary coordination between Member\u00a0States, should draw up a report on the application of the relevant provisions regarding the coordinated assessment procedure. In the event that the findings of the report are negative, the Commission should submit a proposal to extend the period of participation on a voluntary basis in the coordinated assessment procedure.\n\n\n\n\n\n\n\n\n\n\n\n\n(69)\n\n\nSponsors should report certain adverse events and device deficiencies that occur during clinical investigations to the Member\u00a0States in which those clinical investigations are being conducted. Member\u00a0States should have the possibility of terminating or suspending the investigations or revoking the authorisation for those investigations, if considered necessary to ensure a high level of protection of the subjects participating in a clinical investigation. Such information should be communicated to the other Member\u00a0States.\n\n\n\n\n\n\n\n\n\n\n\n\n(70)\n\n\nThe sponsor of a clinical investigation should submit a summary of results of the clinical investigation that is easily understandable for the intended user together with the clinical investigation report, where applicable, within the timelines laid down in this Regulation. Where it is not possible to submit the summary of the results within the defined timelines for scientific reasons, the sponsor should justify this and specify when the results will be submitted.\n\n\n\n\n\n\n\n\n\n\n\n\n(71)\n\n\nThis Regulation should cover clinical investigations intended to gather clinical evidence for the purpose of demonstrating conformity of devices and should also lay down basic requirements regarding ethical and scientific assessments for other types of clinical investigations of medical devices.\n\n\n\n\n\n\n\n\n\n\n\n\n(72)\n\n\nIncapacitated subjects, minors, pregnant women and breastfeeding women require specific protection measures. However, it should be left to Member\u00a0States to determine the legally designated representatives of incapacitated subjects and minors.\n\n\n\n\n\n\n\n\n\n\n\n\n(73)\n\n\nThe principles of replacement, reduction and refinement in the area of animal experimentation laid down in the Directive\u00a02010/63/EU of the European Parliament and of the Council\u00a0(24) should be observed. In particular, the unnecessary duplication of tests and studies should be avoided.\n\n\n\n\n\n\n\n\n\n\n\n\n(74)\n\n\nManufacturers should play an active role during the post-market phase by systematically and actively gathering information from post-market experience with their devices in order to update their technical documentation and cooperate with the national competent authorities in charge of vigilance and market surveillance activities. To this end, manufacturers should establish a comprehensive post-market surveillance system, set up under their quality management system and based on a post-market surveillance plan. Relevant data and information gathered through post-market surveillance, as well as lessons learned from any implemented preventive and/or corrective actions, should be used to update any relevant part of technical documentation, such as those relating to risk assessment and clinical evaluation, and should also serve the purpose of transparency.\n\n\n\n\n\n\n\n\n\n\n\n\n(75)\n\n\nIn order to better protect health and safety regarding devices on the market, the electronic system on vigilance for devices should be made more effective by creating a central portal at Union level for reporting serious incidents and field safety corrective actions.\n\n\n\n\n\n\n\n\n\n\n\n\n(76)\n\n\nMember\u00a0States should take appropriate measures to raise awareness among healthcare professionals, users and patients about the importance of reporting incidents. Healthcare professionals, users and patients should be encouraged and enabled to report suspected serious incidents at national level using harmonised formats. The national competent authorities should inform manufacturers of any suspected serious incidents and, where a manufacturer confirms that such an incident has occurred, the authorities concerned should ensure that appropriate follow-up action is taken in order to minimise recurrence of such incidents.\n\n\n\n\n\n\n\n\n\n\n\n\n(77)\n\n\nThe evaluation of reported serious incidents and field safety corrective actions should be conducted at national level but coordination should be ensured where similar incidents have occurred or field safety corrective actions have to be carried out in more than one Member\u00a0State, with the objective of sharing resources and ensuring consistency regarding the corrective action.\n\n\n\n\n\n\n\n\n\n\n\n\n(78)\n\n\nIn the context of the investigation of incidents, the competent authorities should take into account, where appropriate, the information provided by and views of relevant stakeholders, including patient and healthcare professionals' organisations and manufacturers' associations.\n\n\n\n\n\n\n\n\n\n\n\n\n(79)\n\n\nThe reporting of serious adverse events or device deficiencies during clinical investigations and the reporting of serious incidents occurring after a device has been placed on the market should be clearly distinguished to avoid double reporting.\n\n\n\n\n\n\n\n\n\n\n\n\n(80)\n\n\nRules on market surveillance should be included in this Regulation to reinforce the rights and obligations of the national competent authorities, to ensure effective coordination of their market surveillance activities and to clarify the applicable procedures.\n\n\n\n\n\n\n\n\n\n\n\n\n(81)\n\n\nAny statistically significant increase in the number or severity of incidents that are not serious or in expected side-effects that could have a significant impact on the benefit-risk analysis and which could lead to unacceptable risks should be reported to the competent authorities in order to permit their assessment and the adoption of appropriate measures.\n\n\n\n\n\n\n\n\n\n\n\n\n(82)\n\n\nAn expert committee, the Medical Device Coordination Group (MDCG), composed of persons designated by the Member\u00a0States based on their role and expertise in the field of medical devices including in vitro diagnostic medical devices, should be established to fulfil the tasks conferred on it by this Regulation and by Regulation\u00a0(EU)\u00a02017/746 of the European Parliament and of the Council\u00a0(25), to provide advice to the Commission and to assist the Commission and the Member\u00a0States in ensuring a harmonised implementation of this Regulation. The MDCG should be able to establish subgroups in order to have access to necessary in-depth technical expertise in the field of medical devices including in vitro diagnostic medical devices. When establishing subgroups, appropriate consideration should be given to the possibility of involving existing groups at Union level in the field of medical devices.\n\n\n\n\n\n\n\n\n\n\n\n\n(83)\n\n\nExpert panels and expert laboratories should be designated by the Commission on the basis of their up-to-date clinical, scientific or technical expertise, with the aim of providing scientific, technical and clinical assistance to the Commission, the MDCG, manufacturers and notified bodies in relation to the implementation of this Regulation. Moreover, expert panels should fulfil the tasks of providing an opinion on clinical evaluation assessment reports of notified bodies in the case of certain high-risk devices.\n\n\n\n\n\n\n\n\n\n\n\n\n(84)\n\n\nCloser coordination between national competent authorities through information exchange and coordinated assessments under the direction of a coordinating authority is essential for ensuring a consistently high level of health and safety protection within the internal market, in particular in the areas of clinical investigations and vigilance. The principle of coordinated exchange and assessment should also apply across other authority activities described in this Regulation, such as the designation of notified bodies and should be encouraged in the area of market surveillance of devices. Joint working, coordination and communication of activities should also lead to more efficient use of resources and expertise at national level.\n\n\n\n\n\n\n\n\n\n\n\n\n(85)\n\n\nThe Commission should provide scientific, technical and corresponding logistical support to coordinating national authorities and ensure that the regulatory system for devices is effectively and uniformly implemented at Union level based on sound scientific evidence.\n\n\n\n\n\n\n\n\n\n\n\n\n(86)\n\n\nThe Union and, where appropriate, the Member\u00a0States should actively participate in international regulatory cooperation in the field of medical devices to facilitate the exchange of safety-related information regarding medical devices and to foster the further development of international regulatory guidelines that promote the adoption in other jurisdictions of regulations that lead to a level of health and safety protection equivalent to that set by this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(87)\n\n\nMember\u00a0States should take all necessary measures to ensure that the provisions of this Regulation are implemented, including by laying down effective, proportionate and dissuasive penalties for their infringement.\n\n\n\n\n\n\n\n\n\n\n\n\n(88)\n\n\nWhilst this Regulation should not affect the right of Member\u00a0States to levy fees for activities at national level, Member\u00a0States should, in order to ensure transparency, inform the Commission and the other Member\u00a0States before they decide on the level and structure of such fees. In order to further ensure transparency, the structure and level of the fees should be publicly available on request.\n\n\n\n\n\n\n\n\n\n\n\n\n(89)\n\n\nThis Regulation respects the fundamental rights and observes the principles recognised in particular by the Charter and in particular human dignity, the integrity of the person, the protection of personal data, the freedom of art and science, the freedom to conduct business and the right to property. This Regulation should be applied by the Member\u00a0States in accordance with those rights and principles.\n\n\n\n\n\n\n\n\n\n\n\n\n(90)\n\n\nThe power to adopt delegated acts in accordance with Article\u00a0290 TFEU should be delegated to the Commission in order to amend certain non-essential provisions of this Regulation. It is of particular importance that the Commission carry out appropriate consultations during its preparatory work, including at expert level, and that those consultations be conducted in accordance with the principles laid down in the Interinstitutional Agreement of 13\u00a0April\u00a02016 on Better Law-Making\u00a0(26). In particular, to ensure equal participation in the preparation of delegated acts, the European Parliament and the Council receive all documents at the same time as Member\u00a0States' experts, and their experts systematically have access to meetings of Commission expert groups dealing with preparation of delegated acts.\n\n\n\n\n\n\n\n\n\n\n\n\n(91)\n\n\nIn order to ensure uniform conditions for the implementation of this Regulation, implementing powers should\u00a0be conferred on the Commission. Those powers should be exercised in accordance with Regulation\u00a0(EU)\u00a0No\u00a0182/2011 of the European Parliament and of the Council\u00a0(27).\n\n\n\n\n\n\n\n\n\n\n\n\n(92)\n\n\nThe advisory procedure should be used for implementing acts that set out the form and presentation of the data elements of manufacturers' summaries of safety and clinical performance, and that establish the model for certificates of free sale, given that such implementing acts are of a procedural nature and do not directly have an impact on health and safety at Union level.\n\n\n\n\n\n\n\n\n\n\n\n\n(93)\n\n\nThe Commission should adopt immediately applicable implementing acts where, in duly justified cases relating to the extension to the territory of the Union of a national derogation from the applicable conformity assessment procedures, imperative grounds of urgency so require.\n\n\n\n\n\n\n\n\n\n\n\n\n(94)\n\n\nIn order to enable it to designate issuing entities, expert panels and expert laboratories, implementing powers should be conferred on the Commission.\n\n\n\n\n\n\n\n\n\n\n\n\n(95)\n\n\nTo allow economic operators, especially SMEs, notified bodies, Member\u00a0States and the Commission to adapt to the changes introduced by this Regulation and to ensure its proper application, it is appropriate to provide for a sufficient transitional period for that adaptation and for the organisational arrangements that are to be made. However, certain parts of the Regulation that directly affect Member\u00a0States and the Commission should be implemented as soon as possible. It is also particularly important that, by the date of application of this Regulation, a sufficient number of notified bodies be designated in accordance with the new requirements so as to avoid any shortage of medical devices on the market. Nonetheless, it is necessary that any designation of a notified body in accordance with the requirements of this Regulation prior to the date of its application be without prejudice to the validity of the designation of those notified bodies under Directives\u00a090/385/EEC and 93/42/EEC and to their capacity to continue issuing valid certificates under those two Directives until the date of application of this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(96)\n\n\nIn order to ensure a smooth transition to the new rules for registration of devices and of certificates, the obligation to submit the relevant information to the electronic systems set up at Union level pursuant to this Regulation should, in the event that the corresponding IT\u00a0systems are developed according to plan, only become fully effective from 18\u00a0months after the date of application of this Regulation. During this transitional period, certain provisions of Directives\u00a090/385/EEC and 93/42/EEC should remain in force. However, in order to avoid multiple registrations, economic operators and notified bodies who register in the relevant electronic systems set up at Union level pursuant to this Regulation should be considered to be in compliance with the registration requirements adopted by the Member\u00a0States pursuant to those provisions.\n\n\n\n\n\n\n\n\n\n\n\n\n(97)\n\n\nIn order to provide for a smooth introduction of the UDI system, the moment of application of the obligation to place the UDI carrier on the label of the device should vary from one to five years after the date of application of this Regulation depending upon the class of the device concerned.\n\n\n\n\n\n\n\n\n\n\n\n\n(98)\n\n\nDirectives\u00a090/385/EEC and 93/42/EEC should be repealed to ensure that only one set of rules applies to the placing of medical devices on the market and the related aspects covered by this Regulation. Manufacturers' obligations as regards the making available of documentation regarding devices they placed on the market and manufacturers' and Member\u00a0States' obligations as regards vigilance activities for devices placed on the market pursuant to those Directives should however continue to apply. While it should be left to Member\u00a0States to decide how to organise vigilance activities, it is desirable for them to have the possibility of reporting incidents related to devices placed on the market pursuant to the Directives using the same tools as those for reporting on devices placed on the market pursuant to this Regulation. It is furthermore appropriate, in order to ensure a smooth transition from the old regime to the new regime, to provide that Commission Regulation\u00a0(EU)\u00a0No\u00a0207/2012\u00a0(28) and Commission Regulation\u00a0(EU)\u00a0No\u00a0722/2012\u00a0(29) should remain in force and continue to apply unless and until repealed by implementing acts adopted by the Commission pursuant to this Regulation.\nDecision\u00a02010/227/EU adopted in implementation of those Directives and Directive\u00a098/79/EC should also remain in force and continue to apply until the date when Eudamed becomes fully functional. Conversely, no such maintenance in force is required for Commission Directives\u00a02003/12/EC\u00a0(30) and 2005/50/EC\u00a0(31) and Commission Implementing Regulation (EU)\u00a0No\u00a0920/2013\u00a0(32).\n\n\n\n\n\n\n\n\n\n\n\n\n(99)\n\n\nThe requirements of this Regulation should be applicable to all devices placed on the market or put into service from the date of application of this Regulation. However, in order to provide for a smooth transition it should be possible, for a limited period of time from that date, for devices to be placed on the market or put into service by virtue of a valid certificate issued pursuant to Directive\u00a090/385/EEC or pursuant to Directive\u00a093/42/EEC.\n\n\n\n\n\n\n\n\n\n\n\n\n(100)\n\n\nThe European Data Protection Supervisor has given an opinion\u00a0(33) pursuant to Article\u00a028(2) of\u00a0Regulation\u00a0(EC)\u00a0No\u00a045/2001.\n\n\n\n\n\n\n\n\n\n\n\n\n(101)\n\n\nSince the objectives of this Regulation, namely to ensure the smooth functioning of the internal market as regards medical devices and to ensure high standards of quality and safety for medical devices, thus ensuring a high level of protection of health and safety of patients, users and other persons, cannot be sufficiently achieved by the Member\u00a0States but can rather, by reason of its scale and effects, be better achieved at Union level, the Union may adopt measures, in accordance with the principle of subsidiarity as set out in Article\u00a05 of the Treaty on European Union. In accordance with the principle of proportionality, as set out in that Article, this Regulation does not go beyond what is necessary in order to achieve those objectives,\n\n\n\n\n\nHAVE ADOPTED THIS REGULATION:\n\n\n\nCHAPTER I\n\n\nSCOPE AND DEFINITIONS\n\n\n\nArticle\u00a01\n\nSubject matter and scope\n\n\n1.\u00a0\u00a0\u00a0This Regulation lays down rules concerning the placing on the market, making available on the market or putting into service of medical devices for human use and accessories for such devices in the Union. This Regulation also applies to clinical investigations concerning such medical devices and accessories conducted in the Union.\n\n\n2.\u00a0\u00a0\u00a0This Regulation shall also apply, as from the date of application of common specifications adopted pursuant to Article\u00a09, to the groups of products without an intended medical purpose that are listed in Annex\u00a0XVI, taking into account the state of the art, and in particular existing harmonised standards for analogous devices with a medical purpose, based on similar technology. The common specifications for each of the groups of products listed in Annex\u00a0XVI shall address, at least, application of risk management as set out in Annex\u00a0I for the group of products in question and, where necessary, clinical evaluation regarding safety.\nThe necessary common specifications shall be adopted by 26 May 2020. They shall apply as from six months after the date of their entry into force or from 26 May 2020, whichever is the latest.\nNotwithstanding Article\u00a0122, Member\u00a0States' measures regarding the qualification of the products covered by Annex\u00a0XVI as medical devices pursuant to Directive\u00a093/42/EEC shall remain valid until the date of application, as referred to in the first subparagraph, of the relevant common specifications for that group of products.\nThis Regulation also applies to clinical investigations conducted in the Union concerning the products referred to in the first subparagraph.\n\n\n3.\u00a0\u00a0\u00a0Devices with both a medical and a non-medical intended purpose shall fulfil cumulatively the requirements applicable to devices with an intended medical purpose and those applicable to devices without an intended medical purpose.\n\n\n4.\u00a0\u00a0\u00a0For the purposes of this Regulation, medical devices, accessories for medical devices, and products listed in Annex\u00a0XVI to which this Regulation applies pursuant to paragraph\u00a02 shall hereinafter be referred to as \u2018devices\u2019.\n\n\n5.\u00a0\u00a0\u00a0Where justified on account of the similarity between a device with an intended medical purpose placed on the market and a product without an intended medical purpose in respect of their characteristics and risks, the Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 to amend the list in Annex\u00a0XVI, by adding new groups of products, in order to protect the health and safety of users or other persons or other aspects of public health.\n\n\n6.\u00a0\u00a0\u00a0This Regulation does not apply to:\n\n\n\n\n\n\n(a)\n\n\n\nin vitro diagnostic medical devices covered by Regulation\u00a0(EU)\u00a02017/746;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nmedicinal products as defined in point\u00a02 of Article\u00a01 of Directive\u00a02001/83/EC. In deciding whether a product falls under Directive\u00a02001/83/EC or under this Regulation, particular account shall be taken of the principal mode of action of the product;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nadvanced therapy medicinal products covered by Regulation\u00a0(EC)\u00a0No\u00a01394/2007;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nhuman blood, blood products, plasma or blood cells of human origin or devices which incorporate, when placed on the market or put into service, such blood products, plasma or cells, except for devices referred to in paragraph\u00a08 of this Article;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\ncosmetic products covered by Regulation\u00a0(EC)\u00a0No\u00a01223/2009;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\ntransplants, tissues or cells of animal origin, or their derivatives, or products containing or consisting of them; however this Regulation does apply to devices manufactured utilising tissues or cells of animal origin, or their derivatives, which are non-viable or are rendered non-viable;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\ntransplants, tissues or cells of human origin, or their derivatives, covered by Directive\u00a02004/23/EC, or products containing or consisting of them; however this Regulation does apply to devices manufactured utilising derivatives of tissues or cells of human origin which are non-viable or are rendered non-viable;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nproducts, other than those referred to in points (d), (f) and (g), that contain or consist of viable biological material or viable organisms, including living micro-organisms, bacteria, fungi or viruses in order to achieve or support the intended purpose of the product;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nfood covered by Regulation (EC)\u00a0No\u00a0178/2002.\n\n\n\n\n\n\n7.\u00a0\u00a0\u00a0Any device which, when placed on the market or put into service, incorporates as an integral part an in vitro diagnostic medical device as defined in point\u00a02 of Article\u00a02 of Regulation\u00a0(EU)\u00a02017/746, shall be governed by this Regulation. The requirements of Regulation\u00a0(EU)\u00a02017/746 shall apply to the in vitro diagnostic medical device part of the device.\n\n\n8.\u00a0\u00a0\u00a0Any device which, when placed on the market or put into service, incorporates, as an integral part, a substance which, if used separately, would be considered to be a medicinal product as defined in point\u00a02 of Article\u00a01 of Directive\u00a02001/83/EC, including a medicinal product derived from human blood or human plasma as defined in point\u00a010 of Article\u00a01 of that Directive, and that has an action ancillary to that of the device, shall be assessed and authorised in accordance with this Regulation.\nHowever, if the action of that substance is principal and not ancillary to that of the device, the integral product shall be governed by Directive\u00a02001/83/EC or Regulation\u00a0(EC)\u00a0No\u00a0726/2004 of the European Parliament and of the Council\u00a0(34), as applicable. In that case, the relevant general safety and performance requirements set out in Annex\u00a0I to this Regulation shall apply as far as the safety and performance of the device part are concerned.\n\n\n9.\u00a0\u00a0\u00a0Any device which is intended to administer a medicinal product as defined in point\u00a02 of Article\u00a01 of Directive\u00a02001/83/EC shall be governed by this Regulation, without prejudice to the provisions of that Directive\u00a0and of Regulation\u00a0(EC)\u00a0No\u00a0726/2004 with regard to the medicinal product.\nHowever, if the device intended to administer a medicinal product and the medicinal product are placed on the market in such a way that they form a single integral product which is intended exclusively for use in the given combination and which is not reusable, that single integral product shall be governed by Directive\u00a02001/83/EC or Regulation\u00a0(EC)\u00a0No\u00a0726/2004, as applicable. In that case, the relevant general safety and performance requirements set out in Annex\u00a0I to this Regulation shall apply as far as the safety and performance of the device part of the single integral product are concerned.\n\n\n10.\u00a0\u00a0\u00a0Any device which, when placed on the market or put into service, incorporates, as an integral part, non-viable tissues or cells of human origin or their derivatives that have an action ancillary to that of the device shall be assessed and authorised in accordance with this Regulation. In that case, the provisions for donation, procurement and testing laid down in Directive\u00a02004/23/EC shall apply.\nHowever, if the action of those tissues or cells or their derivatives is principal and not ancillary to that of the device and the product is not governed by Regulation\u00a0(EC)\u00a0No\u00a01394/2007, the product shall be governed by Directive\u00a02004/23/EC. In that case, the relevant general safety and performance requirements set out in Annex\u00a0I to this Regulation shall apply as far as the safety and performance of the device part are concerned.\n\n\n11.\u00a0\u00a0\u00a0This Regulation is specific Union legislation within the meaning of Article\u00a02(3) of Directive\u00a02014/30/EU.\n\n\n12.\u00a0\u00a0\u00a0Devices that are also machinery within the meaning of point\u00a0(a) of the second paragraph\u00a0of Article\u00a02 of Directive\u00a02006/42/EC of the European Parliament and of the Council\u00a0(35) shall, where a hazard relevant under that Directive\u00a0exists, also meet the essential health and safety requirements set out in Annex\u00a0I to that Directive\u00a0to the extent to which those requirements are more specific than the general safety and performance requirements set out in Chapter\u00a0II of Annex\u00a0I to this Regulation.\n\n\n13.\u00a0\u00a0\u00a0This Regulation shall not affect the application of Directive\u00a02013/59/Euratom.\n\n\n14.\u00a0\u00a0\u00a0This Regulation shall not affect the right of a Member\u00a0State to restrict the use of any specific type of device in relation to aspects not covered by this Regulation.\n\n\n15.\u00a0\u00a0\u00a0This Regulation shall not affect national law concerning the organisation, delivery or financing of health services and medical care, such as the requirement that certain devices may only be supplied on a medical prescription, the requirement that only certain health professionals or healthcare institutions may dispense or use certain devices or that their use be accompanied by specific professional counselling.\n\n\n16.\u00a0\u00a0\u00a0Nothing in this Regulation shall restrict the freedom of the press or the freedom of expression in the media in so far as those freedoms are guaranteed in the Union and in the Member\u00a0States, in particular under Article\u00a011 of the Charter of Fundamental Rights of the European Union.\n\n\n\nArticle\u00a02\n\nDefinitions\n\nFor the purposes of this Regulation, the following definitions apply:\n\n\n\n\n\n\n(1)\n\n\n\u2018medical device\u2019 means any instrument, apparatus, appliance, software, implant, reagent, material or other article intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the following specific medical purposes:\n\n\n\n\n\n\n\u2014\n\n\ndiagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndiagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninvestigation, replacement or modification of the anatomy or of a physiological or pathological process or state,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nproviding information by means of in vitro examination of specimens derived from the human body, including organ, blood and tissue donations,\n\n\n\n\nand which does not achieve its principal intended action by pharmacological, immunological or metabolic means, in or on the human body, but which may be assisted in its function by such means.\nThe following products shall also be deemed to be medical devices:\n\n\n\n\n\n\n\u2014\n\n\ndevices for the control or support of conception;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nproducts specifically intended for the cleaning, disinfection or sterilisation of devices as referred to in Article\u00a01(4) and of those referred to in the first paragraph\u00a0of this point.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(2)\n\n\n\u2018accessory for a medical device\u2019 means an article which, whilst not being itself a medical device, is intended by its manufacturer to be used together with one or several particular medical device(s) to specifically enable the medical device(s) to be used in accordance with its/their intended purpose(s) or to specifically and directly assist the medical functionality of the medical device(s) in terms of its/their intended purpose(s);\n\n\n\n\n\n\n\n\n\n\n(3)\n\n\n\u2018custom-made device\u2019 means any device specifically made in accordance with a written prescription of any person authorised by national law by virtue of that person's professional qualifications which gives, under that person's responsibility, specific design characteristics, and is intended for the sole use of a particular patient exclusively to meet their individual conditions and needs.\nHowever, mass-produced devices which need to be adapted to meet the specific requirements of any professional user and devices which are mass-produced by means of industrial manufacturing processes in accordance with the written prescriptions of any authorised person shall not be considered to be custom-made devices;\n\n\n\n\n\n\n\n\n\n\n(4)\n\n\n\u2018active device\u2019 means any device, the operation of which depends on a source of energy other than that generated by the human body for that purpose, or by gravity, and which acts by changing the density of or converting that energy. Devices intended to transmit energy, substances or other elements between an active device and the patient, without any significant change, shall not be deemed to be active devices.\nSoftware shall also be deemed to be an active device;\n\n\n\n\n\n\n\n\n\n\n(5)\n\n\n\u2018implantable device\u2019 means any device, including those that are partially or wholly absorbed, which is intended:\n\n\n\n\n\n\n\u2014\n\n\nto be totally introduced into the human body, or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nto replace an epithelial surface or the surface of the eye,\n\n\n\n\nby clinical intervention and which is intended to remain in place after the procedure.\nAny device intended to be partially introduced into the human body by clinical intervention and intended to remain in place after the procedure for at least 30\u00a0days shall also be deemed to be an implantable device;\n\n\n\n\n\n\n\n\n\n\n(6)\n\n\n\u2018invasive device\u2019 means any device which, in whole or in part, penetrates inside the body, either through a body orifice or through the surface of the body;\n\n\n\n\n\n\n\n\n\n\n(7)\n\n\n\u2018generic device group\u2019 means a set of devices having the same or similar intended purposes or a commonality of technology allowing them to be classified in a generic manner not reflecting specific characteristics;\n\n\n\n\n\n\n\n\n\n\n(8)\n\n\n\u2018single-use device\u2019 means a device that is intended to be used on one individual during a single procedure;\n\n\n\n\n\n\n\n\n\n\n(9)\n\n\n\u2018falsified device\u2019 means any device with a false presentation of its identity and/or of its source and/or its CE\u00a0marking certificates or documents relating to CE\u00a0marking procedures. This definition does not include unintentional non-compliance and is without prejudice to infringements of intellectual property rights;\n\n\n\n\n\n\n\n\n\n\n(10)\n\n\n\u2018procedure pack\u2019 means a combination of products packaged together and placed on the market with the purpose of being used for a specific medical purpose;\n\n\n\n\n\n\n\n\n\n\n(11)\n\n\n\u2018system\u2019 means a combination of products, either packaged together or not, which are intended to be inter-connected or combined to achieve a specific medical purpose;\n\n\n\n\n\n\n\n\n\n\n(12)\n\n\n\u2018intended purpose\u2019 means the use for which a device is intended according to the data supplied by the manufacturer on the label, in the instructions for use or in promotional or sales materials or statements and as specified by the manufacturer in the clinical evaluation;\n\n\n\n\n\n\n\n\n\n\n(13)\n\n\n\u2018label\u2019 means the written, printed or graphic information appearing either on the device itself, or on the packaging of each unit or on the packaging of multiple devices;\n\n\n\n\n\n\n\n\n\n\n(14)\n\n\n\u2018instructions for use\u2019 means the information provided by the manufacturer to inform the user of a device's intended purpose and proper use and of any precautions to be taken;\n\n\n\n\n\n\n\n\n\n\n(15)\n\n\n\u2018Unique Device Identifier\u2019 (\u2018UDI\u2019) means a series of numeric or alphanumeric characters that is created through internationally accepted device identification and coding standards and that allows unambiguous identification of specific devices on the market;\n\n\n\n\n\n\n\n\n\n\n(16)\n\n\n\u2018non-viable\u2019 means having no potential for metabolism or multiplication;\n\n\n\n\n\n\n\n\n\n\n(17)\n\n\n\u2018derivative\u2019 means a \u2018non-cellular substance\u2019 extracted from human or animal tissue or cells through a manufacturing process. The final substance used for manufacturing of the device in this case does not contain any cells or tissues;\n\n\n\n\n\n\n\n\n\n\n(18)\n\n\n\u2018nanomaterial\u2019 means a natural, incidental or manufactured material containing particles in an unbound state or as an aggregate or as an agglomerate and where, for\u00a050 % or more of the particles in the number size distribution, one or more external dimensions is in the size range 1-100\u00a0nm;\nFullerenes, graphene flakes and single-wall carbon nanotubes with one or more external dimensions below 1\u00a0nm shall also be deemed to be nanomaterials;\n\n\n\n\n\n\n\n\n\n\n(19)\n\n\n\u2018particle\u2019, for the purposes of the definition of nanomaterial in point\u00a0(18), means a minute piece of matter with defined physical boundaries;\n\n\n\n\n\n\n\n\n\n\n(20)\n\n\n\u2018agglomerate\u2019, for the purposes of the definition of nanomaterial in point\u00a0(18), means a collection of weakly bound particles or aggregates where the resulting external surface area is similar to the sum of the surface areas of the individual components;\n\n\n\n\n\n\n\n\n\n\n(21)\n\n\n\u2018aggregate\u2019, for the purposes of the definition of nanomaterial in point\u00a0(18), means a particle comprising of strongly bound or fused particles;\n\n\n\n\n\n\n\n\n\n\n(22)\n\n\n\u2018performance\u2019 means the ability of a device to achieve its intended purpose as stated by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(23)\n\n\n\u2018risk\u2019 means the combination of the probability of occurrence of harm and the severity of that harm;\n\n\n\n\n\n\n\n\n\n\n(24)\n\n\n\u2018benefit-risk determination\u2019 means the analysis of all assessments of benefit and risk of possible relevance for the use of the device for the intended purpose, when used in accordance with the intended purpose given by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(25)\n\n\n\u2018compatibility\u2019 is the ability of a device, including software, when used together with one or more other devices in accordance with its intended purpose, to:\n\n\n\n\n\n\n(a)\n\n\nperform without losing or compromising the ability to perform as intended, and/or\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nintegrate and/or operate without the need for modification or adaption of any part of the combined devices, and/or\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nbe used together without conflict/interference or adverse reaction.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(26)\n\n\n\u2018interoperability\u2019 is the ability of two or more devices, including software, from the same manufacturer or from different manufacturers, to:\n\n\n\n\n\n\n(a)\n\n\nexchange information and use the information that has been exchanged for the correct execution of a specified function without changing the content of the data, and/or\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ncommunicate with each other, and/or\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nwork together as intended.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(27)\n\n\n\u2018making available on the market\u2019 means any supply of a device, other than an investigational device, for distribution, consumption or use on the Union market in the course of a commercial activity, whether in return for payment or free of charge;\n\n\n\n\n\n\n\n\n\n\n(28)\n\n\n\u2018placing on the market\u2019 means the first making available of a device, other than an investigational device, on the Union market;\n\n\n\n\n\n\n\n\n\n\n(29)\n\n\n\u2018putting into service\u2019 means the stage at which a device, other than an investigational device, has been made available to the final user as being ready for use on the Union market for the first time for its intended purpose;\n\n\n\n\n\n\n\n\n\n\n(30)\n\n\n\u2018manufacturer\u2019 means a natural or legal person who manufactures or fully refurbishes a device or has a device designed, manufactured or fully refurbished, and markets that device under its name or trademark;\n\n\n\n\n\n\n\n\n\n\n(31)\n\n\n\u2018fully refurbishing\u2019, for the purposes of the definition of manufacturer, means the complete rebuilding of a device already placed on the market or put into service, or the making of a new device from used devices, to bring it into conformity with this Regulation, combined with the assignment of a new lifetime to the refurbished device;\n\n\n\n\n\n\n\n\n\n\n(32)\n\n\n\u2018authorised representative\u2019 means any natural or legal person established within the Union who has received and accepted a written mandate from a manufacturer, located outside the Union, to act on the manufacturer's behalf in relation to specified tasks with regard to the latter's obligations under this Regulation;\n\n\n\n\n\n\n\n\n\n\n(33)\n\n\n\u2018importer\u2019 means any natural or legal person established within the Union that places a device from a third country on the Union market;\n\n\n\n\n\n\n\n\n\n\n(34)\n\n\n\u2018distributor\u2019 means any natural or legal person in the supply chain, other than the manufacturer or the importer, that makes a device available on the market, up until the point of putting into service;\n\n\n\n\n\n\n\n\n\n\n(35)\n\n\n\u2018economic operator\u2019 means a manufacturer, an authorised representative, an importer, a distributor or the person referred to in Article\u00a022(1) and 22(3);\n\n\n\n\n\n\n\n\n\n\n(36)\n\n\n\u2018health institution\u2019 means an organisation the primary purpose of which is the care or treatment of patients or the promotion of public health;\n\n\n\n\n\n\n\n\n\n\n(37)\n\n\n\u2018user\u2019 means any healthcare professional or lay person who uses a device;\n\n\n\n\n\n\n\n\n\n\n(38)\n\n\n\u2018lay person\u2019 means an individual who does not have formal education in a relevant field of healthcare or medical discipline;\n\n\n\n\n\n\n\n\n\n\n(39)\n\n\n\u2018reprocessing\u2019 means a process carried out on a used device in order to allow its safe reuse including cleaning, disinfection, sterilisation and related procedures, as well as testing and restoring the technical and functional safety of the used device;\n\n\n\n\n\n\n\n\n\n\n(40)\n\n\n\u2018conformity assessment\u2019 means the process demonstrating whether the requirements of this Regulation relating to a device have been fulfilled;\n\n\n\n\n\n\n\n\n\n\n(41)\n\n\n\u2018conformity assessment body\u2019 means a body that performs third-party conformity assessment activities including calibration, testing, certification and inspection;\n\n\n\n\n\n\n\n\n\n\n(42)\n\n\n\u2018notified body\u2019 means a conformity assessment body designated in accordance with this Regulation;\n\n\n\n\n\n\n\n\n\n\n(43)\n\n\n\u2018CE marking of conformity\u2019 or \u2018CE marking\u2019 means a marking by which a manufacturer indicates that a device is in conformity with the applicable requirements set out in this Regulation and other applicable Union harmonisation legislation providing for its affixing;\n\n\n\n\n\n\n\n\n\n\n(44)\n\n\n\u2018clinical evaluation\u2019 means a systematic and planned process to continuously generate, collect, analyse and assess the clinical data pertaining to a device in order to verify the safety and performance, including clinical benefits, of the device when used as intended by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(45)\n\n\n\u2018clinical investigation\u2019 means any systematic investigation involving one or more human subjects, undertaken to assess the safety or performance of a device;\n\n\n\n\n\n\n\n\n\n\n(46)\n\n\n\u2018investigational device\u2019 means a device that is assessed in a clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(47)\n\n\n\u2018clinical investigation plan\u2019 means a document that describes the rationale, objectives, design, methodology, monitoring, statistical considerations, organisation and conduct of a clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(48)\n\n\n\u2018clinical data\u2019 means information concerning safety or performance that is generated from the use of a device and is sourced from the following:\n\n\n\n\n\n\n\u2014\n\n\nclinical investigation(s) of the device concerned,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclinical investigation(s) or other studies reported in scientific literature, of a device for which equivalence to the device in question can be demonstrated,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreports published in peer reviewed scientific literature on other clinical experience of either the device in question or a device for which equivalence to the device in question can be demonstrated,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclinically relevant information coming from post-market surveillance, in particular the post-market clinical follow-up;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(49)\n\n\n\u2018sponsor\u2019 means any individual, company, institution or organisation which takes responsibility for the initiation, for the management and setting up of the financing of the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(50)\n\n\n\u2018subject\u2019 means an individual who participates in a clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(51)\n\n\n\u2018clinical evidence\u2019 means clinical data and clinical evaluation results pertaining to a device of a sufficient amount and quality to allow a qualified assessment of whether the device is safe and achieves the intended clinical benefit(s), when used as intended by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(52)\n\n\n\u2018clinical performance\u2019 means the ability of a device, resulting from any direct or indirect medical effects which stem from its technical or functional characteristics, including diagnostic characteristics, to achieve its intended purpose as claimed by the manufacturer, thereby leading to a clinical benefit for patients, when used as intended by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(53)\n\n\n\u2018clinical benefit\u2019 means the positive impact of a device on the health of an individual, expressed in terms of a meaningful, measurable, patient-relevant clinical outcome(s), including outcome(s) related to diagnosis, or a positive impact on patient management or public health;\n\n\n\n\n\n\n\n\n\n\n(54)\n\n\n\u2018investigator\u2019 means an individual responsible for the conduct of a clinical investigation at a clinical investigation site;\n\n\n\n\n\n\n\n\n\n\n(55)\n\n\n\u2018informed consent\u2019 means a subject's free and voluntary expression of his or her willingness to participate in a particular clinical investigation, after having been informed of all aspects of the clinical investigation that are relevant to the subject's decision to participate or, in the case of minors and of incapacitated subjects, an authorisation or agreement from their legally designated representative to include them in the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(56)\n\n\n\u2018ethics committee\u2019 means an independent body established in a Member\u00a0State in accordance with the law of that Member\u00a0State and empowered to give opinions for the purposes of this Regulation, taking into account the views of laypersons, in particular patients or patients' organisations;\n\n\n\n\n\n\n\n\n\n\n(57)\n\n\n\u2018adverse event\u2019 means any untoward medical occurrence, unintended disease or injury or any untoward clinical signs, including an abnormal laboratory finding, in subjects, users or other persons, in the context of a clinical investigation, whether or not related to the investigational device;\n\n\n\n\n\n\n\n\n\n\n(58)\n\n\n\u2018serious adverse event\u2019 means any adverse event that led to any of the following:\n\n\n\n\n\n\n(a)\n\n\ndeath,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nserious deterioration in the health of the subject, that resulted in any of the following:\n\n\n\n\n\n\n(i)\n\n\nlife-threatening illness or injury,\n\n\n\n\n\n\n\n\n\n\n(ii)\n\n\npermanent impairment of a body structure or a body function,\n\n\n\n\n\n\n\n\n\n\n(iii)\n\n\nhospitalisation or prolongation of patient hospitalisation,\n\n\n\n\n\n\n\n\n\n\n(iv)\n\n\nmedical or surgical intervention to prevent life-threatening illness or injury or permanent impairment to a body structure or a body function,\n\n\n\n\n\n\n\n\n\n\n(v)\n\n\nchronic disease,\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nfoetal distress, foetal death or a congenital physical or mental impairment or birth defect;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(59)\n\n\n\u2018device deficiency\u2019 means any inadequacy in the identity, quality, durability, reliability, safety or performance of an\u00a0investigational device, including malfunction, use errors or inadequacy in information supplied by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(60)\n\n\n\u2018post-market surveillance\u2019 means all activities carried out by manufacturers in cooperation with other economic operators to institute and keep up to date a systematic procedure to proactively collect and review experience gained from devices they place on the market, make available on the market or put into service for the purpose of identifying any need to immediately apply any necessary corrective or preventive actions;\n\n\n\n\n\n\n\n\n\n\n(61)\n\n\n\u2018market surveillance\u2019 means the activities carried out and measures taken by competent authorities to check and ensure that devices comply with the requirements set out in the relevant Union harmonisation legislation and do not endanger health, safety or any other aspect of public interest protection;\n\n\n\n\n\n\n\n\n\n\n(62)\n\n\n\u2018recall\u2019 means any measure aimed at achieving the return of a device that has already been made available to the end user;\n\n\n\n\n\n\n\n\n\n\n(63)\n\n\n\u2018withdrawal\u2019 means any measure aimed at preventing a device in the supply chain from being further made available on the market;\n\n\n\n\n\n\n\n\n\n\n(64)\n\n\n\u2018incident\u2019 means any malfunction or deterioration in the characteristics or performance of a device made available on the market, including use-error due to ergonomic features, as well as any inadequacy in the information supplied by the manufacturer and any undesirable side-effect;\n\n\n\n\n\n\n\n\n\n\n(65)\n\n\n\u2018serious incident\u2019 means any incident that directly or indirectly led, might have led or might lead to any of the following:\n\n\n\n\n\n\n(a)\n\n\nthe death of a patient, user or other person,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe temporary or permanent serious deterioration of a patient's, user's or other person's state of health,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\na serious public health threat;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(66)\n\n\n\u2018serious public health threat\u2019 means an event which could result in imminent risk of death, serious deterioration in a person's state of health, or serious illness, that may require prompt remedial action, and that may cause significant morbidity or mortality in humans, or that is unusual or unexpected for the given place and time;\n\n\n\n\n\n\n\n\n\n\n(67)\n\n\n\u2018corrective action\u2019 means action taken to eliminate the cause of a potential or actual non-conformity or other undesirable situation;\n\n\n\n\n\n\n\n\n\n\n(68)\n\n\n\u2018field safety corrective action\u2019 means corrective action taken by a manufacturer for technical or medical reasons to prevent or reduce the risk of a serious incident in relation to a device made available on the market;\n\n\n\n\n\n\n\n\n\n\n(69)\n\n\n\u2018field safety notice\u2019 means a communication sent by a manufacturer to users or customers in relation to a field safety corrective action;\n\n\n\n\n\n\n\n\n\n\n(70)\n\n\n\u2018harmonised standard\u2019 means a European standard as defined in point\u00a0(1)(c) of Article\u00a02 of Regulation\u00a0(EU)\u00a0No\u00a01025/2012;\n\n\n\n\n\n\n\n\n\n\n(71)\n\n\n\u2018common specifications\u2019 (CS) means a set of technical and/or clinical requirements, other than a standard, that provides a means of complying with the legal obligations applicable to a device, process or system.\n\n\n\n\n\n\nArticle\u00a03\n\nAmendment of certain definitions\n\nThe Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 in order to amend the definition of nanomaterial set out in point\u00a0(18) and the related definitions in points\u00a0(19), (20) and (21) of Article\u00a02 in the light of technical and scientific progress and taking into account definitions agreed at Union and international level.\n\n\nArticle\u00a04\n\nRegulatory status of products\n\n\n1.\u00a0\u00a0\u00a0Without prejudice to Article\u00a02(2) of Directive\u00a02001/83/EC, upon a duly substantiated request of a Member\u00a0State, the Commission shall, after consulting the Medical Device Coordination Group established under Article\u00a0103 of this Regulation\u00a0(\u2018MDCG\u2019), by means of implementing acts, determine whether or not a specific product, or category or group of products, falls within the definitions of \u2018medical device\u2019 or \u2018accessory for a medical device\u2019. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3) of this Regulation.\n\n\n2.\u00a0\u00a0\u00a0The Commission may also, on its own initiative, after consulting the MDCG, decide, by means of implementing acts, on the issues referred to in paragraph\u00a01 of this Article. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n3.\u00a0\u00a0\u00a0The Commission shall ensure that Member\u00a0States share expertise in the fields of medical devices, in vitro diagnostic medical devices, medicinal products, human tissues and cells, cosmetics, biocides, food and, if necessary, other products, in order to determine the appropriate regulatory status of a product, or category or group of products.\n\n\n4.\u00a0\u00a0\u00a0When deliberating on the possible regulatory status as a device of products involving medicinal products, human tissues and cells, biocides or food products, the Commission shall ensure an appropriate level of consultation of the European Medicines Agency\u00a0(EMA), the European Chemicals Agency\u00a0(ECHA) and the European Food Safety Authority\u00a0(EFSA), as relevant.\n\n\n\n\nCHAPTER II\n\n\nMAKING AVAILABLE ON THE MARKET AND PUTTING INTO SERVICE OF DEVICES, OBLIGATIONS OF ECONOMIC OPERATORS, REPROCESSING, CE MARKING, FREE MOVEMENT\n\n\n\nArticle\u00a05\n\nPlacing on the market and putting into service\n\n\n1.\u00a0\u00a0\u00a0A device may be placed on the market or put into service only if it complies with this Regulation when duly supplied and properly installed, maintained and used in accordance with its intended purpose.\n\n\n2.\u00a0\u00a0\u00a0A device shall meet the general safety and performance requirements set out in Annex\u00a0I which apply to it, taking into account its intended purpose.\n\n\n3.\u00a0\u00a0\u00a0Demonstration of conformity with the general safety and performance requirements shall include a clinical evaluation in accordance with Article\u00a061.\n\n\n4.\u00a0\u00a0\u00a0Devices that are manufactured and used within health institutions shall be considered as having been put into service.\n\n\n5.\u00a0\u00a0\u00a0With the exception of the relevant general safety and performance requirements set out in Annex\u00a0I, the requirements of this Regulation shall not apply to devices, manufactured and used only within health institutions established in the Union, provided that all of the following conditions are met:\n\n\n\n\n\n\n(a)\n\n\nthe devices are not transferred to another legal entity,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nmanufacture and use of the devices occur under appropriate quality management systems,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe health institution justifies in its documentation that the target patient group's specific needs cannot be met, or cannot be met at the appropriate level of performance by an equivalent device available on the market,\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe health institution provides information upon request on the use of such devices to its competent authority, which shall include a justification of their manufacturing, modification and use;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe health institution draws up a declaration which it shall make publicly available, including:\n\n\n\n\n\n\n(i)\n\n\nthe name and address of the manufacturing health institution;\n\n\n\n\n\n\n\n\n\n\n(ii)\n\n\nthe details necessary to identify the devices;\n\n\n\n\n\n\n\n\n\n\n(iii)\n\n\na declaration that the devices meet the general safety and performance requirements set out in Annex\u00a0I to this Regulation and, where applicable, information on which requirements are not fully met with a reasoned justification therefor,\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe health institution draws up documentation that makes it possible to have an understanding of the manufacturing facility, the manufacturing process, the design and performance data of the devices, including the intended purpose, and that is sufficiently detailed to enable the competent authority to ascertain that the general safety and performance requirements set out in Annex\u00a0I to this Regulation are met;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthe health institution takes all necessary measures to ensure that all devices are manufactured in accordance with the documentation referred to in point\u00a0(f), and\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe health institution reviews experience gained from clinical use of the devices and takes all necessary corrective actions.\n\n\n\n\nMember\u00a0States may require that such health institutions submit to the competent authority any further relevant information about such devices which have been manufactured and used on their territory. Member\u00a0States shall retain the right to restrict the manufacture and the use of any specific type of such devices and shall be permitted access to inspect the activities of the health institutions.\nThis paragraph\u00a0shall not apply to devices that are manufactured on an industrial scale.\n\n\n6.\u00a0\u00a0\u00a0In order to ensure the uniform application of Annex\u00a0I, the Commission may adopt implementing acts to the extent necessary to resolve issues of divergent interpretation and of practical application. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a06\n\nDistance sales\n\n\n1.\u00a0\u00a0\u00a0A device offered by means of information society services, as defined in point\u00a0(b) of Article\u00a01(1) of Directive\u00a0(EU)\u00a02015/1535, to a natural or legal person established in the Union shall comply with this Regulation.\n\n\n2.\u00a0\u00a0\u00a0Without prejudice to national law regarding the exercise of the medical profession, a device that is not placed on the market but used in the context of a commercial activity, whether in return for payment or free of charge, for the provision of a diagnostic or therapeutic service offered by means of information society services as defined in point\u00a0(b) of Article\u00a01(1) of Directive\u00a0(EU)\u00a02015/1535 or by other means of communication, directly or through intermediaries, to a natural or legal person established in the Union shall comply with this Regulation.\n\n\n3.\u00a0\u00a0\u00a0Upon request by a competent authority, any natural or legal person offering a device in accordance with paragraph\u00a01 or providing a service in accordance with paragraph\u00a02 shall make available a copy of the EU\u00a0declaration of conformity of the device concerned.\n\n\n4.\u00a0\u00a0\u00a0A Member\u00a0State may, on grounds of protection of public health, require a provider of information society services, as defined in point\u00a0(b) of Article\u00a01(1) of Directive\u00a0(EU)\u00a02015/1535, to cease its activity.\n\n\n\nArticle\u00a07\n\nClaims\n\nIn the labelling, instructions for use, making available, putting into service and advertising of devices, it shall be prohibited to use text, names, trademarks, pictures and figurative or other signs that may mislead the user or the patient with regard to the device's intended purpose, safety and performance by:\n\n\n\n\n\n\n(a)\n\n\nascribing functions and properties to the device which the device does not have;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ncreating a false impression regarding treatment or diagnosis, functions or properties which the device does not have;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nfailing to inform the user or the patient of a likely risk associated with the use of the device in line with its intended purpose;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nsuggesting uses for the device other than those stated to form part of the intended purpose for which the conformity assessment was carried out.\n\n\n\n\n\n\nArticle\u00a08\n\nUse of harmonised standards\n\n\n1.\u00a0\u00a0\u00a0Devices that are in conformity with the relevant harmonised standards, or the relevant parts of those standards, the references of which have been published in the Official Journal of the European Union, shall be presumed to be in conformity with the requirements of this Regulation covered by those standards or parts thereof.\nThe first subparagraph\u00a0shall also apply to system or process requirements to be fulfilled in accordance with this Regulation by economic operators or sponsors, including those relating to quality management systems, risk management, post-market surveillance systems, clinical investigations, clinical evaluation or post-market clinical follow-up\u00a0(\u2018PMCF\u2019).\nReferences in this Regulation to harmonised standards shall be understood as meaning harmonised standards the references of which have been published in the Official Journal of the European Union.\n\n\n2.\u00a0\u00a0\u00a0References in this Regulation to harmonised standards shall also include the monographs of the European Pharmacopoeia adopted in accordance with the Convention on the Elaboration of a European Pharmacopoeia, in particular on surgical sutures and on interaction between medicinal products and materials used in devices containing such medicinal products, provided that references to those monographs have been published in the Official Journal of the European Union.\n\n\n\nArticle\u00a09\n\nCommon specifications\n\n\n1.\u00a0\u00a0\u00a0Without prejudice to Article\u00a01(2) and 17(5) and the deadline laid down in those provisions, where no harmonised standards exist or where relevant harmonised standards are not sufficient, or where there is a need to address public health concerns, the Commission, after having consulted the MDCG, may, by means of implementing acts, adopt common specifications (CS) in respect of the general safety and performance requirements set out in Annex\u00a0I, the technical documentation set out in Annexes\u00a0II and III, the clinical evaluation and post-market clinical follow-up set out in Annex\u00a0XIV or the requirements regarding clinical investigation set out in Annex\u00a0XV. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n2.\u00a0\u00a0\u00a0Devices that are in conformity with the CS referred to in paragraph\u00a01 shall be presumed to be in conformity with the requirements of this Regulation covered by those CS or the relevant parts of those CS.\n\n\n3.\u00a0\u00a0\u00a0Manufacturers shall comply with the CS referred to in paragraph\u00a01 unless they can duly justify that they have adopted solutions that ensure a level of safety and performance that is at least equivalent thereto.\n\n\n4.\u00a0\u00a0\u00a0Notwithstanding paragraph\u00a03, manufacturers of products listed in Annex\u00a0XVI shall comply with the relevant CS for those products.\n\n\n\nArticle\u00a010\n\nGeneral obligations of manufacturers\n\n\n1.\u00a0\u00a0\u00a0When placing their devices on the market or putting them into service, manufacturers shall ensure that they have been designed and manufactured in accordance with the requirements of this Regulation.\n\n\n2.\u00a0\u00a0\u00a0Manufacturers shall establish, document, implement and maintain a system for risk management as described in Section\u00a03 of Annex\u00a0I.\n\n\n3.\u00a0\u00a0\u00a0Manufacturers shall conduct a clinical evaluation in accordance with the requirements set out in Article\u00a061 and Annex\u00a0XIV, including a PMCF.\n\n\n4.\u00a0\u00a0\u00a0Manufacturers of devices other than custom-made devices shall draw up and keep up to date technical documentation for those devices. The technical documentation shall be such as to allow the conformity of the device with the requirements of this Regulation to be assessed. The technical documentation shall include the elements set out in Annexes\u00a0II and\u00a0III.\nThe Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 amending, in the light of technical progress, the Annexes\u00a0II and III.\n\n\n5.\u00a0\u00a0\u00a0Manufacturers of custom-made devices shall draw up, keep up to date and keep available for competent authorities documentation in accordance with Section\u00a02 of Annex\u00a0XIII.\n\n\n6.\u00a0\u00a0\u00a0Where compliance with the applicable requirements has been demonstrated following the applicable conformity assessment procedure, manufacturers of devices, other than custom-made or investigational devices, shall draw up an EU declaration of conformity in accordance with Article\u00a019, and affix the CE marking of conformity in accordance with Article\u00a020.\n\n\n7.\u00a0\u00a0\u00a0Manufacturers shall comply with the obligations relating to the UDI system referred to in Article\u00a027 and with the registration obligations referred to in Articles\u00a029 and 31.\n\n\n8.\u00a0\u00a0\u00a0Manufacturers shall keep the technical documentation, the EU declaration of conformity and, if applicable, a copy of any relevant certificate, including any amendments and supplements, issued in accordance with Article\u00a056, available for the competent authorities for a period of at least 10 years after the last device covered by the EU\u00a0declaration of conformity has been placed on the market. In the case of implantable devices, the period shall be at least 15 years after the last device has been placed on the market.\nUpon request by a competent authority, the manufacturer shall, as indicated therein, provide that technical documentation in its entirety or a summary thereof.\nA manufacturer with a registered place of business outside the Union shall, in order to allow its authorised representative to fulfil the tasks mentioned in Article\u00a011(3), ensure that the authorised representative has the necessary documentation permanently available.\n\n\n9.\u00a0\u00a0\u00a0Manufacturers shall ensure that procedures are in place to keep series production in conformity with the requirements of this Regulation. Changes in device design or characteristics and changes in the harmonised standards or CS by reference to which the conformity of a device is declared shall be adequately taken into account in a timely manner. Manufacturers of devices, other than investigational devices, shall establish, document, implement, maintain, keep up to date and continually improve a quality management system that shall ensure compliance with this Regulation in the most effective manner and in a manner that is proportionate to the risk class and the type of device.\nThe quality management system shall cover all parts and elements of a manufacturer's organisation dealing with the quality of processes, procedures and devices. It shall govern the structure, responsibilities, procedures, processes and management resources required to implement the principles and actions necessary to achieve compliance with the provisions of this Regulation.\nThe quality management system shall address at least the following aspects:\n\n\n\n\n\n\n(a)\n\n\na strategy for regulatory compliance, including compliance with conformity assessment procedures and procedures for management of modifications to the devices covered by the system;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nidentification of applicable general safety and performance requirements and exploration of options to address those requirements;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nresponsibility of the management;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nresource management, including selection and control of suppliers and sub-contractors;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nrisk management as set out in in Section\u00a03 of Annex\u00a0I;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nclinical evaluation in accordance with Article\u00a061 and Annex\u00a0XIV, including PMCF;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nproduct realisation, including planning, design, development, production and service provision;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nverification of the UDI assignments made in accordance with Article\u00a027(3) to all relevant devices and ensuring consistency and validity of information provided in accordance with Article\u00a029;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nsetting-up, implementation and maintenance of a post-market surveillance system, in accordance with Article\u00a083;\n\n\n\n\n\n\n\n\n\n\n(j)\n\n\nhandling communication with competent authorities, notified bodies, other economic operators, customers and/or other stakeholders;\n\n\n\n\n\n\n\n\n\n\n(k)\n\n\nprocesses for reporting of serious incidents and field safety corrective actions in the context of vigilance;\n\n\n\n\n\n\n\n\n\n\n(l)\n\n\nmanagement of corrective and preventive actions and verification of their effectiveness;\n\n\n\n\n\n\n\n\n\n\n(m)\n\n\nprocesses for monitoring and measurement of output, data analysis and product improvement.\n\n\n\n\n\n\n10.\u00a0\u00a0\u00a0Manufacturers of devices shall implement and keep up to date the post-market surveillance system in accordance with Article\u00a083.\n\n\n11.\u00a0\u00a0\u00a0Manufacturers shall ensure that the device is accompanied by the information set out in Section\u00a023 of Annex\u00a0I in an official Union language(s) determined by the Member\u00a0State in which the device is made available to the user or patient. The particulars on the label shall be indelible, easily legible and clearly comprehensible to the intended user or patient.\n\n\n12.\u00a0\u00a0\u00a0Manufacturers who consider or have reason to believe that a device which they have placed on the market or put into service is not in conformity with this Regulation shall immediately take the necessary corrective action to bring that device into conformity, to withdraw it or to recall it, as appropriate. They shall inform the distributors of the device in question and, where applicable, the authorised representative and importers accordingly.\nWhere the device presents a serious risk, manufacturers shall immediately inform the competent authorities of the Member\u00a0States in which they made the device available and, where applicable, the notified body that issued a certificate for the device in accordance with Article\u00a056, in particular, of the non-compliance and of any corrective action taken.\n\n\n13.\u00a0\u00a0\u00a0Manufacturers shall have a system for recording and reporting of incidents and field safety corrective actions as described in Articles\u00a087 and 88.\n\n\n14.\u00a0\u00a0\u00a0Manufacturers shall, upon request by a competent authority, provide it with all the information and documentation necessary to demonstrate the conformity of the device, in an official Union language determined by the Member\u00a0State concerned. The competent authority of the Member\u00a0State in which the manufacturer has its registered place of business may require that the manufacturer provide samples of the device free of charge or, where that is impracticable, grant access to the device. Manufacturers shall cooperate with a competent authority, at its request, on any corrective action taken to eliminate or, if that is not possible, mitigate the risks posed by devices which they have placed on the market or put into service.\nIf the manufacturer fails to cooperate or the information and documentation provided is incomplete or incorrect, the competent authority may, in order to ensure the protection of public health and patient safety, take all appropriate measures to prohibit or restrict the device's being made available on its national market, to withdraw the device from that market or to recall it until the manufacturer cooperates or provides complete and correct information.\nIf a competent authority considers or has reason to believe that a device has caused damage, it shall, upon request, facilitate the provision of the information and documentation referred to in the first subparagraph\u00a0to the potentially injured patient or user and, as appropriate, the patient's or user's successor in title, the patient's or user's health insurance company or other third parties affected by the damage caused to the patient or user, without prejudice to data protection rules and, unless there is an overriding public interest in disclosure, without prejudice to the protection of intellectual property rights.\nThe competent authority need not comply with the obligation laid down in the third subparagraph\u00a0where disclosure of the information and documentation referred to in the first subparagraph\u00a0is ordinarily dealt with in the context of legal proceedings.\n\n\n15.\u00a0\u00a0\u00a0Where manufacturers have their devices designed or manufactured by another legal or natural person the information on the identity of that person shall be part of the information to be submitted in accordance with Article\u00a030(1).\n\n\n16.\u00a0\u00a0\u00a0Natural or legal persons may claim compensation for damage caused by a defective device in accordance with applicable Union and national law.\nManufacturers shall, in a manner that is proportionate to the risk class, type of device and the size of the enterprise, have measures in place to provide sufficient financial coverage in respect of their potential liability under Directive\u00a085/374/EEC, without prejudice to more protective measures under national law.\n\n\n\nArticle\u00a011\n\nAuthorised representative\n\n\n1.\u00a0\u00a0\u00a0Where the manufacturer of a device is not established in a Member\u00a0State, the device may only be placed on the Union market if the manufacturer designates a sole authorised representative.\n\n\n2.\u00a0\u00a0\u00a0The designation shall constitute the authorised representative's mandate, it shall be valid only when accepted in writing by the authorised representative and shall be effective at least for all devices of the same generic device group.\n\n\n3.\u00a0\u00a0\u00a0The authorised representative shall perform the tasks specified in the mandate agreed between it and the manufacturer. The authorised representative shall provide a copy of the mandate to the competent authority, upon request.\nThe mandate shall require, and the manufacturer shall enable, the authorised representative to perform at least the following tasks in relation to the devices that it covers:\n\n\n\n\n\n\n(a)\n\n\nverify that the EU declaration of conformity and technical documentation have been drawn up and, where applicable, that an appropriate conformity assessment procedure has been carried out by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nkeep available a copy of the technical documentation, the EU declaration of conformity and, if applicable, a copy of the relevant certificate, including any amendments and supplements, issued in accordance with Article\u00a056, at the disposal of competent authorities for the period referred to in Article\u00a010(8);\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\ncomply with the registration obligations laid down in Article\u00a031 and verify that the manufacturer has complied with the registration obligations laid down in Articles\u00a027 and 29;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nin response to a request from a competent authority, provide that competent authority with all the information and documentation necessary to demonstrate the conformity of a device, in an official Union language determined by the Member\u00a0State concerned;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nforward to the manufacturer any request by a competent authority of the Member\u00a0State in which the authorised representative has its registered place of business for samples, or access to a device and verify that the competent authority receives the samples or is given access to the device;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\ncooperate with the competent authorities on any preventive or corrective action taken to eliminate or, if that is not possible, mitigate the risks posed by devices;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nimmediately inform the manufacturer about complaints and reports from healthcare professionals, patients and users about suspected incidents related to a device for which they have been designated;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nterminate the mandate if the manufacturer acts contrary to its obligations under this Regulation.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0The mandate referred to in paragraph\u00a03 of this Article\u00a0shall not delegate the manufacturer's obligations laid down in Article\u00a010(1), (2), (3), (4), (6), (7), (9), (10), (11) and (12).\n\n\n5.\u00a0\u00a0\u00a0Without prejudice to paragraph\u00a04 of this Article, where the manufacturer is not established in a Member\u00a0State and has not complied with the obligations laid down in Article\u00a010, the authorised representative shall be legally liable for defective devices on the same basis as, and jointly and severally with, the manufacturer.\n\n\n6.\u00a0\u00a0\u00a0An authorised representative who terminates its mandate on the ground referred to in point\u00a0(h) of paragraph\u00a03 shall immediately inform the competent authority of the Member\u00a0State in which it is established and, where applicable, the notified body that was involved in the conformity assessment for the device of the termination of the mandate and the reasons therefor.\n\n\n7.\u00a0\u00a0\u00a0Any reference in this Regulation to the competent authority of the Member\u00a0State in which the manufacturer has its registered place of business shall be understood as a reference to the competent authority of the Member\u00a0State in which the authorised representative, designated by a manufacturer referred to in paragraph\u00a01, has its registered place of business.\n\n\n\nArticle\u00a012\n\nChange of authorised representative\n\nThe detailed arrangements for a change of authorised representative shall be clearly defined in an agreement between the manufacturer, where practicable the outgoing authorised representative, and the incoming authorised representative. That agreement shall address at least the following aspects:\n\n\n\n\n\n\n(a)\n\n\nthe date of termination of the mandate of the outgoing authorised representative and date of beginning of the mandate of the incoming authorised representative;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe date until which the outgoing authorised representative may be indicated in the information supplied by the manufacturer, including any promotional material;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe transfer of documents, including confidentiality aspects and property rights;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe obligation of the outgoing authorised representative after the end of the mandate to forward to the manufacturer or incoming authorised representative any complaints or reports from healthcare professionals, patients or users about suspected incidents related to a device for which it had been designated as authorised representative.\n\n\n\n\n\n\nArticle\u00a013\n\nGeneral obligations of importers\n\n\n1.\u00a0\u00a0\u00a0Importers shall place on the Union market only devices that are in conformity with this Regulation.\n\n\n2.\u00a0\u00a0\u00a0In order to place a device on the market, importers shall verify that:\n\n\n\n\n\n\n(a)\n\n\nthe device has been CE marked and that the EU declaration of conformity of the device has been drawn up;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\na manufacturer is identified and that an authorised representative in accordance with Article\u00a011 has been designated by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe device is labelled in accordance with this Regulation and accompanied by the required instructions for use;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nwhere applicable, a UDI has been assigned by the manufacturer in accordance with Article\u00a027.\n\n\n\n\nWhere an importer considers or has reason to believe that a device is not in conformity with the requirements of this Regulation, it shall not place the device on the market until it has been brought into conformity and shall inform the manufacturer and the manufacturer's authorised representative. Where the importer considers or has reason to believe that the device presents a serious risk or is a falsified device, it shall also inform the competent authority of the Member\u00a0State in which the importer is established.\n\n\n3.\u00a0\u00a0\u00a0Importers shall indicate on the device or on its packaging or in a document accompanying the device their name, registered trade name or registered trade mark, their registered place of business and the address at which they can be contacted, so that their location can be established. They shall ensure that any additional label does not obscure any information on the label provided by the manufacturer.\n\n\n4.\u00a0\u00a0\u00a0Importers shall verify that the device is registered in the electronic system in accordance with Article\u00a029. Importers shall add their details to the registration in accordance with Article\u00a031.\n\n\n5.\u00a0\u00a0\u00a0Importers shall ensure that, while a device is under their responsibility, storage or transport conditions do not jeopardise its compliance with the general safety and performance requirements set out in Annex\u00a0I and shall comply with the conditions set by the manufacturer, where available.\n\n\n6.\u00a0\u00a0\u00a0Importers shall keep a register of complaints, of non-conforming devices and of recalls and withdrawals, and provide the manufacturer, authorised representative and distributors with any information requested by them, in order to allow them to investigate complaints.\n\n\n7.\u00a0\u00a0\u00a0Importers who consider or have reason to believe that a device which they have placed on the market is not in conformity with this Regulation shall immediately inform the manufacturer and its authorised representative. Importers shall co-operate with the manufacturer, the manufacturer's authorised representative and the competent authorities to ensure that the necessary corrective action to bring that device into conformity, to withdraw or recall it is taken. Where the device presents a serious risk, they shall also immediately inform the competent authorities of the Member\u00a0States in which they made the device available and, if applicable, the notified body that issued a certificate in accordance with Article\u00a056 for the device in question, giving details, in particular, of the non-compliance and of any corrective action taken.\n\n\n8.\u00a0\u00a0\u00a0Importers who have received complaints or reports from healthcare professionals, patients or users about suspected incidents related to a device which they have placed on the market shall immediately forward this information to the manufacturer and its authorised representative.\n\n\n9.\u00a0\u00a0\u00a0Importers shall, for the period referred to in Article\u00a010(8), keep a copy of the EU\u00a0declaration of conformity and, if applicable, a copy of any relevant certificate, including any amendments and supplements, issued in accordance with Article\u00a056.\n\n\n10.\u00a0\u00a0\u00a0Importers shall cooperate with competent authorities, at the latters' request, on any action taken to eliminate or, if that is not possible, mitigate the risks posed by devices which they have placed on the market. Importers, upon request by a competent authority of the Member\u00a0State in which the importer has its registered place of business, shall provide samples of the device free of charge or, where that is impracticable, grant access to the device.\n\n\n\nArticle\u00a014\n\nGeneral obligations of distributors\n\n\n1.\u00a0\u00a0\u00a0When making a device available on the market, distributors shall, in the context of their activities, act with due care in relation to the requirements applicable.\n\n\n2.\u00a0\u00a0\u00a0Before making a device available on the market, distributors shall verify that all of the following requirements are met:\n\n\n\n\n\n\n(a)\n\n\nthe device has been CE marked and that the EU declaration of conformity of the device has been drawn up;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe device is accompanied by the information to be supplied by the manufacturer in accordance with Article\u00a010(11);\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nfor imported devices, the importer has complied with the requirements set out in Article\u00a013(3);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthat, where applicable, a UDI has been assigned by the manufacturer.\n\n\n\n\nIn order to meet the requirements referred to in points (a), (b) and (d) of the first subparagraph\u00a0the distributor may apply a sampling method that is representative of the devices supplied by that distributor.\nWhere a distributor considers or has reason to believe that a device is not in conformity with the requirements of this Regulation, it shall not make the device available on the market until it has been brought into conformity, and shall inform the manufacturer and, where applicable, the manufacturer's authorised representative, and the importer. Where the distributor considers or has reason to believe that the device presents a serious risk or is a falsified device, it shall also inform the competent authority of the Member\u00a0State in which it is established.\n\n\n3.\u00a0\u00a0\u00a0Distributors shall ensure that, while the device is under their responsibility, storage or transport conditions comply with the conditions set by the manufacturer.\n\n\n4.\u00a0\u00a0\u00a0Distributors that consider or have reason to believe that a device which they have made available on the market is not in conformity with this Regulation shall immediately inform the manufacturer and, where applicable, the manufacturer's authorised representative and the importer. Distributors shall co-operate with the manufacturer and, where applicable, the manufacturer's authorised representative, and the importer, and with competent authorities to ensure that the necessary corrective action to bring that device into conformity, to withdraw or to recall it, as appropriate, is taken. Where the distributor considers or has reason to believe that the device presents a serious risk, it shall also immediately inform the competent authorities of the Member\u00a0States in which it made the device available, giving details, in particular, of the non-compliance and of any corrective action taken.\n\n\n5.\u00a0\u00a0\u00a0Distributors that have received complaints or reports from healthcare professionals, patients or users about suspected incidents related to a device they have made available, shall immediately forward this information to the manufacturer and, where applicable, the manufacturer's authorised representative, and the importer. They shall keep a register of complaints, of non-conforming devices and of recalls and withdrawals, and keep the manufacturer and, where available, the authorised representative and the importer informed of such monitoring and provide them with any information upon their request.\n\n\n6.\u00a0\u00a0\u00a0Distributors shall, upon request by a competent authority, provide it with all the information and documentation that is at their disposal and is necessary to demonstrate the conformity of a device.\nDistributors shall be considered to have fulfilled the obligation referred to in the first subparagraph\u00a0when the manufacturer or, where applicable, the authorised representative for the device in question provides the required information. Distributors shall cooperate with competent authorities, at their request, on any action taken to eliminate the risks posed by devices which they have made available on the market. Distributors, upon request by a competent authority, shall provide free samples of the device or, where that is impracticable, grant access to the device.\n\n\n\nArticle\u00a015\n\nPerson responsible for regulatory compliance\n\n\n1.\u00a0\u00a0\u00a0Manufacturers shall have available within their organisation at least one person responsible for regulatory compliance who possesses the requisite expertise in the field of medical devices. The requisite expertise shall be demonstrated by either of the following qualifications:\n\n\n\n\n\n\n(a)\n\n\na diploma, certificate or other evidence of formal qualification, awarded on completion of a university degree or of a course of study recognised as equivalent by the Member\u00a0State concerned, in law, medicine, pharmacy, engineering or another relevant scientific discipline, and at least one year of professional experience in regulatory affairs or in quality management systems relating to medical devices;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nfour years of professional experience in regulatory affairs or in quality management systems relating to medical devices.\n\n\n\n\nWithout prejudice to national provisions regarding professional qualifications, manufacturers of custom-made devices may demonstrate the requisite expertise referred to in the first subparagraph\u00a0by having at least two years of professional experience within a relevant field of manufacturing.\n\n\n2.\u00a0\u00a0\u00a0Micro and small enterprises within the meaning of Commission Recommendation\u00a02003/361/EC\u00a0(36) shall not be required to have the person responsible for regulatory compliance within their organisation but shall have such person permanently and continuously at their disposal.\n\n\n3.\u00a0\u00a0\u00a0The person responsible for regulatory compliance shall at least be responsible for ensuring that:\n\n\n\n\n\n\n(a)\n\n\nthe conformity of the devices is appropriately checked, in accordance with the quality management system under which the devices are manufactured, before a device is released;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe technical documentation and the EU declaration of conformity are drawn up and kept up-to-date;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe post-market surveillance obligations are complied with in accordance with Article\u00a010(10);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe reporting obligations referred to in Articles\u00a087 to 91 are fulfilled;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nin the case of investigational devices, the statement referred to in Section\u00a04.1 of Chapter II of Annex\u00a0XV is issued.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0If a number of persons are jointly responsible for regulatory compliance in accordance with paragraphs 1, 2 and 3, their respective areas of responsibility shall be stipulated in writing.\n\n\n5.\u00a0\u00a0\u00a0The person responsible for regulatory compliance shall suffer no disadvantage within the manufacturer's organisation in relation to the proper fulfilment of his or her duties, regardless of whether or not they are employees of the organisation.\n\n\n6.\u00a0\u00a0\u00a0Authorised representatives shall have permanently and continuously at their disposal at least one person responsible for regulatory compliance who possesses the requisite expertise regarding the regulatory requirements for medical devices in the Union. The requisite expertise shall be demonstrated by either of the following qualifications:\n\n\n\n\n\n\n(a)\n\n\na diploma, certificate or other evidence of formal qualification, awarded on completion of a university degree or of a course of study recognised as equivalent by the Member\u00a0State concerned, in law, medicine, pharmacy, engineering or another relevant scientific discipline, and at least one year of professional experience in regulatory affairs or in quality management systems relating to medical devices;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nfour years of professional experience in regulatory affairs or in quality management systems relating to medical devices.\n\n\n\n\n\n\n\nArticle\u00a016\n\nCases in which obligations of manufacturers apply to importers, distributors or other persons\n\n\n1.\u00a0\u00a0\u00a0A distributor, importer or other natural or legal person shall assume the obligations incumbent on manufacturers if it does any of the following:\n\n\n\n\n\n\n(a)\n\n\nmakes available on the market a device under its name, registered trade name or registered trade mark, except in cases where a distributor or importer enters into an agreement with a manufacturer whereby the manufacturer is identified as such on the label and is responsible for meeting the requirements placed on manufacturers in this Regulation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nchanges the intended purpose of a device already placed on the market or put into service;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nmodifies a device already placed on the market or put into service in such a way that compliance with the applicable requirements may be affected.\n\n\n\n\nThe first subparagraph\u00a0shall not apply to any person who, while not considered a manufacturer as defined in point\u00a0(30) of Article\u00a02, assembles or adapts for an individual patient a device already on the market without changing its intended purpose.\n\n\n2.\u00a0\u00a0\u00a0For the purposes of point\u00a0(c) of paragraph\u00a01, the following shall not be considered to be a modification of a device that could affect its compliance with the applicable requirements:\n\n\n\n\n\n\n(a)\n\n\nprovision, including translation, of the information supplied by the manufacturer, in accordance with Section\u00a023 of Annex\u00a0I, relating to a device already placed on the market and of further information which is necessary in order to market the device in the relevant Member\u00a0State;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nchanges to the outer packaging of a device already placed on the market, including a change of pack size, if the repackaging is necessary in order to market the device in the relevant Member\u00a0State and if it is carried out in such conditions that the original condition of the device cannot be affected by it. In the case of devices placed on the market in sterile condition, it shall be presumed that the original condition of the device is adversely affected if the packaging that is necessary for maintaining the sterile condition is opened, damaged or otherwise negatively affected by the repackaging.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0A distributor or importer that carries out any of the activities mentioned in points\u00a0(a) and\u00a0(b) of paragraph\u00a02 shall indicate on the device or, where that is impracticable, on its packaging or in a document accompanying the device, the activity carried out together with its name, registered trade name or registered trade mark, registered place of business and the address at which it can be contacted, so that its location can be established.\nDistributors and importers shall ensure that they have in place a quality management system that includes procedures which ensure that the translation of information is accurate and up-to-date, and that the activities mentioned in points\u00a0(a) and\u00a0(b) of paragraph\u00a02 are performed by a means and under conditions that preserve the original condition of the device and that the packaging of the repackaged device is not defective, of poor quality or untidy. The quality management system shall cover, inter\u00a0alia, procedures ensuring that the distributor or importer is informed of any corrective action taken by the manufacturer in relation to the device in question in order to respond to safety issues or to bring it into conformity with this Regulation.\n\n\n4.\u00a0\u00a0\u00a0At least 28 days prior to making the relabelled or repackaged device available on the market, distributors or importers carrying out any of the activities mentioned in points\u00a0(a) and (b) of paragraph\u00a02 shall inform the manufacturer and the competent authority of the Member\u00a0State in which they plan to make the device available of the intention to make the relabelled or repackaged device available and, upon request, shall provide the manufacturer and the competent authority with a sample or mock-up of the relabelled or repackaged device, including any translated label and instructions for use. Within the same period of 28\u00a0days, the distributor or importer shall submit to the competent authority a certificate, issued by a notified body designated for the type of devices that are subject to activities mentioned in points\u00a0(a) and\u00a0(b) of paragraph\u00a02, attesting that the quality management system of the distributer or importer complies with the requirements laid down in paragraph\u00a03.\n\n\n\nArticle\u00a017\n\nSingle-use devices and their reprocessing\n\n\n1.\u00a0\u00a0\u00a0Reprocessing and further use of single-use devices may only take place where permitted by national law and only in accordance with this Article.\n\n\n2.\u00a0\u00a0\u00a0Any natural or legal person who reprocesses a single-use device to make it suitable for further use within the Union shall be considered to be the manufacturer of the reprocessed device and shall assume the obligations incumbent on manufacturers laid down in this Regulation, which include obligations relating to the traceability of the reprocessed device in accordance with Chapter III of this Regulation. The reprocessor of the device shall be considered to be a producer for the purpose of Article\u00a03(1) of Directive\u00a085/374/EEC.\n\n\n3.\u00a0\u00a0\u00a0By way of derogation from paragraph\u00a02, as regards single-use devices that are reprocessed and used within a health institution, Member\u00a0States may decide not to apply all of the rules relating to manufacturers' obligations laid down in this Regulation provided that they ensure that:\n\n\n\n\n\n\n(a)\n\n\nthe safety and performance of the reprocessed device is equivalent to that of the original device and the requirements in points (a), (b), (d), (e), (f), (g) and (h) of Article\u00a05(5) are complied with;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe reprocessing is performed in accordance with CS detailing the requirements concerning:\n\n\n\n\n\n\n\u2014\n\n\nrisk management, including the analysis of the construction and material, related properties of the device (reverse engineering) and procedures to detect changes in the design of the original device as well as of its planned application after reprocessing,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe validation of procedures for the entire process, including cleaning steps,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe product release and performance testing,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe quality management system,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe reporting of incidents involving devices that have been reprocessed, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe traceability of reprocessed devices.\n\n\n\n\n\n\n\n\nMember\u00a0States shall encourage, and may require, health institutions to provide information to patients on the use of reprocessed devices within the health institution and, where appropriate, any other relevant information on the reprocessed devices that patients are treated with.\nMember\u00a0States shall notify the Commission and the other Member\u00a0States of the national provisions introduced pursuant to this paragraph\u00a0and the grounds for introducing them. The Commission shall keep the information publicly available.\n\n\n4.\u00a0\u00a0\u00a0Member\u00a0States may choose to apply the provisions referred to in paragraph\u00a03 also as regards single-use devices that are reprocessed by an external reprocessor at the request of a health institution, provided that the reprocessed device in its entirety is returned to that health institution and the external reprocessor complies with the requirements referred to in points (a) and (b) of paragraph\u00a03.\n\n\n5.\u00a0\u00a0\u00a0The Commission shall adopt, in accordance with Article\u00a09(1), the necessary CS referred to in point\u00a0(b) of paragraph\u00a03 by 26 May 2020. Those CS shall be consistent with the latest scientific evidence and shall address the application of the general requirements on safety and performance laid down in in this Regulation. In the event that those CS are not adopted by 26 May 2020, reprocessing shall be performed in accordance with any relevant harmonised standards and national provisions that cover the aspects outlined in point\u00a0(b) of paragraph\u00a03. Compliance with CS or, in the absence of CS, with any relevant harmonised standards and national provisions, shall be certified by a notified body.\n\n\n6.\u00a0\u00a0\u00a0Only single-use devices that have been placed on the market in accordance with this Regulation, or prior to 26\u00a0May 2020 in accordance with Directive\u00a093/42/EEC, may be reprocessed.\n\n\n7.\u00a0\u00a0\u00a0Only reprocessing of single-use devices that is considered safe according to the latest scientific evidence may be carried out.\n\n\n8.\u00a0\u00a0\u00a0The name and address of the legal or natural person referred to in paragraph\u00a02 and the other relevant information referred to in Section\u00a023 of Annex\u00a0I shall be indicated on the label and, where applicable, in the instructions for use of the reprocessed device.\nThe name and address of the manufacturer of the original single-use device shall no longer appear on the label, but shall be mentioned in the instructions for use of the reprocessed device.\n\n\n9.\u00a0\u00a0\u00a0A Member\u00a0State that permits reprocessing of single-use devices may maintain or introduce national provisions that are stricter than those laid down in this Regulation and which restrict or prohibit, within its territory, the following:\n\n\n\n\n\n\n(a)\n\n\nthe reprocessing of single-use devices and the transfer of single-use devices to another Member\u00a0State or to a third country with a view to their reprocessing;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe making available or further use of reprocessed single-use devices.\n\n\n\n\nMember\u00a0States shall notify the Commission and the other Member\u00a0States of those national provisions. The Commission shall make such information publicly available.\n\n\n10.\u00a0\u00a0\u00a0The Commission shall by 27 May 2024 draw up a report on the operation of this Article\u00a0and submit it to the European Parliament and to the Council. On the basis of that report, the Commission shall, if appropriate, make proposals for amendments to this Regulation.\n\n\n\nArticle\u00a018\n\nImplant card and information to be supplied to the patient with an implanted device\n\n\n1.\u00a0\u00a0\u00a0The manufacturer of an implantable device shall provide together with the device the following:\n\n\n\n\n\n\n(a)\n\n\ninformation allowing the identification of the device, including the device name, serial number, lot number, the UDI, the device model, as well as the name, address and the website of the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nany warnings, precautions or measures to be taken by the patient or a healthcare professional with regard to reciprocal interference with reasonably foreseeable external influences, medical examinations or environmental conditions;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nany information about the expected lifetime of the device and any necessary follow-up;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nany other information to ensure safe use of the device by the patient, including the information in point\u00a0(u) of Section\u00a023.4 of Annex\u00a0I.\n\n\n\n\nThe information referred to in the first subparagraph\u00a0shall be provided, for the purpose of making it available to the particular patient who has been implanted with the device, by any means that allow rapid access to that information and shall be stated in the language(s) determined by the concerned Member\u00a0State. The information shall be written in a way that is readily understood by a lay person and shall be updated where appropriate. Updates of the information shall be made available to the patient via the website mentioned in point\u00a0(a) of the first subparagraph.\nIn addition, the manufacturer shall provide the information referred to in point\u00a0(a) of the first subparagraph\u00a0on an implant card delivered with the device.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States shall require health institutions to make the information referred to in paragraph\u00a01 available, by any means that allow rapid access to that information, to any patients who have been implanted with the device, together with the implant card, which shall bear their identity.\n\n\n3.\u00a0\u00a0\u00a0The following implants shall be exempted from the obligations laid down in this Article: sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips and connectors. The Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 to amend this list by adding other types of implants to it or by removing implants therefrom.\n\n\n\nArticle\u00a019\n\nEU declaration of conformity\n\n\n1.\u00a0\u00a0\u00a0The EU\u00a0declaration of conformity shall state that the requirements specified in this Regulation have been fulfilled in relation to the device that is covered. The manufacturer shall continuously update the EU\u00a0declaration of conformity. The EU\u00a0declaration of conformity shall, as a minimum, contain the information set out in Annex\u00a0IV and shall be translated into an official Union language or languages required by the Member\u00a0State(s) in which the device is made available.\n\n\n2.\u00a0\u00a0\u00a0Where, concerning aspects not covered by this Regulation, devices are subject to other Union legislation which also requires an EU declaration of conformity by the manufacturer that fulfilment of the requirements of that legislation has been demonstrated, a single EU\u00a0declaration of conformity shall be drawn up in respect of all Union acts applicable to the device. The declaration shall contain all the information required for identification of the Union legislation to which the declaration relates.\n\n\n3.\u00a0\u00a0\u00a0By drawing up the EU\u00a0declaration of conformity, the manufacturer shall assume responsibility for compliance with the requirements of this Regulation and all other Union legislation applicable to the device.\n\n\n4.\u00a0\u00a0\u00a0The Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 amending the minimum content of the EU declaration of conformity set out in Annex\u00a0IV in the light of technical progress.\n\n\n\nArticle\u00a020\n\nCE marking of conformity\n\n\n1.\u00a0\u00a0\u00a0Devices, other than custom-made or investigational devices, considered to be in conformity with the requirements of this Regulation shall bear the CE marking of conformity, as presented in Annex\u00a0V.\n\n\n2.\u00a0\u00a0\u00a0The CE marking shall be subject to the general principles set out in Article\u00a030 of Regulation\u00a0(EC)\u00a0No\u00a0765/2008.\n\n\n3.\u00a0\u00a0\u00a0The CE marking shall be affixed visibly, legibly and indelibly to the device or its sterile packaging. Where such affixing is not possible or not warranted on account of the nature of the device, the CE marking shall be affixed to the packaging. The CE marking shall also appear in any instructions for use and on any sales packaging.\n\n\n4.\u00a0\u00a0\u00a0The CE marking shall be affixed before the device is placed on the market. It may be followed by a pictogram or any other mark indicating a special risk or use.\n\n\n5.\u00a0\u00a0\u00a0Where applicable, the CE marking shall be followed by the identification number of the notified body responsible for the conformity assessment procedures set out in Article\u00a052. The identification number shall also be indicated in any promotional material which mentions that a device fulfils the requirements for CE marking.\n\n\n6.\u00a0\u00a0\u00a0Where devices are subject to other Union legislation which also provides for the affixing of the CE marking, the CE marking shall indicate that the devices also fulfil the requirements of that other legislation.\n\n\n\nArticle\u00a021\n\nDevices for special purposes\n\n\n1.\u00a0\u00a0\u00a0Member\u00a0States shall not create obstacles to:\n\n\n\n\n\n\n(a)\n\n\ninvestigational devices being supplied to an investigator for the purpose of a clinical investigation if they meet the conditions laid down in Articles\u00a062 to 80 and Article\u00a082, in the implementing acts adopted pursuant to Article\u00a081 and in Annex\u00a0XV;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ncustom-made devices being made available on the market if Article\u00a052(8) and Annex\u00a0XIII have been complied with.\n\n\n\n\nThe devices referred to in the first subparagraph\u00a0shall not bear the CE marking, with the exception of the devices referred to in Article\u00a074.\n\n\n2.\u00a0\u00a0\u00a0Custom-made devices shall be accompanied by the statement referred to in Section\u00a01 of Annex\u00a0XIII, which shall be made available to the particular patient or user identified by name, an acronym or a numerical code.\nMember\u00a0States may require that the manufacturer of a custom-made device submit to the competent authority a list of such devices which have been made available in their territory.\n\n\n3.\u00a0\u00a0\u00a0At trade fairs, exhibitions, demonstrations or similar events, Member\u00a0States shall not create obstacles to the showing of devices which do not comply with this Regulation, provided a visible sign clearly indicates that such devices are intended for presentation or demonstration purposes only and cannot be made available until they have been brought into compliance with this Regulation.\n\n\n\nArticle\u00a022\n\nSystems and procedure packs\n\n\n1.\u00a0\u00a0\u00a0Natural or legal persons shall draw up a statement if they combine devices bearing a CE\u00a0marking with the following other devices or products, in a manner that is compatible with the intended purpose of the devices or other products and within the limits of use specified by their manufacturers, in order to place them on the market as a system or procedure pack:\n\n\n\n\n\n\n(a)\n\n\nother devices bearing the CE marking;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\n\nin vitro diagnostic medical devices bearing the CE marking in conformity with Regulation\u00a0(EU)\u00a02017/746;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nother products which are in conformity with legislation that applies to those products only where they are used within a medical procedure or their presence in the system or procedure pack is otherwise justified.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0In the statement made pursuant to paragraph\u00a01, the natural or legal person concerned shall declare that:\n\n\n\n\n\n\n(a)\n\n\nthey verified the mutual compatibility of the devices and, if applicable other products, in accordance with the manufacturers' instructions and have carried out their activities in accordance with those instructions;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthey packaged the system or procedure pack and supplied relevant information to users incorporating the information to be supplied by the manufacturers of the devices or other products which have been put together;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe activity of combining devices and, if applicable, other products as a system or procedure pack was subject to appropriate methods of internal monitoring, verification and validation.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0Any natural or legal person who sterilises systems or procedure packs referred to in paragraph\u00a01 for the purpose of placing them on the market shall, at their choice, apply one of the procedures set out in Annex\u00a0IX or the procedure set out in Part A of Annex\u00a0XI. The application of those procedures and the involvement of the notified body shall be limited to the aspects of the procedure relating to ensuring sterility until the sterile packaging is opened or damaged. The natural or legal person shall draw up a statement declaring that sterilisation has been carried out in accordance with the manufacturer's instructions.\n\n\n4.\u00a0\u00a0\u00a0Where the system or procedure pack incorporates devices which do not bear the CE\u00a0marking or where the chosen combination of devices is not compatible in view of their original intended purpose, or where the sterilisation has not been carried out in accordance with the manufacturer's instructions, the system or procedure pack shall be treated as a device in its own right and shall be subject to the relevant conformity assessment procedure pursuant to Article\u00a052. The natural or legal person shall assume the obligations incumbent on manufacturers.\n\n\n5.\u00a0\u00a0\u00a0The systems or procedure packs referred to in paragraph\u00a01 of this Article\u00a0shall not themselves bear an additional CE marking but they shall bear the name, registered trade name or registered trade mark of the person referred to in paragraphs 1 and 3 of this Article\u00a0as well as the address at which that person can be contacted, so that the person's location can be established. Systems or procedure packs shall be accompanied by the information referred to in Section\u00a023 of Annex\u00a0I. The statement referred to in paragraph\u00a02 of this Article\u00a0shall be kept at the disposal of the competent authorities, after the system or procedure pack has been put together, for the period that is applicable under Article\u00a010(8) to the devices that have been combined. Where those periods differ, the longest period shall apply.\n\n\n\nArticle\u00a023\n\nParts and components\n\n\n1.\u00a0\u00a0\u00a0Any natural or legal person who makes available on the market an item specifically intended to replace an identical or similar integral part or component of a device that is defective or worn in order to maintain or restore the function of the device without changing its performance or safety characteristics or its intended purpose, shall ensure that the item does not adversely affect the safety and performance of the device. Supporting evidence shall be kept available for the competent authorities of the Member\u00a0States.\n\n\n2.\u00a0\u00a0\u00a0An item that is intended specifically to replace a part or component of a device and that significantly changes the performance or safety characteristics or the intended purpose of the device shall be considered to be a device and shall meet the requirements laid down in this Regulation.\n\n\n\nArticle\u00a024\n\nFree movement\n\nExcept where otherwise provided for in this Regulation, Member\u00a0States shall not refuse, prohibit or restrict the making available on the market or putting into service within their territory of devices which comply with the requirements of this Regulation.\n\n\n\nCHAPTER III\n\n\nIDENTIFICATION AND TRACEABILITY OF DEVICES, REGISTRATION OF DEVICES AND OF ECONOMIC OPERATORS, SUMMARY OF SAFETY AND CLINICAL PERFORMANCE, EUROPEAN DATABASE ON MEDICAL DEVICES\n\n\n\nArticle\u00a025\n\nIdentification within the supply chain\n\n\n1.\u00a0\u00a0\u00a0Distributors and importers shall co-operate with manufacturers or authorised representatives to achieve an appropriate level of traceability of devices.\n\n\n2.\u00a0\u00a0\u00a0Economic operators shall be able to identify the following to the competent authority, for the period referred to in Article\u00a010(8):\n\n\n\n\n\n\n(a)\n\n\nany economic operator to whom they have directly supplied a device;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nany economic operator who has directly supplied them with a device;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nany health institution or healthcare professional to which they have directly supplied a device.\n\n\n\n\n\n\n\nArticle\u00a026\n\nMedical devices nomenclature\n\nTo facilitate the functioning of the European database on medical devices (\u2018Eudamed\u2019) as referred to in Article\u00a033, the Commission shall ensure that an internationally recognised medical devices nomenclature is available free of charge to manufacturers and other natural or legal persons required by this Regulation to use that nomenclature. The Commission shall also endeavour to ensure that that nomenclature is available to other stakeholders free of charge, where reasonably practicable.\n\n\nArticle\u00a027\n\nUnique Device Identification system\n\n\n1.\u00a0\u00a0\u00a0The Unique Device Identification system (\u2018UDI system\u2019) described in Part C of Annex\u00a0VI shall allow the identification and facilitate the traceability of devices, other than custom-made and investigational devices, and shall consist of the following:\n\n\n\n\n\n\n(a)\n\n\nproduction of a UDI that comprises the following:\n\n\n\n\n\n\n(i)\n\n\na UDI device identifier (\u2018UDI-DI\u2019) specific to a manufacturer and a device, providing access to the information laid down in Part B of Annex\u00a0VI;\n\n\n\n\n\n\n\n\n\n\n(ii)\n\n\na UDI production identifier (\u2018UDI-PI\u2019) that identifies the unit of device production and if applicable the packaged devices, as specified in Part\u00a0C of Annex\u00a0VI;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nplacing of the UDI on the label of the device or on its packaging;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nstorage of the UDI by economic operators, health institutions and healthcare professionals, in accordance with the conditions laid down in paragraphs 8 and 9 of this Article\u00a0respectively;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nestablishment of an electronic system for Unique Device Identification\u00a0(\u2018UDI database\u2019) in accordance with Article\u00a028.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The Commission shall, by means of implementing acts, designate one or several entities to operate a system for assignment of UDIs pursuant to this Regulation (\u2018issuing entity\u2019). That entity or those entities shall satisfy all of the following criteria:\n\n\n\n\n\n\n(a)\n\n\nthe entity is an organisation with legal personality;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nits system for the assignment of UDIs is adequate to identify a device throughout its distribution and use in accordance with the requirements of this Regulation;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nits system for the assignment of UDIs conforms to the relevant international standards;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe entity gives access to its system for the assignment of UDIs to all interested users in accordance with a set of predetermined and transparent terms and conditions;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe entity undertakes to do the following:\n\n\n\n\n\n\n(i)\n\n\noperate its system for the assignment of UDIs for at least 10 years after its designation;\n\n\n\n\n\n\n\n\n\n\n(ii)\n\n\nmake available to the Commission and to the Member\u00a0States, upon request, information concerning its system for the assignment of UDIs;\n\n\n\n\n\n\n\n\n\n\n(iii)\n\n\nremain in compliance with the criteria for designation and the terms of designation.\n\n\n\n\n\n\n\n\nWhen designating issuing entities, the Commission shall endeavour to ensure that UDI\u00a0carriers, as defined in Part C of Annex\u00a0VI, are universally readable regardless of the system used by the issuing entity, with a view to minimising financial and administrative burdens for economic operators and health institutions.\n\n\n3.\u00a0\u00a0\u00a0Before placing a device, other than a custom-made device, on the market, the manufacturer shall assign to the device and, if applicable, to all higher levels of packaging, a UDI created in compliance with the rules of the issuing entity designated by the Commission in accordance with paragraph\u00a02.\nBefore a device, other than a custom-made or investigational device, is placed on the market the manufacturer shall ensure that the information referred to in Part B of Annex\u00a0VI of the device in question are correctly submitted and transferred to the UDI database referred to in Article\u00a028.\n\n\n4.\u00a0\u00a0\u00a0UDI carriers shall be placed on the label of the device and on all higher levels of packaging. Higher levels of packaging shall not be understood to include shipping containers.\n\n\n5.\u00a0\u00a0\u00a0The UDI shall be used for reporting serious incidents and field safety corrective actions in accordance with Article\u00a087.\n\n\n6.\u00a0\u00a0\u00a0The Basic UDI-DI, as defined in Part C of Annex\u00a0VI, of the device shall appear on the EU\u00a0declaration of conformity referred to in Article\u00a019.\n\n\n7.\u00a0\u00a0\u00a0As part of the technical documentation referred to in Annex\u00a0II, the manufacturer shall keep up-to-date a list of all UDIs that it has assigned.\n\n\n8.\u00a0\u00a0\u00a0Economic operators shall store and keep, preferably by electronic means, the UDI of the devices which they have supplied or with which they have been supplied, if those devices belong to:\n\n\n\n\n\n\n\u2014\n\n\nclass III implantable devices;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe devices, categories or groups of devices determined by a measure referred to in point\u00a0(a) of paragraph\u00a011.\n\n\n\n\n\n\n9.\u00a0\u00a0\u00a0Health institutions shall store and keep preferably by electronic means the UDI of the devices which they have supplied or with which they have been supplied, if those devices belong to class III implantable devices.\nFor devices other than class III implantable devices, Member\u00a0States shall encourage, and may require, health institutions to store and keep, preferably by electronic means, the UDI of the devices with which they have been supplied.\nMember\u00a0States shall encourage, and may require, healthcare professionals to store and keep preferably by electronic means, the UDI of the devices with which they have been supplied with.\n\n\n10.\u00a0\u00a0\u00a0The Commission is empowered to adopt delegated acts in accordance with Article\u00a0115:\n\n\n\n\n\n\n(a)\n\n\namending the list of information set out in Part B of Annex\u00a0VI in the light of technical progress; and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\namending Annex\u00a0VI in the light of international developments and technical progress in the field of Unique Device Identification.\n\n\n\n\n\n\n11.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, specify the detailed arrangements and the procedural aspects for the UDI system with a view to ensuring its harmonised application in relation to any of the following:\n\n\n\n\n\n\n(a)\n\n\ndetermining the devices, categories or groups of devices to which the obligation laid down in paragraph\u00a08 is to apply;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nspecifying the data to be included in the UDI-PI of specific devices or device groups;\n\n\n\n\nThe implementing acts referred to in the first subparagraph\u00a0shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n12.\u00a0\u00a0\u00a0When adopting the measures referred to in paragraph\u00a011, the Commission shall take into account all of the following:\n\n\n\n\n\n\n(a)\n\n\nconfidentiality and data protection as referred to in Articles\u00a0109 and 110\u00a0respectively;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe risk-based approach;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe cost-effectiveness of the measures;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe convergence of UDI systems developed at international level;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe need to avoid duplications in the UDI system;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe needs of the healthcare systems of the Member\u00a0States, and where possible, compatibility with other medical device identification systems that are used by stakeholders.\n\n\n\n\n\n\n\nArticle\u00a028\n\nUDI database\n\n\n1.\u00a0\u00a0\u00a0The Commission, after consulting the MDCG shall set up and manage a UDI database to validate, collate, process and make available to the public the information mentioned in Part B of Annex\u00a0VI.\n\n\n2.\u00a0\u00a0\u00a0When designing the UDI database, the Commission shall take into account the general principles set out in Section\u00a05 of Part C of Annex\u00a0VI. The UDI database shall be designed in particular such that no UDI-PIs and no commercially confidential product information can be included therein.\n\n\n3.\u00a0\u00a0\u00a0The core data elements to be provided to the UDI database, referred to in Part\u00a0B of Annex\u00a0VI, shall be accessible to the public free of charge.\n\n\n4.\u00a0\u00a0\u00a0The technical design of the UDI database shall ensure maximum accessibility to information stored therein, including multi-user access and automatic uploads and downloads of that information. The Commission shall provide for technical and administrative support to manufacturers and other users of the UDI database.\n\n\n\nArticle\u00a029\n\nRegistration of devices\n\n\n1.\u00a0\u00a0\u00a0Before placing a device, other than a custom-made device, on the market, the manufacturer shall, in accordance with the rules of the issuing entity referred to in Article\u00a027(2), assign a Basic UDI-DI as defined in Part C of Annex\u00a0VI to the device and shall provide it to the UDI database together with the other core data elements referred to in Part B of Annex\u00a0VI related to that device.\n\n\n2.\u00a0\u00a0\u00a0Before placing on the market a system or procedure pack pursuant to Article\u00a022(1) and (3), that is not a custom-made device, the natural or legal person responsible shall assign to the system or procedure pack, in compliance with the rules of the issuing entity, a Basic UDI-DI and shall provide it to the UDI database together with the other core data elements referred to in Part B of Annex\u00a0VI related to that system or procedure pack.\n\n\n3.\u00a0\u00a0\u00a0For devices that are the subject of a conformity assessment as referred to in Article\u00a052(3) and in the second and third subparagraphs\u00a0of Article\u00a052(4), the assignment of a Basic UDI-DI referred to in paragraph\u00a01 of this Article\u00a0shall be done before the manufacturer applies to a notified body for that assessment.\nFor the devices referred to in the first subparagraph, the notified body shall include a reference to the Basic UDI-DI on the certificate issued in accordance with point\u00a0(a) of Section\u00a04 of Chapter I of Annex\u00a0XII and confirm in Eudamed that the information referred to in Section\u00a02.2 of Part A of Annex\u00a0VI is correct. After the issuing of the relevant certificate and before placing the device on the market, the manufacturer shall provide the Basic UDI-DI to the UDI database together with the other core data elements referred to in Part B of Annex\u00a0VI related to that device.\n\n\n4.\u00a0\u00a0\u00a0Before placing a device on the market, other than a custom-made device, the manufacturer shall enter or if, already provided, verify in Eudamed the information referred to in Section\u00a02 of Part A of Annex\u00a0VI, with the exception of Section\u00a02.2 thereof, and shall thereafter keep the information updated.\n\n\n\nArticle\u00a030\n\nElectronic system for registration of economic operators\n\n\n1.\u00a0\u00a0\u00a0The Commission, after consulting the MDCG, shall set up and manage an electronic system to create the single registration number referred to in Article\u00a031(2) and to collate and process information that is necessary and proportionate to identify the manufacturer and, where applicable, the authorised representative and the importer. The details regarding the information to be provided to that electronic system by the economic operators are laid down in Section\u00a01 of Part A of Annex\u00a0VI.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States may maintain or introduce national provisions on registration of distributors of devices which have been made available on their territory.\n\n\n3.\u00a0\u00a0\u00a0Within two weeks of placing a device, other than a custom-made device, on the market, importers shall verify that the manufacturer or authorised representative has provided to the electronic system the information referred to in paragraph\u00a01.\nWhere applicable, importers shall inform the relevant authorised representative or manufacturer if the information referred to in paragraph\u00a01 is not included or is incorrect. Importers shall add their details to the relevant entry/entries.\n\n\n\nArticle\u00a031\n\nRegistration of manufacturers, authorised representatives and importers\n\n\n1.\u00a0\u00a0\u00a0Before placing a device, other than a custom-made device, on the market, manufacturers, authorised representatives and importers shall, in order to register, submit to the electronic system referred to in Article\u00a030 the information referred to in Section\u00a01 of Part A of Annex\u00a0VI, provided that they have not already registered in accordance with this Article. In cases where the conformity assessment procedure requires the involvement of a notified body pursuant to Article\u00a052, the information referred to in Section\u00a01 of Part\u00a0A of Annex\u00a0VI shall be provided to that electronic system before applying to the notified body.\n\n\n2.\u00a0\u00a0\u00a0After having verified the data entered pursuant to paragraph\u00a01, the competent authority shall obtain a single registration number (\u2018SRN\u2019) from the electronic system referred to in Article\u00a030 and issue it to the manufacturer, the authorised representative or the importer.\n\n\n3.\u00a0\u00a0\u00a0The manufacturer shall use the SRN when applying to a notified body for conformity assessment and for accessing Eudamed in order to fulfil its obligations under Article\u00a029.\n\n\n4.\u00a0\u00a0\u00a0Within one week of any change occurring in relation to the information referred to in paragraph\u00a01 of this Article, the economic operator shall update the data in the electronic system referred to in Article\u00a030.\n\n\n5.\u00a0\u00a0\u00a0Not later than one year after submission of the information in accordance with paragraph\u00a01, and every second year thereafter, the economic operator shall confirm the accuracy of the data. In the event of a failure to do so within six months of those deadlines, any Member\u00a0State may take appropriate corrective measures within its territory until that economic operator complies with that obligation.\n\n\n6.\u00a0\u00a0\u00a0Without prejudice to the economic operator's responsibility for the data, the competent authority shall verify the confirmed data referred to in Section\u00a01 of Part A of Annex\u00a0VI.\n\n\n7.\u00a0\u00a0\u00a0The data entered pursuant to paragraph\u00a01 of this Article\u00a0in the electronic system referred to in Article\u00a030 shall be accessible to the public.\n\n\n8.\u00a0\u00a0\u00a0The competent authority may use the data to charge the manufacturer, the authorised representative or the importer a fee pursuant to Article\u00a0111.\n\n\n\nArticle\u00a032\n\nSummary of safety and clinical performance\n\n\n1.\u00a0\u00a0\u00a0For implantable devices and for class III devices, other than custom-made or investigational devices, the manufacturer shall draw up a summary of safety and clinical performance.\nThe summary of safety and clinical performance shall be written in a way that is clear to the intended user and, if relevant, to the patient and shall be made available to the public via Eudamed.\nThe draft of the summary of safety and clinical performance shall be part of the documentation to be submitted to the notified body involved in the conformity assessment pursuant to Article\u00a052 and shall be validated by that body. After its validation, the notified body shall upload the summary to Eudamed. The manufacturer shall mention on the label or instructions for use where the summary is available.\n\n\n2.\u00a0\u00a0\u00a0The summary of safety and clinical performance shall include at least the following aspects:\n\n\n\n\n\n\n(a)\n\n\nthe identification of the device and the manufacturer, including the Basic UDI-DI and, if already issued, the SRN;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe intended purpose of the device and any indications, contraindications and target populations;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\na description of the device, including a reference to previous generation(s) or variants if such exist, and a description of the differences, as well as, where relevant, a description of any accessories, other devices and products, which are intended to be used in combination with the device;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\npossible diagnostic or therapeutic alternatives;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nreference to any harmonised standards and CS applied;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe summary of clinical evaluation as referred to in Annex\u00a0XIV, and relevant information on post-market clinical follow-up;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nsuggested profile and training for users;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\ninformation on any residual risks and any undesirable effects, warnings and precautions.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, set out the form and the presentation of the data elements to be included in the summary of safety and clinical performance. Those implementing acts shall be adopted in accordance with the advisory procedure referred to in Article\u00a0114(2).\n\n\n\nArticle\u00a033\n\nEuropean database on medical devices\n\n\n1.\u00a0\u00a0\u00a0The Commission, after consulting the MDCG, shall set up, maintain and manage the European database on medical devices (\u2018Eudamed\u2019) for the following purposes:\n\n\n\n\n\n\n(a)\n\n\nto enable the public to be adequately informed about devices placed on the market, the corresponding certificates issued by notified bodies and about the relevant economic operators;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nto enable unique identification of devices within the internal market and to facilitate their traceability;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nto enable the public to be adequately informed about clinical investigations and to enable sponsors of clinical investigations to comply with obligations under Articles\u00a062 to 80, Article\u00a082, and any acts adopted pursuant to Article\u00a081;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nto enable manufacturers to comply with the information obligations laid down in Articles\u00a087 to 90 or in any acts adopted pursuant to Article\u00a091;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nto enable the competent authorities of the Member\u00a0States and the Commission to carry out their tasks relating to this Regulation on a well-informed basis and to enhance the cooperation between them.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0Eudamed shall include the following electronic systems:\n\n\n\n\n\n\n(a)\n\n\nthe electronic system for registration of devices referred to in Article\u00a029(4);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe UDI-database referred to in Article\u00a028;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe electronic system on registration of economic operators referred to in Article\u00a030;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe electronic system on notified bodies and on certificates referred to in Article\u00a057;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe electronic system on clinical investigations referred to in Article\u00a073;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe electronic system on vigilance and post-market surveillance referred to in Article\u00a092;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthe electronic system on market surveillance referred to in Article\u00a0100.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0When designing Eudamed the Commission shall give due consideration to compatibility with national databases and national web-interfaces to allow for import and export of data.\n\n\n4.\u00a0\u00a0\u00a0The data shall be entered into Eudamed by the Member\u00a0States, notified bodies, economic operators and sponsors as specified in the provisions on the electronic systems referred to in paragraph\u00a02. The Commission shall provide for technical and administrative support to users of Eudamed.\n\n\n5.\u00a0\u00a0\u00a0All the information collated and processed by Eudamed shall be accessible to the Member\u00a0States and to the Commission. The information shall be accessible to notified bodies, economic operators, sponsors and the public to the extent specified in the provisions on the electronic systems referred to in paragraph\u00a02.\nThe Commission shall ensure that public parts of Eudamed are presented in a user-friendly and easily-searchable format.\n\n\n6.\u00a0\u00a0\u00a0Eudamed shall contain personal data only insofar as necessary for the electronic systems referred to in paragraph\u00a02 of this Article\u00a0to collate and process information in accordance with this Regulation. Personal data shall be kept in a form which permits identification of data subjects for periods no longer than those referred to in Article\u00a010(8).\n\n\n7.\u00a0\u00a0\u00a0The Commission and the Member\u00a0States shall ensure that data subjects may effectively exercise their rights to information, of access, to rectification and to object in accordance with Regulation\u00a0(EC)\u00a0No\u00a045/2001 and Directive\u00a095/46/EC, respectively. They shall also ensure that data subjects may effectively exercise the right of access to data relating to them, and the right to have inaccurate or incomplete data corrected and erased. Within their respective responsibilities, the Commission and the Member\u00a0States shall ensure that inaccurate and unlawfully processed data are deleted, in accordance with the applicable legislation. Corrections and deletions shall be carried out as soon as possible, but no later than 60\u00a0days after a request is made by a data subject.\n\n\n8.\u00a0\u00a0\u00a0The Commission shall, by means of implementing acts, lay down the detailed arrangements necessary for the setting up and maintenance of Eudamed. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3). When adopting those implementing acts, the Commission shall ensure that, as far as possible, the system is developed in such a way as to avoid having to enter the same information twice within the same module or in different modules of the system.\n\n\n9.\u00a0\u00a0\u00a0In relation to its responsibilities under this Article\u00a0and the processing of personal data involved therein, the Commission shall be considered to be the controller of Eudamed and its electronic systems.\n\n\n\nArticle\u00a034\n\nFunctionality of Eudamed\n\n\n1.\u00a0\u00a0\u00a0The Commission shall, in collaboration with the MDCG, draw up the functional specifications for Eudamed. The Commission shall draw up a plan for the implementation of those specifications by 26 May 2018. That plan shall seek to ensure that Eudamed is fully functional at a date that allows the Commission to publish the notice referred to in paragraph\u00a03 of this Article\u00a0by 25 March 2020 and that all other relevant deadlines laid down in Article\u00a0123 of this Regulation and in Article\u00a0113 of Regulation\u00a0(EU)\u00a02017/746 are met.\n\n\n2.\u00a0\u00a0\u00a0The Commission shall, on the basis of an independent audit report, inform the MDCG when it has verified that Eudamed has achieved full functionality and Eudamed meets the functional specifications drawn up pursuant to paragraph\u00a01.\n\n\n3.\u00a0\u00a0\u00a0The Commission shall, after consultation with the MDCG and when it is satisfied that the conditions referred to in paragraph\u00a02 have been fulfilled, publish a notice to that effect in the Official Journal of the European Union.\n\n\n\n\nCHAPTER IV\n\n\nNOTIFIED BODIES\n\n\n\nArticle\u00a035\n\nAuthorities responsible for notified bodies\n\n\n1.\u00a0\u00a0\u00a0Any Member\u00a0State that intends to designate a conformity assessment body as a notified body, or has designated a notified body, to carry out conformity assessment activities under this Regulation shall appoint an authority (\u2018authority responsible for notified bodies\u2019), which may consist of separate constituent entities under national law and shall be responsible for setting up and carrying out the necessary procedures for the assessment, designation and notification of conformity assessment bodies and for the monitoring of notified bodies, including subcontractors and subsidiaries of those bodies.\n\n\n2.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall be established, organised and operated so as to safeguard the objectivity and impartiality of its activities and to avoid any conflicts of interests with conformity assessment bodies.\n\n\n3.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall be organised in a manner such that each decision relating to designation or notification is taken by personnel different from those who carried out the assessment.\n\n\n4.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall not perform any activities that notified bodies perform on a commercial or competitive basis.\n\n\n5.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall safeguard the confidential aspects of the information it obtains. However, it shall exchange information on notified bodies with other Member\u00a0States, the Commission and, when required, with other regulatory authorities.\n\n\n6.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall have a sufficient number of competent personnel permanently available for the proper performance of its tasks.\nWhere the authority responsible for notified bodies is a different authority from the national competent authority for medical devices, it shall ensure that the national authority responsible for medical devices is consulted on relevant matters.\n\n\n7.\u00a0\u00a0\u00a0Member\u00a0States shall make publicly available general information on their measures governing the assessment, designation and notification of conformity assessment bodies and for the monitoring of notified bodies, and on changes which have a significant impact on such tasks.\n\n\n8.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall participate in the peer-review activities provided for in Article\u00a048.\n\n\n\nArticle\u00a036\n\nRequirements relating to notified bodies\n\n\n1.\u00a0\u00a0\u00a0Notified bodies shall fulfil the tasks for which they are designated in accordance with this Regulation. They shall satisfy the organisational and general requirements and the quality management, resource and process requirements that are necessary to fulfil those tasks. In particular, notified bodies shall comply with Annex\u00a0VII.\nIn order to meet the requirements referred to in the first subparagraph, notified bodies shall have permanent availability of sufficient administrative, technical and scientific personnel in accordance with Section\u00a03.1.1 of Annex\u00a0VII and personnel with relevant clinical expertise in accordance with Section\u00a03.2.4 of Annex\u00a0VII, where possible employed by the notified body itself.\nThe personnel referred to in Sections 3.2.3 and 3.2.7 of Annex\u00a0VII shall be employed by the notified body itself and shall not be external experts or subcontractors.\n\n\n2.\u00a0\u00a0\u00a0Notified bodies shall make available and submit upon request all relevant documentation, including the manufacturer's documentation, to the authority responsible for notified bodies to allow it to conduct its assessment, designation, notification, monitoring and surveillance activities and to facilitate the assessment outlined in this Chapter.\n\n\n3.\u00a0\u00a0\u00a0In order to ensure the uniform application of the requirements set out in Annex\u00a0VII, the Commission may adopt implementing acts, to the extent necessary to resolve issues of divergent interpretation and of practical application. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a037\n\nSubsidiaries and subcontracting\n\n\n1.\u00a0\u00a0\u00a0Where a notified body subcontracts specific tasks connected with conformity assessment or has recourse to a subsidiary for specific tasks connected with conformity assessment, it shall verify that the subcontractor or the subsidiary meets the applicable requirements set out in Annex\u00a0VII and shall inform the authority responsible for notified bodies accordingly.\n\n\n2.\u00a0\u00a0\u00a0Notified bodies shall take full responsibility for the tasks performed on their behalf by subcontractors or subsidiaries.\n\n\n3.\u00a0\u00a0\u00a0Notified bodies shall make publicly available a list of their subsidiaries.\n\n\n4.\u00a0\u00a0\u00a0Conformity assessment activities may be subcontracted or carried out by a subsidiary provided that the legal or natural person that applied for conformity assessment has been informed accordingly.\n\n\n5.\u00a0\u00a0\u00a0Notified bodies shall keep at the disposal of the authority responsible for notified bodies all relevant documents concerning the verification of the qualifications of the subcontractor or the subsidiary and the work carried out by them under this Regulation.\n\n\n\nArticle\u00a038\n\nApplication by conformity assessment bodies for designation\n\n\n1.\u00a0\u00a0\u00a0Conformity assessment bodies shall submit an application for designation to the authority responsible for notified bodies.\n\n\n2.\u00a0\u00a0\u00a0The application shall specify the conformity assessment activities as defined in this Regulation, and the types of devices for which the body is applying to be designated, and shall be supported by documentation demonstrating compliance with Annex\u00a0VII.\nIn respect of the organisational and general requirements and the quality management requirements set out in Sections\u00a01 and 2 of Annex\u00a0VII, a valid accreditation certificate and the corresponding evaluation report delivered by a national accreditation body in accordance with Regulation\u00a0(EC)\u00a0No\u00a0765/2008 may be submitted and shall be taken into consideration during the assessment described in Article\u00a039. However, the applicant shall make available all the documentation referred to in the first subparagraph\u00a0to demonstrate compliance with those requirements upon request.\n\n\n3.\u00a0\u00a0\u00a0The notified body shall update the documentation referred to in paragraph\u00a02 whenever relevant changes occur, in order to enable the authority responsible for notified bodies to monitor and verify continuous compliance with all the requirements set out in Annex\u00a0VII.\n\n\n\nArticle\u00a039\n\nAssessment of the application\n\n\n1.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall within 30 days check that the application referred to in Article\u00a038 is complete and shall request the applicant to provide any missing information. Once the application is complete that authority shall send it to the Commission.\nThe authority responsible for notified bodies shall review the application and supporting documentation in accordance with its own procedures and shall draw up a preliminary assessment report.\n\n\n2.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall submit the preliminary assessment report to the Commission which shall immediately transmit it to the MDCG.\n\n\n3.\u00a0\u00a0\u00a0Within 14 days of the submission referred to in paragraph\u00a02 of this Article, the Commission, in conjunction with the MDCG, shall appoint a joint assessment team made up of three experts, unless the specific circumstances require a different number of experts, chosen from the list referred to in Article\u00a040(2). One of the experts shall be a representative of the Commission who shall coordinate the activities of the joint assessment team. The other two experts shall come from Member\u00a0States other than the one in which the applicant conformity assessment body is established.\nThe joint assessment team shall be comprised of experts who are competent to assess the conformity assessment activities and the types of devices which are the subject of the application or, in particular when the assessment procedure is initiated in accordance with Article\u00a047(3), to ensure that the specific concern can be appropriately assessed.\n\n\n4.\u00a0\u00a0\u00a0Within 90 days of its appointment, the joint assessment team shall review the documentation submitted with the application in accordance with Article\u00a038. The joint assessment team may provide feedback to, or require clarification from, the authority responsible for notified bodies on the application and on the planned on-site assessment.\nThe authority responsible for notified bodies together with the joint assessment team shall plan and conduct an on-site assessment of the applicant conformity assessment body and, where relevant, of any subsidiary or subcontractor, located inside or outside the Union, to be involved in the conformity assessment process.\nThe on-site assessment of the applicant body shall be led by the authority responsible for notified bodies.\n\n\n5.\u00a0\u00a0\u00a0Findings regarding non-compliance of an applicant conformity assessment body with the requirements set out in Annex\u00a0VII shall be raised during the assessment process and discussed between the authority responsible for notified bodies and the joint assessment team with a view to reaching consensus and resolving any diverging opinions, with respect to the assessment of the application.\nAt the end of the on-site assessment, the authority responsible for notified bodies shall list for the applicant conformity assessment body the non-compliances resulting from the assessment and summarise the assessment by the joint assessment team.\nWithin a specified timeframe, the applicant conformity assessment body shall submit to the national authority a corrective and preventive action plan to address the non-compliances.\n\n\n6.\u00a0\u00a0\u00a0The joint assessment team shall document any remaining diverging opinions with respect to the assessment within 30 days of completion of the on-site assessment and send them to the authority responsible for notified bodies.\n\n\n7.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall following receipt of a corrective and preventive action plan from the applicant body assess whether non-compliances identified during the assessment have been appropriately addressed. This plan shall indicate the root cause of the identified non-compliances and shall include a timeframe for implementation of the actions therein.\nThe authority responsible for notified bodies shall having confirmed the corrective and preventive action plan forward it and its opinion thereon to the joint assessment team. The joint assessment team may request of the authority responsible for notified bodies further clarification and modifications.\nThe authority responsible for notified bodies shall draw up its final assessment report which shall include:\n\n\n\n\n\n\n\u2014\n\n\nthe result of the assessment,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nconfirmation that the corrective and preventive actions have been appropriately addressed and, where required, implemented,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nany remaining diverging opinion with the joint assessment team, and, where applicable,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe recommended scope of designation.\n\n\n\n\n\n\n8.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall submit its final assessment report and, if applicable, the draft designation to the Commission, the MDCG and the joint assessment team.\n\n\n9.\u00a0\u00a0\u00a0The joint assessment team shall provide a final opinion regarding the assessment report prepared by the authority responsible for notified bodies and, if applicable, the draft designation within 21 days of receipt of those documents to the Commission, which shall immediately submit that final opinion to the MDCG. Within 42 days of receipt of the opinion of the joint assessment team, the MDCG shall issue a recommendation with regard to the draft designation, which the authority responsible for notified bodies shall duly take into consideration for its decision on the designation of the notified body.\n\n\n10.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, adopt measures setting out the detailed arrangements specifying procedures and reports for the application for designation referred to in Article\u00a038 and the assessment of the application set out in this Article. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a040\n\nNomination of experts for joint assessment of applications for notification\n\n\n1.\u00a0\u00a0\u00a0The Member\u00a0States and the Commission shall nominate experts qualified in the assessment of conformity assessment bodies in the field of medical devices to participate in the activities referred to in Articles\u00a039 and 48.\n\n\n2.\u00a0\u00a0\u00a0The Commission shall maintain a list of the experts nominated pursuant to paragraph\u00a01 of this Article, together with information on their specific field of competence and expertise. That list shall be made available to Member\u00a0States competent authorities through the electronic system referred to in Article\u00a057.\n\n\n\nArticle\u00a041\n\nLanguage requirements\n\nAll documents required pursuant to Articles\u00a038 and 39 shall be drawn up in a language or languages which shall be determined by the Member\u00a0State concerned.\nMember\u00a0States, in applying the first paragraph, shall consider accepting and using a commonly understood language in the medical field, for all or part of the documentation concerned.\nThe Commission shall provide translations of the documentation pursuant to Articles\u00a038 and 39, or parts thereof into an official Union language, such as is necessary for that documentation to be readily understood by the joint assessment team appointed in accordance with Article\u00a039(3).\n\n\nArticle\u00a042\n\nDesignation and notification procedure\n\n\n1.\u00a0\u00a0\u00a0Member\u00a0States may only designate conformity assessment bodies for which the assessment pursuant to Article\u00a039 was completed and which comply with Annex\u00a0VII.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States shall notify the Commission and the other Member\u00a0States of the conformity assessment bodies they have designated, using the electronic notification tool within the database of notified bodies developed and managed by the Commission\u00a0(NANDO).\n\n\n3.\u00a0\u00a0\u00a0The notification shall clearly specify, using the codes referred to in paragraph\u00a013 of this Article, the scope of the designation indicating the conformity assessment activities as defined in this Regulation and the types of devices which the notified body is authorised to assess and, without prejudice to Article\u00a044, any conditions associated with the designation.\n\n\n4.\u00a0\u00a0\u00a0The notification shall be accompanied by the final assessment report of the authority responsible for notified bodies, the final opinion of the joint assessment team referred to in Article\u00a039(9) and the recommendation of the MDCG. Where the notifying Member\u00a0State does not follow the recommendation of the MDCG, it shall provide a duly substantiated justification.\n\n\n5.\u00a0\u00a0\u00a0The notifying Member\u00a0State shall, without prejudice to Article\u00a044, inform the Commission and the other Member\u00a0States of any conditions associated with the designation and provide documentary evidence regarding the arrangements in place to ensure that the notified body will be monitored regularly and will continue to satisfy the requirements set out in Annex\u00a0VII.\n\n\n6.\u00a0\u00a0\u00a0Within 28 days of the notification referred to in paragraph\u00a02, a Member\u00a0State or the Commission may raise written objections, setting out its arguments, with regard either to the notified body or to its monitoring by the authority responsible for notified bodies. Where no objection is raised, the Commission shall publish in NANDO the notification within 42 days of its having been notified as referred to in paragraph\u00a02.\n\n\n7.\u00a0\u00a0\u00a0When a Member\u00a0State or the Commission raises objections in accordance with paragraph\u00a06, the Commission shall bring the matter before the MDCG within 10 days of the expiry of the period referred to in paragraph\u00a06. After consulting the parties involved, the MDCG shall give its opinion at the latest within 40 days of the matter having been brought before it. Where the MDCG is of the opinion that the notification can be accepted, the Commission shall publish in NANDO the notification within 14 days.\n\n\n8.\u00a0\u00a0\u00a0Where the MDCG, after having been consulted in accordance with paragraph\u00a07, confirms the existing objection or raises another objection, the notifying Member\u00a0State shall provide a written response to the MDCG opinion within 40\u00a0days of its receipt. The response shall address the objections raised in the opinion, and set out the reasons for the notifying Member\u00a0State's decision to designate or not designate the conformity assessment body.\n\n\n9.\u00a0\u00a0\u00a0Where the notifying Member\u00a0State decides to uphold its decision to designate the conformity assessment body, having given its reasons in accordance with paragraph\u00a08, the Commission shall publish in NANDO the notification within 14 days of being informed thereof.\n\n\n10.\u00a0\u00a0\u00a0When publishing the notification in NANDO, the Commission shall also add to the electronic system referred to in Article\u00a057 the information relating to the notification of the notified body along with the documents mentioned in paragraph\u00a04 of this Article\u00a0and the opinion and responses referred to in paragraphs 7 and 8 of this Article.\n\n\n11.\u00a0\u00a0\u00a0The designation shall become valid the day after the notification is published in NANDO. The published notification shall state the scope of lawful conformity assessment activity of the notified body.\n\n\n12.\u00a0\u00a0\u00a0The conformity assessment body concerned may perform the activities of a notified body only after the designation has become valid in accordance with paragraph\u00a011.\n\n\n13.\u00a0\u00a0\u00a0The Commission shall by 26 November 2017, by means of implementing acts, draw up a list of codes and corresponding types of devices for the purpose of specifying the scope of the designation of notified bodies. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3). The Commission, after consulting the MDCG, may update this list based, inter\u00a0alia, on information arising from the coordination activities described in Article\u00a048.\n\n\n\nArticle\u00a043\n\nIdentification number and list of notified bodies\n\n\n1.\u00a0\u00a0\u00a0The Commission shall assign an identification number to each notified body for which the notification becomes valid in accordance with Article\u00a042(11). It shall assign a single identification number even when the body is notified under several Union acts. If they are successfully designated in accordance with this Regulation, bodies notified pursuant to Directives\u00a090/385/EEC and 93/42/EEC shall retain the identification number assigned to them pursuant to those Directives.\n\n\n2.\u00a0\u00a0\u00a0The Commission shall make the list of the bodies notified under this Regulation, including the identification numbers that have been assigned to them and the conformity assessment activities as defined in this Regulation and the types of devices for which they have been notified, accessible to the public in NANDO. It shall also make this list available on the electronic system referred to in Article\u00a057. The Commission shall ensure that the list is kept up to date.\n\n\n\nArticle\u00a044\n\nMonitoring and re-assessment of notified bodies\n\n\n1.\u00a0\u00a0\u00a0Notified bodies shall, without delay, and at the latest within 15 days, inform the authority responsible for notified bodies of relevant changes which may affect their compliance with the requirements set out in Annex\u00a0VII or their ability to conduct the conformity assessment activities relating to the devices for which they have been designated.\n\n\n2.\u00a0\u00a0\u00a0The authorities responsible for notified bodies shall monitor the notified bodies established on their territory and their subsidiaries and subcontractors to ensure ongoing compliance with the requirements and the fulfilment of its obligations set out in this Regulation. Notified bodies shall, upon request by their authority responsible for notified bodies, supply all relevant information and documents, required to enable the authority, the Commission and other Member\u00a0States to verify compliance.\n\n\n3.\u00a0\u00a0\u00a0Where the Commission or the authority of a Member\u00a0State submits a request to a notified body established on the territory of another Member\u00a0State relating to a conformity assessment carried out by that notified body, it shall send a copy of that request to the authority responsible for notified bodies of that other Member\u00a0State. The notified body concerned shall respond without delay and within 15 days at the latest to the request. The authority responsible for notified bodies of the Member\u00a0State in which the body is established shall ensure that requests submitted by authorities of any other Member\u00a0State or by the Commission are resolved by the notified body unless there is a legitimate reason for not doing so in which case the matter may be referred to the MDCG.\n\n\n4.\u00a0\u00a0\u00a0At least once a year, the authorities responsible for notified bodies shall re-assess whether the notified bodies established on their respective territory and, where appropriate, the subsidiaries and subcontractors under the responsibility of those notified bodies still satisfy the requirements and fulfil their obligations set out in Annex\u00a0VII. That review shall include an on-site audit of each notified body and, where necessary, of its subsidiaries and subcontractors.\nThe authority responsible for notified bodies shall conduct its monitoring and assessment activities according to an annual assessment plan to ensure that it can effectively monitor the continued compliance of the notified body with the requirements of this Regulation. That plan shall provide a reasoned schedule for the frequency of assessment of the notified body and, in particular, associated subsidiaries and subcontractors. The authority shall submit its annual plan for monitoring or assessment for each notified body for which it is responsible to the MDCG and to the Commission.\n\n\n5.\u00a0\u00a0\u00a0The monitoring of notified bodies by the authority responsible for notified bodies shall include observed audits of notified body personnel, including where necessary any personnel from subsidiaries and subcontractors, as that personnel is in the process of conducting quality management system assessments at a manufacturer's facility.\n\n\n6.\u00a0\u00a0\u00a0The monitoring of notified bodies conducted by the authority responsible for notified bodies shall consider data arising from market surveillance, vigilance and post-market surveillance to help guide its activities.\nThe authority responsible for notified bodies shall provide for a systematic follow-up of complaints and other information, including from other Member\u00a0States, which may indicate non-fulfilment of the obligations by a notified body or its deviation from common or best practice.\n\n\n7.\u00a0\u00a0\u00a0The authority responsible for notified bodies may in addition to regular monitoring or on-site assessments conduct short-notice, unannounced or \u2018for-cause\u2019 reviews if needed to address a particular issue or to verify compliance.\n\n\n8.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall review the assessments by notified bodies of manufacturers' technical documentation, in particular the clinical evaluation documentation as further outlined in Article\u00a045.\n\n\n9.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall document and record any findings regarding non-compliance of the notified body with the requirements set out in Annex\u00a0VII and shall monitor the timely implementation of corrective and preventive actions.\n\n\n10.\u00a0\u00a0\u00a0Three years after notification of a notified body, and again every fourth year thereafter, a complete re-assessment to determine whether the notified body still satisfies the requirements set out in Annex\u00a0VII shall be conducted by the authority responsible for notified bodies of the Member\u00a0State in which the body is established and by a joint assessment team appointed for the purpose of the procedure described in Articles\u00a038 and\u00a039.\n\n\n11.\u00a0\u00a0\u00a0The Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 in order to amend paragraph\u00a010 to modify the frequency at which the complete re-assessment referred to in that paragraph\u00a0is to be carried out.\n\n\n12.\u00a0\u00a0\u00a0The Member\u00a0States shall report to the Commission and to the MDCG, at least once a year, on their monitoring and on-site assessment activities regarding notified bodies and, where applicable, subsidiaries and subcontractors. The report shall provide details of the outcome of those activities, including activities pursuant to paragraph\u00a07, and shall be treated as confidential by the MDCG and the Commission; however it shall contain a summary which shall be made publicly available.\nThe summary of the report shall be uploaded to the electronic system referred to in Article\u00a057.\n\n\n\nArticle\u00a045\n\nReview of notified body assessment of technical documentation and clinical evaluation documentation\n\n\n1.\u00a0\u00a0\u00a0The authority responsible for notified bodies, as part of its ongoing monitoring of notified bodies, shall review an appropriate number of notified body assessments of manufacturers' technical documentation, in particular the clinical evaluation documentation as referred to in points (c) and (d) of Section\u00a06.1 of Annex\u00a0II to verify the conclusions drawn by the notified body based on the information presented by the manufacturer. The reviews by the authority responsible for notified bodies shall be conducted both off-site and on-site.\n\n\n2.\u00a0\u00a0\u00a0The sampling of files to be reviewed in accordance with paragraph\u00a01 shall be planned and representative of the types and risk of devices certified by the notified body, in particular high-risk devices, and be appropriately justified and documented in a sampling plan, which shall be made available by the authority responsible for notified bodies to the MDCG upon request.\n\n\n3.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall review whether the assessment by the notified body was conducted appropriately and shall check the procedures used, associated documentation and the conclusions drawn by the notified body. Such checking shall include the technical documentation and clinical evaluation documentation of the manufacturer upon which the notified body has based its assessment. Such reviews shall be conducted utilising CS.\n\n\n4.\u00a0\u00a0\u00a0Those reviews shall also form part of the re-assessment of notified bodies in accordance with Article\u00a044(10) and the joint assessment activities referred to in Article\u00a047(3). The reviews shall be conducted utilising appropriate expertise.\n\n\n5.\u00a0\u00a0\u00a0Based on the reports of the reviews and assessments by the authority responsible for notified bodies or joint assessment teams, on input from the market surveillance, vigilance and post-market surveillance activities described in Chapter\u00a0VII, on the continuous monitoring of technical progress, or on the identification of concerns and emerging issues concerning the safety and performance of devices, the MDCG may recommend that the sampling, carried out under this Article, cover a greater or lesser proportion of the technical documentation and clinical evaluation documentation assessed by a notified body.\n\n\n6.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, adopt measures setting out the detailed arrangements, associated documents for, and coordination of, the review of assessments of technical documentation and clinical evaluation documentation, as referred to in this Article. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a046\n\nChanges to designations and notifications\n\n\n1.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall notify the Commission and the other Member\u00a0States of any relevant changes to the designation of a notified body.\nThe procedures described in Article\u00a039 and in Article\u00a042 shall apply to extensions of the scope of the designation.\nFor changes to the designation other than extensions of its scope, the procedures laid down in the following paragraphs shall apply.\n\n\n2.\u00a0\u00a0\u00a0The Commission shall immediately publish the amended notification in NANDO. The Commission shall immediately enter information on the changes to the designation of the notified body in the electronic system referred to in Article\u00a057.\n\n\n3.\u00a0\u00a0\u00a0Where a notified body decides to cease its conformity assessment activities it shall inform the authority responsible for notified bodies and the manufacturers concerned as soon as possible and in the case of a planned cessation one year before ceasing its activities. The certificates may remain valid for a temporary period of nine months after cessation of the notified body's activities on condition that another notified body has confirmed in writing that it will assume responsibilities for the devices covered by those certificates. The new notified body shall complete a full assessment of the devices affected by the end of that period before issuing new certificates for those devices. Where the notified body has ceased its activity, the authority responsible for notified bodies shall withdraw the designation.\n\n\n4.\u00a0\u00a0\u00a0Where a authority responsible for notified bodies has ascertained that a notified body no longer meets the requirements set out in Annex\u00a0VII, or that it is failing to fulfil its obligations or has not implemented the necessary corrective measures, the authority shall suspend, restrict, or fully or partially withdraw the designation, depending on the seriousness of the failure to meet those requirements or fulfil those obligations. A\u00a0suspension shall not exceed a period of one year, renewable once for the same period.\nThe authority responsible for notified bodies shall immediately inform the Commission and the other Member\u00a0States of any suspension, restriction or withdrawal of a designation.\n\n\n5.\u00a0\u00a0\u00a0Where its designation has been suspended, restricted, or fully or partially withdrawn, the notified body shall inform the manufacturers concerned at the latest within 10 days.\n\n\n6.\u00a0\u00a0\u00a0In the event of restriction, suspension or withdrawal of a designation, the authority responsible for notified bodies shall take appropriate steps to ensure that the files of the notified body concerned are kept and make them available to authorities in other Member\u00a0States responsible for notified bodies and to authorities responsible for market surveillance at their request.\n\n\n7.\u00a0\u00a0\u00a0In the event of restriction, suspension or withdrawal of a designation, the authority responsible for notified bodies shall:\n\n\n\n\n\n\n(a)\n\n\nassess the impact on the certificates issued by the notified body;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nsubmit a report on its findings to the Commission and the other Member\u00a0States within three months of having notified the changes to the designation;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nrequire the notified body to suspend or withdraw, within a reasonable period of time determined by the authority, any certificates which were unduly issued to ensure the safety of devices on the market;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nenter into the electronic system referred to in Article\u00a057 information in relation to certificates of which it has required their suspension or withdrawal;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\ninform the competent authority for medical devices of the Member\u00a0State in which the manufacturer has its registered place of business through the electronic system referred to in Article\u00a057 of the certificates for which it has required suspension or withdrawal. That competent authority shall take the appropriate measures, where necessary to avoid a potential risk to the health or safety of patients, users or others.\n\n\n\n\n\n\n8.\u00a0\u00a0\u00a0With the exception of certificates unduly issued, and where a designation has been suspended or restricted, the certificates shall remain valid in the following circumstances:\n\n\n\n\n\n\n(a)\n\n\nthe authority responsible for notified bodies has confirmed, within one month of the suspension or restriction, that there is no safety issue in relation to certificates affected by the suspension or restriction, and the authority responsible for notified bodies has outlined a timeline and actions anticipated to remedy the suspension or restriction; or\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe authority responsible for notified bodies has confirmed that no certificates relevant to the suspension will be issued, amended or re-issued during the course of the suspension or restriction, and states whether the notified body has the capability of continuing to monitor and remain responsible for existing certificates issued for the period of the suspension or restriction. In the event that the authority responsible for notified bodies determines that the notified body does not have the capability to support existing certificates issued, the manufacturer shall provide, to the competent authority for medical devices of the Member\u00a0State in which the manufacturer of the device covered by the certificate has its registered place of business, within three months of the suspension or restriction, a written confirmation that another qualified notified body is temporarily assuming the functions of the notified body to monitor and remain responsible for the certificates during the period of suspension or restriction.\n\n\n\n\n\n\n9.\u00a0\u00a0\u00a0With the exception of certificates unduly issued, and where a designation has been withdrawn, the certificates shall remain valid for a period of nine months in the following circumstances:\n\n\n\n\n\n\n(a)\n\n\nwhere the competent authority for medical devices of the Member\u00a0State in which the manufacturer of the device covered by the certificate has its registered place of business has confirmed that there is no safety issue associated with the devices in question; and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nanother notified body has confirmed in writing that it will assume immediate responsibilities for those devices and will have completed assessment of them within twelve months of the withdrawal of the designation.\n\n\n\n\nIn the circumstances referred to in the first subparagraph, the competent authority for medical devices of the Member\u00a0State in which the manufacturer of the device covered by the certificate has its place of business may extend the provisional validity of the certificates for further periods of three months, which altogether shall not exceed twelve\u00a0months.\nThe authority or the notified body assuming the functions of the notified body affected by the change of designation shall immediately inform the Commission, the other Member\u00a0States and the other notified bodies thereof.\n\n\n\nArticle\u00a047\n\nChallenge to the competence of notified bodies\n\n\n1.\u00a0\u00a0\u00a0The Commission, in conjunction with the MDCG, shall investigate all cases where concerns have been brought to its attention regarding the continued fulfilment by a notified body, or of one or more of its subsidiaries or subcontractors, of the requirements set out in Annex\u00a0VII or the obligations to which they are subject. It shall ensure that the relevant authority responsible for notified bodies is informed and is given an opportunity to investigate those concerns.\n\n\n2.\u00a0\u00a0\u00a0The notifying Member\u00a0State shall provide the Commission, on request, with all information regarding the designation of the notified body concerned.\n\n\n3.\u00a0\u00a0\u00a0The Commission, in conjunction with the MDCG, may initiate, as applicable, the assessment procedure described in Article\u00a039(3) and (4), where there is reasonable concern about the ongoing compliance of a notified body or a subsidiary or subcontractor of the notified body with the requirements set out in Annex\u00a0VII and where the investigation by the authority responsible for notified bodies is not deemed to have fully addressed the concerns or upon request of the authority responsible for notified bodies. The reporting and outcome of that assessment shall follow the principles of Article\u00a039. Alternatively, depending on the severity of the issue, the Commission, in conjunction with the MDCG, may request that the authority responsible for notified bodies allow the participation of up to two experts from the list established pursuant to Article\u00a040 in an on-site assessment as part of the planned monitoring and assessment activities in accordance with Article\u00a044 and as outlined in the annual assessment plan described in Article\u00a044(4).\n\n\n4.\u00a0\u00a0\u00a0Where the Commission ascertains that a notified body no longer meets the requirements for its designation, it shall inform the notifying Member\u00a0State accordingly and request it to take the necessary corrective measures, including the suspension, restriction or withdrawal of the designation if necessary.\nWhere the Member\u00a0State fails to take the necessary corrective measures, the Commission may, by means of implementing acts, suspend, restrict or withdraw the designation. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3). It shall notify the Member\u00a0State concerned of its decision and update NANDO and the electronic system referred to in Article\u00a057.\n\n\n5.\u00a0\u00a0\u00a0The Commission shall ensure that all confidential information obtained in the course of its investigations is treated accordingly.\n\n\n\nArticle\u00a048\n\nPeer review and exchange of experience between authorities responsible for notified bodies\n\n\n1.\u00a0\u00a0\u00a0The Commission shall provide for the organisation of exchange of experience and coordination of administrative practice between the authorities responsible for notified bodies. Such exchange shall cover elements including:\n\n\n\n\n\n\n(a)\n\n\ndevelopment of best practice documents relating to the activities of the authorities responsible for notified bodies;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ndevelopment of guidance documents for notified bodies in relation to the implementation of this Regulation;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\ntraining and qualification of the experts referred to in Article\u00a040;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nmonitoring of trends relating to changes to notified body designations and notifications and trends in certificate withdrawals and transfers between notified bodies;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nmonitoring of the application and applicability of scope codes referred to in Article\u00a042(13);\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\ndevelopment of a mechanism for peer reviews between authorities and the Commission;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nmethods of communication to the public on the monitoring and surveillance activities of authorities and the Commission on notified bodies.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The authorities responsible for notified bodies shall participate in a peer review every third year through the mechanism developed pursuant to paragraph\u00a01 of this\u00a0Article. Such reviews shall normally be conducted in parallel with the on-site joint assessments described in Article\u00a039. Alternatively, an authority may make the choice of having such reviews take place as part of its monitoring activities referred to in Article\u00a044.\n\n\n3.\u00a0\u00a0\u00a0The Commission shall participate in the organisation and provide support to the implementation of the peer review mechanism.\n\n\n4.\u00a0\u00a0\u00a0The Commission shall compile an annual summary report of the peer review activities, which shall be made publicly available.\n\n\n5.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, adopt measures setting out the detailed arrangements and related documents for the peer review mechanism and training and qualification as referred to in paragraph\u00a01 of this Article. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a049\n\nCoordination of notified bodies\n\nThe Commission shall ensure that appropriate coordination and cooperation between notified bodies is put in place and operated in the form of a coordination group of notified bodies in the field of medical devices, including in vitro diagnostic medical devices. This group shall meet on a regular basis and at least annually.\nThe bodies notified under this Regulation shall participate in the work of that group.\nThe Commission may establish the specific arrangements for the functioning of the coordination group of notified bodies.\n\n\nArticle\u00a050\n\nList of standard fees\n\nNotified bodies shall establish lists of their standard fees for the conformity assessment activities that they carry out and shall make those lists publicly available.\n\n\n\nCHAPTER V\n\n\nCLASSIFICATION AND CONFORMITY ASSESSMENT\n\n\n\n\nSECTION\u00a01\n\n\n\n\nClassification\n\n\n\n\nArticle\u00a051\n\nClassification of devices\n\n\n1.\u00a0\u00a0\u00a0Devices shall be divided into classes I, IIa, IIb and III, taking into account the intended purpose of the devices and their inherent risks. Classification shall be carried out in accordance with Annex\u00a0VIII.\n\n\n2.\u00a0\u00a0\u00a0Any dispute between the manufacturer and the notified body concerned, arising from the application of Annex\u00a0VIII, shall be referred for a decision to the competent authority of the Member\u00a0State in which the manufacturer has its registered place of business. In cases where the manufacturer has no registered place of business in the Union and has not yet designated an authorised representative, the matter shall be referred to the competent authority of the Member\u00a0State in which the authorised representative referred to in the last indent of point\u00a0(b) of the second paragraph\u00a0of Section\u00a02.2 of Annex\u00a0IX has its registered place of business. Where the notified body concerned is established in a Member\u00a0State other than that of the manufacturer, the competent authority shall adopt its decision after consultation with the competent authority of the Member\u00a0State that designated the notified body.\nThe competent authority of the Member\u00a0State in which the manufacturer has its registered place of business shall notify the MDCG and the Commission of its decision. The decision shall be made available upon request.\n\n\n3.\u00a0\u00a0\u00a0At the request of a Member\u00a0State the Commission shall after consulting the MDCG, decide, by means of implementing acts, on the following:\n\n\n\n\n\n\n(a)\n\n\napplication of Annex\u00a0VIII to a given device, or category or group of devices, with a view to determining the classification of such devices;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthat a device, or category or group of devices, shall for reasons of public health based on new scientific evidence, or based on any information which becomes available in the course of the vigilance and market surveillance activities be reclassified, by way of derogation from Annex\u00a0VIII.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0The Commission may also, on its own initiative and after consulting the MDCG, decide, by means of implementing acts, on the issues referred to in points (a) and (b) of paragraph\u00a03.\n\n\n5.\u00a0\u00a0\u00a0In order to ensure the uniform application of Annex\u00a0VIII, and taking account of the relevant scientific opinions of the relevant scientific committees, the Commission may adopt implementing acts to the extent necessary to resolve issues of divergent interpretation and of practical application.\n\n\n6.\u00a0\u00a0\u00a0The implementing acts referred to in paragraphs 3, 4 and 5 of this Article\u00a0shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\n\n\nSECTION\u00a02\n\n\n\n\nConformity assessment\n\n\n\n\nArticle\u00a052\n\nConformity assessment procedures\n\n\n1.\u00a0\u00a0\u00a0Prior to placing a device on the market, manufacturers shall undertake an assessment of the conformity of that device, in accordance with the applicable conformity assessment procedures set out in Annexes\u00a0IX to XI.\n\n\n2.\u00a0\u00a0\u00a0Prior to putting into service a device that is not placed on the market, manufacturers shall undertake an assessment of the conformity of that device, in accordance with the applicable conformity assessment procedures set out in Annexes\u00a0IX to XI.\n\n\n3.\u00a0\u00a0\u00a0Manufacturers of class\u00a0III devices, other than custom-made or investigational devices, shall be subject to a conformity assessment as specified in Annex\u00a0IX. Alternatively, the manufacturer may choose to apply a conformity assessment as specified in Annex\u00a0X coupled with a conformity assessment as specified in Annex\u00a0XI.\n\n\n4.\u00a0\u00a0\u00a0Manufacturers of class IIb devices, other than custom-made or investigational devices, shall be subject to a conformity assessment as specified in Chapters\u00a0I and III of Annex\u00a0IX, and including an assessment of the technical documentation as specified in Section\u00a04 of that Annex\u00a0of at least one representative device per generic device group.\nHowever, for class\u00a0IIb implantable devices, except sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips and connectors, the assessment of the technical documentation as specified in Section 4 of Annex IX shall apply for every device.\nAlternatively, the manufacturer may choose to apply a conformity assessment based on type examination as specified in Annex\u00a0X coupled with a conformity assessment based on product conformity verification as specified in Annex\u00a0XI.\n\n\n5.\u00a0\u00a0\u00a0Where justified in view of well-established technologies, similar to those used in the exempted devices listed in the second subparagraph\u00a0of paragraph\u00a04 of this Article, being used in other class IIb implantable devices, or where justified in order to protect the health and safety of patients, users or other persons or other aspects of public health, the Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 to amend that list by adding other types of class IIb implantable devices to that list or removing devices therefrom.\n\n\n6.\u00a0\u00a0\u00a0Manufacturers of class IIa devices, other than custom-made or investigational devices, shall be subject to a conformity assessment as specified in Chapters\u00a0I and III of Annex\u00a0IX, and including an assessment of the technical documentation as specified in Section\u00a04 of that Annex\u00a0of at least one representative device for each category of devices.\nAlternatively, the manufacturer may choose to draw up the technical documentation set out in Annexes\u00a0II and III coupled with a conformity assessment as specified in Section\u00a010 or Section\u00a018 of Annex\u00a0XI. The assessment of the technical documentation shall apply for at least one representative device for each category of devices.\n\n\n7.\u00a0\u00a0\u00a0Manufacturers of class I devices, other than custom-made or investigational devices, shall declare the conformity of their products by issuing the EU\u00a0declaration of conformity referred to in Article\u00a019 after drawing up the technical documentation set out in Annexes\u00a0II and III. If those devices are placed on the market in sterile condition, have a measuring function or are reusable surgical instruments, the manufacturer shall apply the procedures set out in Chapters\u00a0I and III of Annex\u00a0IX, or in Part\u00a0A of Annex\u00a0XI. However, the involvement of the notified body in those procedures shall be limited:\n\n\n\n\n\n\n(a)\n\n\nin the case of devices placed on the market in sterile condition, to the aspects relating to establishing, securing and maintaining sterile conditions;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nin the case of devices with a measuring function, to the aspects relating to the conformity of the devices with the metrological requirements;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nin the case of reusable surgical instruments, to the aspects relating to the reuse of the device, in particular cleaning, disinfection, sterilization, maintenance and functional testing and the related instructions for use.\n\n\n\n\n\n\n8.\u00a0\u00a0\u00a0Manufacturers of custom-made devices shall follow the procedure set out in Annex\u00a0XIII and draw up the statement set out in Section\u00a01 of that Annex\u00a0before placing such devices on the market.\nIn addition to the procedure applicable pursuant to the first subparagraph, manufacturers of class III custom-made implantable devices shall be subject to the conformity assessment as specified in Chapter\u00a0I of Annex\u00a0IX. Alternatively, the manufacturer may choose to apply a conformity assessment as specified in Part A of Annex\u00a0XI.\n\n\n9.\u00a0\u00a0\u00a0In addition to the procedures applicable pursuant to paragraph\u00a03, 4, 6, or 7 of this Article, in the case of devices referred to in the first subparagraph\u00a0of Article\u00a01(8), the procedure specified in Section\u00a05.2 of Annex\u00a0IX or Section\u00a06 of Annex\u00a0X, as applicable, shall also apply.\n\n\n10.\u00a0\u00a0\u00a0In addition to the procedures applicable pursuant to paragraph\u00a03, 4, 6, or 7 of this Article, in the case of devices that are covered by this Regulation in accordance with point\u00a0(f) or (g) of Article\u00a01(6) and with the first subparagraph\u00a0of Article\u00a01(10), the procedure specified in Section\u00a05.3 of Annex\u00a0IX or Section\u00a06 of Annex\u00a0X, as applicable, shall also apply.\n\n\n11.\u00a0\u00a0\u00a0In addition to the procedures applicable pursuant to paragraph\u00a03, 4, 6, or 7, in the case of devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed by or locally dispersed in the human body, the procedure specified in Section\u00a05.4 of Annex\u00a0IX or Section\u00a06 of Annex\u00a0X, as applicable, shall also apply.\n\n\n12.\u00a0\u00a0\u00a0The Member\u00a0State in which the notified body is established may require that all or certain documents, including the technical documentation, audit, assessment and inspection reports, relating to the procedures referred to in paragraphs 1 to 7 and 9 to 11 be made available in an official Union language(s) determined by that Member\u00a0State. In the absence of such requirement, those documents shall be available in any official Union language acceptable to the notified body.\n\n\n13.\u00a0\u00a0\u00a0Investigational devices shall be subject to the requirements set out in Articles\u00a062 to\u00a081.\n\n\n14.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, specify detailed arrangements and procedural aspects with a view to ensuring the harmonised application of the conformity assessment procedures by the notified bodies for any of the following aspects:\n\n\n\n\n\n\n(a)\n\n\nthe frequency and the sampling basis of the assessment of the technical documentation on a representative basis as set out in the third paragraph\u00a0of Section\u00a02.3 and in Section\u00a03.5 of Annex\u00a0IX in the case of class\u00a0IIa and class\u00a0IIb devices, and in Section\u00a010.2 of Annex\u00a0XI in the case of class\u00a0IIa devices;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe minimum frequency of unannounced on-site audits and sample tests to be conducted by notified bodies in accordance with Section\u00a03.4 of Annex\u00a0IX, taking into account the risk-class and the type of device;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe physical, laboratory or other tests to be carried out by notified bodies in the context of sample tests, assessment of the technical documentation and type examination in accordance with Sections 3.4 and 4.3 of Annex\u00a0IX, Section\u00a03 of Annex\u00a0X and Section\u00a015 of Annex\u00a0XI.\n\n\n\n\nThe implementing acts referred to in the first subparagraph\u00a0shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a053\n\nInvolvement of notified bodies in conformity assessment procedures\n\n\n1.\u00a0\u00a0\u00a0Where the conformity assessment procedure requires the involvement of a notified body, the manufacturer may apply to a notified body of its choice, provided that the chosen notified body is designated for conformity assessment activities related to the types of devices concerned. The manufacturer may not lodge an application in parallel with another notified body for the same conformity assessment procedure.\n\n\n2.\u00a0\u00a0\u00a0The notified body concerned shall, by means of the electronic system referred to in Article\u00a057, inform the other notified bodies of any manufacturer that withdraws its application prior to the notified body's decision regarding the conformity assessment.\n\n\n3.\u00a0\u00a0\u00a0When applying to a notified body under paragraph\u00a01, manufacturers shall declare whether they have withdrawn an application with another notified body prior to the decision of that notified body and provide information about any previous application for the same conformity assessment that has been refused by another notified body.\n\n\n4.\u00a0\u00a0\u00a0The notified body may require any information or data from the manufacturer, which is necessary in order to properly conduct the chosen conformity assessment procedure.\n\n\n5.\u00a0\u00a0\u00a0Notified bodies and the personnel of notified bodies shall carry out their conformity assessment activities with the highest degree of professional integrity and the requisite technical and scientific competence in the specific field and shall be free from all pressures and inducements, particularly financial, which might influence their judgement or the results of their conformity assessment activities, especially as regards persons or groups with an interest in the results of those activities.\n\n\n\nArticle\u00a054\n\nClinical evaluation consultation procedure for certain class III and class IIb devices\n\n\n1.\u00a0\u00a0\u00a0In addition to the procedures applicable pursuant to Article\u00a052, a notified body shall also follow the procedure regarding clinical evaluation consultation as specified in Section\u00a05.1 of Annex\u00a0IX or as referred to in Section\u00a06 of Annex\u00a0X, as applicable, when performing a conformity assessment of the following devices:\n\n\n\n\n\n\n(a)\n\n\nclass III implantable devices, and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nclass IIb active devices intended to administer and/or remove a medicinal product, as referred to in Section\u00a06.4 of Annex\u00a0VIII (Rule 12).\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The procedure referred to in paragraph\u00a01 shall not be required for the devices referred to therein:\n\n\n\n\n\n\n(a)\n\n\nin the case of renewal of a certificate issued under this Regulation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nwhere the device has been designed by modifying a device already marketed by the same manufacturer for the same intended purpose, provided that the manufacturer has demonstrated to the satisfaction of the notified body that the modifications do not adversely affect the benefit-risk ratio of the device; or\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nwhere the principles of the clinical evaluation of the device type or category have been addressed in a CS referred to in Article\u00a09 and the notified body confirms that the clinical evaluation of the manufacturer for this device is in compliance with the relevant CS for clinical evaluation of that kind of device.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0The notified body shall notify the competent authorities, the authority responsible for notified bodies and the Commission through the electronic system referred to in Article\u00a057 of whether or not the procedure referred to in paragraph\u00a01 of this Article\u00a0is to be applied. That notification shall be accompanied by the clinical evaluation assessment report.\n\n\n4.\u00a0\u00a0\u00a0The Commission shall draw up an annual overview of devices which have been subject to the procedure specified in Section\u00a05.1 of Annex\u00a0IX and referred to in Section\u00a06 of Annex\u00a0X. The annual overview shall include the notifications in accordance with paragraph\u00a03 of this Article\u00a0and point\u00a0(e) of Section\u00a05.1 of Annex\u00a0IX and a listing of the cases where the notified body did not follow the advice from the expert panel. The Commission shall submit this overview to the European Parliament, to the Council and to the MDCG.\n\n\n5.\u00a0\u00a0\u00a0The Commission shall by 27 May 2025 draw up a report on the operation of this Article\u00a0and submit it to the European Parliament and to the Council. The report shall take into account the annual overviews and any available relevant recommendations from the MDCG. On the basis of that report the Commission shall, if appropriate, make proposals for amendments to this Regulation.\n\n\n\nArticle\u00a055\n\nMechanism for scrutiny of conformity assessments of certain class III and class IIb devices\n\n\n1.\u00a0\u00a0\u00a0A notified body shall notify the competent authorities of certificates it has granted to devices for which the conformity assessment has been performed pursuant to Article\u00a054(1). Such notification shall take place through the electronic system referred to in Article\u00a057 and shall include the summary of safety and clinical performance pursuant to Article\u00a032, the assessment report by the notified body, the instructions for use referred to in Section\u00a023.4 of Annex\u00a0I, and, where applicable, the scientific opinion of the expert panels referred to in Section\u00a05.1 of Annex\u00a0IX or Section\u00a06 of Annex\u00a0X, as applicable. In the case of divergent views between the notified body and the expert panels, a full justification shall also be included.\n\n\n2.\u00a0\u00a0\u00a0A competent authority and, where applicable, the Commission may, based on reasonable concerns apply further procedures in accordance with Article\u00a044, 45, 46, 47 or 94 and, where deemed necessary, take appropriate measures in accordance with Articles\u00a095 and\u00a097.\n\n\n3.\u00a0\u00a0\u00a0The MDCG and, where applicable, the Commission, may, based on reasonable concerns, request scientific advice from the expert panels in relation to the safety and performance of any device.\n\n\n\nArticle\u00a056\n\nCertificates of conformity\n\n\n1.\u00a0\u00a0\u00a0The certificates issued by the notified bodies in accordance with Annexes\u00a0IX, X and XI shall be in an official Union language determined by the Member\u00a0State in which the notified body is established or otherwise in an official Union language acceptable to the notified body. The minimum content of the certificates shall be as set out in Annex\u00a0XII.\n\n\n2.\u00a0\u00a0\u00a0The certificates shall be valid for the period they indicate, which shall not exceed five years. On application by the manufacturer, the validity of the certificate may be extended for further periods, each not exceeding five years, based on a re-assessment in accordance with the applicable conformity assessment procedures. Any supplement to a certificate shall remain valid as long as the certificate which it supplements is valid.\n\n\n3.\u00a0\u00a0\u00a0Notified bodies may impose restrictions to the intended purpose of a device to certain groups of patients or require manufacturers to undertake specific PMCF studies pursuant to Part B of Annex\u00a0XIV.\n\n\n4.\u00a0\u00a0\u00a0Where a notified body finds that the requirements of this Regulation are no longer met by the manufacturer, it shall, taking account of the principle of proportionality, suspend or withdraw the certificate issued or impose any restrictions on it unless compliance with such requirements is ensured by appropriate corrective action taken by the manufacturer within an appropriate deadline set by the notified body. The notified body shall give the reasons for its decision.\n\n\n5.\u00a0\u00a0\u00a0The notified body shall enter in the electronic system referred to in Article\u00a057 any information regarding certificates issued, including amendments and supplements thereto, and regarding suspended, reinstated, withdrawn or refused certificates and restrictions imposed on certificates. Such information shall be accessible to the public.\n\n\n6.\u00a0\u00a0\u00a0In the light of technical progress, the Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 amending the minimum content of the certificates set out in Annex\u00a0XII.\n\n\n\nArticle\u00a057\n\nElectronic system on notified bodies and on certificates of conformity\n\n\n1.\u00a0\u00a0\u00a0The Commission, after consulting the MDCG, shall set up and manage an electronic system to collate and process the following information:\n\n\n\n\n\n\n(a)\n\n\nthe list of subsidiaries referred to in Article\u00a037(3);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe list of experts referred to in Article\u00a040(2);\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe information relating to the notification referred to in Article\u00a042(10) and the amended notifications referred to in Article\u00a046(2);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe list of notified bodies referred to in Article\u00a043(2);\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe summary of the report referred to in Article\u00a044(12);\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe notifications for conformity assessments and certificates referred to in Articles\u00a054(3) and 55(1);\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nwithdrawal or refusals of applications for the certificates as referred to in Article\u00a053(2) and Section\u00a04.3 of Annex\u00a0VII;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe information regarding certificates referred to in Article\u00a056(5);\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nthe summary of safety and clinical performance referred to in Article\u00a032.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The information collated and processed by the electronic system shall be accessible to the competent authorities of the Member\u00a0States, to the Commission, where appropriate to the notified bodies and where provided elsewhere in this regulation or in Regulation\u00a0(EU)\u00a02017/746 to the public.\n\n\n\nArticle\u00a058\n\nVoluntary change of notified body\n\n\n1.\u00a0\u00a0\u00a0In cases where a manufacturer terminates its contract with a notified body and enters into a contract with another notified body in respect of the conformity assessment of the same device, the detailed arrangements for the change of notified body shall be clearly defined in an agreement between the manufacturer, the incoming notified body and, where practicable the outgoing notified body. That agreement shall cover at least the following aspects:\n\n\n\n\n\n\n(a)\n\n\nthe date on which the certificates issued by the outgoing notified body become invalid;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe date until which the identification number of the outgoing notified body may be indicated in the information supplied by the manufacturer, including any promotional material;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe transfer of documents, including confidentiality aspects and property rights;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe date after which the conformity assessment tasks of the outgoing notified body is assigned to the incoming notified body;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe last serial number or lot number for which the outgoing notified body is responsible.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The outgoing notified body shall withdraw the certificates it has issued for the device concerned on the date on which they become invalid.\n\n\n\nArticle\u00a059\n\nDerogation from the conformity assessment procedures\n\n\n1.\u00a0\u00a0\u00a0By way of derogation from Article\u00a052, any competent authority may authorise, on a duly justified request, the placing on the market or putting into service within the territory of the Member\u00a0State concerned, of a specific device for which the procedures referred to in that Article\u00a0have not been carried out but use of which is in the interest of public health or patient safety or health.\n\n\n2.\u00a0\u00a0\u00a0The Member\u00a0State shall inform the Commission and the other Member\u00a0States of any decision to authorise the placing on the market or putting into service of a device in accordance with paragraph\u00a01 where such authorisation is granted for use other than for a single patient.\n\n\n3.\u00a0\u00a0\u00a0Following a notification pursuant to paragraph\u00a02 of this Article, the Commission, in exceptional cases relating to public health or patient safety or health, may, by means of implementing acts, extend for a limited period of time the validity of an authorisation granted by a Member\u00a0State in accordance with paragraph\u00a01 of this Article\u00a0to the territory of the Union and set the conditions under which the device may be placed on the market or put into service. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\nOn duly justified imperative grounds of urgency relating to the health and safety of humans, the Commission shall adopt immediately applicable implementing acts in accordance with the procedure referred to in Article\u00a0114(4).\n\n\n\nArticle\u00a060\n\nCertificate of free sale\n\n\n1.\u00a0\u00a0\u00a0For the purpose of export and upon request by a manufacturer or an authorised representative, the Member\u00a0State in which the manufacturer or the authorised representative has its registered place of business shall issue a certificate of free sale declaring that the manufacturer or the authorised representative, as applicable, has its registered place of business on its territory and that the device in question bearing the CE\u00a0marking in accordance with this Regulation may be marketed in the Union. The certificate of free sale shall set out the Basic UDI-DI of the device as provided to the UDI\u00a0database under Article\u00a029. Where a notified body has issued a certificate pursuant to Article\u00a056, the certificate of free sale shall set out the unique number identifying the certificate issued by the notified body, as referred to in Section\u00a03 of Chapter\u00a0II of Annex\u00a0XII.\n\n\n2.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, establish a model for certificates of free sale, taking into account international practice as regards the use of certificates of free sale. Those implementing acts shall be adopted in accordance with the advisory procedure referred to in Article\u00a0114(2).\n\n\n\n\n\nCHAPTER VI\n\n\nCLINICAL EVALUATION AND CLINICAL INVESTIGATIONS\n\n\n\nArticle\u00a061\n\nClinical evaluation\n\n\n1.\u00a0\u00a0\u00a0Confirmation of conformity with relevant general safety and performance requirements set out in Annex\u00a0I under the normal conditions of the intended use of the device, and the evaluation of the undesirable side-effects and of the acceptability of the benefit-risk- ratio referred to in Sections 1 and 8 of Annex\u00a0I, shall be based on clinical data providing sufficient clinical evidence, including where applicable relevant data as referred to in Annex\u00a0III.\nThe manufacturer shall specify and justify the level of clinical evidence necessary to demonstrate conformity with the relevant general safety and performance requirements. That level of clinical evidence shall be appropriate in view of the characteristics of the device and its intended purpose.\nTo that end, manufacturers shall plan, conduct and document a clinical evaluation in accordance with this Article\u00a0and Part A of Annex\u00a0XIV.\n\n\n2.\u00a0\u00a0\u00a0For all class III devices and for the class IIb devices referred to in point\u00a0(b) of Article\u00a054(1), the manufacturer may, prior to its clinical evaluation and/or investigation, consult an expert panel as referred to in Article\u00a0106, with the aim of reviewing the manufacturer's intended clinical development strategy and proposals for clinical investigation. The manufacturer shall give due consideration to the views expressed by the expert panel. Such consideration shall be documented in the clinical evaluation report referred to in paragraph\u00a012 of this Article.\nThe manufacturer may not invoke any rights to the views expressed by the expert panel with regard to any future conformity assessment procedure.\n\n\n3.\u00a0\u00a0\u00a0A clinical evaluation shall follow a defined and methodologically sound procedure based on the following:\n\n\n\n\n\n\n(a)\n\n\na critical evaluation of the relevant scientific literature currently available relating to the safety, performance, design characteristics and intended purpose of the device, where the following conditions are satisfied:\n\n\n\n\n\n\n\u2014\n\n\nit is demonstrated that the device subject to clinical evaluation for the intended purpose is equivalent to the device to which the data relate, in accordance with Section\u00a03 of Annex\u00a0XIV, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe data adequately demonstrate compliance with the relevant general safety and performance requirements;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\na critical evaluation of the results of all available clinical investigations, taking duly into consideration whether the investigations were performed under Articles\u00a062 to\u00a080, any acts adopted pursuant to Article\u00a081, and Annex\u00a0XV; and\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\na consideration of currently available alternative treatment options for that purpose, if any.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0In the case of implantable devices and class III devices, clinical investigations shall be performed, except if:\n\n\n\n\n\n\n\u2014\n\n\nthe device has been designed by modifications of a device already marketed by the same manufacturer,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe modified device has been demonstrated by the manufacturer to be equivalent to the marketed device, in accordance with Section\u00a03 of Annex\u00a0XIV and this demonstration has been endorsed by the notified body, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe clinical evaluation of the marketed device is sufficient to demonstrate conformity of the modified device with the relevant safety and performance requirements.\n\n\n\n\nIn this case, the notified body shall check that the PMCF plan is appropriate and includes post market studies to demonstrate the safety and performance of the device.\nIn addition, clinical investigations need not be performed in the cases referred to in paragraph\u00a06.\n\n\n5.\u00a0\u00a0\u00a0A manufacturer of a device demonstrated to be equivalent to an already marketed device not manufactured by him, may also rely on paragraph\u00a04 in order not to perform a clinical investigation provided that the following conditions are fulfilled in addition to what is required in that paragraph:\n\n\n\n\n\n\n\u2014\n\n\nthe two manufacturers have a contract in place that explicitly allows the manufacturer of the second device full access to the technical documentation on an ongoing basis, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe original clinical evaluation has been performed in compliance with the requirements of this Regulation,\n\n\n\n\nand the manufacturer of the second device provides clear evidence thereof to the notified body.\n\n\n6.\u00a0\u00a0\u00a0The requirement to perform clinical investigations pursuant to paragraph\u00a04 shall not apply to implantable devices and class III devices:\n\n\n\n\n\n\n(a)\n\n\nwhich have been lawfully placed on the market or put into service in accordance with Directive\u00a090/385/EEC or Directive\u00a093/42/EEC and for which the clinical evaluation:\n\n\n\n\n\n\n\u2014\n\n\nis based on sufficient clinical data, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nis in compliance with the relevant product-specific CS for the clinical evaluation of that kind of device, where such a CS is available; or\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthat are sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips or connectors for which the clinical evaluation is based on sufficient clinical data and is in compliance with the relevant product-specific CS, where such a CS is available.\n\n\n\n\n\n\n7.\u00a0\u00a0\u00a0Cases in which paragraph\u00a04 is not applied by virtue of paragraph\u00a06 shall be justified in the clinical evaluation report by the manufacturer and in the clinical evaluation assessment report by the notified body.\n\n\n8.\u00a0\u00a0\u00a0Where justified in view of well-established technologies, similar to those used in the exempted devices listed in point\u00a0(b) of paragraph\u00a06 of this Article, being used in other devices, or where justified in order to protect the health and safety of patients, users or other persons or other aspects of public health, the Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 to amend the list of exempted devices referred to in the second subparagraph\u00a0of Article\u00a052(4) and in point\u00a0(b) of paragraph\u00a06 of this Article, by adding other types of implantable or class III devices to that list or removing devices therefrom.\n\n\n9.\u00a0\u00a0\u00a0In the case of the products without an intended medical purpose listed in Annex\u00a0XVI, the requirement to demonstrate a clinical benefit in accordance with this Chapter and Annexes\u00a0XIV and XV shall be understood as a requirement to demonstrate the performance of the device. Clinical evaluations of those products shall be based on relevant data concerning safety, including data from post-market surveillance, PMCF, and, where applicable, specific clinical investigation. Clinical investigations shall be performed for those products unless reliance on existing clinical data from an analogous medical device is duly justified.\n\n\n10.\u00a0\u00a0\u00a0Without prejudice to paragraph\u00a04, where the demonstration of conformity with general safety and performance requirements based on clinical data is not deemed appropriate, adequate justification for any such exception shall be given based on the results of the manufacturer's risk management and on consideration of the specifics of the interaction between the device and the human body, the clinical performance intended and the claims of the manufacturer. In such a case, the manufacturer shall duly substantiate in the technical documentation referred to in Annex\u00a0II why it considers a demonstration of conformity with general safety and performance requirements that is based on the results of non-clinical testing methods alone, including performance evaluation, bench testing and pre-clinical evaluation, to be adequate.\n\n\n11.\u00a0\u00a0\u00a0The clinical evaluation and its documentation shall be updated throughout the life cycle of the device concerned with clinical data obtained from the implementation of the manufacturer's PMCF plan in accordance with Part B of Annex\u00a0XIV and the post-market surveillance plan referred to in Article\u00a084.\nFor class III devices and implantable devices, the PMCF evaluation report and, if indicated, the summary of safety and clinical performance referred to in Article\u00a032 shall be updated at least annually with such data.\n\n\n12.\u00a0\u00a0\u00a0The clinical evaluation, its results and the clinical evidence derived from it shall be documented in a clinical evaluation report as referred to in Section\u00a04 of Annex\u00a0XIV, which, except for custom-made devices, shall be part of the technical documentation referred to in Annex\u00a0II relating to the device concerned.\n\n\n13.\u00a0\u00a0\u00a0Where necessary to ensure the uniform application of Annex\u00a0XIV, the Commission may, having due regard to technical and scientific progress, adopt implementing acts to the extent necessary to resolve issues of divergent interpretation and of practical application. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a062\n\nGeneral requirements regarding clinical investigations conducted to demonstrate conformity of devices\n\n\n1.\u00a0\u00a0\u00a0Clinical investigations shall be designed, authorised, conducted, recorded and reported in accordance with the provisions of this Article\u00a0and of Articles\u00a063 to 80, the acts adopted pursuant to Article\u00a081, and Annex\u00a0XV, where carried out as part of the clinical evaluation for conformity assessment purposes, for one or more of the following purposes:\n\n\n\n\n\n\n(a)\n\n\nto establish and verify that, under normal conditions of use, a device is designed, manufactured and packaged in such a way that it is suitable for one or more of the specific purposes listed in point\u00a0(1) of Article\u00a02, and achieves the performance intended as specified by its manufacturer;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nto establish and verify the clinical benefits of a device as specified by its manufacturer;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nto establish and verify the clinical safety of the device and to determine any undesirable side-effects, under normal conditions of use of the device, and assess whether they constitute acceptable risks when weighed against the benefits to be achieved by the device.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0Where the sponsor of a clinical investigation is not established in the Union, that sponsor shall ensure that a natural or legal person is established in the Union as its legal representative. Such legal representative shall be responsible for ensuring compliance with the sponsor's obligations pursuant to this Regulation, and shall be the addressee for all communications with the sponsor provided for in this Regulation. Any communication with that legal representative shall be deemed to be a communication with the sponsor.\nMember\u00a0States may choose not to apply the first subparagraph\u00a0to clinical investigations to be conducted solely on their territory, or on their territory and the territory of a third country, provided that they ensure that the sponsor establishes at least a contact person on their territory in respect of that clinical investigation who shall be the addressee for all communications with the sponsor provided for in this Regulation.\n\n\n3.\u00a0\u00a0\u00a0Clinical investigations shall be designed and conducted in such a way that the rights, safety, dignity and well-being of the subjects participating in a clinical investigation are protected and prevail over all other interests and the clinical data generated are scientifically valid, reliable and robust.\nClinical investigations shall be subject to scientific and ethical review. The ethical review shall be performed by an ethics committee in accordance with national law. Member\u00a0States shall ensure that the procedures for review by ethics committees are compatible with the procedures set out in this Regulation for the assessment of the application for authorisation of a clinical investigation. At least one lay person shall participate in the ethical review.\n\n\n4.\u00a0\u00a0\u00a0A clinical investigation as referred to in paragraph\u00a01 may be conducted only where all of the following conditions are met:\n\n\n\n\n\n\n(a)\n\n\nthe clinical investigation is the subject of an authorisation by the Member\u00a0State(s) in which the clinical investigation is to be conducted, in accordance with this Regulation, unless otherwise stated;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nan ethics committee, set up in accordance with national law, has not issued a negative opinion in relation to the clinical investigation, which is valid for that entire Member\u00a0State under its national law;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe sponsor, or its legal representative or a contact person pursuant to paragraph\u00a02, is established in the Union;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nvulnerable populations and subjects are appropriately protected in accordance with Articles\u00a064 to 68;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe anticipated benefits to the subjects or to public health justify the foreseeable risks and inconveniences and compliance with this condition is constantly monitored;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe subject or, where the subject is not able to give informed consent, his or her legally designated representative has given informed consent in accordance with Article\u00a063;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthe subject or, where the subject is not able to give informed consent, his or her legally designated representative, has been provided with the contact details of an entity where further information can be received in case of need;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe rights of the subject to physical and mental integrity, to privacy and to the protection of the data concerning him or her in accordance with Directive\u00a095/46/EC are safeguarded;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nthe clinical investigation has been designed to involve as little pain, discomfort, fear and any other foreseeable risk as possible for the subjects, and both the risk threshold and the degree of distress are specifically defined in the clinical investigation plan and constantly monitored;\n\n\n\n\n\n\n\n\n\n\n(j)\n\n\nthe medical care provided to the subjects is the responsibility of an appropriately qualified medical doctor or, where appropriate, a qualified dental practitioner or any other person entitled by national law to provide the relevant patient care under clinical investigation conditions;\n\n\n\n\n\n\n\n\n\n\n(k)\n\n\nno undue influence, including that of a financial nature, is exerted on the subject, or, where applicable, on his or her legally designated representatives, to participate in the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(l)\n\n\nthe investigational device(s) in question conform(s) to the applicable general safety and performance requirements set out in Annex\u00a0I apart from the aspects covered by the clinical investigation and that, with regard to those aspects, every precaution has been taken to protect the health and safety of the subjects. This includes, where appropriate, technical and biological safety testing and pre-clinical evaluation, as well as provisions in the field of occupational safety and accident prevention, taking into consideration the state of the art;\n\n\n\n\n\n\n\n\n\n\n(m)\n\n\nthe requirements of Annex\u00a0XV are fulfilled.\n\n\n\n\n\n\n5.\u00a0\u00a0\u00a0Any subject, or, where the subject is not able to give informed consent, his or her legally designated representative, may, without any resulting detriment and without having to provide any justification, withdraw from the clinical investigation at any time by revoking his or her informed consent. Without prejudice to Directive\u00a095/46/EC, the withdrawal of the informed consent shall not affect the activities already carried out and the use of data obtained based on informed consent before its withdrawal.\n\n\n6.\u00a0\u00a0\u00a0The investigator shall be a person exercising a profession which is recognised in the Member\u00a0State concerned as qualifying for the role of investigator on account of having the necessary scientific knowledge and experience in patient care. Other personnel involved in conducting a clinical investigation shall be suitably qualified, by education, training or experience in the relevant medical field and in clinical research methodology, to perform their tasks.\n\n\n7.\u00a0\u00a0\u00a0The facilities where the clinical investigation is to be conducted shall be suitable for the clinical investigation and shall be similar to the facilities where the device is intended to be used.\n\n\n\nArticle\u00a063\n\nInformed consent\n\n\n1.\u00a0\u00a0\u00a0Informed consent shall be written, dated and signed by the person performing the interview referred to in point\u00a0(c) of paragraph\u00a02, and by the subject or, where the subject is not able to give informed consent, his or her legally designated representative after having been duly informed in accordance with paragraph\u00a02. Where the subject is unable to write, consent may be given and recorded through appropriate alternative means in the presence of at least one impartial witness. In that case, the witness shall sign and date the informed consent document. The subject or, where the subject is not able to give informed consent, his or her legally designated representative shall be provided with a copy of the document or the record, as appropriate, by which informed consent has been given. The informed consent shall be documented. Adequate time shall be given for the subject or his or her legally designated representative to consider his or her decision to participate in the clinical investigation.\n\n\n2.\u00a0\u00a0\u00a0Information given to the subject or, where the subject is not able to give informed consent, his or her legally designated representative for the purposes of obtaining his or her informed consent shall:\n\n\n\n\n\n\n(a)\n\n\nenable the subject or his or her legally designated representative to understand:\n\n\n\n\n\n\n(i)\n\n\nthe nature, objectives, benefits, implications, risks and inconveniences of the clinical investigations;\n\n\n\n\n\n\n\n\n\n\n(ii)\n\n\nthe subject's rights and guarantees regarding his or her protection, in particular his or her right to refuse to participate in and the right to withdraw from the clinical investigation at any time without any resulting detriment and without having to provide any justification;\n\n\n\n\n\n\n\n\n\n\n(iii)\n\n\nthe conditions under which the clinical investigations is to be conducted, including the expected duration of the subject's participation in the clinical investigation; and\n\n\n\n\n\n\n\n\n\n\n(iv)\n\n\nthe possible treatment alternatives, including the follow-up measures if the participation of the subject in the clinical investigation is discontinued;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nbe kept comprehensive, concise, clear, relevant, and understandable to the subject or his or her legally designated representative;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nbe provided in a prior interview with a member of the investigating team who is appropriately qualified under national law;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\ninclude information about the applicable damage compensation system referred to in Article\u00a069; and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\ninclude the Union-wide unique single identification number of the clinical investigation referred to in Article\u00a070(1) and information about the availability of the clinical investigation results in accordance with paragraph\u00a06 of this Article.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0The information referred to in paragraph\u00a02 shall be prepared in writing and be available to the subject or, where the subject is not able to give informed consent, his or her legally designated representative.\n\n\n4.\u00a0\u00a0\u00a0In the interview referred to in point\u00a0(c) of paragraph\u00a02, special attention shall be paid to the information needs of specific patient populations and of individual subjects, as well as to the methods used to give the information.\n\n\n5.\u00a0\u00a0\u00a0In the interview referred to in point\u00a0(c) of paragraph\u00a02, it shall be verified that the subject has understood the information.\n\n\n6.\u00a0\u00a0\u00a0The subject shall be informed that a clinical investigation report and a summary presented in terms understandable to the intended user will be made available pursuant to Article\u00a077(5) in the electronic system on clinical investigations referred to in Article\u00a073 irrespective of the outcome of the clinical investigation, and shall be informed, to the extent possible, when they have become available.\n\n\n7.\u00a0\u00a0\u00a0This Regulation is without prejudice to national law requiring that, in addition to the informed consent given by the legally designated representative, a minor who is capable of forming an opinion and assessing the information given to him or her, shall also assent in order to participate in a clinical investigation.\n\n\n\nArticle\u00a064\n\nClinical investigations on incapacitated subjects\n\n\n1.\u00a0\u00a0\u00a0In the case of incapacitated subjects who have not given, or have not refused to give, informed consent before the onset of their incapacity, a clinical investigation may be conducted only where, in addition to the conditions set out in Article\u00a062(4), all of the following conditions are met:\n\n\n\n\n\n\n(a)\n\n\nthe informed consent of their legally designated representative has been obtained;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe incapacitated subjects have received the information referred to in Article\u00a063(2) in a way that is adequate in view of their capacity to understand it;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe explicit wish of an incapacitated subject who is capable of forming an opinion and assessing the information referred to in Article\u00a063(2) to refuse participation in, or to withdraw from, the clinical investigation at any time, is respected by the investigator;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nno incentives or financial inducements are given to subjects or their legally designated representatives, except for compensation for expenses and loss of earnings directly related to the participation in the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe clinical investigation is essential with respect to incapacitated subjects and data of comparable validity cannot be obtained in clinical investigations on persons able to give informed consent, or by other research methods;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe clinical investigation relates directly to a medical condition from which the subject suffers;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthere are scientific grounds for expecting that participation in the clinical investigation will produce a direct benefit to the incapacitated subject outweighing the risks and burdens involved.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The subject shall as far as possible take part in the informed consent procedure.\n\n\n\nArticle\u00a065\n\nClinical investigations on minors\n\nA clinical investigation on minors may be conducted only where, in addition to the conditions set out in Article\u00a062(4), all of the following conditions are met:\n\n\n\n\n\n\n(a)\n\n\nthe informed consent of their legally designated representative has been obtained;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe minors have received the information referred to in Article\u00a063(2) in a way adapted to their age and mental maturity and from investigators or members of the investigating team who are trained or experienced in working with children;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe explicit wish of a minor who is capable of forming an opinion and assessing the information referred to in Article\u00a063(2) to refuse participation in, or to withdraw from, the clinical investigation at any time, is respected by the investigator;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nno incentives or financial inducements are given to the subject or his or her legally designated representative except for compensation for expenses and loss of earnings directly related to the participation in the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe clinical investigation is intended to investigate treatments for a medical condition that only occurs in minors or the clinical investigation is essential with respect to minors to validate data obtained in clinical investigations on persons able to give informed consent or by other research methods;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe clinical investigation either relates directly to a medical condition from which the minor concerned suffers or is of such a nature that it can only be carried out on minors;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthere are scientific grounds for expecting that participation in the clinical investigation will produce a direct benefit to the minor subject outweighing the risks and burdens involved;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe minor shall take part in the informed consent procedure in a way adapted to his or her age and mental maturity;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nif during a clinical investigation the minor reaches the age of legal competence to give informed consent as defined in national law, his or her express informed consent shall be obtained before that subject can continue to participate in the clinical investigation.\n\n\n\n\n\n\nArticle\u00a066\n\nClinical investigations on pregnant or breastfeeding women\n\nA clinical investigation on pregnant or breastfeeding women may be conducted only where, in addition to the conditions set out in Article\u00a062(4), all of the following conditions are met:\n\n\n\n\n\n\n(a)\n\n\nthe clinical investigation has the potential to produce a direct benefit for the pregnant or breastfeeding woman concerned, or her embryo, foetus or child after birth, outweighing the risks and burdens involved;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nwhere research is undertaken on breastfeeding women, particular care is taken to avoid any adverse impact on the health of the child;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nno incentives or financial inducements are given to the subject except for compensation for expenses and loss of earnings directly related to the participation in the clinical investigation.\n\n\n\n\n\n\nArticle\u00a067\n\nAdditional national measures\n\nMember\u00a0States may maintain additional measures regarding persons performing mandatory military service, persons deprived of liberty, persons who, due to a judicial decision, cannot take part in clinical investigations, or persons in residential care institutions.\n\n\nArticle\u00a068\n\nClinical investigations in emergency situations\n\n\n1.\u00a0\u00a0\u00a0By way of derogation from point\u00a0(f) of Article\u00a062(4), from points (a) and (b) of Article\u00a064(1) and from points (a) and (b) of Article\u00a065, informed consent to participate in a clinical investigation may be obtained, and information on the clinical investigation may be given, after the decision to include the subject in the clinical investigation, provided that that decision is taken at the time of the first intervention on the subject, in accordance with the clinical investigation plan for that clinical investigation and that all of the following conditions are fulfilled:\n\n\n\n\n\n\n(a)\n\n\ndue to the urgency of the situation, caused by a sudden life-threatening or other sudden serious medical condition, the subject is unable to provide prior informed consent and to receive prior information on the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthere are scientific grounds to expect that participation of the subject in the clinical investigation will have the potential to produce a direct clinically relevant benefit for the subject resulting in a measurable health-related improvement alleviating the suffering and/or improving the health of the subject, or in the diagnosis of its condition;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nit is not possible within the therapeutic window to supply all prior information to and obtain prior informed consent from his or her legally designated representative;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe investigator certifies that he or she is not aware of any objections to participate in the clinical investigation previously expressed by the subject;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe clinical investigation relates directly to the subject's medical condition because of which it is not possible within the therapeutic window to obtain prior informed consent from the subject or from his or her legally designated representative and to supply prior information, and the clinical investigation is of such a nature that it may be conducted exclusively in emergency situations;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe clinical investigation poses a minimal risk to, and imposes a minimal burden on, the subject in comparison with the standard treatment of the subject's condition.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0Following an intervention pursuant to paragraph\u00a01 of this Article, informed consent in accordance with Article\u00a063 shall be sought to continue the participation of the subject in the clinical investigation, and information on the clinical investigation shall be given, in accordance with the following requirements:\n\n\n\n\n\n\n(a)\n\n\nregarding incapacitated subjects and minors, the informed consent shall be sought by the investigator from his or her legally designated representative without undue delay and the information referred to in Article\u00a063(2) shall be given as soon as possible to the subject and to his or her legally designated representative;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nregarding other subjects, the informed consent shall be sought by the investigator without undue delay from the subject or his or her legally designated representative, whichever can be done sooner, and the information referred to in Article\u00a063(2) shall be given as soon as possible to the subject or his or her legally designated representative, as applicable.\n\n\n\n\nFor the purposes of point\u00a0(b) where informed consent has been obtained from the legally designated representative, informed consent to continue the participation in the clinical investigation shall be obtained from the subject as soon as he or she is capable of giving informed consent.\n\n\n3.\u00a0\u00a0\u00a0If the subject or, where applicable, his or her legally designated representative does not give consent, he or she shall be informed of the right to object to the use of data obtained from the clinical investigation.\n\n\n\nArticle\u00a069\n\nDamage compensation\n\n\n1.\u00a0\u00a0\u00a0Member\u00a0States shall ensure that systems for compensation for any damage suffered by a subject resulting from participation in a clinical investigation conducted on their territory are in place in the form of insurance, a guarantee, or a similar arrangement that is equivalent as regards its purpose and which is appropriate to the nature and the extent of the risk.\n\n\n2.\u00a0\u00a0\u00a0The sponsor and the investigator shall make use of the system referred to in paragraph\u00a01 in the form appropriate for the Member\u00a0State in which the clinical investigation is conducted.\n\n\n\nArticle\u00a070\n\nApplication for clinical investigations\n\n\n1.\u00a0\u00a0\u00a0The sponsor of a clinical investigation shall submit an application to the Member\u00a0State(s) in which the clinical investigation is to be conducted (referred to for the purposes of this Article\u00a0as \u2018Member\u00a0State concerned\u2019) accompanied by the documentation referred to in Chapter II of Annex\u00a0XV.\nThe application shall be submitted by means of the electronic system referred to in Article\u00a073, which shall generate a Union-wide unique single identification number for the clinical investigation, which shall be used for all relevant communication in relation to that clinical investigation. Within 10 days of it receiving the application, the Member\u00a0State concerned shall notify the sponsor as to whether the clinical investigation falls within the scope of this Regulation and as to whether the application dossier is complete in accordance with Chapter II of Annex\u00a0XV.\n\n\n2.\u00a0\u00a0\u00a0Within one week of any change occurring in relation to the documentation referred to in Chapter II of Annex\u00a0XV, the sponsor shall update the relevant data in the electronic system referred to in Article\u00a073 and make that change to the documentation clearly identifiable. The Member\u00a0State concerned shall be notified of the update by means of that electronic system.\n\n\n3.\u00a0\u00a0\u00a0Where the Member\u00a0State concerned finds that the clinical investigation applied for does not fall within the scope of this Regulation or that the application dossier is not complete, it shall inform the sponsor thereof and shall set a time limit of maximum 10 days for the sponsor to comment or to complete the application by means of the electronic system referred to in Article\u00a073. The Member\u00a0State concerned may extend this period by a maximum of 20 days where appropriate.\nWhere the sponsor has not provided comments nor completed the application within the time limit referred to in the first subparagraph, the application shall be deemed to have lapsed. Where the sponsor considers the application does fall under the scope of this Regulation and/or is complete but the Member\u00a0State concerned does not, the application shall be considered to have been rejected. The Member\u00a0State concerned shall provide for an appeal procedure in respect of such refusal.\nThe Member\u00a0State concerned shall notify the sponsor within five days of receipt of the comments or of the requested additional information, whether the clinical investigation is considered as falling within the scope of this Regulation and the application is complete.\n\n\n4.\u00a0\u00a0\u00a0The Member\u00a0State concerned may also extend the period referred to in paragraph\u00a01 and\u00a03 each by a further five\u00a0days.\n\n\n5.\u00a0\u00a0\u00a0For the purposes of this Chapter, the date on which the sponsor is notified in accordance with paragraph\u00a01 or 3 shall be the validation date of the application. Where the sponsor is not notified, the validation date shall be the last day of the periods referred to in paragraphs\u00a01, 3 and 4 respectively.\n\n\n6.\u00a0\u00a0\u00a0During the period when the application is being assessed, the Member\u00a0State may request additional information from the sponsor. The expiry of the period laid down in point\u00a0(b) of paragraph\u00a07 shall be suspended from the date of the first request until such time as the additional information has been received.\n\n\n7.\u00a0\u00a0\u00a0The sponsor may start the clinical investigation in the following circumstances:\n\n\n\n\n\n\n(a)\n\n\nin the case of investigational class I devices or in the case of non-invasive class\u00a0IIa and class\u00a0IIb devices, unless otherwise stated by national law, immediately after the validation date of the application pursuant to paragraph\u00a05, and provided that a negative opinion which is valid for the entire Member\u00a0State, under national law, has not been issued by an ethics committee in the Member\u00a0State concerned in respect of the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nin the case of investigational devices, other than those referred to in point\u00a0(a), as soon as the Member\u00a0State concerned has notified the sponsor of its authorisation, and provided that a negative opinion which is valid for the entire Member\u00a0State, under national law, has not been issued by an ethics committee in the Member\u00a0State concerned in respect of the clinical investigation. The Member\u00a0State shall notify the sponsor of the authorisation within 45\u00a0days of the validation date referred to in paragraph\u00a05. The Member\u00a0State may extend this period by a further 20\u00a0days for the purpose of consulting with experts.\n\n\n\n\n\n\n8.\u00a0\u00a0\u00a0The Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 amending, in the light of technical progress and global regulatory developments, the requirements laid down in Chapter\u00a0II of Annex\u00a0XV.\n\n\n9.\u00a0\u00a0\u00a0In order to ensure the uniform application of the requirements laid down in Chapter\u00a0II of Annex\u00a0XV, the Commission may adopt implementing acts to the extent necessary to resolve issues of divergent interpretation and of practical application. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a071\n\nAssessment by Member\u00a0States\n\n\n1.\u00a0\u00a0\u00a0Member\u00a0States shall ensure that the persons validating and assessing the application, or deciding on it, do not have conflicts of interest, are independent of the sponsor, the investigators involved and of natural or legal persons financing the clinical investigation, as well as free of any other undue influence.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States shall ensure that the assessment is done jointly by an appropriate number of persons who collectively have the necessary qualifications and experience.\n\n\n3.\u00a0\u00a0\u00a0Member\u00a0States shall assess whether the clinical investigation is designed in such a way that potential remaining risks to subjects or third persons, after risk minimization, are justified, when weighed against the clinical benefits to be expected. They shall, while taking into account applicable CS or harmonised standards, examine in particular:\n\n\n\n\n\n\n(a)\n\n\nthe demonstration of compliance of the investigational device(s) with the applicable general safety and performance requirements, apart from the aspects covered by the clinical investigation, and whether, with regard to those aspects, every precaution has been taken to protect the health and safety of the subjects. This includes, where appropriate, assurance of technical and biological safety testing and pre-clinical evaluation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nwhether the risk-minimisation solutions employed by the sponsor are described in harmonised standards and, in those cases where the sponsor does not use harmonised standards, whether the risk-minimisation solutions provide a level of protection that is equivalent to that provided by harmonised standards;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nwhether the measures planned for the safe installation, putting into service and maintenance of the investigational device are adequate;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe reliability and robustness of the data generated in the clinical investigation, taking account of statistical approaches, design of the investigation and methodological aspects, including sample size, comparator and endpoints;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nwhether the requirements of Annex\u00a0XV are met;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nin the case of devices for sterile use, evidence of the validation of the manufacturer's sterilisation procedures or information on the reconditioning and sterilisation procedures which have to be conducted by the investigation site;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthe demonstration of the safety, quality and usefulness of any components of animal or human origin or of substances, which may be considered medicinal products in accordance with Directive\u00a02001/83/EC.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0Member\u00a0States shall refuse the authorisation of the clinical investigation if:\n\n\n\n\n\n\n(a)\n\n\nthe application dossier submitted pursuant to Article\u00a070(1) remains incomplete;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe device or the submitted documents, especially the investigation plan and the investigator's brochure, do not correspond to the state of scientific knowledge, and the clinical investigation, in particular, is not suitable for providing evidence for the safety, performance characteristics or benefit of the device on subjects or patients,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe requirements of Article\u00a062 are not met, or\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nany assessment under paragraph\u00a03 is negative.\n\n\n\n\nMember\u00a0States shall provide for an appeal procedure in respect of a refusal pursuant to the first subparagraph.\n\n\n\nArticle\u00a072\n\nConduct of a clinical investigation\n\n\n1.\u00a0\u00a0\u00a0The sponsor and the investigator shall ensure that the clinical investigation is conducted in accordance with the approved clinical investigation plan.\n\n\n2.\u00a0\u00a0\u00a0In order to verify that the rights, safety and well-being of subjects are protected, that the reported data are reliable and robust, and that the conduct of the clinical investigation is in compliance with the requirements of this Regulation, the sponsor shall ensure adequate monitoring of the conduct of a clinical investigation. The extent and nature of the monitoring shall be determined by the sponsor on the basis of an assessment that takes into consideration all characteristics of the clinical investigation including the following:\n\n\n\n\n\n\n(a)\n\n\nthe objective and methodology of the clinical investigation; and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe degree of deviation of the intervention from normal clinical practice.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0All clinical investigation information shall be recorded, processed, handled, and stored by the sponsor or investigator, as applicable, in such a way that it can be accurately reported, interpreted and verified while the confidentiality of records and the personal data of the subjects remain protected in accordance with the applicable law on personal data protection.\n\n\n4.\u00a0\u00a0\u00a0Appropriate technical and organisational measures shall be implemented to protect information and personal data processed against unauthorised or unlawful access, disclosure, dissemination, alteration, or destruction or accidental loss, in particular where the processing involves transmission over a network.\n\n\n5.\u00a0\u00a0\u00a0Member\u00a0States shall inspect, at an appropriate level, investigation site(s) to check that clinical investigations are conducted in accordance with the requirements of this Regulation and with the approved investigation plan.\n\n\n6.\u00a0\u00a0\u00a0The sponsor shall establish a procedure for emergency situations which enables the immediate identification and, where necessary, an immediate recall of the devices used in the investigation.\n\n\n\nArticle\u00a073\n\nElectronic system on clinical investigations\n\n\n1.\u00a0\u00a0\u00a0The Commission shall, in collaboration with the Member\u00a0States, set up, manage and maintain an electronic system:\n\n\n\n\n\n\n(a)\n\n\nto create the single identification numbers for clinical investigations referred to in Article\u00a070(1);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nto be used as an entry point for the submission of all applications or notifications for clinical investigations referred to in Articles\u00a070, 74, 75 and 78 and for all other submission of data, or processing of data in this context;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nfor the exchange of information relating to clinical investigations in accordance with this Regulation between the Member\u00a0States and between them and the Commission including the exchange of information referred to in Articles\u00a070 and\u00a076;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nfor information to be provided by the sponsor in accordance with Article\u00a077, including the clinical investigation report and its summary as required in paragraph\u00a05 of that Article;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nfor reporting on serious adverse events and device deficiencies and related updates referred to in Article\u00a080.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0When setting up the electronic system referred in paragraph\u00a01 of this Article, the Commission shall ensure that it is interoperable with the EU database for clinical trials on medicinal products for human use set up in accordance with Article\u00a081 of Regulation\u00a0(EU)\u00a0No\u00a0536/2014 of the European Parliament and of the Council\u00a0(37) as concerns combined clinical investigations of devices with a clinical trial under that Regulation.\n\n\n3.\u00a0\u00a0\u00a0The information referred to in point\u00a0(c) of paragraph\u00a01 shall only be accessible to the Member\u00a0States and the Commission. The information referred to in the other points of that paragraph\u00a0shall be accessible to the public, unless, for all or parts of that information, confidentiality of the information is justified on any of the following grounds:\n\n\n\n\n\n\n(a)\n\n\nprotection of personal data in accordance with Regulation\u00a0(EC)\u00a0No\u00a045/2001;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nprotection of commercially confidential information, especially in the investigators brochure, in particular through taking into account the status of the conformity assessment for the device, unless there is an overriding public interest in disclosure;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\neffective supervision of the conduct of the clinical investigation by the Member\u00a0State(s) concerned.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0No\u00a0personal data of subjects shall be publicly available.\n\n\n5.\u00a0\u00a0\u00a0The user interface of the electronic system referred to in paragraph\u00a01 shall be available in all official languages of the Union.\n\n\n\nArticle\u00a074\n\nClinical investigations regarding devices bearing the CE marking\n\n\n1.\u00a0\u00a0\u00a0Where a clinical investigation is to be conducted to further assess, within the scope of its intended purpose, a device which already bears the CE marking in accordance with Article\u00a020(1), (\u2018PMCF investigation\u2019), and where the investigation would involve submitting subjects to procedures additional to those performed under the normal conditions of use of the device and those additional procedures are invasive or burdensome, the sponsor shall notify the Member\u00a0States concerned at least 30 days prior to its commencement by means of the electronic system referred to in Article\u00a073. The sponsor shall include the documentation referred to in Chapter II of Annex\u00a0XV as part of the notification. Points (b) to (k) and (m) of Article\u00a062(4), Article\u00a075, Article\u00a076, Article\u00a077, Article\u00a080(5) and the relevant provisions of Annex\u00a0XV shall apply to PMCF\u00a0investigations.\n\n\n2.\u00a0\u00a0\u00a0Where a clinical investigation is to be conducted to assess, outside the scope of its intended purpose, a device which already bears the CE marking in accordance with Article\u00a020(1), Articles\u00a062 to 81 shall apply.\n\n\n\nArticle\u00a075\n\nSubstantial modifications to clinical investigations\n\n\n1.\u00a0\u00a0\u00a0If a sponsor intends to introduce modifications to a clinical investigation that are likely to have a substantial impact on the safety, health or rights of the subjects or on the robustness or reliability of the clinical data generated by the investigation, it shall notify, within one week, by means of the electronic system referred to in Article\u00a073 the Member\u00a0State(s) in which the clinical investigation is being or is to be conducted of the reasons for and the nature of those modifications. The sponsor shall include an updated version of the relevant documentation referred to in Chapter\u00a0II of Annex\u00a0XV as part of the notification. Changes to the relevant documentation shall be clearly identifiable.\n\n\n2.\u00a0\u00a0\u00a0The Member\u00a0State shall assess any substantial modification to the clinical investigation in accordance with the procedure laid down in Article\u00a071.\n\n\n3.\u00a0\u00a0\u00a0The sponsor may implement the modifications referred to in paragraph\u00a01 at the earliest 38\u00a0days after the notification referred to in that paragraph, unless:\n\n\n\n\n\n\n(a)\n\n\nthe Member\u00a0State in which the clinical investigation is being or is to be conducted has notified the sponsor of its refusal based on the grounds referred to in Article\u00a071(4) or on considerations of public health, subject and user safety or health, of public policy, or\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nan ethics committee in that Member\u00a0State has issued a negative opinion in relation to the substantial modification to the clinical investigation, which, in accordance with national law, is valid for that entire Member\u00a0State.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0The Member\u00a0State(s) concerned may extend the period referred to in paragraph\u00a03 by a further seven days, for the purpose of consulting with experts.\n\n\n\nArticle\u00a076\n\nCorrective measures to be taken by Member\u00a0States and information exchange between Member\u00a0States\n\n\n1.\u00a0\u00a0\u00a0Where a Member\u00a0State in which a clinical investigation is being or is to be conducted has grounds for considering that the requirements set out in this Regulation are not met, it may take at least any of the following measures on its territory:\n\n\n\n\n\n\n(a)\n\n\nrevoke the authorisation for the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nsuspend or terminate the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nrequire the sponsor to modify any aspect of the clinical investigation.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0Before the Member\u00a0State concerned takes any of the measures referred to in paragraph\u00a01 it shall, except where immediate action is required, ask the sponsor or the investigator or both for their opinion. That opinion shall be delivered within seven days.\n\n\n3.\u00a0\u00a0\u00a0Where a Member\u00a0State has taken a measure referred to in paragraph\u00a01 of this Article\u00a0or has refused a clinical investigation, or has been notified by the sponsor of the early termination of a clinical investigation on safety grounds, that Member\u00a0State shall communicate the corresponding decision and the grounds therefor to all Member\u00a0States and the Commission by means of the electronic system referred to in Article\u00a073.\n\n\n4.\u00a0\u00a0\u00a0Where an application is withdrawn by the sponsor prior to a decision by a Member\u00a0State, that information shall be made available through the electronic system referred to in Article\u00a073 to all Member\u00a0States and the Commission.\n\n\n\nArticle\u00a077\n\nInformation from the sponsor at the end of a clinical investigation or in the event of a temporary halt or early termination\n\n\n1.\u00a0\u00a0\u00a0If the sponsor has temporarily halted a clinical investigation or has terminated a clinical investigation early, it shall inform within 15 days the Member\u00a0State in which that clinical investigation has been temporarily halted or terminated early, through the electronic system referred to in Article\u00a073, of the temporary halt or early termination, providing a justification. In the event that the sponsor has temporarily halted or terminated early the clinical investigation on safety grounds, it shall inform all Member\u00a0States in which that clinical investigation is being conducted thereof within 24 hours.\n\n\n2.\u00a0\u00a0\u00a0The end of a clinical investigation shall be deemed to coincide with the last visit of the last subject unless another point in time for such end is set out in the clinical investigation plan.\n\n\n3.\u00a0\u00a0\u00a0The sponsor shall notify each Member\u00a0State in which a clinical investigation was being conducted of the end of that clinical investigation in that Member\u00a0State. That notification shall be made within 15 days of the end of the clinical investigation in relation to that Member\u00a0State.\n\n\n4.\u00a0\u00a0\u00a0If an investigation is conducted in more than one Member\u00a0State, the sponsor shall notify all Member\u00a0States in which that clinical investigation was conducted of the end of the clinical investigation in all Member\u00a0States. That notification shall be made within 15 days of that end of the clinical investigation.\n\n\n5.\u00a0\u00a0\u00a0Irrespective of the outcome of the clinical investigation, within one year of the end of the clinical investigation or within three months of the early termination or temporary halt, the sponsor shall submit to the Member\u00a0States in which a clinical investigation was conducted a clinical investigation report as referred to in Section\u00a02.8 of Chapter I and Section\u00a07 of Chapter III of Annex\u00a0XV.\nThe clinical investigation report shall be accompanied by a summary presented in terms that are easily understandable to the intended user. Both the report and summary shall be submitted by the sponsor by means of the electronic system referred to in Article\u00a073.\nWhere, for scientific reasons, it is not possible to submit the clinical investigation report within one year of the end of the investigation, it shall be submitted as soon as it is available. In such case, the clinical investigation plan referred to in Section\u00a03 of Chapter\u00a0II of Annex\u00a0XV shall specify when the results of the clinical investigation are going to be available, together with a justification.\n\n\n6.\u00a0\u00a0\u00a0The Commission shall issue guidelines regarding the content and structure of the summary of the clinical investigation report.\nIn addition, the Commission may issue guidelines for the formatting and sharing of raw data, for cases where the sponsor decides to share raw data on a voluntary basis. Those guidelines may take as a basis and adapt, where possible, existing guidelines for sharing of raw data in the field of clinical investigations.\n\n\n7.\u00a0\u00a0\u00a0The summary and the clinical investigation report referred to in paragraph\u00a05 of this Article\u00a0shall become publicly accessible through the electronic system referred to in Article\u00a073, at the latest when the device is registered in accordance with Article\u00a029 and before it is placed on the market. In cases of early termination or temporary halt, the summary and the report shall become publicly accessible immediately after submission.\nIf the device is not registered in accordance with Article\u00a029 within one year of the summary and the report having been entered into the electronic system pursuant to paragraph\u00a05 of this Article, they shall become publicly accessible at that point in time.\n\n\n\nArticle\u00a078\n\nCoordinated assessment procedure for clinical investigations\n\n\n1.\u00a0\u00a0\u00a0By means of the electronic system referred to in Article\u00a073, the sponsor of a clinical investigation to be conducted in more than one Member\u00a0State may submit, for the purpose of Article\u00a070, a single application that, upon receipt, is transmitted electronically to all Member\u00a0States in which the clinical investigation is to be conducted.\n\n\n2.\u00a0\u00a0\u00a0The sponsor shall propose in the single application referred to in paragraph\u00a01 that one of the Member\u00a0States in which the clinical investigation is to be conducted acts as coordinating Member\u00a0State. The Member\u00a0States in which the clinical investigation is to be conducted shall, within six days of submission of the application, agree on one of them taking the role of the coordinating Member\u00a0State. If they do not agree on a coordinating Member\u00a0State, the coordinating Member\u00a0State proposed by the sponsor shall assume that role.\n\n\n3.\u00a0\u00a0\u00a0Under the direction of the coordinating Member\u00a0State referred to in paragraph\u00a02, the Member\u00a0States concerned shall coordinate their assessment of the application, in particular of the documentation referred to in Chapter II of Annex\u00a0XV.\nHowever, the completeness of the documentation referred to in Sections 1.13, 3.1.3, 4.2, 4.3 and 4.4 of Chapter II of Annex\u00a0XV shall be assessed separately by each Member\u00a0State concerned in accordance with Article\u00a070(1) to (5).\n\n\n4.\u00a0\u00a0\u00a0With regard to documentation other than that referred to in the second subparagraph\u00a0of paragraph\u00a03, the coordinating Member\u00a0State shall:\n\n\n\n\n\n\n(a)\n\n\nwithin six days of receipt of the single application, notify the sponsor that it is the coordinating Member\u00a0State (\u2018notification date\u2019);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nfor the purpose of the validation of the application, take into account any considerations submitted within seven days of the notification date by any Member\u00a0State concerned;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nwithin 10 days of the notification date, assess whether the clinical investigation falls within the scope of this Regulation and whether the application is complete, and shall notify the sponsor accordingly. Article\u00a070(1) and (3) to (5) shall apply to the coordinating Member\u00a0State in relation to that assessment;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nestablish the results of its assessment in a draft assessment report to be transmitted within 26\u00a0days of the validation date to the Member\u00a0States concerned. By day\u00a038 after the validation date, the other Member\u00a0States concerned shall transmit their comments and proposals on the draft assessment report and the underlying application to the coordinating Member\u00a0State which shall take due account of those comments and proposals in its finalisation of the final assessment report, to be transmitted within 45\u00a0days of the validation date to the sponsor and the other Member\u00a0States concerned.\n\n\n\n\nThe final assessment report shall be taken into account by all Member\u00a0States concerned when deciding on the sponsor's application in accordance with Article\u00a070(7).\n\n\n5.\u00a0\u00a0\u00a0As regards the assessment of the documentation referred to in the second subparagraph\u00a0of paragraph\u00a03, each Member\u00a0State concerned may request, on a single occasion, additional information from the sponsor. The sponsor shall submit the requested additional information within the period set by the Member\u00a0State concerned, which shall not exceed 12\u00a0days from the receipt of the request. The expiry of the last deadline pursuant to point\u00a0(d) of paragraph\u00a04 shall be suspended from the date of the request until such time as the additional information has been received.\n\n\n6.\u00a0\u00a0\u00a0For class\u00a0IIb and class\u00a0III devices, the coordinating Member\u00a0State may also extend the periods referred to in paragraph\u00a04 by a further 50 days, for the purpose of consulting with experts.\n\n\n7.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, further specify the procedures and timescales for coordinated assessments to be taken into account by Member\u00a0States concerned when deciding on the sponsor's application. Such implementing acts may also set out the procedures and timescales for coordinated assessment in the case of substantial modifications pursuant to paragraph\u00a012 of this Article, in the case of reporting of adverse events pursuant to Article\u00a080(4) and in the case of clinical investigations of combination products between medical devices and medicinal products, where the latter are under a concurrent coordinated assessment of a clinical trial under Regulation\u00a0(EU)\u00a0No\u00a0536/2014. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n8.\u00a0\u00a0\u00a0Where the conclusion of the coordinating Member\u00a0State concerning the area of coordinated assessment is that the conduct of the clinical investigation is acceptable or acceptable subject to compliance with specific conditions, that conclusion shall be deemed to be the conclusion of all Member\u00a0States concerned.\nNotwithstanding the first subparagraph, a Member\u00a0State concerned may only disagree with the conclusion of the coordinating Member\u00a0State concerning the area of coordinated assessment on the following grounds:\n\n\n\n\n\n\n(a)\n\n\nwhen it considers that participation in the clinical investigation would lead to a subject receiving treatment inferior to that received in normal clinical practice in that Member\u00a0State concerned;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ninfringement of national law; or\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nconsiderations as regards subject safety and data reliability and robustness submitted under point\u00a0(b) of paragraph\u00a04.\n\n\n\n\nWhere one of the Member\u00a0States concerned disagrees with the conclusion on the basis of the second subparagraph\u00a0of this paragraph, it shall communicate its disagreement, together with a detailed justification, through the electronic system referred to in Article\u00a073, to the Commission, to all other Member\u00a0States concerned and to the sponsor.\n\n\n9.\u00a0\u00a0\u00a0Where the conclusion of the coordinating Member\u00a0State concerning the area of coordinated assessment is that the clinical investigation is not acceptable, that conclusion shall be deemed to be the conclusion of all Member\u00a0States concerned.\n\n\n10.\u00a0\u00a0\u00a0A Member\u00a0State concerned shall refuse to authorise a clinical investigation if it disagrees with the conclusion of the coordinating Member\u00a0State as regards any of the grounds referred to in the second subparagraph\u00a0of paragraph\u00a08, or if it finds, on duly justified grounds, that the aspects addressed in Sections 1.13, 3.1.3, 4.2, 4.3 and 4.4 of Chapter\u00a0II of Annex\u00a0XV are not complied with, or where an ethics committee has issued a negative opinion in relation to that clinical investigation, which is valid, in accordance with national law, for that entire Member\u00a0State. That Member\u00a0State shall provide for an appeal procedure in respect of such refusal.\n\n\n11.\u00a0\u00a0\u00a0Each Member\u00a0State concerned shall notify the sponsor through the electronic system referred to in Article\u00a073 as to whether the clinical investigation is authorised, whether it is authorised subject to conditions, or whether authorisation has been refused. Notification shall be done by way of one single decision within five days of the transmission, pursuant to point\u00a0(d) of paragraph\u00a04, by the coordinating Member\u00a0State of the final assessment report. Where an authorisation of a clinical investigation is subject to conditions, those conditions may only be such that, by their nature, they cannot be fulfilled at the time of that authorisation.\n\n\n12.\u00a0\u00a0\u00a0Any substantial modifications as referred to in Article\u00a075 shall be notified to the Member\u00a0States concerned by means of the electronic system referred to in Article\u00a073. Any assessment as to whether there are grounds for disagreement as referred to in the second subparagraph\u00a0of paragraph\u00a08 of this Article\u00a0shall be carried out under the direction of the coordinating Member\u00a0State, except for substantial modifications concerning Sections 1.13, 3.1.3, 4.2, 4.3 and 4.4 of Chapter II of Annex\u00a0XV, which shall be assessed separately by each Member\u00a0State concerned.\n\n\n13.\u00a0\u00a0\u00a0The Commission shall provide administrative support to the coordinating Member\u00a0State in the accomplishment of its tasks under this Chapter.\n\n\n14.\u00a0\u00a0\u00a0The procedure set out in this Article\u00a0shall, until 27 May 2027, be applied only by those of the Member\u00a0States in which the clinical investigation is to be conducted which have agreed to apply it. After 27 May 2027, all Member\u00a0States shall be required to apply that procedure.\n\n\n\nArticle\u00a079\n\nReview of coordinated assessment procedure\n\nBy 27 May 2026, the Commission shall submit to the European Parliament and to the Council a report on experience gained from the application of Article\u00a078 and, if necessary, propose a review of Article\u00a078(14) and point\u00a0(h) of Article\u00a0123(3).\n\n\nArticle\u00a080\n\nRecording and reporting of adverse events that occur during clinical investigations\n\n\n1.\u00a0\u00a0\u00a0The sponsor shall fully record all of the following:\n\n\n\n\n\n\n(a)\n\n\nany adverse event of a type identified in the clinical investigation plan as being critical to the evaluation of the results of that clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nany serious adverse event;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nany device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention had not occurred, or circumstances had been less fortunate;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nany new findings in relation to any event referred to in points (a) to (c).\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The sponsor shall report, without delay to all Member\u00a0States in which the clinical investigation is being conducted, all of the following by means of the electronic system referred to in Article\u00a073:\n\n\n\n\n\n\n(a)\n\n\nany serious adverse event that has a causal relationship with the investigational device, the comparator or the investigation procedure or where such causal relationship is reasonably possible;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nany device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention had not occurred, or circumstances had been less fortunate;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nany new findings in relation to any event referred to in points (a) and (b).\n\n\n\n\nThe period for reporting shall take account of the severity of the event. Where necessary to ensure timely reporting, the sponsor may submit an initial report that is incomplete followed up by a complete report.\nUpon request by any Member\u00a0State in which the clinical investigation is being conducted, the sponsor shall provide all information referred to in paragraph\u00a01.\n\n\n3.\u00a0\u00a0\u00a0The sponsor shall also report to the Member\u00a0States in which the clinical investigation is being conducted any event referred to in paragraph\u00a02 of this Article\u00a0that occurred in third countries in which a clinical investigation is performed under the same clinical investigation plan as the one applying to a clinical investigation covered by this Regulation by means of the electronic system referred to in Article\u00a073.\n\n\n4.\u00a0\u00a0\u00a0In the case of a clinical investigation for which the sponsor has used the single application referred to in Article\u00a078, the sponsor shall report any event as referred to in paragraph\u00a02 of this Article\u00a0by means of the electronic system referred to in Article\u00a073. Upon receipt, this report shall be transmitted electronically to all Member\u00a0States in which the clinical investigation is being conducted.\nUnder the direction of the coordinating Member\u00a0State referred to in Article\u00a078(2), the Member\u00a0States shall coordinate their assessment of serious adverse events and device deficiencies to determine whether to modify, suspend or terminate the clinical investigation or whether to revoke the authorisation for that clinical investigation.\nThis paragraph\u00a0shall not affect the rights of the other Member\u00a0States to perform their own evaluation and to adopt measures in accordance with this Regulation in order to ensure the protection of public health and patient safety. The coordinating Member\u00a0State and the Commission shall be kept informed of the outcome of any such evaluation and the adoption of any such measures.\n\n\n5.\u00a0\u00a0\u00a0In the case of PMCF investigations referred to in Article\u00a074(1), the provisions on vigilance laid down in Articles\u00a087 to 90 and in the acts adopted pursuant to Article\u00a091 shall apply instead of this Article.\n\n\n6.\u00a0\u00a0\u00a0Notwithstanding paragraph\u00a05, this Article\u00a0shall apply where a causal relationship between the serious adverse event and the preceding investigational procedure has been established.\n\n\n\nArticle\u00a081\n\nImplementing acts\n\nThe Commission may, by means of implementing acts, establish the detailed arrangements and procedural aspects necessary for the implementation of this Chapter as regards the following:\n\n\n\n\n\n\n(a)\n\n\nharmonised electronic forms for the application for clinical investigations and their assessment as referred to in Articles\u00a070 and 78, taking into account specific categories or groups of devices;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe functioning of the electronic system referred to in Article\u00a073;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nharmonised electronic forms for the notification of PMCF investigations as referred to in Article\u00a074(1), and of substantial modifications as referred to in Article\u00a075;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe exchange of information between Member\u00a0States as referred to in Article\u00a076;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nharmonised electronic forms for the reporting of serious adverse events and device deficiencies as referred to in Article\u00a080;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe timelines for the reporting of serious adverse events and device deficiencies, taking into account the severity of the event to be reported as referred to in Article\u00a080;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nuniform application of the requirements regarding the clinical evidence or data needed to demonstrate compliance with the general safety and performance requirements set out in Annex\u00a0I.\n\n\n\n\nThe implementing acts referred to in the first paragraph\u00a0shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\nArticle\u00a082\n\nRequirements regarding other clinical investigations\n\n\n1.\u00a0\u00a0\u00a0Clinical investigations, not performed pursuant to any of the purposes listed in Article\u00a062(1), shall comply with the provisions of Article\u00a062 (2) and (3), points (b), (c), (d), (f), (h), and (l) of Article\u00a062(4) and Article\u00a062(6).\n\n\n2.\u00a0\u00a0\u00a0In order to protect the rights, safety, dignity and well-being of subjects and the scientific and ethical integrity of clinical investigations not performed for any of the purposes listed in Article\u00a062(1), each Member\u00a0State shall define any additional requirements for such investigations, as appropriate for each Member\u00a0State concerned.\n\n\n\n\nCHAPTER VII\n\n\nPOST-MARKET SURVEILLANCE, VIGILANCE AND MARKET SURVEILLANCE\n\n\n\n\nSECTION 1\n\n\n\n\nPost-market surveillance\n\n\n\n\nArticle\u00a083\n\nPost-market surveillance system of the manufacturer\n\n\n1.\u00a0\u00a0\u00a0For each device, manufacturers shall plan, establish, document, implement, maintain and update a post-market surveillance system in a manner that is proportionate to the risk class and appropriate for the type of device. That system shall be an integral part of the manufacturer's quality management system referred to in Article\u00a010(9).\n\n\n2.\u00a0\u00a0\u00a0The post-market surveillance system shall be suited to actively and systematically gathering, recording and analysing relevant data on the quality, performance and safety of a device throughout its entire lifetime, and to drawing the necessary conclusions and to determining, implementing and monitoring any preventive and corrective actions.\n\n\n3.\u00a0\u00a0\u00a0Data gathered by the manufacturer's post-market surveillance system shall in particular be used:\n\n\n\n\n\n\n(a)\n\n\nto update the benefit-risk determination and to improve the risk management as referred to in Chapter I of Annex\u00a0I;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nto update the design and manufacturing information, the instructions for use and the labelling;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nto update the clinical evaluation;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nto update the summary of safety and clinical performance referred to in Article\u00a032;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nfor the identification of needs for preventive, corrective or field safety corrective action;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nfor the identification of options to improve the usability, performance and safety of the device;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nwhen relevant, to contribute to the post-market surveillance of other devices; and\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nto detect and report trends in accordance with Article\u00a088.\n\n\n\n\nThe technical documentation shall be updated accordingly.\n\n\n4.\u00a0\u00a0\u00a0If, in the course of the post-market surveillance, a need for preventive or corrective action or both is identified, the manufacturer shall implement the appropriate measures and inform the competent authorities concerned and, where applicable, the notified body. Where a serious incident is identified or a field safety corrective action is implemented, it shall be reported in accordance with Article\u00a087.\n\n\n\nArticle\u00a084\n\nPost-market surveillance plan\n\nThe post-market surveillance system referred to in Article\u00a083 shall be based on a post-market surveillance plan, the requirements for which are set out in Section\u00a01.1 of Annex\u00a0III. For devices other than custom-made devices, the post-market surveillance plan shall be part of the technical documentation specified in Annex\u00a0II.\n\n\nArticle\u00a085\n\nPost-market surveillance report\n\nManufacturers of class I devices shall prepare a post-market surveillance report summarising the results and conclusions of the analyses of the post-market surveillance data gathered as a result of the post-market surveillance plan referred to in Article\u00a084 together with a rationale and description of any preventive and corrective actions taken. The report shall be updated when necessary and made available to the competent authority upon request.\n\n\nArticle\u00a086\n\nPeriodic safety update report\n\n\n1.\u00a0\u00a0\u00a0Manufacturers of class IIa, class IIb and class III devices shall prepare a periodic safety update report (\u2018PSUR\u2019) for each device and where relevant for each category or group of devices summarising the results and conclusions of the analyses of the post-market surveillance data gathered as a result of the post-market surveillance plan referred to in Article\u00a084 together with a rationale and description of any preventive and corrective actions taken. Throughout the lifetime of the device concerned, that PSUR shall set out:\n\n\n\n\n\n\n(a)\n\n\nthe conclusions of the benefit-risk determination;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe main findings of the PMCF; and\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe volume of sales of the device and an estimate evaluation of the size and other characteristics of the population using the device and, where practicable, the usage frequency of the device.\n\n\n\n\nManufacturers of class IIb and class III devices shall update the PSUR at least annually. That PSUR shall, except in the case of custom-made devices, be part of the technical documentation as specified in Annexes\u00a0II and\u00a0III.\nManufacturers of class IIa devices shall update the PSUR when necessary and at least every two years. That PSUR shall, except in the case of custom-made devices, be part of the technical documentation as specified in Annexes\u00a0II and\u00a0III.\nFor custom-made devices, the PSUR shall be part of the documentation referred to in Section\u00a02 of Annex\u00a0XIII.\n\n\n2.\u00a0\u00a0\u00a0For class III devices or implantable devices, manufacturers shall submit PSURs by means of the electronic system referred to in Article\u00a092 to the notified body involved in the conformity assessment in accordance with Article\u00a052. The notified body shall review the report and add its evaluation to that electronic system with details of any action taken. Such PSURs and the evaluation by the notified body shall be made available to competent authorities through that electronic system.\n\n\n3.\u00a0\u00a0\u00a0For devices other than those referred to in paragraph\u00a02, manufacturers shall make PSURs available to the notified body involved in the conformity assessment and, upon request, to competent authorities.\n\n\n\n\n\nSECTION 2\n\n\n\n\nVigilance\n\n\n\n\nArticle\u00a087\n\nReporting of serious incidents and field safety corrective actions\n\n\n1.\u00a0\u00a0\u00a0Manufacturers of devices made available on the Union market, other than investigational devices, shall report, to the relevant competent authorities, in accordance with Articles\u00a092(5) and (7), the following:\n\n\n\n\n\n\n(a)\n\n\nany serious incident involving devices made available on the Union market, except expected side-effects which are clearly documented in the product information and quantified in the technical documentation and are subject to trend reporting pursuant to Article\u00a088;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nany field safety corrective action in respect of devices made available on the Union market, including any field safety corrective action undertaken in a third country in relation to a device which is also legally made available on the Union market, if the reason for the field safety corrective action is not limited to the device made available in the third country.\n\n\n\n\nThe reports referred to in the first subparagraph\u00a0shall be submitted through the electronic system referred to in Article\u00a092.\n\n\n2.\u00a0\u00a0\u00a0As a general rule, the period for the reporting referred to in paragraph\u00a01 shall take account of the severity of the serious incident.\n\n\n3.\u00a0\u00a0\u00a0Manufacturers shall report any serious incident as referred to in point\u00a0(a) of paragraph\u00a01 immediately after they have established the causal relationship between that incident and their device or that such causal relationship is reasonably possible and not later than 15\u00a0days after they become aware of the incident.\n\n\n4.\u00a0\u00a0\u00a0Notwithstanding paragraph\u00a03, in the event of a serious public health threat the report referred to in paragraph\u00a01 shall be provided immediately, and not later than 2 days after the manufacturer becomes aware of that threat.\n\n\n5.\u00a0\u00a0\u00a0Notwithstanding paragraph\u00a03, in the event of death or an unanticipated serious deterioration in a person's state of health the report shall be provided immediately after the manufacturer has established or as soon as it suspects a causal relationship between the device and the serious incident but not later than 10 days after the date on which the manufacturer becomes aware of the serious incident.\n\n\n6.\u00a0\u00a0\u00a0Where necessary to ensure timely reporting, the manufacturer may submit an initial report that is incomplete followed up by a complete report.\n\n\n7.\u00a0\u00a0\u00a0If, after becoming aware of a potentially reportable incident, the manufacturer is uncertain about whether the incident is reportable, it shall nevertheless submit a report within the timeframe required in accordance with paragraphs\u00a02 to 5.\n\n\n8.\u00a0\u00a0\u00a0Except in cases of urgency in which the manufacturer needs to undertake field safety corrective action immediately, the manufacturer shall, without undue delay, report the field safety corrective action referred to in point\u00a0(b) of paragraph\u00a01 in advance of the field safety corrective action being undertaken.\n\n\n9.\u00a0\u00a0\u00a0For similar serious incidents that occur with the same device or device type and for which the root cause has been identified or a field safety corrective action implemented or where the incidents are common and well documented, the manufacturer may provide periodic summary reports instead of individual serious incident reports, on condition that the coordinating competent authority referred to in Article\u00a089(9), in consultation with the competent authorities referred to in point\u00a0(a) of Article\u00a092(8), has agreed with the manufacturer on the format, content and frequency of the periodic summary reporting. Where a single competent authority is referred to in points (a) and (b) of Article\u00a092(8), the manufacturer may provide periodic summary reports following agreement with that competent authority.\n\n\n10.\u00a0\u00a0\u00a0The Member\u00a0States shall take appropriate measures such as organising targeted information campaigns, to encourage and enable healthcare professionals, users and patients to report to the competent authorities suspected serious incidents referred to in point\u00a0(a) of paragraph\u00a01.\nThe competent authorities shall record centrally at national level reports they receive from healthcare professionals, users and patients.\n\n\n11.\u00a0\u00a0\u00a0Where a competent authority of a Member\u00a0State obtains such reports on suspected serious incidents referred to in point\u00a0(a) of paragraph\u00a01 from healthcare professionals, users or patients, it shall take the necessary steps to ensure that the manufacturer of the device concerned is informed of the suspected serious incident without delay.\nWhere the manufacturer of the device concerned considers that the incident is a serious incident, it shall provide a report in accordance with paragraphs 1 to 5 of this Article\u00a0on that serious incident to the competent authority of the Member\u00a0State in which that serious incident occurred and shall take the appropriate follow-up action in accordance with Article\u00a089.\nWhere the manufacturer of the device concerned considers that the incident is not a serious incident or is an expected undesirable side-effect, which will be covered by trend reporting in accordance with Article\u00a088, it shall provide an explanatory statement. If the competent authority does not agree with the conclusion of the explanatory statement, it may require the manufacturer to provide a report in accordance with paragraphs 1 to 5 of this Article\u00a0and require it to ensure that appropriate follow-up action is taken in accordance with Article\u00a089.\n\n\n\nArticle\u00a088\n\nTrend reporting\n\n\n1.\u00a0\u00a0\u00a0Manufacturers shall report, by means of the electronic system referred to in Article\u00a092, any statistically significant increase in the frequency or severity of incidents that are not serious incidents or that are expected undesirable side-effects that could have a significant impact on the benefit-risk analysis referred to in Sections 1 and 5 of Annex\u00a0I and which have led or may lead to risks to the health or safety of patients, users or other persons that are unacceptable when weighed against the intended benefits. The significant increase shall be established in comparison to the foreseeable frequency or severity of such incidents in respect of the device, or category or group of devices, in question during a specific period as specified in the technical documentation and product information.\nThe manufacturer shall specify how to manage the incidents referred to in the first subparagraph\u00a0and the methodology used for determining any statistically significant increase in the frequency or severity of such incidents, as well as the observation period, in the post-market surveillance plan referred to in Article\u00a084.\n\n\n2.\u00a0\u00a0\u00a0The competent authorities may conduct their own assessments on the trend reports referred to in paragraph\u00a01 and require the manufacturer to adopt appropriate measures in accordance with this Regulation in order to ensure the protection of public health and patient safety. Each competent authority shall inform the Commission, the other competent authorities and the notified body that issued the certificate, of the results of such assessment and of the adoption of such measures.\n\n\n\nArticle\u00a089\n\nAnalysis of serious incidents and field safety corrective actions\n\n\n1.\u00a0\u00a0\u00a0Following the reporting of a serious incident pursuant to Article\u00a087(1), the manufacturer shall, without delay, perform the necessary investigations in relation to the serious incident and the devices concerned. This shall include a risk assessment of the incident and field safety corrective action taking into account criteria as referred to in paragraph\u00a03 of this Article\u00a0as appropriate.\nThe manufacturer shall co-operate with the competent authorities and where relevant with the notified body concerned during the investigations referred to in the first subparagraph\u00a0and shall not perform any investigation which involves altering the device or a sample of the batch concerned in a way which may affect any subsequent evaluation of the causes of the incident, prior to informing the competent authorities of such action.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States shall take the necessary steps to ensure that any information regarding a serious incident that has occurred within their territory, or a field safety corrective action that has been or is to be undertaken within their territory, and that is brought to their knowledge in accordance with Article\u00a087 is evaluated centrally at national level by their competent authority, if possible together with the manufacturer, and, where relevant, the notified body concerned.\n\n\n3.\u00a0\u00a0\u00a0In the context of the evaluation referred to in paragraph\u00a02, the competent authority shall evaluate the risks arising from the reported serious incident and evaluate any related field safety corrective actions, taking into account the protection of public health and criteria such as causality, detectability and probability of recurrence of the problem, frequency of use of the device, probability of occurrence of direct or indirect harm, the severity of that harm, the clinical benefit of the device, intended and potential users, and population affected. The competent authority shall also evaluate the adequacy of the field safety corrective action envisaged or undertaken by the manufacturer and the need for, and kind of, any other corrective action, in particular taking into account the principle of inherent safety contained in Annex\u00a0I.\nUpon request by the national competent authority, manufacturers shall provide all documents necessary for the risk assessment.\n\n\n4.\u00a0\u00a0\u00a0The competent authority shall monitor the manufacturer's investigation of a serious incident. Where necessary, a competent authority may intervene in a manufacturer's investigation or initiate an independent investigation.\n\n\n5.\u00a0\u00a0\u00a0The manufacturer shall provide a final report to the competent authority setting out its findings from the investigation by means of the electronic system referred to in Article\u00a092. The report shall set out conclusions and where relevant indicate corrective actions to be taken.\n\n\n6.\u00a0\u00a0\u00a0In the case of devices referred to in the first subparagraph\u00a0of Article\u00a01(8) and where the serious incident or field safety corrective action may be related to a substance which, if used separately, would be considered to be a medicinal product, the evaluating competent authority or the coordinating competent authority referred to in paragraph\u00a09 of this Article\u00a0shall, inform the national competent authority or the EMA, depending on which issued the scientific opinion on that substance under Article\u00a052(9), of that serious incident or field safety corrective action.\nIn the case of devices covered by this Regulation in accordance with point\u00a0(g) of Article\u00a01(6) and where the serious incident or field safety corrective action may be related to the derivatives of tissues or cells of human origin utilised for\u00a0the manufacture of the device, and in the case of devices falling under this Regulation pursuant to Article\u00a01(10), the\u00a0competent authority or the coordinating competent authority referred to in paragraph\u00a09 of this Article\u00a0shall inform the competent authority for human tissues and cells that was consulted by the notified body in accordance with Article\u00a052(10).\n\n\n7.\u00a0\u00a0\u00a0After carrying out the evaluation in accordance with paragraph\u00a03 of this Article, the evaluating competent authority shall, through the electronic system referred to in Article\u00a092, inform, without delay, the other competent authorities of the corrective action taken or envisaged by the manufacturer or required of it to minimise the risk of recurrence of the serious incident, including information on the underlying events and the outcome of its assessment.\n\n\n8.\u00a0\u00a0\u00a0The manufacturer shall ensure that information about the field safety corrective action taken is brought without delay to the attention of users of the device in question by means of a field safety notice. The field safety notice shall be edited in an official Union language or languages determined by the Member\u00a0State in which the field safety corrective action is taken. Except in cases of urgency, the content of the draft field safety notice shall be submitted to the evaluating competent authority or, in the cases referred to in paragraph\u00a09, to the coordinating competent authority to allow it to make comments. Unless duly justified by the situation of the individual Member\u00a0State, the content of the field safety notice shall be consistent in all Member\u00a0States.\nThe field safety notice shall allow the correct identification of the device or devices involved, in particular by including the relevant UDIs, and the correct identification, in particular, by including the SRN, if already issued, of the manufacturer that has undertaken the field safety corrective action. The field safety notice shall explain, in a clear manner, without understating the level of risk, the reasons for the field safety corrective action with reference to the device malfunction and associated risks for patients, users or other persons, and shall clearly indicate all the actions to be taken by users.\nThe manufacturer shall enter the field safety notice in the electronic system referred to in Article\u00a092 through which that notice shall be accessible to the public.\n\n\n9.\u00a0\u00a0\u00a0The competent authorities shall actively participate in a procedure in order to coordinate their assessments referred to in paragraph\u00a03 in the following cases:\n\n\n\n\n\n\n(a)\n\n\nwhere there is concern regarding a particular serious incident or cluster of serious incidents relating to the same device or type of device of the same manufacturer in more than one Member\u00a0State;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nwhere the appropriateness of a field safety corrective action that is proposed by a manufacturer in more than one Member\u00a0State is in question.\n\n\n\n\nThat coordinated procedure shall cover the following:\n\n\n\n\n\n\n\u2014\n\n\ndesignation of a coordinating competent authority on a case by case basis, when required;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndefining the coordinated assessment process, including the tasks and responsibilities of the coordinating competent authority and the involvement of other competent authorities.\n\n\n\n\nUnless otherwise agreed between the competent authorities, the coordinating competent authority shall be the competent authority of the Member\u00a0State in which the manufacturer has its registered place of business.\nThe coordinating competent authority shall, through the electronic system referred to in Article\u00a092, inform the manufacturer, the other competent authorities and the Commission that it has assumed the role of coordinating authority.\n\n\n10.\u00a0\u00a0\u00a0The designation of a coordinating competent authority shall not affect the rights of the other competent authorities to perform their own assessment and to adopt measures in accordance with this Regulation in order to ensure the protection of public health and patient safety. The coordinating competent authority and the Commission shall be kept informed of the outcome of any such assessment and the adoption of any such measures.\n\n\n11.\u00a0\u00a0\u00a0The Commission shall provide administrative support to the coordinating competent authority in the accomplishment of its tasks under this Chapter.\n\n\n\nArticle\u00a090\n\nAnalysis of vigilance data\n\nThe Commission shall, in collaboration with the Member\u00a0States, put in place systems and processes to actively monitor the data available in the electronic system referred to in Article\u00a092, in order to identify trends, patterns or signals in the data that may reveal new risks or safety concerns.\nWhere a previously unknown risk is identified or the frequency of an anticipated risk significantly and adversely changes the benefit-risk determination, the competent authority or, where appropriate, the coordinating competent authority shall inform the manufacturer, or where applicable the authorised representative, which shall then take the necessary corrective actions.\n\n\nArticle\u00a091\n\nImplementing acts\n\nThe Commission may, by means of implementing acts, and after consultation of the MDCG, adopt the detailed arrangements and procedural aspects necessary for the implementation of Articles\u00a085 to\u00a090 and 92 as regards the following:\n\n\n\n\n\n\n(a)\n\n\nthe typology of serious incidents and field safety corrective actions in relation to specific devices, or categories or groups of devices;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe reporting of serious incidents and field safety corrective actions and field safety notices, and the provision of periodic summary reports, post-market surveillance reports, PSURs and trend reports by manufacturers as referred to in Articles\u00a085, 86, 87, 88 and 89 respectively;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nstandard structured forms for electronic and non-electronic reporting, including a minimum data set for reporting of suspected serious incidents by healthcare professionals, users and patients;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\ntimelines for the reporting of field safety corrective actions, and for the provision by manufacturers of periodic summary reports and trend reports, taking into account the severity of the incident to be reported as referred to in Article\u00a087;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nharmonised forms for the exchange of information between competent authorities as referred to in Article\u00a089;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nprocedures for the designation of a coordinating competent authority; the coordinated evaluation process, including tasks and responsibilities of the coordinating competent authority and involvement of other competent authorities in this process.\n\n\n\n\nThe implementing acts referred to in the first paragraph\u00a0shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\nArticle\u00a092\n\nElectronic system on vigilance and on post-market surveillance\n\n\n1.\u00a0\u00a0\u00a0The Commission shall, in collaboration with the Member\u00a0States, set up and manage an electronic system to collate and process the following information:\n\n\n\n\n\n\n(a)\n\n\nthe reports by manufacturers on serious incidents and field safety corrective actions referred to in Article\u00a087(1) and Article\u00a089(5);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe periodic summary reports by manufacturers referred to in Article\u00a087(9);\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe reports by manufacturers on trends referred to in Article\u00a088;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe PSURs referred to in Article\u00a086;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe field safety notices by manufacturers referred to in Article\u00a089(8);\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe information to be exchanged between the competent authorities of the Member\u00a0States and between them and the Commission in accordance with Article\u00a089(7) and\u00a0(9).\n\n\n\n\nThat electronic system shall include relevant links to the UDI database.\n\n\n2.\u00a0\u00a0\u00a0The information referred to in paragraph\u00a01 of this Article\u00a0shall be made available through the electronic system to the competent authorities of the Member\u00a0States and to the Commission. The notified bodies shall also have access to that information to the extent that it relates to devices for which they issued a certificate in accordance with Article\u00a053.\n\n\n3.\u00a0\u00a0\u00a0The Commission shall ensure that healthcare professionals and the public have appropriate levels of access to the electronic system referred to in paragraph\u00a01.\n\n\n4.\u00a0\u00a0\u00a0On the basis of arrangements between the Commission and competent authorities of third countries or international organisations, the Commission may grant those competent authorities or international organisations access to the electronic system referred to in paragraph\u00a01 at the appropriate level. Those arrangements shall be based on reciprocity and make provision for confidentiality and data protection equivalent to those applicable in the Union.\n\n\n5.\u00a0\u00a0\u00a0The reports on serious incidents referred to in point\u00a0(a) of Article\u00a087(1) shall be automatically transmitted, upon receipt, via the electronic system referred to in paragraph\u00a01 of this Article, to the competent authority of the Member\u00a0State in which the incident occurred.\n\n\n6.\u00a0\u00a0\u00a0The trend reports referred to in Article\u00a088(1) shall be automatically transmitted upon receipt via the electronic system referred to in paragraph\u00a01 of this Article\u00a0to the competent authorities of the Member\u00a0State in which the incidents occurred.\n\n\n7.\u00a0\u00a0\u00a0The reports on field safety corrective actions referred to in point\u00a0(b) of Article\u00a087(1) shall be automatically transmitted upon receipt via the electronic system referred to in paragraph\u00a01 of this Article\u00a0to the competent authorities of the following Member\u00a0States:\n\n\n\n\n\n\n(a)\n\n\nthe Member\u00a0States in which the field safety corrective action is being or is to be undertaken;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe Member\u00a0State in which the manufacturer has its registered place of business.\n\n\n\n\n\n\n8.\u00a0\u00a0\u00a0The periodic summary reports referred to in Article\u00a087(9) shall be automatically transmitted upon receipt via the electronic system referred to in paragraph\u00a01 of this Article\u00a0to the competent authority of:\n\n\n\n\n\n\n(a)\n\n\nthe Member\u00a0State or Member\u00a0States participating in the coordination procedure in accordance with Article\u00a089(9) and which have agreed on the periodic summary report;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe Member\u00a0State in which the manufacturer has its registered place of business.\n\n\n\n\n\n\n9.\u00a0\u00a0\u00a0The information referred to in paragraphs 5 to 8 of this Article\u00a0shall be automatically transmitted, upon receipt, through the electronic system referred to in paragraph\u00a01 of this Article, to the notified body that issued the certificate for the device in question in accordance with Article\u00a056.\n\n\n\n\n\nSECTION 3\n\n\n\n\nMarket surveillance\n\n\n\n\nArticle\u00a093\n\nMarket surveillance activities\n\n\n1.\u00a0\u00a0\u00a0The competent authorities shall perform appropriate checks on the conformity characteristics and performance of devices including, where appropriate, a review of documentation and physical or laboratory checks on the basis of adequate samples. The competent authorities shall, in particular, take account of established principles regarding risk assessment and risk management, vigilance data and complaints.\n\n\n2.\u00a0\u00a0\u00a0The competent authorities shall draw up annual surveillance activity plans and allocate a sufficient number of material and competent human resources in order to carry out those activities taking into account the European market surveillance programme developed by the MDCG pursuant to Article\u00a0105 and local circumstances.\n\n\n3.\u00a0\u00a0\u00a0In order to fulfil the obligations laid down in paragraph\u00a01, the competent authorities:\n\n\n\n\n\n\n(a)\n\n\nmay require economic operators to, inter\u00a0alia, make available the documentation and information necessary for the purpose of carrying out the authorities' activities and, where justified, to provide the necessary samples of devices or access to devices free of charge; and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nshall carry out both announced and, if necessary, unannounced inspections of the premises of economic operators, as well as suppliers and/or subcontractors, and, where necessary, at the facilities of professional users.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0The competent authorities shall prepare an annual summary of the results of their surveillance activities and make it accessible to other competent authorities by means of the electronic system referred to in Article\u00a0100.\n\n\n5.\u00a0\u00a0\u00a0The competent authorities may confiscate, destroy or otherwise render inoperable devices that present an unacceptable risk or falsified devices where they deem it necessary to do so in the interests of the protection of public health.\n\n\n6.\u00a0\u00a0\u00a0Following each inspection carried out for the purposes referred to in paragraph\u00a01, the competent authority shall draw up a report on the findings of the inspection that concern compliance with the legal and technical requirements applicable under this Regulation. The report shall set out any corrective actions needed.\n\n\n7.\u00a0\u00a0\u00a0The competent authority which carried out the inspection shall communicate the content of the report referred to in paragraph\u00a06 of this Article\u00a0to the economic operator that has been the subject of the inspection. Before adopting the final report, the competent authority shall give that economic operator the opportunity to submit comments. That final inspection report shall be entered in the electronic system provided for in Article\u00a0100.\n\n\n8.\u00a0\u00a0\u00a0The Member\u00a0States shall review and assess the functioning of their market surveillance activities. Such reviews and assessments shall be carried out at least every four years and the results thereof shall be communicated to the other Member\u00a0States and the Commission. Each Member\u00a0State shall make a summary of the results accessible to the public by means of the electronic system referred to in Article\u00a0100.\n\n\n9.\u00a0\u00a0\u00a0The competent authorities of the Member\u00a0States shall coordinate their market surveillance activities, cooperate with each other and share with each other and with the Commission the results thereof, to provide for a harmonised and high level of market surveillance in all Member\u00a0States.\nWhere appropriate, the competent authorities of the Member\u00a0States shall agree on work-sharing, joint market surveillance activities and specialisation.\n\n\n10.\u00a0\u00a0\u00a0Where more than one authority in a Member\u00a0State is responsible for market surveillance and external border controls, those authorities shall cooperate with each other, by sharing information relevant to their role and functions.\n\n\n11.\u00a0\u00a0\u00a0Where appropriate, the competent authorities of the Member\u00a0States shall cooperate with the competent authorities of third countries with a view to exchanging information and technical support and promoting activities relating to market surveillance.\n\n\n\nArticle\u00a094\n\nEvaluation of devices suspected of presenting an unacceptable risk or other non-compliance\n\nWhere the competent authorities of a Member\u00a0State, based on data obtained by vigilance or market surveillance activities or on other information, have reason to believe that a device:\n\n\n\n\n\n\n(a)\n\n\nmay present an unacceptable risk to the health or safety of patients, users or other persons, or to other aspects of the protection of public health; or\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\notherwise does not comply with the requirements laid down in this Regulation,\n\n\n\n\nthey shall carry out an evaluation of the device concerned covering all requirements laid down in this Regulation relating to the risk presented by the device, or to any other non-compliance of the device.\nThe relevant economic operators shall cooperate with the competent authorities.\n\n\nArticle\u00a095\n\nProcedure for dealing with devices presenting an unacceptable risk to health and safety\n\n\n1.\u00a0\u00a0\u00a0Where, having performed an evaluation pursuant to Article\u00a094, the competent authorities find that the device presents an unacceptable risk to the health or safety of patients, users or other persons, or to other aspects of the protection of public health, they shall without delay require the manufacturer of the devices concerned, its authorised representative and all other relevant economic operators to take all appropriate and duly justified corrective action to bring the device into compliance with the requirements of this Regulation relating to the risk presented by the device and, in a manner that is proportionate to the nature of the risk, to restrict the making available of the device on the market, to subject the making available of the device to specific requirements, to withdraw the device from the market, or to recall it, within a reasonable period that is clearly defined and communicated to the relevant economic operator.\n\n\n2.\u00a0\u00a0\u00a0The competent authorities shall, without delay, notify the Commission, the other Member\u00a0States and, where a certificate has been issued in accordance with Article\u00a056 for the device concerned, the notified body that issued that certificate, of the results of the evaluation and of the actions which they have required the economic operators to take, by means of the electronic system referred to in Article\u00a0100.\n\n\n3.\u00a0\u00a0\u00a0The economic operators as referred to in paragraph\u00a01 shall, without delay, ensure that all appropriate corrective action is taken throughout the Union in respect of all the devices concerned that they have made available on the market.\n\n\n4.\u00a0\u00a0\u00a0Where the economic operator as referred to in paragraph\u00a01 does not take adequate corrective action within the period referred to in paragraph\u00a01, the competent authorities shall take all appropriate measures to prohibit or restrict the making available of the device on their national market, to withdraw the device from that market or to recall it.\nThe competent authorities shall notify the Commission, the other Member\u00a0States and the notified body referred to in paragraph\u00a02 of this Article, without delay, of those measures, by means of the electronic system referred to in Article\u00a0100.\n\n\n5.\u00a0\u00a0\u00a0The notification referred to in paragraph\u00a04 shall include all available details, in particular the data necessary for the identification and tracing of the non-compliant device, the origin of the device, the nature of and the reasons for the non-compliance alleged and the risk involved, the nature and duration of the national measures taken and the arguments put forward by the relevant economic operator.\n\n\n6.\u00a0\u00a0\u00a0Member\u00a0States other than the Member\u00a0State initiating the procedure shall, without delay, inform the Commission and the other Member\u00a0States, by means of the electronic system referred to in Article\u00a0100, of any additional relevant information at their disposal relating to the non-compliance of the device concerned and of any measures adopted by them in relation to the device concerned.\nIn the event of disagreement with the notified national measure, they shall, without delay, inform the Commission and the other Member\u00a0States of their objections, by means of the electronic system referred to in Article\u00a0100.\n\n\n7.\u00a0\u00a0\u00a0Where, within two months of receipt of the notification referred to in paragraph\u00a04, no objection has been raised by either a Member\u00a0State or the Commission in respect of any measures taken by a Member\u00a0State, those measures shall be deemed to be justified.\nIn that case, all Member\u00a0States shall ensure that corresponding appropriate restrictive or prohibitive measures, including withdrawing, recalling or limiting the availability of the device on their national market, are taken without delay in respect of the device concerned.\n\n\n\nArticle\u00a096\n\nProcedure for evaluating national measures at Union level\n\n\n1.\u00a0\u00a0\u00a0Where, within two months of receipt of the notification referred to in Article\u00a095(4), objections are raised by a Member\u00a0State against a measure taken by another Member\u00a0State, or where the Commission considers the measure to be contrary to Union law, the Commission shall, after consulting the competent authorities concerned and, where necessary, the economic operators concerned, evaluate that national measure. On the basis of the results of that evaluation, the Commission may decide, by means of implementing acts, whether or not the national measure is justified. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n2.\u00a0\u00a0\u00a0Where the Commission considers the national measure to be justified as referred to in paragraph\u00a01 of this Article, the second subparagraph\u00a0of Article\u00a095(7) shall apply. If the Commission considers the national measure to be unjustified, the Member\u00a0State concerned shall withdraw the measure.\nWhere the Commission does not adopt a decision pursuant to paragraph\u00a01 of this Article\u00a0within eight months of receipt of the notification referred to in Article\u00a095(4), the national measure shall be considered to be justified.\n\n\n3.\u00a0\u00a0\u00a0Where a Member\u00a0State or the Commission considers that the risk to health and safety emanating from a device cannot be mitigated satisfactorily by means of measures taken by the Member\u00a0State or Member\u00a0States concerned, the Commission, at the request of a Member\u00a0State or on its own initiative, may take, by means of implementing acts, the necessary and duly justified measures to ensure the protection of health and safety, including measures restricting or prohibiting the placing on the market and putting into service of the device concerned. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a097\n\nOther non-compliance\n\n\n1.\u00a0\u00a0\u00a0Where, having performed an evaluation pursuant to Article\u00a094, the competent authorities of a Member\u00a0State find that a device does not comply with the requirements laid down in this Regulation but does not present an unacceptable risk to the health or safety of patients, users or other persons, or to other aspects of the protection of public health, they shall require the relevant economic operator to bring the non-compliance concerned to an end within a reasonable period that is clearly defined and communicated to the economic operator and that is proportionate to the non-compliance.\n\n\n2.\u00a0\u00a0\u00a0Where the economic operator does not bring the non-compliance to an end within the period referred to in paragraph\u00a01 of this Article, the Member\u00a0State concerned shall, without delay, take all appropriate measures to restrict or prohibit the product being made available on the market or to ensure that it is recalled or withdrawn from the market. That Member\u00a0State shall inform the Commission and the other Member\u00a0States, without delay, of those measures, by means of the electronic system referred to in Article\u00a0100.\n\n\n3.\u00a0\u00a0\u00a0In order to ensure the uniform application of this Article, the Commission may, by means of implementing acts, specify appropriate measures to be taken by competent authorities to address given types of non-compliance. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a098\n\nPreventive health protection measures\n\n\n1.\u00a0\u00a0\u00a0Where a Member\u00a0State, after having performed an evaluation which indicates a potential risk related to a device or a specific category or group of devices, considers that, in order to protect the health and safety of patients, users or other persons or other aspects of public health, the making available on the market or putting into service of a device or a specific category or group of devices should be prohibited, restricted or made subject to particular requirements or that such device or category or group of devices should be withdrawn from the market or recalled, it may take any necessary and justified measures.\n\n\n2.\u00a0\u00a0\u00a0The Member\u00a0State referred to in paragraph\u00a01 shall immediately notify the Commission and all other Member\u00a0States, giving the reasons for its decision, by means of the electronic system referred to in Article\u00a0100.\n\n\n3.\u00a0\u00a0\u00a0The Commission, in consultation with the MDCG and, where necessary, the economic operators concerned, shall assess the national measures taken. The Commission may decide, by means of implementing acts, whether the national measures are justified or not. In the absence of a Commission decision within six months of their notification, the national measures shall be considered to be justified. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n4.\u00a0\u00a0\u00a0Where the assessment referred to in paragraph\u00a03 of this Article\u00a0demonstrates that the making available on the market or putting into service of a device, specific category or group of devices should be prohibited, restricted or made subject to particular requirements or that such device or category or group of devices should be withdrawn from the market or recalled in all Member\u00a0States in order to protect the health and safety of patients, users or other persons or other aspects of public health, the Commission may adopt implementing acts to take the necessary and duly justified measures. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a099\n\nGood administrative practice\n\n\n1.\u00a0\u00a0\u00a0Any measure adopted by the competent authorities of the Member\u00a0States pursuant to Articles\u00a095 to 98 shall state the exact grounds on which it is based. Where such a measure is addressed to a specific economic operator, the competent authority shall notify without delay the economic operator concerned of that measure, and shall at the same time inform that economic operator of the remedies available under the law or the administrative practice of the Member\u00a0State concerned and of the time limits to which such remedies are subject. Where the measure is of general applicability, it shall be appropriately published.\n\n\n2.\u00a0\u00a0\u00a0Except in cases where immediate action is necessary for reasons of unacceptable risk to human health or safety, the economic operator concerned shall be given the opportunity to make submissions to the competent authority within an appropriate period of time that is clearly defined before any measure is adopted.\nWhere action has been taken without the economic operator having had the opportunity to make submissions as referred to in the first subparagraph, it shall be given the opportunity to make submissions as soon as possible and the action taken shall be reviewed promptly thereafter.\n\n\n3.\u00a0\u00a0\u00a0Any measure adopted shall be immediately withdrawn or amended upon the economic operator's demonstrating that it has taken effective corrective action and that the device is in compliance with the requirements of this Regulation.\n\n\n4.\u00a0\u00a0\u00a0Where a measure adopted pursuant to Articles\u00a095 to 98 concerns a device for which a notified body has been involved in the conformity assessment, the competent authorities shall by means of the electronic system referred to in Article\u00a0100 inform the relevant notified body and the authority responsible for the notified body of the measure taken.\n\n\n\nArticle\u00a0100\n\nElectronic system on market surveillance\n\n\n1.\u00a0\u00a0\u00a0The Commission, in collaboration with the Member\u00a0States, shall set up and manage an electronic system to collate and process the following information:\n\n\n\n\n\n\n(a)\n\n\nsummaries of the results of the surveillance activities referred to in Article\u00a093(4);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe final inspection report referred to in Article\u00a093(7);\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\ninformation in relation to devices presenting an unacceptable risk to health and safety as referred to in Article\u00a095(2), (4) and (6);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\ninformation in relation to non-compliance of products as referred to in Article\u00a097(2);\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\ninformation in relation to the preventive health protection measures referred to in Article\u00a098(2);\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nsummaries of the results of the reviews and assessments of the market surveillance activities of the Member\u00a0States referred to in 93(8).\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The information referred to in paragraph\u00a01 of this Article\u00a0shall be immediately transmitted through the electronic system to all competent authorities concerned and, where applicable, to the notified body that issued a certificate in accordance with Article\u00a056 for the device concerned and be accessible to the Member\u00a0States and to the Commission.\n\n\n3.\u00a0\u00a0\u00a0Information exchanged between Member\u00a0States shall not be made public where to do so might impair market surveillance activities and co-operation between Member\u00a0States.\n\n\n\n\n\nCHAPTER VIII\n\n\nCOOPERATION BETWEEN MEMBER\u00a0STATES, MEDICAL DEVICE COORDINATION GROUP, EXPERT LABORATORIES, EXPERT PANELS AND DEVICE REGISTERS\n\n\n\nArticle\u00a0101\n\nCompetent authorities\n\nThe Member\u00a0States shall designate the competent authority or authorities responsible for the implementation of this Regulation. They shall entrust their authorities with the powers, resources, equipment and knowledge necessary for the proper performance of their tasks pursuant to this Regulation. The Member\u00a0States shall communicate the names and contact details of the competent authorities to the Commission which shall publish a list of competent authorities.\n\n\nArticle\u00a0102\n\nCooperation\n\n\n1.\u00a0\u00a0\u00a0The competent authorities of the Member\u00a0States shall cooperate with each other and with the Commission. The Commission shall provide for the organisation of exchanges of information necessary to enable this Regulation to be applied uniformly.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States shall, with the support of the Commission, participate, where appropriate, in initiatives developed at international level with the aim of ensuring cooperation between regulatory authorities in the field of medical devices.\n\n\n\nArticle\u00a0103\n\nMedical Device Coordination Group\n\n\n1.\u00a0\u00a0\u00a0A Medical Device Coordination Group (\u2018MDCG\u2019) is hereby established.\n\n\n2.\u00a0\u00a0\u00a0Each Member\u00a0State shall appoint to the MDCG, for a three-year term which may be renewed, one member and one alternate each with expertise in the field of medical devices, and one member and one alternate with expertise in the field of in vitro diagnostic medical devices. A Member\u00a0State may choose to appoint only one member and one alternate, each with expertise in both fields.\nThe members of the MDCG shall be chosen for their competence and experience in the field of medical devices and in vitro diagnostic medical devices. They shall represent the competent authorities of the Member\u00a0States. The names and affiliation of members shall be made public by the Commission.\nThe alternates shall represent and vote for the members in their absence.\n\n\n3.\u00a0\u00a0\u00a0The MDCG shall meet at regular intervals and, where the situation requires, upon request by the Commission or a Member\u00a0State. The meetings shall be attended either by the members appointed for their role and expertise in the field of medical devices, or by the members appointed for their expertise in the field of in vitro diagnostic medical devices, or by the members appointed for their expertise in both fields, or their alternates, as appropriate.\n\n\n4.\u00a0\u00a0\u00a0The MDCG shall use its best endeavours to reach consensus. If such consensus cannot be reached, the MDCG shall decide by a majority of its members. Members with diverging positions may request that their positions and the grounds on which they are based be recorded in the MDCG's position.\n\n\n5.\u00a0\u00a0\u00a0The MDCG shall be chaired by a representative of the Commission. The chair shall not take part in votes of the MDCG.\n\n\n6.\u00a0\u00a0\u00a0The MDCG may invite, on a case-by-case basis, experts and other third parties to attend meetings or provide written contributions.\n\n\n7.\u00a0\u00a0\u00a0The MDCG may establish standing or temporary sub-groups. Where appropriate, organisations representing the interests of the medical device industry, healthcare professionals, laboratories, patients and consumers at Union level shall be invited to such sub-groups in the capacity of observers.\n\n\n8.\u00a0\u00a0\u00a0The MDCG shall establish its rules of procedure which shall, in particular, lay down procedures for the following:\n\n\n\n\n\n\n\u2014\n\n\nthe adoption of opinions or recommendations or other positions, including in cases of urgency;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe delegation of tasks to reporting and co-reporting members;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe implementation of Article\u00a0107 regarding conflict of interests;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe functioning of sub-groups.\n\n\n\n\n\n\n9.\u00a0\u00a0\u00a0The MDCG shall have the tasks laid down in Article\u00a0105 of this Regulation and Article\u00a099 of Regulation (EU)\u00a02017/746.\n\n\n\nArticle\u00a0104\n\nSupport by the Commission\n\nThe Commission shall support the functioning of the cooperation between national competent authorities. It shall, in particular, provide for the organisation of exchanges of experience between the competent authorities and provide technical, scientific and logistic support to the MDCG and its sub-groups. It shall organise the meetings of the MDCG and its sub-groups, participate in those meetings and ensure the appropriate follow-up.\n\n\nArticle\u00a0105\n\nTasks of the MDCG\n\nUnder this Regulation, the MDCG shall have the following tasks:\n\n\n\n\n\n\n(a)\n\n\nto contribute to the assessment of applicant conformity assessment bodies and notified bodies pursuant to the provisions set out in Chapter IV;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nto advise the Commission, at its request, in matters concerning the coordination group of notified bodies as established pursuant to Article\u00a049;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nto contribute to the development of guidance aimed at ensuring effective and harmonised implementation of this Regulation, in particular regarding the designation and monitoring of notified bodies, application of the general safety and performance requirements and conduct of clinical evaluations and investigations by manufacturers, assessment by notified bodies and vigilance activities;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nto contribute to the continuous monitoring of technical progress and assessment of whether the general safety and performance requirements laid down in this Regulation and Regulation\u00a0(EU)\u00a02017/746 are adequate to ensure safety and performance of devices, and thereby contribute to identifying whether there is a need to amend Annex\u00a0I to this Regulation;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nto contribute to the development of device standards, of CS and of scientific guidelines, including product specific guidelines, on clinical investigation of certain devices in particular implantable devices and class III devices;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nto assist the competent authorities of the Member\u00a0States in their coordination activities in particular in the fields of classification and the determination of the regulatory status of devices, clinical investigations, vigilance and market surveillance including the development and maintenance of a framework for a European market surveillance programme with the objective of achieving efficiency and harmonisation of market surveillance in the Union, in accordance with Article\u00a093;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nto provide advice, either on its own initiative or at request of the Commission, in the assessment of any issue related to the implementation of this Regulation;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nto contribute to harmonised administrative practice with regard to devices in the Member\u00a0States.\n\n\n\n\n\n\nArticle\u00a0106\n\nProvision of scientific, technical and clinical opinions and advice\n\n\n1.\u00a0\u00a0\u00a0The Commission shall, by means of implementing acts and in consultation with the MDCG, make provision for expert panels to be designated for the assessment of the clinical evaluation in relevant medical fields as referred to in paragraph\u00a09 of this Article\u00a0and to provide views in accordance with Article\u00a048(6) of Regulation\u00a0(EU)\u00a02017/746 on the performance evaluation of certain in vitro diagnostic medical devices and, where necessary, for categories or groups of devices, or for specific hazards relating to categories or groups of devices, observing the principles of highest scientific competence, impartiality, independence and transparency. The same principles shall apply where the Commission decides to appoint expert laboratories in accordance with paragraph\u00a07 of this Article.\n\n\n2.\u00a0\u00a0\u00a0Expert panels and expert laboratories may be designated in areas where the Commission, in consultation with the MDCG, has identified a need for the provision of consistent scientific, technical and/or clinical advice or laboratory expertise in relation to the implementation of this Regulation. Expert panels and expert laboratories may be appointed on a standing or temporary basis.\n\n\n3.\u00a0\u00a0\u00a0Expert panels shall consist of advisors appointed by the Commission on the basis of up-to-date clinical, scientific or technical expertise in the field and with a geographical distribution that reflects the diversity of scientific and clinical approaches in the Union. The Commission shall determine the number of members of each panel in accordance with the requisite needs.\nThe members of expert panels shall perform their tasks with impartiality and objectivity. They shall neither seek nor take instructions from notified bodies or manufacturers. Each member shall draw up a declaration of interests, which shall be made publicly available.\nThe Commission shall establish systems and procedures to actively manage and prevent potential conflicts of interest.\n\n\n4.\u00a0\u00a0\u00a0Expert panels shall take into account relevant information provided by stakeholders including patients' organisations and healthcare professionals when preparing their scientific opinions.\n\n\n5.\u00a0\u00a0\u00a0The Commission, following consultation with the MDCG, may appoint advisors to expert panels following publication in the Official Journal of the European Union and on the Commission website following a call for expressions of interest. Depending on the type of task and the need for specific expertise, advisors may be appointed to the expert panels for a maximum period of three years and their appointment may be renewed.\n\n\n6.\u00a0\u00a0\u00a0The Commission, following consultation with the MDCG, may include advisors on a central list of available experts who, whilst not being formally appointed to a panel, are available to provide advice and to support the work of the expert panel as needed. That list shall be published on the Commission website.\n\n\n7.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts and following consultation with the MDCG, designate expert laboratories, on the basis of their expertise in:\n\n\n\n\n\n\n\u2014\n\n\nphysico-chemical characterisation, or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmicrobiological, biocompatibility, mechanical, electrical, electronic or non-clinical biological and toxicological testing\n\n\n\n\nof specific devices, categories or groups of devices.\nThe Commission shall only designate expert laboratories for which a Member\u00a0State or the Joint Research Centre has submitted an application for designation.\n\n\n8.\u00a0\u00a0\u00a0Expert laboratories shall satisfy the following criteria:\n\n\n\n\n\n\n(a)\n\n\nhave adequate and appropriately qualified staff with adequate knowledge and experience in the field of the devices for which they are designated;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\npossess the necessary equipment to carry out the tasks assigned to them;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nhave the necessary knowledge of international standards and best practices;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nhave an appropriate administrative organisation and structure;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nensure that their staff observe the confidentiality of information and data obtained in carrying out their tasks.\n\n\n\n\n\n\n9.\u00a0\u00a0\u00a0Expert panels appointed for clinical evaluation in relevant medical fields shall fulfil the tasks provided for in Article\u00a054(1) and Article\u00a061(2) and Section\u00a05.1 of Annex\u00a0IX or Section\u00a06 of Annex\u00a0X, as applicable.\n\n\n10.\u00a0\u00a0\u00a0Expert panels and expert laboratories may have the following tasks, depending on the requisite needs:\n\n\n\n\n\n\n(a)\n\n\nto provide scientific, technical and clinical assistance to the Commission and the MDCG in relation to the implementation of this Regulation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nto contribute to the development and maintenance of appropriate guidance and CS for:\n\n\n\n\n\n\n\u2014\n\n\nclinical investigations,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclinical evaluation and PMCF,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nperformance studies,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nperformance evaluation and post-market performance follow-up,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nphysico-chemical characterisation, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmicrobiological, biocompatibility, mechanical, electrical, electronic or non-clinical toxicological testing\n\n\n\n\nfor specific devices, or a category or group of devices, or for specific hazards related to a category or group of devices;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nto develop and review clinical evaluation guidance and performance evaluation guidance for performance of conformity assessment in line with the state of the art with regard to clinical evaluation, performance evaluation, physico-chemical characterisation, and microbiological, biocompatibility, mechanical, electrical, electronic or non-clinical toxicological testing;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nto contribute to the development of standards at international level, ensuring that such standards reflect the state of the art;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nto provide opinions in response to consultations by manufacturers in accordance with Article\u00a061(2), notified bodies and Member\u00a0States in accordance with paragraphs\u00a011 to 13 of this Article.\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nto contribute to identification of concerns and emerging issues on the safety and performance of medical devices;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nto provide views in accordance with Article\u00a048(4) of Regulation\u00a0(EU)\u00a02017/746 on the performance evaluation of certain in vitro diagnostic medical devices.\n\n\n\n\n\n\n11.\u00a0\u00a0\u00a0The Commission, shall facilitate the access of Member\u00a0States and notified bodies and manufacturers to advice provided by expert panels and expert laboratories concerning, inter\u00a0alia, the criteria for an appropriate data set for assessment of the conformity of a device, in particular with regard to the clinical data required for clinical evaluation, with regard to physico-chemical characterisation, and with regard to microbiological, biocompatibility, mechanical, electrical, electronic and non-clinical toxicological testing.\n\n\n12.\u00a0\u00a0\u00a0When adopting its scientific opinion in accordance with paragraph\u00a09, the members of the expert panels shall use their best endeavours to reach consensus. If consensus cannot be reached, the expert panels shall decide by a majority of their members, and the scientific opinion shall mention the divergent positions and the grounds on which they are based.\nThe Commission shall publish the scientific opinion and advice delivered in accordance with paragraphs 9 and 11 of this Article, ensuring consideration of aspects of confidentiality as set out in Article\u00a0109. The clinical evaluation guidance referred to in point\u00a0(c) of paragraph\u00a010 shall be published following consultation with the MDCG.\n\n\n13.\u00a0\u00a0\u00a0The Commission may require manufacturers and notified bodies to pay fees for the advice provided by expert panels and expert laboratories. The structure and the level of fees as well as the scale and structure of recoverable costs shall be adopted by the Commission by means of implementing acts, taking into account the objectives of the adequate implementation of this Regulation, protection of health and safety, support of innovation and cost-effectiveness and the necessity to achieve active participation in the expert panels. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n14.\u00a0\u00a0\u00a0The fees payable to the Commission in accordance with the procedure under paragraph\u00a013 of this Article\u00a0shall be set in a transparent manner and on the basis of the costs for the services provided. The fees payable shall be reduced in the case of a clinical evaluation consultation procedure initiated in accordance with point\u00a0(c) of Section\u00a05.1 of Annex\u00a0IX involving a manufacturer who is a micro, small or medium-sized enterprise within the meaning of Recommendation\u00a02003/361/EC.\n\n\n15.\u00a0\u00a0\u00a0The Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 to amend the tasks of expert panels and expert laboratories referred to in paragraph\u00a010 of this Article.\n\n\n\nArticle\u00a0107\n\nConflict of interests\n\n\n1.\u00a0\u00a0\u00a0Members of the MDCG, its sub-groups, and members of expert panels and expert laboratories shall not have financial or other interests in the medical device industry which could affect their impartiality. They shall undertake to act in the public interest and in an independent manner. They shall declare any direct or indirect interests they may have in the medical device industry and update that declaration whenever a relevant change occurs. The declaration of interests shall be made publicly available on the Commission website. This Article\u00a0shall not apply to the representatives of stakeholder organisations participating in the sub-groups of the MDCG.\n\n\n2.\u00a0\u00a0\u00a0Experts and other third parties invited by the MDCG on a case-by-case basis shall declare any interests they may have in the issue in question.\n\n\n\nArticle\u00a0108\n\nDevice registers and databanks\n\nThe Commission and the Member\u00a0States shall take all appropriate measures to encourage the establishment of registers and databanks for specific types of devices setting common principles to collect comparable information. Such registers and databanks shall contribute to the independent evaluation of the long-term safety and performance of devices, or the traceability of implantable devices, or all of such characteristics.\n\n\n\nCHAPTER IX\n\n\nCONFIDENTIALITY, DATA PROTECTION, FUNDING AND PENALTIES\n\n\n\nArticle\u00a0109\n\nConfidentiality\n\n\n1.\u00a0\u00a0\u00a0Unless otherwise provided for in this Regulation and without prejudice to existing national provisions and practices in the Member\u00a0States on confidentiality, all parties involved in the application of this Regulation shall respect the confidentiality of information and data obtained in carrying out their tasks in order to protect the following:\n\n\n\n\n\n\n(a)\n\n\npersonal data, in accordance with Article\u00a0110;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ncommercially confidential information and trade secrets of a natural or legal person, including intellectual property rights; unless disclosure is in the public interest;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe effective implementation of this Regulation, in particular for the purpose of inspections, investigations or audits.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0Without prejudice to paragraph\u00a01, information exchanged on a confidential basis between competent authorities and between competent authorities and the Commission shall not be disclosed without the prior agreement of the originating authority.\n\n\n3.\u00a0\u00a0\u00a0Paragraphs 1 and 2 shall not affect the rights and obligations of the Commission, Member\u00a0States and notified bodies with regard to exchange of information and the dissemination of warnings, nor the obligations of the persons concerned to provide information under criminal law.\n\n\n4.\u00a0\u00a0\u00a0The Commission and Member\u00a0States may exchange confidential information with regulatory authorities of third countries with which they have concluded bilateral or multilateral confidentiality arrangements.\n\n\n\nArticle\u00a0110\n\nData protection\n\n\n1.\u00a0\u00a0\u00a0Member\u00a0States shall apply Directive\u00a095/46/EC to the processing of personal data carried out in the Member\u00a0States pursuant to this Regulation.\n\n\n2.\u00a0\u00a0\u00a0Regulation\u00a0(EC)\u00a0No\u00a045/2001 shall apply to the processing of personal data carried out by the Commission pursuant to this Regulation.\n\n\n\nArticle\u00a0111\n\nLevying of fees\n\n\n1.\u00a0\u00a0\u00a0This Regulation shall be without prejudice to the possibility for Member\u00a0States to levy fees for the activities set out in this Regulation, provided that the level of the fees is set in a transparent manner and on the basis of cost-recovery principles.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States shall inform the Commission and the other Member\u00a0States at least three months before the structure and level of fees is to be adopted. The structure and level of fees shall be made publicly available on request.\n\n\n\nArticle\u00a0112\n\nFunding of activities related to designation and monitoring of notified bodies\n\nThe costs associated with joint assessment activities shall be covered by the Commission. The Commission shall, by means of implementing acts, lay down the scale and structure of recoverable costs and other necessary implementing rules. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\nArticle\u00a0113\n\nPenalties\n\nThe Member\u00a0States shall lay down the rules on penalties applicable for infringement of the provisions of this Regulation and shall take all measures necessary to ensure that they are implemented. The penalties provided for shall be effective, proportionate, and dissuasive. The Member\u00a0States shall notify the Commission of those rules and of those measures by 25 February 2020 and shall notify it, without delay, of any subsequent amendment affecting them.\n\n\n\nCHAPTER X\n\n\nFINAL PROVISIONS\n\n\n\nArticle\u00a0114\n\nCommittee procedure\n\n\n1.\u00a0\u00a0\u00a0The Commission shall be assisted by a Committee on Medical Devices. That Committee shall be a committee within the meaning of Regulation\u00a0(EU)\u00a0No\u00a0182/2011.\n\n\n2.\u00a0\u00a0\u00a0Where reference is made to this paragraph, Article\u00a04 of Regulation\u00a0(EU)\u00a0No\u00a0182/2011 shall apply.\n\n\n3.\u00a0\u00a0\u00a0Where reference is made to this paragraph, Article\u00a05 of Regulation\u00a0(EU)\u00a0No\u00a0182/2011 shall apply.\nWhere the committee delivers no opinion, the Commission shall not adopt the draft implementing act and the third subparagraph\u00a0of Article\u00a05(4) of Regulation\u00a0(EU)\u00a0No\u00a0182/2011 shall apply.\n\n\n4.\u00a0\u00a0\u00a0Where reference is made to this paragraph, Article\u00a08 of Regulation\u00a0(EU)\u00a0No\u00a0182/2011, in conjunction with Article\u00a04 or 5 thereof, as appropriate, shall apply.\n\n\n\nArticle\u00a0115\n\nExercise of the delegation\n\n\n1.\u00a0\u00a0\u00a0The power to adopt delegated acts is conferred on the Commission subject to the conditions laid down in this Article.\n\n\n2.\u00a0\u00a0\u00a0The power to adopt delegated acts referred to in Articles\u00a01(5), 3, 10(4), 18(3), 19(4), 27(10), 44(11), 52(5), 56(6), 61(8), 70(8) and 106(15) shall be conferred on the Commission for a period of five years from 25 May 2017. The Commission shall draw up a report in respect of the delegation of power not later than nine months before the end of the five-year period. The delegation of power shall be tacitly extended for periods of an identical duration, unless the European Parliament or the Council opposes such extension not later than three months before the end of each period.\n\n\n3.\u00a0\u00a0\u00a0The delegation of power referred to in Articles\u00a01(5), 3, 10(4), 18(3), 19(4), 27(10), 44(11), 52(5), 56(6), 61(8), 70(8) and 106(15) may be revoked at any time by the European Parliament or by the Council. A decision to revoke shall put an end to the delegation of the power specified in that decision. It shall take effect the day following the publication of the decision in the Official Journal of the European Union or at a later date specified therein. It shall not affect the validity of any delegated acts already in force.\n\n\n4.\u00a0\u00a0\u00a0Before adopting a delegated act, the Commission shall consult experts designated by each Member\u00a0State in accordance with the principles laid down in the Interinstitutional Agreement of 13 April 2016 on Better Law-Making.\n\n\n5.\u00a0\u00a0\u00a0As soon as it adopts a delegated act, the Commission shall notify it simultaneously to the European Parliament and to the Council.\n\n\n6.\u00a0\u00a0\u00a0A delegated act adopted pursuant to Articles\u00a01(5), 3, 10(4), 18(3), 19(4), 27(10), 44(11), 52(5), 56(6), 61(8), 70(8) and 106(15) shall enter into force only if no objection has been expressed either by the European Parliament or by the Council within a period of three months of notification of that act to the European Parliament and the Council or if, before the expiry of that period, the European Parliament and the Council have both informed the Commission that they will not object. That period shall be extended by three months at the initiative of the European Parliament or of the Council.\n\n\n\nArticle\u00a0116\n\nSeparate delegated acts for different delegated powers\n\nThe Commission shall adopt a separate delegated act in respect of each power delegated to it pursuant to this Regulation.\n\n\nArticle\u00a0117\n\nAmendment to Directive\u00a02001/83/EC\n\nIn Annex\u00a0I to Directive\u00a02001/83/EC, point 12 of Section\u00a03.2. is replaced by the following:\n\n\n\n\n\n\n\n\u2018(12)\n\n\nWhere, in accordance with the second subparagraph\u00a0of Article\u00a01(8) or the second subparagraph\u00a0of Article\u00a01(9) of Regulation\u00a0(EU)\u00a02017/745 of the European Parliament and of the Council\u00a0(*1), a product is governed by this Directive, the marketing authorisation dossier shall include, where available, the results of the assessment of the conformity of the device part with the relevant general safety and performance requirements set out in Annex\u00a0I to that Regulation contained in the manufacturer's EU declaration of conformity or the relevant certificate issued by a notified body allowing the manufacturer to affix a CE\u00a0marking to the medical device.\nIf the dossier does not include the results of the conformity assessment referred to in the first subparagraph\u00a0and where for the conformity assessment of the device, if used separately, the involvement of a notified body is required in accordance with Regulation\u00a0(EU)\u00a02017/745, the authority shall require the applicant to provide an opinion on the conformity of the device part with the relevant general safety and performance requirements set out in Annex\u00a0I to that Regulation issued by a notified body designated in accordance with that Regulation for the type of device in question.\n\n\n\n\n\n\n\nArticle\u00a0118\n\nAmendment to Regulation\u00a0(EC)\u00a0No\u00a0178/2002\n\nIn the third paragraph\u00a0of Article\u00a02 of Regulation\u00a0(EC)\u00a0No\u00a0178/2002, the following point is added:\n\n\n\n\n\n\n\n\u2018(i)\n\n\nmedical devices within the meaning of Regulation\u00a0(EU)\u00a02017/745 of the European Parliament and of the Council\u00a0(*2).\n\n\n\n\n\n\n\nArticle\u00a0119\n\nAmendment to Regulation\u00a0(EC)\u00a0No\u00a01223/2009\n\nIn Article\u00a02 of Regulation\u00a0(EC)\u00a0No\u00a01223/2009, the following paragraph\u00a0is added:\n\n\n\u20184.\u00a0\u00a0\u00a0The Commission may, at the request of a Member\u00a0State or on its own initiative, adopt the necessary measures to determine whether or not a specific product or group of products falls within the definition \u2018cosmetic product\u2019. Those measures shall be adopted in accordance with the regulatory procedure referred to in Article\u00a032(2).\u2019.\n\n\n\n\nArticle\u00a0120\n\nTransitional provisions\n\n\n1.\u00a0\u00a0\u00a0From 26 May 2020, any publication of a notification in respect of a notified body in accordance with Directives\u00a090/385/EEC and 93/42/EEC shall become void.\n\n\n2.\u00a0\u00a0\u00a0Certificates issued by notified bodies in accordance with Directives\u00a090/385/EEC and 93/42/EEC prior to 25 May 2017 shall remain valid until the end of the period indicated on the certificate, except for certificates issued in accordance with Annex\u00a04 to Directive\u00a090/385/EEC or Annex\u00a0IV to Directive\u00a093/42/EEC which shall become void at the latest on 27 May 2022.\nCertificates issued by notified bodies in accordance with Directives\u00a090/385/EEC and 93/42/EEC from 25 May 2017 shall remain valid until the end of the period indicated on the certificate, which shall not exceed five years from its issuance. They shall however become void at the latest on 27 May 2024.\n\n\n3.\u00a0\u00a0\u00a0By way of derogation from Article\u00a05 of this Regulation, a device with a certificate that was issued in accordance with Directive\u00a090/385/EEC or Directive\u00a093/42/EEC and which is valid by virtue of paragraph\u00a02 of this Article\u00a0may only be placed on the market or put into service provided that from the date of application of this Regulation it continues to comply with either of those Directives, and provided there are no significant changes in the design and intended purpose. However, the requirements of this Regulation relating to post-market surveillance, market surveillance, vigilance, registration of economic operators and of devices shall apply in place of the corresponding requirements in those\u00a0Directives.\nWithout prejudice to Chapter\u00a0IV and paragraph\u00a01 of this Article, the notified body that issued the certificate referred to in the first subparagraph\u00a0shall continue to be responsible for the appropriate surveillance in respect of all of the applicable requirements relating to the devices it has certified.\n\n\n4.\u00a0\u00a0\u00a0Devices lawfully placed on the market pursuant to Directives\u00a090/385/EEC and 93/42/EEC prior to 26 May 2020, and devices placed on the market from 26 May 2020 by virtue of a certificate as referred to in paragraph\u00a02 of this Article, may continue to be made available on the market or put into service until 27 May 2025.\n\n\n5.\u00a0\u00a0\u00a0By way of derogation from Directives\u00a090/385/EEC and 93/42/EEC, devices which comply with this Regulation may be placed on the market prior to 26 May 2020.\n\n\n6.\u00a0\u00a0\u00a0By way of derogation from Directives\u00a090/385/EEC and 93/42/EEC, conformity assessment bodies which comply with this Regulation may be designated and notified prior 26 May 2020. Notified bodies which are designated and notified in accordance with this Regulation may carry out the conformity assessment procedures laid down in this Regulation and issue certificates in accordance with this Regulation prior to 26 May 2020.\n\n\n7.\u00a0\u00a0\u00a0As regards devices subject to the consultation procedure laid down in Article\u00a054, paragraph\u00a05 of this Article\u00a0shall apply provided that the necessary appointments to the MDCG and expert panels have been made.\n\n\n8.\u00a0\u00a0\u00a0By way of derogation from Article\u00a010a and point\u00a0(a) of Article\u00a010b(1) of Directive\u00a090/385/EEC and Article\u00a014(1) and (2) and points (a) and (b) of Article\u00a014a(1) of Directive\u00a093/42/EEC, manufacturers, authorised representatives, importers and notified bodies which, during the period starting on the later of the dates referred to point\u00a0(d) of Article\u00a0123(3) and ending 18 months later, comply with Article\u00a029(4) and Article\u00a056(5) of this Regulation shall be considered to comply with the laws and regulations adopted by Member\u00a0States in accordance with, respectively, Article\u00a010a of Directive\u00a090/385/EEC or Article\u00a014(1) and (2) of Directive\u00a093/42/EEC and with, respectively, point\u00a0(a) of Article\u00a010b(1) of Directive\u00a090/385/EEC or points (a) and (b) of Article\u00a014a(1) of Directive\u00a093/42/EEC as specified in Decision 2010/227/EU.\n\n\n9.\u00a0\u00a0\u00a0Authorisations granted by the competent authorities of the Member\u00a0States in accordance with Article\u00a09(9) of Directive\u00a090/385/EEC or Article\u00a011(13) of Directive\u00a093/42/EEC shall keep the validity indicated in the authorisation.\n\n\n10.\u00a0\u00a0\u00a0Devices falling within the scope of this Regulation in accordance with points (f) and (g) of Article\u00a01(6) which have been legally placed on the market or put into service in accordance with the rules in force in the Member\u00a0States prior to 26 May 2020 may continue to be placed on the market and put into service in the Member\u00a0States concerned.\n\n\n11.\u00a0\u00a0\u00a0Clinical investigations which have started to be conducted in accordance with Article\u00a010 of Directive\u00a090/385/EEC or Article\u00a015 of Directive\u00a093/42/EEC prior to 26 May 2020 may continue to be conducted. As of 26 May 2020, however, the reporting of serious adverse events and device deficiencies shall be carried out in accordance with this Regulation.\n\n\n12.\u00a0\u00a0\u00a0Until the Commission has designated, pursuant to Article\u00a027(2), issuing entities, GS1, HIBCC and ICCBBA shall be considered to be designated issuing entities.\n\n\n\nArticle\u00a0121\n\nEvaluation\n\nBy 27 May 2027, the Commission shall assess the application of this Regulation and produce an evaluation report on the progress towards achievement of the objectives contained herein including an assessment of the resources required to implement this Regulation. Special attention shall be given to the traceability of medical devices through the storage, pursuant to Article\u00a027, of the UDI by economic operators, health institutions and health professionals.\n\n\nArticle\u00a0122\n\nRepeal\n\nWithout prejudice to Articles\u00a0120(3) and (4) of this Regulation, and without prejudice to the obligations of the Member\u00a0States and manufacturers as regards vigilance and to the obligations of manufacturers as regards the making available of documentation, under Directives\u00a090/385/EEC and 93/42/EEC, those Directives are repealed with effect from 26 May 2020, with the exception of:\n\n\n\n\n\n\n\u2014\n\n\nArticles\u00a08 and 10, points (b) and (c) of Article\u00a010b(1), Article\u00a010b(2) and Article\u00a010b(3) of Directive\u00a090/385/EEC, and the obligations relating to vigilance and clinical investigations provided for in the corresponding Annexes, which are repealed with effect from the later of the dates referred to in point\u00a0(d) of Article\u00a0123(3) of this Regulation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a010a and point\u00a0(a) of Article\u00a010b(1) of Directive\u00a090/385/EEC, and the obligations relating to registration of devices and economic operators, and to certificate notifications, provided for in the corresponding Annexes, which are repealed with effect from 18\u00a0months after the later of the dates referred to in point\u00a0(d) of Article\u00a0123(3) of this Regulation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a010, points (c) and (d) of Article\u00a014a(1), Article\u00a014a(2), Article\u00a014a(3) and Article\u00a015 of Directive\u00a093/42/EEC, and the obligations relating to vigilance and clinical investigations provided for in the corresponding Annexes, which are repealed with effect from the later of the dates referred to in point\u00a0(d) of Article\u00a0123(3) of this Regulation; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a014(1) and (2) and points (a) and (b) of Article\u00a014a(1) of Directive\u00a093/42/EEC, and the obligations relating to registration of devices and economic operators, and to certificate notifications, provided for in the corresponding Annexes, which are repealed with effect from 18 months after the later of the dates referred to in point\u00a0(d) of Article\u00a0123(3) of this Regulation.\n\n\n\n\nAs regards the devices referred to in Article\u00a0120 (3) and (4) of this Regulation, the Directives referred to in the first\u00a0paragraph\u00a0shall continue to apply until 27 May 2025 to the extent necessary for the application of those paragraphs.\nNotwithstanding the first paragraph, Regulations (EU)\u00a0No\u00a0207/2012 and (EU)\u00a0No\u00a0722/2012 shall remain in force and continue to apply unless and until repealed by implementing acts adopted by the Commission pursuant to this Regulation.\nReferences to the repealed Directives shall be understood as references to this Regulation and shall be read in accordance with the correlation table laid down in Annex\u00a0XVII to this Regulation.\n\n\nArticle\u00a0123\n\nEntry into force and date of application\n\n\n1.\u00a0\u00a0\u00a0This Regulation shall enter into force on the twentieth day following that of its publication in the Official Journal of the European Union.\n\n\n2.\u00a0\u00a0\u00a0It shall apply from 26 May 2020.\n\n\n3.\u00a0\u00a0\u00a0By way of derogation from paragraph\u00a02:\n\n\n\n\n\n\n(a)\n\n\nArticles\u00a035 to 50 shall apply from 26 November 2017. However, from that date until 26 May 2020, the obligations on notified bodies pursuant to Articles\u00a035 to 50 shall apply only to those bodies which submit an application for designation in accordance with Article\u00a038;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nArticles\u00a0101 and 103 shall apply from 26 November 2017;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nArticle\u00a0102 shall apply from 26 May 2018;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nwithout prejudice to the obligations on the Commission pursuant to Article\u00a034, where, due to circumstances that could not reasonably have been foreseen when drafting the plan referred to in Article\u00a034(1), Eudamed is not fully functional on 26\u00a0May 2020, the obligations and requirements that relate to Eudamed shall apply from the date corresponding to six\u00a0months after the date of publication of the notice referred to in Article\u00a034(3). The provisions referred to in the preceding sentence are:\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a029,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a031,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a032,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a033(4),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe second sentence of Article\u00a040(2),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a042(10),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a043(2),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe second subparagraph\u00a0of Article\u00a044(12),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npoints (d) and (e) of Article\u00a046(7),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a053(2),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a054(3),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a055(1),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticles\u00a070 to 77,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nparagraphs 1 to 13 of Article\u00a078,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticles\u00a079 to 82,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a086(2),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticles\u00a087 and 88,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a089(5) and (7), and the third subparagraph\u00a0of Article\u00a089(8),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a090,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a093(4), (7) and (8),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a095(2) and (4),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe last sentence of Article\u00a097(2),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a099(4),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe second sentence of the first subparagraph\u00a0of Article\u00a0120(3).\n\n\n\n\nUntil Eudamed is fully functional, the corresponding provisions of Directives\u00a090/385/EEC and 93/42/EEC shall continue to apply for the purpose of meeting the obligations laid down in the provisions listed in the first paragraph\u00a0of this point regarding exchange of information including, and in particular, information regarding vigilance reporting, clinical investigations, registration of devices and economic operators, and certificate notifications.\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nArticle\u00a029(4) and Article\u00a056(5) shall apply from 18 months after the later of the dates referred to in point\u00a0(d);\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nfor implantable devices and for class III devices Article\u00a027(4) shall apply from 26\u00a0May 2021. For class\u00a0IIa and class\u00a0IIb devices Article\u00a027(4) shall apply from 26\u00a0May 2023. For class I devices Article\u00a027(4) shall apply from 26\u00a0May 2025;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nfor reusable devices that shall bear the UDI carrier on the device itself, Article\u00a027(4) shall apply from two years after the date referred to in point\u00a0(f) of this paragraph\u00a0for the respective class of devices in that point;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nThe procedure set out in Article\u00a078 shall apply from 26 May 2027, without prejudice to Article\u00a078(14);\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nArticle\u00a0120(12) shall apply from 26 May 2019.\n\n\n\n\n\n\n\n\n\n\nThis Regulation shall be binding in its entirety and directly applicable in all Member\u00a0States.\nDone at Strasbourg, 5 April 2017.\n\n\nFor the European Parliament\n\n\nThe President\n\nA. TAJANI\n            \n\n\n\nFor the Council\n\n\nThe President\n\nI. BORG\n            \n\n\n\n\n\n(1)\u00a0\u00a0Opinion of 14 February 2013 (OJ\u00a0C\u00a0133, 9.5.2013, p.\u00a052).\n\n(2)\u00a0\u00a0Position of the European Parliament of 2 April 2014 (not yet published in the Official Journal) and position of the Council at first reading of 7 March 2017 (not yet published in the Official Journal).\n\n(3)\u00a0\u00a0Council Directive\u00a090/385/EEC of 20 June 1990 on the approximation of the laws of the Member\u00a0States relating to active implantable medical devices (OJ\u00a0L\u00a0189, 20.7.1990, p.\u00a017).\n\n(4)\u00a0\u00a0Council Directive\u00a093/42/EEC of 14 June 1993 concerning medical devices (OJ\u00a0L\u00a0169, 12.7.1993, p.\u00a01).\n\n(5)\u00a0\u00a0Regulation (EC)\u00a0No\u00a0178/2002 of the European Parliament and of the Council of 28\u00a0January\u00a02002 laying down the general principles and requirements of food law, establishing the European Food Safety Authority and laying down procedures in matters of food safety (OJ\u00a0L\u00a031, 1.2.2002, p.\u00a01).\n\n(6)\u00a0\u00a0Regulation (EC)\u00a0No\u00a01223/2009 of the European Parliament and of the Council of 30\u00a0November 2009 on cosmetic products (OJ\u00a0L\u00a0342, 22.12.2009, p.\u00a059).\n\n(7)\u00a0\u00a0Directive\u00a02001/83/EC of the European Parliament and of the Council of 6\u00a0November\u00a02001 on the Community code relating to medicinal products for human use (OJ\u00a0L\u00a0311, 28.11.2001, p.\u00a067).\n\n(8)\u00a0\u00a0Regulation (EC)\u00a0No\u00a01394/2007 of the European Parliament and of the Council of 13\u00a0November\u00a02007 on advanced therapy medicinal products and amending Directive\u00a02001/83/EC and Regulation (EC)\u00a0No\u00a0726/2004 (OJ\u00a0L\u00a0324, 10.12.2007, p.\u00a0121).\n\n(9)\u00a0\u00a0Directive\u00a02004/23/EC of the European Parliament and of the Council of 31\u00a0March\u00a02004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells (OJ\u00a0L\u00a0102, 7.4.2004, p.\u00a048).\n\n(10)\u00a0\u00a0Directive\u00a02002/98/EC of the European Parliament and of the Council of 27\u00a0January\u00a02003 setting standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components (OJ\u00a0L\u00a033, 8.2.2003, p.\u00a030).\n\n(11)\u00a0\u00a0Commission Recommendation 2011/696/EU of 18 October 2011 on the definition of nanomaterial (OJ\u00a0L\u00a0275, 20.10.2011, p.\u00a038).\n\n(12)\u00a0\u00a0Directive\u00a02014/30/EU of the European Parliament and of the Council of 26\u00a0February\u00a02014 on the harmonisation of the laws of the Member\u00a0States relating to electromagnetic compatibility (OJ\u00a0L\u00a096, 29.3.2014. p.\u00a079).\n\n(13)\u00a0\u00a0Council Directive\u00a02013/59/Euratom of 5\u00a0December\u00a02013 laying down basic safety standards for protection against the dangers arising from exposure to ionising radiation, and repealing Directives\u00a089/618/Euratom, 90/641/Euratom, 96/29/Euratom, 97/43/Euratom and 2003/122/Euratom (OJ\u00a0L\u00a013, 17.1.2014, p.\u00a01).\n\n(14)\u00a0\u00a0Directive\u00a0(EU)\u00a02015/1535 of the European Parliament and of the Council of 9\u00a0September\u00a02015 laying down a procedure for the provision of information in the field of technical regulations and of rules on Information Society services (OJ\u00a0L\u00a0241, 17.9.2015, p.\u00a01).\n\n(15)\u00a0\u00a0Regulation (EU)\u00a0No\u00a01025/2012 of the European Parliament and of the Council of 25\u00a0October 2012 on European standardisation, amending Council Directives 89/686/EEC and 93/15/EEC and Directives 94/9/EC, 94/25/EC, 95/16/EC, 97/23/EC, 98/34/EC, 2004/22/EC, 2007/23/EC, 2009/23/EC and 2009/105/EC of the European Parliament and of the Council and repealing Council Decision 87/95/EEC and Decision No\u00a01673/2006/EC of the European Parliament and of the Council (OJ\u00a0L\u00a0316, 14.11.2012, p.\u00a012).\n\n(16)\u00a0\u00a0Directive\u00a098/79/EC of the European Parliament and of the Council of 27\u00a0October\u00a01998 on in\u00a0vitro diagnostic medical devices (OJ\u00a0L\u00a0331, 7.12.1998, p.\u00a01).\n\n(17)\u00a0\u00a0Regulation (EC)\u00a0No\u00a0765/2008 of the European Parliament and of the Council of 9\u00a0July\u00a02008 setting out the requirements for accreditation and market surveillance relating to the marketing of products and repealing Regulation (EEC) No\u00a0339/93 (OJ\u00a0L\u00a0218, 13.8.2008, p.\u00a030).\n\n(18)\u00a0\u00a0Decision No\u00a0768/2008/EC of the European Parliament and of the Council of 9\u00a0July\u00a02008 on a common framework for the marketing of products, and repealing Council Decision\u00a093/465/EEC (OJ\u00a0L\u00a0218, 13.8.2008, p.\u00a082).\n\n(19)\u00a0\u00a0Council Directive\u00a085/374/EEC of 25\u00a0July\u00a01985 on the approximation of the laws, regulations and administrative provisions of the Member\u00a0States concerning liability for defective products (OJ\u00a0L\u00a0210, 7.8.1985, p.\u00a029).\n\n(20)\u00a0\u00a0Judgment of 28\u00a0July\u00a02011 in Orifarm and Paranova, joined cases C-400/09 and C-207/10, ECLI:EU:C:2011:519.\n\n(21)\u00a0\u00a0Commission Decision\u00a02010/227/EU of 19 April 2010 on the European Databank for Medical Devices (OJ\u00a0L\u00a0102, 23.4.2010, p.\u00a045).\n\n(22)\u00a0\u00a0Directive\u00a095/46/EC of the European Parliament and of the Council of 24\u00a0October\u00a01995 on the protection of individuals with regard to the processing of personal data and on the free movement of such data (OJ\u00a0L\u00a0281, 23.11.1995, p.\u00a031).\n\n(23)\u00a0\u00a0Regulation (EC)\u00a0No\u00a045/2001 of the European Parliament and of the Council of 18\u00a0December\u00a02000 on the protection of individuals with regard to the processing of personal data by the Community institutions and bodies and on the free movement of such data (OJ\u00a0L\u00a08, 12.1.2001, p.\u00a01).\n\n(24)\u00a0\u00a0Directive\u00a02010/63/EU of the European Parliament and of the Council of 22\u00a0September\u00a02010 on the protection of animals used for scientific purposes (OJ\u00a0L\u00a0276, 20.10.2010, p.\u00a033).\n\n(25)\u00a0\u00a0Regulation (EU)\u00a02017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision\u00a02010/227/EU (see page 176 of this Official Journal).\n\n(26)\u00a0\u00a0\n            OJ\u00a0L\u00a0123, 12.5.2016, p.\u00a01.\n\n(27)\u00a0\u00a0Regulation (EU)\u00a0No\u00a0182/2011 of the European Parliament and of the Council of 16\u00a0February 2011 laying down the rules and general principles concerning mechanisms for control by Member\u00a0States of the Commission's exercise of implementing powers (OJ\u00a0L\u00a055, 28.2.2011, p.\u00a013).\n\n(28)\u00a0\u00a0Commission Regulation (EU)\u00a0No\u00a0207/2012 of 9\u00a0March\u00a02012 on electronic instructions for use of medical devices (OJ\u00a0L\u00a072, 10.3.2012, p.\u00a028).\n\n(29)\u00a0\u00a0Commission Regulation (EU)\u00a0No\u00a0722/2012 of 8 August 2012 concerning particular requirements as regards the requirements laid down in Council Directives 90/385/EEC and 93/42/EEC with respect to active implantable medical devices and medical devices manufactured utilising tissues of animal origin (OJ\u00a0L\u00a0212, 9.8.2012, p.\u00a03).\n\n(30)\u00a0\u00a0Commission Directive\u00a02003/12/EC of 3 February 2003 on the reclassification of breast implants in the framework of Directive\u00a093/42/EEC concerning medical devices (OJ\u00a0L\u00a028, 4.2.2003, p.\u00a043).\n\n(31)\u00a0\u00a0Commission Directive\u00a02005/50/EC of 11 August 2005 on the reclassification of hip, knee and shoulder joint replacements in the framework of Council Directive\u00a093/42/EEC concerning medical devices (OJ\u00a0L\u00a0210, 12.8.2005, p.\u00a041).\n\n(32)\u00a0\u00a0Commission Implementing Regulation (EU)\u00a0No\u00a0920/2013 of 24 September 2013 on the designation and the supervision of notified bodies under Council Directive\u00a090/385/EEC on active implantable medical devices and Council Directive\u00a093/42/EEC on medical devices (OJ\u00a0L\u00a0253, 25.9.2013, p.\u00a08).\n\n(33)\u00a0\u00a0\n            OJ\u00a0C 358, 7.12.2013, p.\u00a010.\n\n(34)\u00a0\u00a0Regulation\u00a0(EC)\u00a0No\u00a0726/2004 of the European Parliament and of the Council of 31\u00a0March\u00a02004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (OJ\u00a0L\u00a0136, 30.4.2004, p.\u00a01).\n\n(35)\u00a0\u00a0Directive\u00a02006/42/EC of the European Parliament and of the Council of 17\u00a0May\u00a02006 on machinery, and amending Directive\u00a095/16/EC (OJ\u00a0L\u00a0157, 9.6.2006, p.\u00a024).\n\n(36)\u00a0\u00a0Commission Recommendation 2003/361/\u0395C of 6\u00a0May\u00a02003 concerning the definition of micro, small and medium-sized enterprises (OJ\u00a0L\u00a0124, 20.5.2003, p.\u00a036).\n\n(37)\u00a0\u00a0Regulation (EU)\u00a0No\u00a0536/2014 of the European Parliament and of the Council of 16\u00a0April\u00a02014 on clinical trials on medicinal products for human use, and repealing Directive\u00a02001/20/EC (OJ\u00a0L\u00a0158, 27.5.2014, p.\u00a01).\n\n\n\n\nANNEXES\n\nI\u00a0\u00a0\u00a0\n\nGeneral safety and performance requirements\n\n\n\nII\u00a0\u00a0\u00a0\n\nTechnical documentation\n\n\n\nIII\u00a0\u00a0\u00a0\n\nTechnical documentation on post-market surveillance\n\n\n\nIV\u00a0\u00a0\u00a0\n\nEU declaration of conformity\n\n\n\nV\u00a0\u00a0\u00a0\n\nCE marking of conformity\n\n\n\nVI\u00a0\u00a0\u00a0\n\nInformation to be submitted upon the registration of devices and economic operators in accordance with Articles\u00a029(4) and 31; core data elements to be provided to the UDI\u00a0database together with the UDI-DI in accordance with Articles\u00a028 and 29;and the UDI\u00a0system\n\n\n\nVII\u00a0\u00a0\u00a0\n\nRequirements to be met by notified bodies\n\n\n\nVIII\u00a0\u00a0\u00a0\n\nClassification rules\n\n\n\nIX\u00a0\u00a0\u00a0\n\nConformity assessment based on a quality management system and assessment of the technical documentation\n\n\n\nX\u00a0\u00a0\u00a0\n\nConformity assessment based on type examination\n\n\n\nXI\u00a0\u00a0\u00a0\n\nConformity assessment based on product conformity verification\n\n\n\nXII\u00a0\u00a0\u00a0\n\nCertificates issued by a notified body\n\n\n\nXIII\u00a0\u00a0\u00a0\n\nProcedure for custom-made devices\n\n\n\nXIV\u00a0\u00a0\u00a0\n\nClinical evaluation and post-market clinical follow-up\n\n\n\nXV\u00a0\u00a0\u00a0\n\nClinical investigations\n\n\n\nXVI\u00a0\u00a0\u00a0\n\nList of groups of products without an intended medical purpose referred to in Article\u00a01(2)\n\n\n\nXVII\u00a0\u00a0\u00a0\n\nCorrelation table\n\n\n\n\n\n\n\nANNEX I\n\nGENERAL SAFETY AND PERFORMANCE REQUIREMENTS\n\nCHAPTER I\n\n\nGENERAL REQUIREMENTS\n\n\n1.\u00a0\u00a0\u00a0Devices shall achieve the performance intended by their manufacturer and shall be designed and manufactured in such a way that, during normal conditions of use, they are suitable for their intended purpose. They shall be safe and effective and shall not compromise the clinical condition or the safety of patients, or the safety and health of users or, where applicable, other persons, provided that any risks which may be associated with their use constitute acceptable risks when weighed against the benefits to the patient and are compatible with a high level of protection of health and safety, taking into account the generally acknowledged state of the art.\n2.\u00a0\u00a0\u00a0The requirement in this Annex\u00a0to reduce risks as far as possible means the reduction of risks as far as possible without adversely affecting the benefit-risk ratio.\n3.\u00a0\u00a0\u00a0Manufacturers shall establish, implement, document and maintain a risk management system.\nRisk management shall be understood as a continuous iterative process throughout the entire lifecycle of a device, requiring regular systematic updating. In carrying out risk management manufacturers shall:\n\n\n\n\n\n\n(a)\n\n\nestablish and document a risk management plan for each device;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nidentify and analyse the known and foreseeable hazards associated with each device;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nestimate and evaluate the risks associated with, and occurring during, the intended use and during reasonably foreseeable misuse;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\neliminate or control the risks referred to in point\u00a0(c) in accordance with the requirements of Section\u00a04;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nevaluate the impact of information from the production phase and, in particular, from the post-market surveillance system, on hazards and the frequency of occurrence thereof, on estimates of their associated risks, as well as on the overall risk, benefit-risk ratio and risk acceptability; and\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nbased on the evaluation of the impact of the information referred to in point\u00a0(e), if necessary amend control measures in line with the requirements of Section\u00a04.\n\n\n\n\n4.\u00a0\u00a0\u00a0Risk control measures adopted by manufacturers for the design and manufacture of the devices shall conform to safety principles, taking account of the generally acknowledged state of the art. To reduce risks, Manufacturers shall manage risks so that the residual risk associated with each hazard as well as the overall residual risk is judged acceptable. In selecting the most appropriate solutions, manufacturers shall, in the following order of priority:\n\n\n\n\n\n\n(a)\n\n\neliminate or reduce risks as far as possible through safe design and manufacture;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nwhere appropriate, take adequate protection measures, including alarms if necessary, in relation to risks that cannot be eliminated; and\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nprovide information for safety (warnings/precautions/contra-indications) and, where appropriate, training to users.\n\n\n\n\nManufacturers shall inform users of any residual risks.\n5.\u00a0\u00a0\u00a0In eliminating or reducing risks related to use error, the manufacturer shall:\n\n\n\n\n\n\n(a)\n\n\nreduce as far as possible the risks related to the ergonomic features of the device and the environment in which the device is intended to be used (design for patient safety), and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ngive consideration to the technical knowledge, experience, education, training and use environment, where applicable, and the medical and physical conditions of intended users (design for lay, professional, disabled or other users).\n\n\n\n\n6.\u00a0\u00a0\u00a0The characteristics and performance of a device shall not be adversely affected to such a degree that the health or safety of the patient or the user and, where applicable, of other persons are compromised during the lifetime of the device, as indicated by the manufacturer, when the device is subjected to the stresses which can occur during normal conditions of use and has been properly maintained in accordance with the manufacturer's instructions.\n7.\u00a0\u00a0\u00a0Devices shall be designed, manufactured and packaged in such a way that their characteristics and performance during their intended use are not adversely affected during transport and storage, for example, through fluctuations of temperature and humidity, taking account of the instructions and information provided by the manufacturer.\n8.\u00a0\u00a0\u00a0All known and foreseeable risks, and any undesirable side-effects, shall be minimised and be acceptable when weighed against the evaluated benefits to the patient and/or user arising from the achieved performance of the device during normal conditions of use.\n9.\u00a0\u00a0\u00a0For the devices referred to in Annex\u00a0XVI, the general safety requirements set out in Sections 1 and 8 shall be understood to mean that the device, when used under the conditions and for the purposes intended, does not present a risk at all or presents a risk that is no more than the maximum acceptable risk related to the product's use which is consistent with a high level of protection for the safety and health of persons.\nCHAPTER II\n\n\nREQUIREMENTS REGARDING DESIGN AND MANUFACTURE\n\n\n10.\u00a0\u00a0\u00a0Chemical, physical and biological properties\n10.1.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to ensure that the characteristics and performance requirements referred to in Chapter I are fulfilled. Particular attention shall be paid to:\n\n\n\n\n\n\n(a)\n\n\nthe choice of materials and substances used, particularly as regards toxicity and, where relevant, flammability;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe compatibility between the materials and substances used and biological tissues, cells and body fluids, taking account of the intended purpose of the device and, where relevant, absorption, distribution, metabolism and excretion;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe compatibility between the different parts of a device which consists of more than one implantable part;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe impact of processes on material properties;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nwhere appropriate, the results of biophysical or modelling research the validity of which has been demonstrated beforehand;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe mechanical properties of the materials used, reflecting, where appropriate, matters such as strength, ductility, fracture resistance, wear resistance and fatigue resistance;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nsurface properties; and\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe confirmation that the device meets any defined chemical and/or physical specifications.\n\n\n\n\n10.2.\u00a0\u00a0\u00a0Devices shall be designed, manufactured and packaged in such a way as to minimise the risk posed by contaminants and residues to patients, taking account of the intended purpose of the device, and to the persons involved in the transport, storage and use of the devices. Particular attention shall be paid to tissues exposed to those contaminants and residues and to the duration and frequency of exposure.\n10.3.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way that they can be used safely with the materials and substances, including gases, with which they enter into contact during their intended use; if the devices are intended to administer medicinal products they shall be designed and manufactured in such a way as to be compatible with the medicinal products concerned in accordance with the provisions and restrictions governing those medicinal products and that the performance of both the medicinal products and of the devices is maintained in accordance with their respective indications and intended use.\n10.4.\u00a0\u00a0\u00a0Substances\n10.4.1.\u00a0\u00a0\u00a0Design and manufacture of devices\nDevices shall be designed and manufactured in such a way as to reduce as far as possible the risks posed by substances or particles, including wear debris, degradation products and processing residues, that may be released from the device.\nDevices, or those parts thereof or those materials used therein that:\n\n\n\n\n\n\n\u2014\n\n\nare invasive and come into direct contact with the human body,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\n(re)administer medicines, body liquids or other substances, including gases, to/from the body, or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntransport or store such medicines, body fluids or substances, including gases, to be (re)administered to the body,\n\n\n\n\nshall only contain the following substances in a concentration that is above 0,1 % weight by weight (w/w) where justified pursuant to Section\u00a010.4.2:\n\n\n\n\n\n\n(a)\n\n\nsubstances which are carcinogenic, mutagenic or toxic to reproduction (\u2018CMR\u2019), of category\u00a01A or 1B, in accordance with Part 3 of Annex\u00a0VI to Regulation (EC)\u00a0No\u00a01272/2008 of the European Parliament and of the Council\u00a0(1), or\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nsubstances having endocrine-disrupting properties for which there is scientific evidence of probable serious effects to human health and which are identified either in accordance with the procedure set out in Article\u00a059 of Regulation\u00a0(EC)\u00a0No\u00a01907/2006 of the European Parliament and of the Council\u00a0(2) or, once a delegated act has been adopted by the Commission pursuant to the first subparagraph\u00a0of Article\u00a05(3) of Regulation\u00a0(EU)\u00a0No\u00a0528/2012 of the European Parliament and the Council\u00a0(3), in accordance with the criteria that are relevant to human health amongst the criteria established therein.\n\n\n\n\n10.4.2.\u00a0\u00a0\u00a0Justification regarding the presence of CMR and/or endocrine-disrupting substances\nThe justification for the presence of such substances shall be based upon:\n\n\n\n\n\n\n(a)\n\n\nan analysis and estimation of potential patient or user exposure to the substance;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nan analysis of possible alternative substances, materials or designs, including, where available, information about independent research, peer-reviewed studies, scientific opinions from relevant scientific committees and an analysis of the availability of such alternatives;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nargumentation as to why possible substance and/ or material substitutes, if available, or design changes, if feasible, are inappropriate in relation to maintaining the functionality, performance and the benefit-risk ratios of the product; including taking into account if the intended use of such devices includes treatment of children or treatment of pregnant or breastfeeding women or treatment of other patient groups considered particularly vulnerable to such substances and/or materials; and\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nwhere applicable and available, the latest relevant scientific committee guidelines in accordance with Sections 10.4.3. and 10.4.4.\n\n\n\n\n10.4.3.\u00a0\u00a0\u00a0Guidelines on phthalates\nFor the purposes of Section\u00a010.4., the Commission shall, as soon as possible and by 26 May 2018, provide the relevant scientific committee with a mandate to prepare guidelines that shall be ready before 26 May 2020. The mandate for the committee shall encompass at least a benefit-risk assessment of the presence of phthalates which belong to either of the groups of substances referred to in points (a) and (b) of Section\u00a010.4.1. The benefit-risk assessment shall take into account the intended purpose and context of the use of the device, as well as any available alternative substances and alternative materials, designs or medical treatments. When deemed appropriate on the basis of the latest scientific evidence, but at least every five years, the guidelines shall be updated.\n10.4.4.\u00a0\u00a0\u00a0Guidelines on other CMR and endocrine-disrupting substances\nSubsequently, the Commission shall mandate the relevant scientific committee to prepare guidelines as referred to in Section\u00a010.4.3. also for other substances referred to in points\u00a0(a) and (b) of Section\u00a010.4.1., where appropriate.\n10.4.5.\u00a0\u00a0\u00a0Labelling\nWhere devices, parts thereof or materials used therein as referred to in Section\u00a010.4.1. contain substances referred to in points (a) or (b) of Section\u00a010.4.1. in a concentration above 0,1 % weight by weight (w/w), the presence of those substances shall be labelled on the device itself and/or on the packaging for each unit or, where appropriate, on the sales packaging, with the list of such substances. If the intended use of such devices includes treatment of children or treatment of pregnant or breastfeeding women or treatment of other patient groups considered particularly vulnerable to such substances and/or materials, information on residual risks for those patient groups and, if applicable, on appropriate precautionary measures shall be given in the instructions for use.\n10.5.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks posed by the unintentional ingress of substances into the device taking into account the device and the nature of the environment in which it is intended to be used.\n10.6.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks linked to the size and the properties of particles which are or can be released into the patient's or user's body, unless they come into contact with intact skin only. Special attention shall be given to nanomaterials.\n11.\u00a0\u00a0\u00a0Infection and microbial contamination\n11.1.\u00a0\u00a0\u00a0Devices and their manufacturing processes shall be designed in such a way as to eliminate or to reduce as far as possible the risk of infection to patients, users and, where applicable, other persons. The design shall:\n\n\n\n\n\n\n(a)\n\n\nreduce as far as possible and appropriate the risks from unintended cuts and pricks, such as needle stick injuries,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nallow easy and safe handling,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nreduce as far as possible any microbial leakage from the device and/or microbial exposure during use, and\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nprevent microbial contamination of the device or its content such as specimens or fluids.\n\n\n\n\n11.2.\u00a0\u00a0\u00a0Where necessary devices shall be designed to facilitate their safe cleaning, disinfection, and/or re-sterilisation.\n11.3.\u00a0\u00a0\u00a0Devices labelled as having a specific microbial state shall be designed, manufactured and packaged to ensure that they remain in that state when placed on the market and remain so under the transport and storage conditions specified by the manufacturer.\n11.4.\u00a0\u00a0\u00a0Devices delivered in a sterile state shall be designed, manufactured and packaged in accordance with appropriate procedures, to ensure that they are sterile when placed on the market and that, unless the packaging which is intended to maintain their sterile condition is damaged, they remain sterile, under the transport and storage conditions specified by the manufacturer, until that packaging is opened at the point of use. It shall be ensured that the integrity of that packaging is clearly evident to the final user.\n11.5.\u00a0\u00a0\u00a0Devices labelled as sterile shall be processed, manufactured, packaged and, sterilised by means of appropriate, validated methods.\n11.6.\u00a0\u00a0\u00a0Devices intended to be sterilised shall be manufactured and packaged in appropriate and controlled conditions and facilities.\n11.7.\u00a0\u00a0\u00a0Packaging systems for non-sterile devices shall maintain the integrity and cleanliness of the product and, where the devices are to be sterilised prior to use, minimise the risk of microbial contamination; the packaging system shall be suitable taking account of the method of sterilisation indicated by the manufacturer.\n11.8.\u00a0\u00a0\u00a0The labelling of the device shall distinguish between identical or similar devices placed on the market in both a sterile and a non-sterile condition additional to the symbol used to indicate that devices are sterile.\n12.\u00a0\u00a0\u00a0Devices incorporating a substance considered to be a medicinal product and devices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body.\n12.1.\u00a0\u00a0\u00a0In the case of devices referred to in the first subparagraph\u00a0of Article\u00a01(8), the quality, safety and usefulness of the substance which, if used separately, would be considered to be a medicinal product within the meaning of point\u00a0(2) of Article\u00a01 of Directive\u00a02001/83/EC, shall be verified by analogy with the methods specified in Annex\u00a0I to Directive\u00a02001/83/EC, as required by the applicable conformity assessment procedure under this Regulation.\n12.2.\u00a0\u00a0\u00a0Devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body, and that are absorbed by or locally dispersed in the human body shall comply, where applicable and in a manner limited to the aspects not covered by this Regulation, with the relevant requirements laid down in Annex\u00a0I to Directive\u00a02001/83/EC for the evaluation of absorption, distribution, metabolism, excretion, local tolerance, toxicity, interaction with other devices, medicinal products or other substances and potential for adverse reactions, as required by the applicable conformity assessment procedure under this Regulation.\n13.\u00a0\u00a0\u00a0Devices incorporating materials of biological origin\n13.1.\u00a0\u00a0\u00a0For devices manufactured utilising derivatives of tissues or cells of human origin which are non-viable or are rendered non-viable covered by this Regulation in accordance with point\u00a0(g) of Article\u00a01(6), the following shall apply:\n\n\n\n\n\n\n(a)\n\n\ndonation, procurement and testing of the tissues and cells shall be done in accordance with Directive\u00a02004/23/EC;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nprocessing, preservation and any other handling of those tissues and cells or their derivatives shall be carried out so as to provide safety for patients, users and, where applicable, other persons. In particular, safety with regard to viruses and other transmissible agents shall be addressed by appropriate methods of sourcing and by implementation of validated methods of elimination or inactivation in the course of the manufacturing process;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe traceability system for those devices shall be complementary and compatible with the traceability and data protection requirements laid down in Directive\u00a02004/23/EC and in Directive\u00a02002/98/EC.\n\n\n\n\n13.2.\u00a0\u00a0\u00a0For devices manufactured utilising tissues or cells of animal origin, or their derivatives, which are non-viable or rendered non-viable the following shall apply:\n\n\n\n\n\n\n(a)\n\n\nwhere feasible taking into account the animal species, tissues and cells of animal origin, or their derivatives, shall originate from animals that have been subjected to veterinary controls that are adapted to the intended use of the tissues. Information on the geographical origin of the animals shall be retained by manufacturers;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nsourcing, processing, preservation, testing and handling of tissues, cells and substances of animal origin, or their derivatives, shall be carried out so as to provide safety for patients, users and, where applicable, other persons. In particular safety with regard to viruses and other transmissible agents shall be addressed by implementation of validated methods of elimination or viral inactivation in the course of the manufacturing process, except when the use of such methods would lead to unacceptable degradation compromising the clinical benefit of the device;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nin the case of devices manufactured utilising tissues or cells of animal origin, or their derivatives, as referred to in Regulation\u00a0(EU)\u00a0No\u00a0722/2012 the particular requirements laid down in that Regulation shall apply.\n\n\n\n\n13.3.\u00a0\u00a0\u00a0For devices manufactured utilising non-viable biological substances other than those referred to in Sections\u00a013.1 and 13.2, the processing, preservation, testing and handling of those substances shall be carried out so as to provide safety for patients, users and, where applicable, other persons, including in the waste disposal chain. In particular, safety with regard to viruses and other transmissible agents shall be addressed by appropriate methods of sourcing and by implementation of validated methods of elimination or inactivation in the course of the manufacturing process.\n14.\u00a0\u00a0\u00a0Construction of devices and interaction with their environment\n14.1.\u00a0\u00a0\u00a0If the device is intended for use in combination with other devices or equipment the whole combination, including the connection system shall be safe and shall not impair the specified performance of the devices. Any restrictions on use applying to such combinations shall be indicated on the label and/or in the instructions for use. Connections which the user has to handle, such as fluid, gas transfer, electrical or mechanical coupling, shall be designed and constructed in such a way as to minimise all possible risks, such as misconnection.\n14.2.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to remove or reduce as far as possible:\n\n\n\n\n\n\n(a)\n\n\nthe risk of injury, in connection with their physical features, including the volume/pressure ratio, dimensional and where appropriate ergonomic features;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nrisks connected with reasonably foreseeable external influences or environmental conditions, such as magnetic fields, external electrical and electromagnetic effects, electrostatic discharge, radiation associated with diagnostic or therapeutic procedures, pressure, humidity, temperature, variations in pressure and acceleration or radio signal interferences;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe risks associated with the use of the device when it comes into contact with materials, liquids, and substances, including gases, to which it is exposed during normal conditions of use;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe risks associated with the possible negative interaction between software and the IT environment within which it operates and interacts;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe risks of accidental ingress of substances into the device;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe risks of reciprocal interference with other devices normally used in the investigations or for the treatment given; and\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nrisks arising where maintenance or calibration are not possible (as with implants), from ageing of materials used or loss of accuracy of any measuring or control mechanism.\n\n\n\n\n14.3.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to minimise the risks of fire or explosion during normal use and in single fault condition. Particular attention shall be paid to devices the intended use of which includes exposure to or use in association with flammable or explosive substances or substances which could cause combustion.\n14.4.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way that adjustment, calibration, and maintenance can be done safely and effectively.\n14.5.\u00a0\u00a0\u00a0Devices that are intended to be operated together with other devices or products shall be designed and manufactured in such a way that the interoperability and compatibility are reliable and safe.\n14.6\u00a0\u00a0\u00a0Any measurement, monitoring or display scale shall be designed and manufactured in line with ergonomic principles, taking account of the intended purpose, users and the environmental conditions in which the devices are intended to be used.\n14.7.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to facilitate their safe disposal and the safe disposal of related waste substances by the user, patient or other person. To that end, manufacturers shall identify and test procedures and measures as a result of which their devices can be safely disposed after use. Such procedures shall be described in the instructions for use.\n15.\u00a0\u00a0\u00a0Devices with a diagnostic or measuring function\n15.1.\u00a0\u00a0\u00a0Diagnostic devices and devices with a measuring function, shall be designed and manufactured in such a way as to provide sufficient accuracy, precision and stability for their intended purpose, based on appropriate scientific and technical methods. The limits of accuracy shall be indicated by the manufacturer.\n15.2.\u00a0\u00a0\u00a0The measurements made by devices with a measuring function shall be expressed in legal units conforming to the provisions of Council Directive\u00a080/181/EEC\u00a0(4).\n16.\u00a0\u00a0\u00a0Protection against radiation\n16.1.\u00a0\u00a0\u00a0General\n\n\n\n\n\n\n(a)\n\n\nDevices shall be designed, manufactured and packaged in such a way that exposure of patients, users and other persons to radiation is reduced as far as possible, and in a manner that is compatible with the intended purpose, whilst not restricting the application of appropriate specified levels for therapeutic and diagnostic purposes.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nThe operating instructions for devices emitting hazardous or potentially hazardous radiation shall contain detailed information as to the nature of the emitted radiation, the means of protecting the patient and the user, and on ways of avoiding misuse and of reducing the risks inherent to installation as far as possible and appropriate. Information regarding the acceptance and performance testing, the acceptance criteria, and the maintenance procedure shall also be specified.\n\n\n\n\n16.2.\u00a0\u00a0\u00a0Intended radiation\n\n\n\n\n\n\n(a)\n\n\nWhere devices are designed to emit hazardous, or potentially hazardous, levels of ionizing and/or non-ionizing radiation necessary for a specific medical purpose the benefit of which is considered to outweigh the risks inherent to the emission, it shall be possible for the user to control the emissions. Such devices shall be designed and manufactured to ensure reproducibility of relevant variable parameters within an acceptable tolerance.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nWhere devices are intended to emit hazardous, or potentially hazardous, ionizing and/or non-ionizing radiation, they shall be fitted, where possible, with visual displays and/or audible warnings of such emissions.\n\n\n\n\n16.3.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way that exposure of patients, users and other persons to the emission of unintended, stray or scattered radiation is reduced as far as possible. Where possible and appropriate, methods shall be selected which reduce the exposure to radiation of patients, users and other persons who may be affected.\n16.4.\u00a0\u00a0\u00a0Ionising radiation\n\n\n\n\n\n\n(a)\n\n\nDevices intended to emit ionizing radiation shall be designed and manufactured taking into account the requirements of the Directive\u00a02013/59/Euratom laying down basic safety standards for protection against the dangers arising from exposure to ionising radiation.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nDevices intended to emit ionising radiation shall be designed and manufactured in such a way as to ensure that, where possible, taking into account the intended use, the quantity, geometry and quality of the radiation emitted can be varied and controlled, and, if possible, monitored during treatment.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nDevices emitting ionising radiation intended for diagnostic radiology shall be designed and manufactured in such a way as to achieve an image and/or output quality that are appropriate to the intended medical purpose whilst minimising radiation exposure of the patient and user.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nDevices that emit ionising radiation and are intended for therapeutic radiology shall be designed and manufactured in such a way as to enable reliable monitoring and control of the delivered dose, the beam type, energy and, where appropriate, the quality of radiation.\n\n\n\n\n17.\u00a0\u00a0\u00a0Electronic programmable systems \u2014 devices that incorporate electronic programmable systems and software that are devices in themselves\n17.1.\u00a0\u00a0\u00a0Devices that incorporate electronic programmable systems, including software, or software that are devices in themselves, shall be designed to ensure repeatability, reliability and performance in line with their intended use. In the event of a single fault condition, appropriate means shall be adopted to eliminate or reduce as far as possible consequent risks or impairment of performance.\n17.2.\u00a0\u00a0\u00a0For devices that incorporate software or for software that are devices in themselves, the software shall be developed and manufactured in accordance with the state of the art taking into account the principles of development life cycle, risk management, including information security, verification and validation.\n17.3.\u00a0\u00a0\u00a0Software referred to in this Section\u00a0that is intended to be used in combination with mobile computing platforms shall be designed and manufactured taking into account the specific features of the mobile platform (e.g. size and contrast ratio of the screen) and the external factors related to their use (varying environment as regards level of light or noise).\n17.4.\u00a0\u00a0\u00a0Manufacturers shall set out minimum requirements concerning hardware, IT networks characteristics and IT security measures, including protection against unauthorised access, necessary to run the software as intended.\n18.\u00a0\u00a0\u00a0Active devices and devices connected to them\n18.1.\u00a0\u00a0\u00a0For non-implantable active devices, in the event of a single fault condition, appropriate means shall be adopted to eliminate or reduce as far as possible consequent risks.\n18.2.\u00a0\u00a0\u00a0Devices where the safety of the patient depends on an internal power supply shall be equipped with a means of determining the state of the power supply and an appropriate warning or indication for when the capacity of the power supply becomes critical. If necessary, such warning or indication shall be given prior to the power supply becoming critical.\n18.3.\u00a0\u00a0\u00a0Devices where the safety of the patient depends on an external power supply shall include an alarm system to signal any power failure.\n18.4.\u00a0\u00a0\u00a0Devices intended to monitor one or more clinical parameters of a patient shall be equipped with appropriate alarm systems to alert the user of situations which could lead to death or severe deterioration of the patient's state of health.\n18.5.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks of creating electromagnetic interference which could impair the operation of the device in question or other devices or equipment in the intended environment.\n18.6.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to provide a level of intrinsic immunity to electromagnetic interference such that is adequate to enable them to operate as\u00a0intended.\n18.7.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to avoid, as far as possible, the risk of accidental electric shocks to the patient, user or any other person, both during normal use of the device and in the event of a single fault condition in the device, provided the device is installed and maintained as indicated by the manufacturer.\n18.8.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to protect, as far as possible, against unauthorised access that could hamper the device from functioning as intended.\n19.\u00a0\u00a0\u00a0Particular requirements for active implantable devices\n19.1.\u00a0\u00a0\u00a0Active implantable devices shall be designed and manufactured in such a way as to remove or minimize as far as possible:\n\n\n\n\n\n\n(a)\n\n\nrisks connected with the use of energy sources with particular reference, where electricity is used, to insulation, leakage currents and overheating of the devices,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nrisks connected with medical treatment, in particular those resulting from the use of defibrillators or high-frequency surgical equipment, and\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nrisks which may arise where maintenance and calibration are impossible, including:\n\n\n\n\n\n\n\u2014\n\n\nexcessive increase of leakage currents,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nageing of the materials used,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nexcess heat generated by the device,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndecreased accuracy of any measuring or control mechanism.\n\n\n\n\n\n\n\n\n19.2.\u00a0\u00a0\u00a0Active implantable devices shall be designed and manufactured in such a way as to ensure\n\n\n\n\n\n\n\u2014\n\n\nif applicable, the compatibility of the devices with the substances they are intended to administer, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe reliability of the source of energy.\n\n\n\n\n19.3.\u00a0\u00a0\u00a0Active implantable devices and, if appropriate, their component parts shall be identifiable to allow any necessary measure to be taken following the discovery of a potential risk in connection with the devices or their component parts.\n19.4.\u00a0\u00a0\u00a0Active implantable devices shall bear a code by which they and their manufacturer can be unequivocally identified (particularly with regard to the type of device and its year of manufacture); it shall be possible to read this code, if necessary, without the need for a surgical operation.\n20.\u00a0\u00a0\u00a0Protection against mechanical and thermal risks\n20.1.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to protect patients and users against mechanical risks connected with, for example, resistance to movement, instability and moving parts.\n20.2.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to reduce to the lowest possible level the risks arising from vibration generated by the devices, taking account of technical progress and of the means available for limiting vibrations, particularly at source, unless the vibrations are part of the specified performance.\n20.3.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to reduce to the lowest possible level the risks arising from the noise emitted, taking account of technical progress and of the means available to reduce noise, particularly at source, unless the noise emitted is part of the specified performance.\n20.4.\u00a0\u00a0\u00a0Terminals and connectors to the electricity, gas or hydraulic and pneumatic energy supplies which the user or other person has to handle, shall be designed and constructed in such a way as to minimise all possible risks.\n20.5.\u00a0\u00a0\u00a0Errors likely to be made when fitting or refitting certain parts which could be a source of risk shall be made impossible by the design and construction of such parts or, failing this, by information given on the parts themselves and/or their housings.\nThe same information shall be given on moving parts and/or their housings where the direction of movement needs to be known in order to avoid a risk.\n20.6.\u00a0\u00a0\u00a0Accessible parts of devices (excluding the parts or areas intended to supply heat or reach given temperatures) and their surroundings shall not attain potentially dangerous temperatures under normal conditions of use.\n21.\u00a0\u00a0\u00a0Protection against the risks posed to the patient or user by devices supplying energy or substances\n21.1.\u00a0\u00a0\u00a0Devices for supplying the patient with energy or substances shall be designed and constructed in such a way that the amount to be delivered can be set and maintained accurately enough to ensure the safety of the patient and of the user.\n21.2.\u00a0\u00a0\u00a0Devices shall be fitted with the means of preventing and/or indicating any inadequacies in the amount of energy delivered or substances delivered which could pose a danger. Devices shall incorporate suitable means to prevent, as far as possible, the accidental release of dangerous levels of energy or substances from an energy and/or substance source.\n21.3.\u00a0\u00a0\u00a0The function of the controls and indicators shall be clearly specified on the devices. Where a device bears instructions required for its operation or indicates operating or adjustment parameters by means of a visual system, such information shall be understandable to the user and, as appropriate, the patient.\n22.\u00a0\u00a0\u00a0Protection against the risks posed by medical devices intended by the manufacturer for use by lay persons\n22.1.\u00a0\u00a0\u00a0Devices for use by lay persons shall be designed and manufactured in such a way that they perform appropriately for their intended purpose taking into account the skills and the means available to lay persons and the influence resulting from variation that can be reasonably anticipated in the lay person's technique and environment. The information and instructions provided by the manufacturer shall be easy for the lay person to understand and apply.\n22.2.\u00a0\u00a0\u00a0Devices for use by lay persons shall be designed and manufactured in such a way as to:\n\n\n\n\n\n\n\u2014\n\n\nensure that the device can be used safely and accurately by the intended user at all stages of the procedure, if necessary after appropriate training and/or information,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreduce, as far as possible and appropriate, the risk from unintended cuts and pricks such as needle stick injuries, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreduce as far as possible the risk of error by the intended user in the handling of the device and, if applicable, in the interpretation of the results.\n\n\n\n\n22.3.\u00a0\u00a0\u00a0Devices for use by lay persons shall, where appropriate, include a procedure by which the lay person:\n\n\n\n\n\n\n\u2014\n\n\ncan verify that, at the time of use, the device will perform as intended by the manufacturer, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif applicable, is warned if the device has failed to provide a valid result.\n\n\n\n\nCHAPTER III\n\n\nREQUIREMENTS REGARDING THE INFORMATION SUPPLIED WITH THE DEVICE\n\n\n23.\u00a0\u00a0\u00a0Label and instructions for use\n23.1.\u00a0\u00a0\u00a0General requirements regarding the information supplied by the manufacturer\nEach device shall be accompanied by the information needed to identify the device and its manufacturer, and by any safety and performance information relevant to the user, or any other person, as appropriate. Such information may appear on the device itself, on the packaging or in the instructions for use, and shall, if the manufacturer has a website, be made available and kept up to date on the website, taking into account the following:\n\n\n\n\n\n\n(a)\n\n\nThe medium, format, content, legibility, and location of the label and instructions for use shall be appropriate to the particular device, its intended purpose and the technical knowledge, experience, education or training of the intended user(s). In particular, instructions for use shall be written in terms readily understood by the intended user and, where appropriate, supplemented with drawings and diagrams.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nThe information required on the label shall be provided on the device itself. If this is not practicable or appropriate, some or all of the information may appear on the packaging for each unit, and/or on the packaging of multiple devices.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nLabels shall be provided in a human-readable format and may be supplemented by machine-readable information, such as radio-frequency identification (\u2018RFID\u2019) or bar codes.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nInstructions for use shall be provided together with devices. By way of exception, instructions for use shall not be required for class I and class IIa devices if such devices can be used safely without any such instructions and unless otherwise provided for elsewhere in this Section.\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nWhere multiple devices are supplied to a single user and/or location, a single copy of the instructions for use may be provided if so agreed by the purchaser who in any case may request further copies to be provided free of charge.\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nInstructions for use may be provided to the user in non-paper format (e.g.\u00a0electronic) to the extent, and only under the conditions, set out in Regulation\u00a0(EU)\u00a0No\u00a0207/2012 or in any subsequent implementing rules adopted pursuant to this Regulation.\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nResidual risks which are required to be communicated to the user and/or other person shall be included as limitations, contra-indications, precautions or warnings in the information supplied by the manufacturer.\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nWhere appropriate, the information supplied by the manufacturer shall take the form of internationally recognised symbols. Any symbol or identification colour used shall conform to the harmonised standards or CS. In areas for which no harmonised standards or CS exist, the symbols and colours shall be described in the documentation supplied with the device.\n\n\n\n\n23.2.\u00a0\u00a0\u00a0Information on the label\nThe label shall bear all of the following particulars:\n\n\n\n\n\n\n(a)\n\n\nthe name or trade name of the device;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe details strictly necessary for a user to identify the device, the contents of the packaging and, where it is not obvious for the user, the intended purpose of the device;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe name, registered trade name or registered trade mark of the manufacturer and the address of its registered place of business;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nif the manufacturer has its registered place of business outside the Union, the name of the authorised representative and address of the registered place of business of the authorised representative;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nwhere applicable, an indication that the device contains or incorporates:\n\n\n\n\n\n\n\u2014\n\n\na medicinal substance, including a human blood or plasma derivative, or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntissues or cells, or their derivatives, of human origin, or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntissues or cells of animal origin, or their derivatives, as referred to in Regulation\u00a0(EU)\u00a0No\u00a0722/2012;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nwhere applicable, information labelled in accordance with Section\u00a010.4.5.;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthe lot number or the serial number of the device preceded by the words LOT NUMBER or SERIAL NUMBER or an equivalent symbol, as appropriate;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe UDI carrier referred to in Article\u00a027(4) and Part C of Annex\u00a0VII;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nan unambiguous indication of t the time limit for using or implanting the device safely, expressed at least in terms of year and month, where this is relevant;\n\n\n\n\n\n\n\n\n\n\n(j)\n\n\nwhere there is no indication of the date until when it may be used safely, the date of manufacture. This date of manufacture may be included as part of the lot number or serial number, provided the date is clearly identifiable;\n\n\n\n\n\n\n\n\n\n\n(k)\n\n\nan indication of any special storage and/or handling condition that applies;\n\n\n\n\n\n\n\n\n\n\n(l)\n\n\nif the device is supplied sterile, an indication of its sterile state and the sterilisation method;\n\n\n\n\n\n\n\n\n\n\n(m)\n\n\nwarnings or precautions to be taken that need to be brought to the immediate attention of the user of the device, and to any other person. This information may be kept to a minimum in which case more detailed information shall appear in the instructions for use, taking into account the intended users;\n\n\n\n\n\n\n\n\n\n\n(n)\n\n\nif the device is intended for single use, an indication of that fact. A manufacturer's indication of single use shall be consistent across the Union;\n\n\n\n\n\n\n\n\n\n\n(o)\n\n\nif the device is a single-use device that has been reprocessed, an indication of that fact, the number of reprocessing cycles already performed, and any limitation as regards the number of reprocessing cycles;\n\n\n\n\n\n\n\n\n\n\n(p)\n\n\nif the device is custom-made, the words \u2018custom-made device\u2019;\n\n\n\n\n\n\n\n\n\n\n(q)\n\n\nan indication that the device is a medical device. If the device is intended for clinical investigation only, the words \u2018exclusively for clinical investigation\u2019;\n\n\n\n\n\n\n\n\n\n\n(r)\n\n\nin the case of devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed by or locally dispersed in the human body, the overall qualitative composition of the device and quantitative information on the main constituent or constituents responsible for achieving the principal intended action;\n\n\n\n\n\n\n\n\n\n\n(s)\n\n\nfor active implantable devices, the serial number, and for other implantable devices, the serial number or the lot number.\n\n\n\n\n23.3.\u00a0\u00a0\u00a0Information on the packaging which maintains the sterile condition of a device (\u2018sterile packaging\u2019)\nThe following particulars shall appear on the sterile packaging:\n\n\n\n\n\n\n(a)\n\n\nan indication permitting the sterile packaging to be recognised as such,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\na declaration that the device is in a sterile condition,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe method of sterilisation,\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe name and address of the manufacturer,\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\na description of the device,\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nif the device is intended for clinical investigations, the words \u2018exclusively for clinical investigations\u2019,\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nif the device is custom-made, the words \u2018custom-made device\u2019,\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe month and year of manufacture,\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nan unambiguous indication of the time limit for using or implanting the device safely expressed at least in terms of year and month, and\n\n\n\n\n\n\n\n\n\n\n(j)\n\n\nan instruction to check the instructions for use for what to do if the sterile packaging is damaged or unintentionally opened before use.\n\n\n\n\n23.4.\u00a0\u00a0\u00a0Information in the instructions for use\nThe instructions for use shall contain all of the following particulars:\n\n\n\n\n\n\n(a)\n\n\nthe particulars referred to in points (a), (c), (e), (f), (k), (l), (n) and (r) of Section\u00a023.2;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe device's intended purpose with a clear specification of indications, contra-indications, the patient target group or groups, and of the intended users, as appropriate;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nwhere applicable, a specification of the clinical benefits to be expected.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nwhere applicable, links to the summary of safety and clinical performance referred to in Article\u00a032;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe performance characteristics of the device;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nwhere applicable, information allowing the healthcare professional to verify if the device is suitable and select the corresponding software and accessories;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nany residual risks, contra-indications and any undesirable side-effects, including information to be conveyed to the patient in this regard;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nspecifications the user requires to use the device appropriately, e.g. if the device has a measuring function, the degree of accuracy claimed for it;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\ndetails of any preparatory treatment or handling of the device before it is ready for use or during its use, such as sterilisation, final assembly, calibration, etc., including the levels of disinfection required to ensure patient safety and all available methods for achieving those levels of disinfection;\n\n\n\n\n\n\n\n\n\n\n(j)\n\n\nany requirements for special facilities, or special training, or particular qualifications of the device user and/or other persons;\n\n\n\n\n\n\n\n\n\n\n(k)\n\n\nthe information needed to verify whether the device is properly installed and is ready to perform safely and as intended by the manufacturer, together with, where relevant:\n\n\n\n\n\n\n\u2014\n\n\ndetails of the nature, and frequency, of preventive and regular maintenance, and of any preparatory cleaning or disinfection,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nidentification of any consumable components and how to replace them,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation on any necessary calibration to ensure that the device operates properly and safely during its intended lifetime, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmethods for eliminating the risks encountered by persons involved in installing, calibrating or servicing devices;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(l)\n\n\nif the device is supplied sterile, instructions in the event of the sterile packaging being damaged or unintentionally opened before use;\n\n\n\n\n\n\n\n\n\n\n(m)\n\n\nif the device is supplied non-sterile with the intention that it is sterilised before use, the appropriate instructions for sterilisation;\n\n\n\n\n\n\n\n\n\n\n(n)\n\n\nif the device is reusable, information on the appropriate processes for allowing reuse, including cleaning, disinfection, packaging and, where appropriate, the validated method of re-sterilisation appropriate to the Member\u00a0State or Member\u00a0States in which the device has been placed on the market. Information shall be provided to identify when the device should no longer be reused, e.g. signs of material degradation or the maximum number of allowable reuses;\n\n\n\n\n\n\n\n\n\n\n(o)\n\n\nan indication, if appropriate, that a device can be reused only if it is reconditioned under the responsibility of the manufacturer to comply with the general safety and performance requirements;\n\n\n\n\n\n\n\n\n\n\n(p)\n\n\nif the device bears an indication that it is for single use, information on known characteristics and technical factors known to the manufacturer that could pose a risk if the device were to be re-used. This information shall be based on a specific section of the manufacturer's risk management documentation, where such characteristics and technical factors shall be addressed in detail. If in accordance with point\u00a0(d) of Section\u00a023.1. no instructions for use are required, this information shall be made available to the user upon request;\n\n\n\n\n\n\n\n\n\n\n(q)\n\n\nfor devices intended for use together with other devices and/or general purpose equipment:\n\n\n\n\n\n\n\u2014\n\n\ninformation to identify such devices or equipment, in order to obtain a safe combination, and/or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation on any known restrictions to combinations of devices and equipment;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(r)\n\n\nif the device emits radiation for medical purposes:\n\n\n\n\n\n\n\u2014\n\n\ndetailed information as to the nature, type and where appropriate, the intensity and distribution of the emitted radiation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe means of protecting the patient, user, or other person from unintended radiation during use of the device;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(s)\n\n\ninformation that allows the user and/or patient to be informed of any warnings, precautions, contra-indications, measures to be taken and limitations of use regarding the device. That information shall, where relevant, allow the user to brief the patient about any warnings, precautions, contra-indications, measures to be taken and limitations of use regarding the device. The information shall cover, where appropriate:\n\n\n\n\n\n\n\u2014\n\n\nwarnings, precautions and/or measures to be taken in the event of malfunction of the device or changes in its performance that may affect safety,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwarnings, precautions and/or measures to be taken as regards the exposure to reasonably foreseeable external influences or environmental conditions, such as magnetic fields, external electrical and electromagnetic effects, electrostatic discharge, radiation associated with diagnostic or therapeutic procedures, pressure, humidity, or temperature,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwarnings, precautions and/or measures to be taken as regards the risks of interference posed by the reasonably foreseeable presence of the device during specific diagnostic investigations, evaluations, or therapeutic treatment or other procedures such as electromagnetic interference emitted by the device affecting other equipment,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif the device is intended to administer medicinal products, tissues or cells of human or animal origin, or their derivatives, or biological substances, any limitations or incompatibility in the choice of substances to be delivered,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwarnings, precautions and/or limitations related to the medicinal substance or biological material that is incorporated into the device as an integral part of the device; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nprecautions related to materials incorporated into the device that contain or consist of CMR substances or endocrine-disrupting substances, or that could result in sensitisation or an allergic reaction by the patient or user;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(t)\n\n\nin the case of devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body and that are absorbed by or locally dispersed in the human body, warnings and precautions, where appropriate, related to the general profile of interaction of the device and its products of metabolism with other devices, medicinal products and other substances as well as contra-indications, undesirable side-effects and risks relating to overdose;\n\n\n\n\n\n\n\n\n\n\n(u)\n\n\nin the case of implantable devices, the overall qualitative and quantitative information on the materials and substances to which patients can be exposed;\n\n\n\n\n\n\n\n\n\n\n(v)\n\n\nwarnings or precautions to be taken in order to facilitate the safe disposal of the device, its accessories and the consumables used with it, if any. This information shall cover, where appropriate:\n\n\n\n\n\n\n\u2014\n\n\ninfection or microbial hazards such as explants, needles or surgical equipment contaminated with potentially infectious substances of human origin, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nphysical hazards such as from sharps.\n\n\n\n\nIf in accordance with the point\u00a0(d) of Section\u00a023.1 no instructions for use are required, this information shall be made available to the user upon request;\n\n\n\n\n\n\n\n\n\n\n(w)\n\n\nfor devices intended for use by lay persons, the circumstances in which the user should consult a healthcare professional;\n\n\n\n\n\n\n\n\n\n\n(x)\n\n\nfor the devices covered by this Regulation pursuant to Article\u00a01(2), information regarding the absence of a clinical benefit and the risks related to use of the device;\n\n\n\n\n\n\n\n\n\n\n(y)\n\n\ndate of issue of the instructions for use or, if they have been revised, date of issue and identifier of the latest revision of the instructions for use;\n\n\n\n\n\n\n\n\n\n\n(z)\n\n\na notice to the user and/or patient that any serious incident that has occurred in relation to the device should be reported to the manufacturer and the competent authority of the Member\u00a0State in which the user and/or patient is established;\n\n\n\n\n\n\n\n\n\n\n(aa)\n\n\ninformation to be supplied to the patient with an implanted device in accordance with Article\u00a018;\n\n\n\n\n\n\n\n\n\n\n(ab)\n\n\nfor devices that incorporate electronic programmable systems, including software, or software that are devices in themselves, minimum requirements concerning hardware, IT networks characteristics and IT security measures, including protection against unauthorised access, necessary to run the software as intended.\n\n\n\n\n\n\n(1)\u00a0\u00a0Regulation (EC)\u00a0No\u00a01272/2008 of the European Parliament and of the Council of 16\u00a0December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation\u00a0(EC)\u00a0No\u00a01907/2006 ( OJ\u00a0L\u00a0353, 31.12.2008, p.\u00a01).\n\n(2)\u00a0\u00a0Regulation (EC)\u00a0No\u00a01907/2006 of the European Parliament and of the Council of 18\u00a0December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) (OJ\u00a0L\u00a0396, 30.12.2006, p.\u00a01).\n\n(3)\u00a0\u00a0Regulation (EU)\u00a0No\u00a0528/2012 of the European Parliament and the Council of 22\u00a0May\u00a02012 concerning the making available on the market of and use of biocidal products (OJ\u00a0L\u00a0167, 27.6.2012, p.\u00a01).\n\n(4)\u00a0\u00a0Council Directive\u00a080/181/EEC of 20 December 1979 on the approximation of the laws of the Member\u00a0States relating to units of measurement and on the repeal of Directive\u00a071/354/EEC (OJ\u00a0L\u00a039, 15.2.1980, p.\u00a040).\n\n\n\n\n\nANNEX II\n\nTECHNICAL DOCUMENTATION\n\nThe technical documentation and, if applicable, the summary thereof to be drawn up by the manufacturer shall be presented in a clear, organised, readily searchable and unambiguous manner and shall include in particular the elements listed in this Annex.\n1.\u00a0\u00a0\u00a0DEVICE DESCRIPTION AND SPECIFICATION, INCLUDING VARIANTS AND ACCESSORIES\n1.1.\u00a0\u00a0\u00a0Device description and specification\n\n\n\n\n\n\n(a)\n\n\nproduct or trade name and a general description of the device including its intended purpose and intended users;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe Basic UDI-DI as referred to in Part C of Annex\u00a0VI assigned by the manufacturer to the device in question, as soon as identification of this device becomes based on a UDI system, or otherwise a clear identification by means of product code, catalogue number or other unambiguous reference allowing traceability;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe intended patient population and medical conditions to be diagnosed, treated and/or monitored and other considerations such as patient selection criteria, indications, contra-indications, warnings;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nprinciples of operation of the device and its mode of action, scientifically demonstrated if necessary;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe rationale for the qualification of the product as a device;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe risk class of the device and the justification for the classification rule(s) applied in accordance with Annex\u00a0VIII;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nan explanation of any novel features;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\na description of the accessories for a device, other devices and other products that are not devices, which are intended to be used in combination with it;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\na description or complete list of the various configurations/variants of the device that are intended to be made available on the market;\n\n\n\n\n\n\n\n\n\n\n(j)\n\n\na general description of the key functional elements, e.g. its parts/components (including software if appropriate), its formulation, its composition, its functionality and, where relevant, its qualitative and quantitative composition. Where appropriate, this shall include labelled pictorial representations (e.g. diagrams, photographs, and drawings), clearly indicating key parts/components, including sufficient explanation to understand the drawings and diagrams;\n\n\n\n\n\n\n\n\n\n\n(k)\n\n\na description of the raw materials incorporated into key functional elements and those making either direct contact with the human body or indirect contact with the body, e.g., during extracorporeal circulation of body fluids;\n\n\n\n\n\n\n\n\n\n\n(l)\n\n\ntechnical specifications, such as features, dimensions and performance attributes, of the device and any variants/configurations and accessories that would typically appear in the product specification made available to the user, for example in brochures, catalogues and similar publications.\n\n\n\n\n1.2.\u00a0\u00a0\u00a0Reference to previous and similar generations of the device\n\n\n\n\n\n\n(a)\n\n\nan overview of the previous generation or generations of the device produced by the manufacturer, where such devices exist;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nan overview of identified similar devices available on the Union or international markets, where such devices exist.\n\n\n\n\n2.\u00a0\u00a0\u00a0INFORMATION TO BE SUPPLIED BY THE MANUFACTURER\nA complete set of:\n\n\n\n\n\n\n\u2014\n\n\nthe label or labels on the device and on its packaging, such as single unit packaging, sales packaging, transport packaging in case of specific management conditions, in the languages accepted in the Member\u00a0States where the device is envisaged to be sold; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe instructions for use in the languages accepted in the Member\u00a0States where the device is envisaged to be sold.\n\n\n\n\n3.\u00a0\u00a0\u00a0DESIGN AND MANUFACTURING INFORMATION\n\n\n\n\n\n\n(a)\n\n\ninformation to allow the design stages applied to the device to be understood;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ncomplete information and specifications, including the manufacturing processes and their validation, their adjuvants, the continuous monitoring and the final product testing. Data shall be fully included in the technical documentation;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nidentification of all sites, including suppliers and sub-contractors, where design and manufacturing activities are performed.\n\n\n\n\n4.\u00a0\u00a0\u00a0GENERAL SAFETY AND PERFORMANCE REQUIREMENTS\nThe documentation shall contain information for the demonstration of conformity with the general safety and performance requirements set out in Annex\u00a0I that are applicable to the device taking into account its intended purpose, and shall include a justification, validation and verification of the solutions adopted to meet those requirements. The demonstration of conformity shall include:\n\n\n\n\n\n\n(a)\n\n\nthe general safety and performance requirements that apply to the device and an explanation as to why others do not apply;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe method or methods used to demonstrate conformity with each applicable general safety and performance requirement;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe harmonised standards, CS or other solutions applied; and\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe precise identity of the controlled documents offering evidence of conformity with each harmonised standard, CS or other method applied to demonstrate conformity with the general safety and performance requirements. The information referred to under this point shall incorporate a cross-reference to the location of such evidence within the full technical documentation and, if applicable, the summary technical documentation.\n\n\n\n\n5.\u00a0\u00a0\u00a0BENEFIT-RISK ANALYSIS AND RISK MANAGEMENT\nThe documentation shall contain information on:\n\n\n\n\n\n\n(a)\n\n\nthe benefit-risk analysis referred to in Sections 1 and 8 of Annex\u00a0I, and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe solutions adopted and the results of the risk management referred to in Section\u00a03 of Annex\u00a0I.\n\n\n\n\n6.\u00a0\u00a0\u00a0PRODUCT VERIFICATION AND VALIDATION\nThe documentation shall contain the results and critical analyses of all verifications and validation tests and/or studies undertaken to demonstrate conformity of the device with the requirements of this Regulation and in particular the applicable general safety and performance requirements.\n6.1.\u00a0\u00a0\u00a0Pre-clinical and clinical data\n\n\n\n\n\n\n(a)\n\n\nresults of tests, such as engineering, laboratory, simulated use and animal tests, and evaluation of published literature applicable to the device, taking into account its intended purpose, or to similar devices, regarding the pre-clinical safety of the device and its conformity with the specifications;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ndetailed information regarding test design, complete test or study protocols, methods of data analysis, in addition to data summaries and test conclusions regarding in particular:\n\n\n\n\n\n\n\u2014\n\n\nthe biocompatibility of the device including the identification of all materials in direct or indirect contact with the patient or user;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nphysical, chemical and microbiological characterisation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nelectrical safety and electromagnetic compatibility;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsoftware verification and validation (describing the software design and development process and evidence of the validation of the software, as used in the finished device. This information shall typically include the summary results of all verification, validation and testing performed both in-house and in a simulated or actual user environment prior to final release. It shall also address all of the different hardware configurations and, where applicable, operating systems identified in the information supplied by the manufacturer);\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nstability, including shelf life; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nperformance and safety.\n\n\n\n\nWhere applicable, conformity with the provisions of Directive\u00a02004/10/EC of the European Parliament and of the Council\u00a0(1) shall be demonstrated.\nWhere no new testing has been undertaken, the documentation shall incorporate a rationale for that decision. An example of such a rationale would be that biocompatibility testing on identical materials was conducted when those materials were incorporated in a previous version of the device that has been legally placed on the market or put into service;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe clinical evaluation report and its updates and the clinical evaluation plan referred to in Article\u00a061(12) and Part A of Annex\u00a0XIV;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe PMCF plan and PMCF evaluation report referred to in Part B of Annex\u00a0XIV or a justification why a PMCF is not applicable.\n\n\n\n\n6.2.\u00a0\u00a0\u00a0Additional information required in specific cases\n\n\n\n\n\n\n(a)\n\n\nWhere a device incorporates, as an integral part, a substance which, if used separately, may be considered to be a medicinal product within the meaning of point 2 of Article\u00a01 of Directive\u00a02001/83/EC, including a medicinal product derived from human blood or human plasma, as referred to in the first subparagraph\u00a0of Article\u00a01(8), a statement indicating this fact. In this case, the documentation shall identify the source of that substance and contain the data of the tests conducted to assess its safety, quality and usefulness, taking account of the intended purpose of the device.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nWhere a device is manufactured utilising tissues or cells of human or animal origin, or their derivatives, and is covered by this Regulation in accordance with points\u00a0(f) and (g) of Article\u00a01(6, and where a device incorporates, as an integral part, tissues or cells of human origin or their derivatives that have an action ancillary to that of the device and is covered by this Regulation in accordance with the first subparagraph\u00a0of Article\u00a01(10), a statement indicating this fact. In such a case, the documentation shall identify all materials of human or animal origin used and provide detailed information concerning the conformity with Sections 13.1. or 13.2., respectively, of Annex\u00a0I.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nIn the case of devices that are composed of substances or combinations of substances that are intended to be introduced into the human body and that are absorbed by or locally dispersed in the human body, detailed information, including test design, complete test or study protocols, methods of data analysis, and data summaries and test conclusions, regarding studies in relation to:\n\n\n\n\n\n\n\u2014\n\n\nabsorption, distribution, metabolism and excretion;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npossible interactions of those substances, or of their products of metabolism in the human body, with other devices, medicinal products or other substances, considering the target population, and its associated medical conditions;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nlocal tolerance; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntoxicity, including single-dose toxicity, repeat-dose toxicity, genotoxicity, carcinogenicity and reproductive and developmental toxicity, as applicable depending on the level and nature of exposure to the device.\n\n\n\n\nIn the absence of such studies, a justification shall be provided.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nIn the case of devices containing CMR or endocrine-disrupting substances referred to in Section\u00a010.4.1 of Annex\u00a0I, the justification referred to in Section\u00a010.4.2 of that Annex.\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nIn the case of devices placed on the market in a sterile or defined microbiological condition, a description of the environmental conditions for the relevant manufacturing steps. In the case of devices placed on the market in a sterile condition, a description of the methods used, including the validation reports, with respect to packaging, sterilisation and maintenance of sterility. The validation report shall address bioburden testing, pyrogen testing and, if applicable, testing for sterilant residues.\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nIn the case of devices placed on the market with a measuring function, a description of the methods used in order to ensure the accuracy as given in the specifications.\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nIf the device is to be connected to other device(s) in order to operate as intended, a description of this combination/configuration including proof that it conforms to the general safety and performance requirements when connected to any such device(s) having regard to the characteristics specified by the manufacturer.\n\n\n\n\n\n\n(1)\u00a0\u00a0Directive\u00a02004/10/EC of the European Parliament and of the Council of 11\u00a0February\u00a02004 on the harmonisation of laws, regulations and administrative provisions relating to the application of the principles of good laboratory practice and the verification of their applications for tests on chemical substances (OJ\u00a0L\u00a050, 20.2.2004, p.\u00a044).\n\n\n\n\n\nANNEX III\n\nTECHNICAL DOCUMENTATION ON POST-MARKET SURVEILLANCE\n\nThe technical documentation on post-market surveillance to be drawn up by the manufacturer in accordance with Articles\u00a083 to 86 shall be presented in a clear, organised, readily searchable and unambiguous manner and shall include in particular the elements described in this Annex.\n1.1.\u00a0\u00a0\u00a0The post-market surveillance plan drawn up in accordance with Article\u00a084.\nThe manufacturer shall prove in a post-market surveillance plan that it complies with the obligation referred to in Article\u00a083.\n\n\n\n\n\n\n(a)\n\n\nThe post-market surveillance plan shall address the collection and utilization of available information, in particular:\n\n\n\n\n\n\n\u2014\n\n\ninformation concerning serious incidents, including information from PSURs, and field safety corrective actions;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nrecords referring to non-serious incidents and data on any undesirable side-effects;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation from trend reporting;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nrelevant specialist or technical literature, databases and/or registers;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation, including feedbacks and complaints, provided by users, distributors and importers; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npublicly available information about similar medical devices.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nThe post-market surveillance plan shall cover at least:\n\n\n\n\n\n\n\u2014\n\n\na proactive and systematic process to collect any information referred to in point\u00a0(a). The process shall allow a correct characterisation of the performance of the devices and shall also allow a comparison to be made between the device and similar products available on the market;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\neffective and appropriate methods and processes to assess the collected data;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsuitable indicators and threshold values that shall be used in the continuous reassessment of the benefit-risk analysis and of the risk management as referred to in Section\u00a03 of Annex\u00a0I;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\neffective and appropriate methods and tools to investigate complaints and analyse market-related experience collected in the field;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmethods and protocols to manage the events subject to the trend report as provided for in Article\u00a088, including the methods and protocols to be used to establish any statistically significant increase in the frequency or severity of incidents as well as the observation period;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmethods and protocols to communicate effectively with competent authorities, notified bodies, economic operators and users;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreference to procedures to fulfil the manufacturers obligations laid down in Articles\u00a083, 84 and 86;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsystematic procedures to identify and initiate appropriate measures including corrective actions;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\neffective tools to trace and identify devices for which corrective actions might be necessary; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na PMCF plan as referred to in Part B of Annex\u00a0XIV, or a justification as to why a PMCF is not applicable.\n\n\n\n\n\n\n\n\n1.2.\u00a0\u00a0\u00a0The PSUR referred to in Article\u00a086 and the post-market surveillance report referred to in Article\u00a085.\n\n\n\n\n\nANNEX IV\n\nEU DECLARATION OF CONFORMITY\n\nThe EU declaration of conformity shall contain all of the following information:\n\n\n\n\n\n\n1.\n\n\nName, registered trade name or registered trade mark and, if already issued, SRN as referred to in Article\u00a031 of the manufacturer, and, if applicable, its authorised representative, and the address of their registered place of business where they can be contacted and their location be established;\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nA statement that the EU declaration of conformity is issued under the sole responsibility of the manufacturer;\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nThe Basic UDI-DI as referred to in Part C of Annex\u00a0VI;\n\n\n\n\n\n\n\n\n\n\n4.\n\n\nProduct and trade name, product code, catalogue number or other unambiguous reference allowing identification and traceability of the device covered by the EU declaration of conformity, such as a photograph, where appropriate, as well as its intended purpose. Except for the product or trade name, the information allowing identification and traceability may be provided by the Basic UDI-DI referred to in point 3;\n\n\n\n\n\n\n\n\n\n\n5.\n\n\nRisk class of the device in accordance with the rules set out in Annex\u00a0VIII;\n\n\n\n\n\n\n\n\n\n\n6.\n\n\nA statement that the device that is covered by the present declaration is in conformity with this Regulation and, if applicable, with any other relevant Union legislation that provides for the issuing of an EU declaration of conformity;\n\n\n\n\n\n\n\n\n\n\n7.\n\n\nReferences to any CS used and in relation to which conformity is declared;\n\n\n\n\n\n\n\n\n\n\n8.\n\n\nWhere applicable, the name and identification number of the notified body, a description of the conformity assessment procedure performed and identification of the certificate or certificates issued;\n\n\n\n\n\n\n\n\n\n\n9.\n\n\nWhere applicable, additional information;\n\n\n\n\n\n\n\n\n\n\n10.\n\n\nPlace and date of issue of the declaration, name and function of the person who signed it as well as an indication for, and on behalf of whom, that person signed, signature.\n\n\n\n\n\n\n\n\n\nANNEX V\n\nCE MARKING OF CONFORMITY\n\n\n\n\n\n\n\n\n\n1.\n\n\nThe CE marking shall consist of the initials \u2018CE\u2019 taking the following form:\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nIf the CE marking is reduced or enlarged, the proportions given in the above graduated drawing shall be respected.\n\n\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nThe various components of the CE marking shall have substantially the same vertical dimension, which may not be less than 5 mm. This minimum dimension may be waived for small-scale devices.\n\n\n\n\n\n\n\n\n\nANNEX VI\n\nINFORMATION TO BE SUBMITTED UPON THE REGISTRATION OF DEVICES AND ECONOMIC OPERATORS IN ACCORDANCE WITH ARTICLES 29(4) AND 31, CORE DATA ELEMENTS TO BE PROVIDED TO THE UDI DATABASE TOGETHER WITH THE UDI-DI IN ACCORDANCE WITH ARTICLES 28 AND 29, AND THE UDI SYSTEM\n\nPART A\n\nINFORMATION TO BE SUBMITTED UPON THE REGISTRATION OF DEVICES AND ECONOMIC OPERATORS IN ACCORDANCE WITH ARTICLES 29(4) AND 31\n\nManufacturers or, when applicable, authorised representatives, and, when applicable, importers shall submit the information referred to in Section\u00a01 and shall ensure that the information on their devices referred to in Section\u00a02 is complete, correct and updated by the relevant party.\n1.\u00a0\u00a0\u00a0Information relating to the economic operator\n\n\n\n\n\n\n1.1.\n\n\ntype of economic operator(manufacturer, authorised representative, or importer),\n\n\n\n\n\n\n\n\n\n\n1.2.\n\n\nname, address and contact details of the economic operator,\n\n\n\n\n\n\n\n\n\n\n1.3.\n\n\nwhere submission of information is carried out by another person on behalf of any of the economic operators mentioned under Section 1.1, the name, address and contact details of that person,\n\n\n\n\n\n\n\n\n\n\n1.4.\n\n\nname address and contact details of the person or persons responsible for regulatory compliance referred to in Article\u00a015.\n\n\n\n\n2.\u00a0\u00a0\u00a0Information relating to the device\n\n\n\n\n\n\n2.1.\n\n\nBasic UDI-DI,\n\n\n\n\n\n\n\n\n\n\n2.2.\n\n\ntype, number and expiry date of the certificate issued by the notified body and the name or identification number of that notified body and the link to the information that appears on the certificate and was entered by the notified body in the electronic system on notified bodies and certificates,\n\n\n\n\n\n\n\n\n\n\n2.3.\n\n\nMember\u00a0State in which the device is to or has been placed on the market in the Union,\n\n\n\n\n\n\n\n\n\n\n2.4.\n\n\nin the case of class IIa, class IIb or class III devices: Member\u00a0States where the device is or is to be made available,\n\n\n\n\n\n\n\n\n\n\n2.5.\n\n\nrisk class of the device,\n\n\n\n\n\n\n\n\n\n\n2.6.\n\n\nreprocessed single-use device (y/n),\n\n\n\n\n\n\n\n\n\n\n2.7.\n\n\npresence of a substance which, if used separately, may be considered to be a medicinal product and name of that substance,\n\n\n\n\n\n\n\n\n\n\n2.8.\n\n\npresence of a substance which, if used separately, may be considered to be a medicinal product derived from human blood or human plasma and name of this substance,\n\n\n\n\n\n\n\n\n\n\n2.9.\n\n\npresence of tissues or cells of human origin, or their derivatives (y/n),\n\n\n\n\n\n\n\n\n\n\n2.10.\n\n\npresence of tissues or cells of animal origin, or their derivatives, as referred to in Regulation\u00a0(EU)\u00a0No\u00a0722/2012 (y/n),\n\n\n\n\n\n\n\n\n\n\n2.11.\n\n\nwhere applicable, the single identification number of the clinical investigation or investigations conducted in relation to the device or a link to the clinical investigation registration in the electronic system on clinical investigations,\n\n\n\n\n\n\n\n\n\n\n2.12.\n\n\nin the case of devices listed in Annex\u00a0XVI, specification as to whether the intended purpose of the device is other than a medical purpose,\n\n\n\n\n\n\n\n\n\n\n2.13.\n\n\nin the case of devices designed and manufactured by another legal or natural person as referred in Article\u00a010(15), the name, address and contact details of that legal or natural person,\n\n\n\n\n\n\n\n\n\n\n2.14.\n\n\nin the case of class III or implantable devices, the summary of safety and clinical performance,\n\n\n\n\n\n\n\n\n\n\n2.15.\n\n\nstatus of the device (on the market, no longer placed on the market, recalled, field safety corrective action initiated).\n\n\n\n\nPART B\n\nCORE DATA ELEMENTS TO BE PROVIDED TO THE UDI DATABASE TOGETHER WITH THE UDI-DI IN ACCORDANCE WITH ARTICLES 28 AND 29\n\nThe manufacturer shall provide to the UDI database the UDI-DI and all of the following information relating to the manufacturer and the device:\n\n\n\n\n\n\n1.\n\n\nquantity per package configuration,\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nthe Basic UDI-DI as referred to in Article\u00a029 and any additional UDI-DIs,\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nthe manner in which production of the device is controlled (expiry date or manufacturing date, lot number, serial number),\n\n\n\n\n\n\n\n\n\n\n4.\n\n\nif applicable, the unit of use UDI-DI (where a UDI is not labelled on the device at the level of its unit of use, a \u2018unit of use\u2019 DI shall be assigned so as to associate the use of a device with a patient),\n\n\n\n\n\n\n\n\n\n\n5.\n\n\nname and address of the manufacturer (as indicated on the label),\n\n\n\n\n\n\n\n\n\n\n6.\n\n\nthe SRN issued in accordance with Article\u00a031(2),\n\n\n\n\n\n\n\n\n\n\n7.\n\n\nif applicable, name and address of the authorised representative (as indicated on the label),\n\n\n\n\n\n\n\n\n\n\n8.\n\n\nthe medical device nomenclature code as provided for in Article\u00a026,\n\n\n\n\n\n\n\n\n\n\n9.\n\n\nrisk class of the device,\n\n\n\n\n\n\n\n\n\n\n10.\n\n\nif applicable, name or trade name,\n\n\n\n\n\n\n\n\n\n\n11.\n\n\nif applicable, device model, reference, or catalogue number,\n\n\n\n\n\n\n\n\n\n\n12.\n\n\nif applicable, clinical size (including volume, length, gauge, diameter),\n\n\n\n\n\n\n\n\n\n\n13.\n\n\nadditional product description (optional),\n\n\n\n\n\n\n\n\n\n\n14.\n\n\nif applicable, storage and/or handling conditions (as indicated on the label or in the instructions for use),\n\n\n\n\n\n\n\n\n\n\n15.\n\n\nif applicable, additional trade names of the device,\n\n\n\n\n\n\n\n\n\n\n16.\n\n\nlabelled as a single-use device (y/n),\n\n\n\n\n\n\n\n\n\n\n17.\n\n\nif applicable, the maximum number of reuses,\n\n\n\n\n\n\n\n\n\n\n18.\n\n\ndevice labelled sterile (y/n),\n\n\n\n\n\n\n\n\n\n\n19.\n\n\nneed for sterilisation before use (y/n),\n\n\n\n\n\n\n\n\n\n\n20.\n\n\ncontaining latex (y/n),\n\n\n\n\n\n\n\n\n\n\n21.\n\n\nwhere applicable, information labelled in accordance with Section\u00a010.4.5 of Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n22.\n\n\nURL for additional information, such as electronic instructions for use (optional),\n\n\n\n\n\n\n\n\n\n\n23.\n\n\nif applicable, critical warnings or contra-indications,\n\n\n\n\n\n\n\n\n\n\n24.\n\n\nstatus of the device (on the market, no longer placed on the market, recalled, field safety corrective action initiated).\n\n\n\n\nPART C\n\nTHE UDI SYSTEM\n\n1.\u00a0\u00a0\u00a0Definitions\nAutomatic identification and data capture (\u2018AIDC\u2019)\nAIDC is a technology used to automatically capture data. AIDC technologies include bar codes, smart cards, biometrics and RFID.\nBasic UDI-DI\nThe Basic UDI-DI is the primary identifier of a device model. It is the DI assigned at the level of the device unit of use. It is the main key for records in the UDI database and is referenced in relevant certificates and EU declarations of conformity.\nUnit of Use DI\nThe Unit of Use DI serves to associate the use of a device with a patient in instances in which a UDI is not labelled on the individual device at the level of its unit of use, for example in the event of several units of the same device being packaged together.\nConfigurable device\nA configurable device is a device that consists of several components which can be assembled by the manufacturer in multiple configurations. Those individual components may be devices in themselves.\nConfigurable devices include computed tomography (CT) systems, ultrasound systems, anaesthesia systems, physiological Monitoring systems, radiology information systems\u00a0(RIS).\nConfiguration\nConfiguration is a combination of items of equipment, as specified by the manufacturer, that operate together as a device to achieve an intended purpose. The combination of items may be modified, adjusted or customized to meet specific needs.\nConfigurations include inter alia:\n\n\n\n\n\n\n\u2014\n\n\ngantries, tubes, tables, consoles and other items of equipment that can be configured/combined to deliver an intended function in computed tomography.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nventilators, breathing circuits, vaporizers combined to deliver an intended function in anaesthesia.\n\n\n\n\nUDI-DI\nThe UDI-DI is a unique numeric or alphanumeric code specific to a model of device and that is also used as the \u2018access key\u2019 to information stored in a UDI database.\nHuman Readable Interpretation (\u2018HRI\u2019)\nHRI is a legible interpretation of the data characters encoded in the UDI carrier.\nPackaging levels\nPackaging levels means the various levels of device packaging that contain a defined quantity of devices, such as a carton or case.\nUDI-PI\nThe UDI-PI is a numeric or alphanumeric code that identifies the unit of device production.\nThe different types of UDI-PIs include serial number, lot number, software identification and manufacturing or expiry date or both types of date.\nRadio Frequency Identification RFID\nRFID is a technology that uses communication through the use of radio waves to exchange data between a reader and an electronic tag attached to an object, for the purpose of identification.\nShipping containers\nA shipping container is a container in relation to which traceability is controlled by a process specific to logistics systems.\nUnique Device Identifier (\u2018UDI\u2019)\nThe UDI is a series of numeric or alphanumeric characters that is created through a globally accepted device identification and coding standard. It allows the unambiguous identification of a specific device on the market. The UDI is comprised of the UDI-DI and the UDI-PI.\nThe word \u2018Unique\u2019 does not imply serialisation of individual production units.\nUDI carrier\nThe UDI carrier is the means of conveying the UDI by using AIDC and, if applicable, its\u00a0HRI.\nUDI carriers include, inter alia, ID/linear bar code, 2D/Matrix bar code, RFID.\n2.\u00a0\u00a0\u00a0General requirements\n2.1.\u00a0\u00a0\u00a0The affixing of the UDI is an additional requirement \u2014 it does not replace any other marking or labelling requirements laid down in Annex\u00a0I to this Regulation.\n2.2.\u00a0\u00a0\u00a0The manufacturer shall assign and maintain unique UDIs for its devices.\n2.3.\u00a0\u00a0\u00a0Only the manufacturer may place the UDI on the device or its packaging.\n2.4.\u00a0\u00a0\u00a0Only coding standards provided by issuing entities designated by the Commission pursuant to Article\u00a027(2) may be used.\n3.\u00a0\u00a0\u00a0The UDI\n3.1.\u00a0\u00a0\u00a0A UDI shall be assigned to the device itself or its packaging. Higher levels of packaging shall have their own UDI.\n3.2.\u00a0\u00a0\u00a0Shipping containers shall be exempted from the requirement in Section\u00a03.1. By way of example, a UDI shall not be required on a logistics unit; where a healthcare provider orders multiple devices using the UDI or model number of individual devices and the manufacturer places those devices in a container for shipping or to protect the individually packaged devices, the container (logistics unit) shall not be subject to UDI requirements.\n3.3.\u00a0\u00a0\u00a0The UDI shall contain two parts: a UDI-DI and a UDI-PI.\n3.4.\u00a0\u00a0\u00a0The UDI-DI shall be unique at each level of device packaging.\n3.5.\u00a0\u00a0\u00a0If a lot number, serial number, software identification or expiry date appears on the label, it shall be part of the UDI-PI. If there is also a manufacturing date on the label, it does not need to be included in the UDI-PI. If there is only a manufacturing date on the label, this shall be used as the UDI-PI.\n3.6.\u00a0\u00a0\u00a0Each component that is considered to be a device and is commercially available on its own shall be assigned a separate UDI unless the components are part of a configurable device that is marked with its own UDI.\n3.7.\u00a0\u00a0\u00a0Systems and procedure packs as referred to in Article\u00a022 shall be assigned and bear their own UDI.\n3.8.\u00a0\u00a0\u00a0The manufacturer shall assign the UDI to a device following the relevant coding standard.\n3.9.\u00a0\u00a0\u00a0A new UDI-DI shall be required whenever there is a change that could lead to misidentification of the device and/or ambiguity in its traceability; in particular, any change of one of the following UDI database data elements shall require a new UDI-DI:\n\n\n\n\n\n\n(a)\n\n\nname or trade name,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ndevice version or model,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nlabelled as single use,\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\npackaged sterile,\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nneed for sterilization before use,\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nquantity of devices provided in a package,\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\ncritical warnings or contra-indications: e.g. containing latex or DEHP.\n\n\n\n\n3.10.\u00a0\u00a0\u00a0Manufacturers that repackage and/or relabel devices, with their own label shall retain a record of the original device manufacturer's UDI.\n4.\u00a0\u00a0\u00a0UDI carrier\n4.1.\u00a0\u00a0\u00a0The UDI carrier (AIDC and HRI representation of the UDI) shall be placed on the label or on the device itself and on all higher levels of device packaging. Higher levels do not include shipping containers.\n4.2.\u00a0\u00a0\u00a0In the event of there being significant space constraints on the unit of use packaging, the UDI carrier may be placed on the next higher packaging level.\n4.3.\u00a0\u00a0\u00a0For single-use devices of classes I and IIa packaged and labelled individually, the UDI\u00a0carrier shall not be required to appear on the packaging but it shall appear on a higher level of packaging, e.g. a carton containing several individually packaged devices. However, when the healthcare provider is not expected to have access, in cases such as in home healthcare settings, to the higher level of device packaging, the UDI shall be placed on the packaging of the individual device.\n4.4.\u00a0\u00a0\u00a0For devices exclusively intended for retail point of sale the UDI-PIs in AIDC shall not be required to appear on the point of sale packaging.\n4.5.\u00a0\u00a0\u00a0When AIDC carriers other than the UDI carrier are part of the product labelling, the UDI\u00a0carrier shall be readily identifiable.\n4.6.\u00a0\u00a0\u00a0If linear bar codes are used, the UDI-DI and UDI-PI may be concatenated or non-concatenated in two or more bar codes. All parts and elements of the linear bar code shall be distinguishable and identifiable.\n4.7.\u00a0\u00a0\u00a0If there are significant constraints limiting the use of both AIDC and HRI on the label, only the AIDC format shall be required to appear on the label. For devices intended to be used outside healthcare facilities, such as devices for home care, the HRI shall however appear on the label even if this results in there being no space for the AIDC.\n4.8.\u00a0\u00a0\u00a0The HRI format shall follow the rules of the UDI code-issuing entity.\n4.9.\u00a0\u00a0\u00a0If the manufacturer is using RFID technology, a linear or 2D bar code in line with the standard provided by the issuing entities shall also be provided on the label.\n4.10.\u00a0\u00a0\u00a0Devices that are reusable shall bear a UDI carrier on the device itself. The UDI carrier for reusable devices that require cleaning, disinfection, sterilisation or refurbishing between patient uses shall be permanent and readable after each process performed to make the device ready for the subsequent use throughout the intended lifetime of the device. The requirement of this Section\u00a0shall not apply to devices in the following circumstances:\n\n\n\n\n\n\n(a)\n\n\nany type of direct marking would interfere with the safety or performance of the device;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe device cannot be directly marked because it is not technologically feasible.\n\n\n\n\n4.11.\u00a0\u00a0\u00a0The UDI carrier shall be readable during normal use and throughout the intended lifetime of the device.\n4.12.\u00a0\u00a0\u00a0If the UDI carrier is readily readable or, in the case of AIDC, scannable, through the device's packaging, the placing of the UDI carrier on the packaging shall not be required.\n4.13.\u00a0\u00a0\u00a0In the case of single finished devices made up of multiple parts that must be assembled before their first use, it shall be sufficient to place the UDI carrier on only one part of each device.\n4.14.\u00a0\u00a0\u00a0The UDI carrier shall be placed in a manner such that the AIDC can be accessed during normal operation or storage.\n4.15.\u00a0\u00a0\u00a0Bar code carriers that include both a UDI-DI and a UDI-PI may also include essential data for the device to operate or other data.\n5.\u00a0\u00a0\u00a0General principles of the UDI database\n5.1.\u00a0\u00a0\u00a0The UDI database shall support the use of all core UDI database data elements referred to in Part B of this Annex.\n5.2.\u00a0\u00a0\u00a0Manufacturers shall be responsible for the initial submission and updates of the identifying information and other device data elements in the UDI database.\n5.3.\u00a0\u00a0\u00a0Appropriate methods/procedures for validation of the data provided shall be implemented.\n5.4.\u00a0\u00a0\u00a0Manufacturers shall periodically verify the correctness of all of the data relevant to devices they have placed on the market, except for devices that are no longer available on the market.\n5.5.\u00a0\u00a0\u00a0The presence of the device UDI-DI in the UDI database shall not be assumed to mean that the device is in conformity with this Regulation.\n5.6.\u00a0\u00a0\u00a0The database shall allow for the linking of all the packaging levels of the device.\n5.7.\u00a0\u00a0\u00a0The data for new UDI-DIs shall be available at the time the device is placed on the market.\n5.8.\u00a0\u00a0\u00a0Manufacturers shall update the relevant UDI database record within 30 days of a change being made to an element, which does not require a new UDI-DI.\n5.9.\u00a0\u00a0\u00a0Internationally-accepted standards for data submission and updates shall, wherever possible, be used by the UDI database.\n5.10.\u00a0\u00a0\u00a0The user interface of the UDI database shall be available in all official languages of the Union. The use of free-text fields shall, however, be minimized in order to reduce translations.\n5.11.\u00a0\u00a0\u00a0Data relating to devices that are no longer available on the market shall be retained in the UDI database.\n6.\u00a0\u00a0\u00a0Rules for specific device types\n6.1.\u00a0\u00a0\u00a0Implantable devices:\n\n\n\n\n\n\n6.1.1.\n\n\nImplantable devices shall, at their lowest level of packaging (\u2018unit packs\u2019), be identified, or marked using AIDC, with a UDI (UDI-DI + UDI-PI);\n\n\n\n\n\n\n\n\n\n\n6.1.2.\n\n\nThe UDI-PI shall have at least the following characteristics:\n\n\n\n\n\n\n(a)\n\n\nthe serial number for active implantable devices,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe serial number or lot number for other implantable devices.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n6.1.3.\n\n\nThe UDI of the implantable device shall be identifiable prior to implantation.\n\n\n\n\n6.2.\u00a0\u00a0\u00a0Reusable devices requiring cleaning, disinfection, sterilisation or refurbishing between uses\n6.2.1.\u00a0\u00a0\u00a0The UDI of such devices shall be placed on the device and be readable after each procedure to make the device ready for the next use.\n6.2.2.\u00a0\u00a0\u00a0The UDI-PI characteristics such as the lot or serial number shall be defined by the manufacturer.\n6.3.\u00a0\u00a0\u00a0Systems and procedure packs as referred to in Article\u00a022\n6.3.1.\u00a0\u00a0\u00a0The natural or legal person referred to in Article\u00a022 shall be responsible for identifying the system or procedure pack with a UDI including both UDI-DI and UDI-PI.\n6.3.2.\u00a0\u00a0\u00a0Device contents of system or procedure packs shall bear a UDI carrier on their packaging or on the device itself.\nExemptions:\n\n\n\n\n\n\n(a)\n\n\nindividual single-use disposable devices, the uses of which are generally known to the persons by whom they are intended to be used, which are contained within a system or procedure pack, and which are not intended for individual use outside the context of the system or procedure pack, shall not be required to bear their own UDI\u00a0carrier;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ndevices that are exempted from bearing a UDI carrier on the relevant level of packaging shall not be required to bear a UDI carrier when included within a system or procedure pack.\n\n\n\n\n6.3.3.\u00a0\u00a0\u00a0Placement of the UDI carrier on systems or procedure packs\n\n\n\n\n\n\n(a)\n\n\nThe system or procedure pack UDI carrier shall as a general rule be affixed to the outside of the packaging.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nThe UDI carrier shall be readable, or, in the case of AIDC, scannable, whether placed on the outside of the packaging of the system or procedure pack or inside transparent packaging.\n\n\n\n\n6.4.\u00a0\u00a0\u00a0Configurable devices:\n6.4.1.\u00a0\u00a0\u00a0A UDI shall be assigned to the configurable device in its entirety and shall be called the configurable device UDI.\n6.4.2.\u00a0\u00a0\u00a0The configurable device UDI-DI shall be assigned to groups of configurations, not per configuration within the group.\u00a0A group of configurations is defined as the collection of possible configurations for a given device as described in the technical documentation.\n6.4.3.\u00a0\u00a0\u00a0A configurable device UDI-PI shall be assigned to each individual configurable device.\n6.4.4.\u00a0\u00a0\u00a0The carrier of the configurable device UDI shall be placed on the assembly that is most unlikely to be exchanged during the lifetime of the system and shall be identified as the configurable device UDI.\n6.4.5.\u00a0\u00a0\u00a0Each component that is considered a device and is commercially available on its own shall be assigned a separate UDI.\n6.5.\u00a0\u00a0\u00a0Device Software\n6.5.1.\u00a0\u00a0\u00a0UDI assignment Criteria\nThe UDI shall be assigned at the system level of the software. Only software which is commercially available on its own and software which constitutes a device in itself shall be subject to that requirement.\nThe software identification shall be considered to be the manufacturing control mechanism and shall be displayed in the UDI-PI.\n6.5.2.\u00a0\u00a0\u00a0A new UDI-DI shall be required whenever there is a modification that changes:\n\n\n\n\n\n\n(a)\n\n\nthe original performance;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe safety or the intended use of the software;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\ninterpretation of data.\n\n\n\n\nSuch modifications include new or modified algorithms, database structures, operating platform, architecture or new user interfaces or new channels for interoperability.\n6.5.3.\u00a0\u00a0\u00a0Minor software revisions shall require a new UDI-PI and not a new UDI-DI.\nMinor software revisions are generally associated with bug fixes, usability enhancements that are not for safety purposes, security patches or operating efficiency.\nMinor software revisions shall be identified by a manufacturer-specific form of identification.\n6.5.4.\u00a0\u00a0\u00a0UDI placement criteria for software\n\n\n\n\n\n\n(a)\n\n\nwhere the software is delivered on a physical medium, e.g. CD or DVD, each packaging level shall bear the human readable and AIDC representation of the complete UDI. The UDI that is applied to the physical medium containing the software and its packaging shall be identical to the UDI assigned to the system level software;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe UDI shall be provided on a readily accessible screen for the user in an easily-readable plain-text format, such as an \u2018about\u2019 file, or included on the start-up screen;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nsoftware lacking a user interface such as middleware for image conversion, shall be capable of transmitting the UDI through an application programming interface (API);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nonly the human readable portion of the UDI shall be required in electronic displays of the software. The marking of UDI using AIDC shall not be required in the electronic displays, such as \u2018about\u2019 menu, splash screen etc.;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe human readable format of the UDI for the software shall include the Application Identifiers (AI) for the standard used by the issuing entities, so as to assist the user in identifying the UDI and determining which standard is being used to create the UDI.\n\n\n\n\n\n\n\n\n\nANNEX VII\n\nREQUIREMENTS TO BE MET BY NOTIFIED BODIES\n\n1.\u00a0\u00a0\u00a0ORGANISATIONAL AND GENERAL REQUIREMENTS\n1.1.\u00a0\u00a0\u00a0Legal status and organisational structure\n1.1.1.\u00a0\u00a0\u00a0Each notified body shall be established under the national law of a Member\u00a0State, or under the law of a third country with which the Union has concluded an agreement in this respect. Its legal personality and status shall be fully documented. Such documentation shall include information about ownership and the legal or natural persons exercising control over the notified body.\n1.1.2.\u00a0\u00a0\u00a0If the notified body is a legal entity that is part of a larger organisation, the activities of that organisation as well as its organisational structure and governance, and the relationship with the notified body shall be clearly documented. In such cases, the requirements of Section\u00a01.2 are applicable to both the notified body and the organisation to which it belongs.\n1.1.3.\u00a0\u00a0\u00a0If a notified body wholly or partly owns legal entities established in a Member\u00a0State or in a third country or is owned by another legal entity, the activities and responsibilities of those entities, as well as their legal and operational relationships with the notified body, shall be clearly defined and documented. Personnel of those entities performing conformity assessment activities under this Regulation shall be subject to the applicable requirements of this Regulation.\n1.1.4.\u00a0\u00a0\u00a0The organisational structure, allocation of responsibilities, reporting lines and operation of the notified body shall be such that they ensure that there is confidence in the performance by the notified body and in the results of the conformity assessment activities it conducts.\n1.1.5.\u00a0\u00a0\u00a0The notified body shall clearly document its organisational structure and the functions, responsibilities and authority of its top-level management and of other personnel who may have an influence upon the performance by the notified body and upon the results of its conformity assessment activities.\n1.1.6.\u00a0\u00a0\u00a0The notified body shall identify the persons in top-level management that have overall authority and responsibility for each of the following:\n\n\n\n\n\n\n\u2014\n\n\nthe provision of adequate resources for conformity assessment activities;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe development of procedures and policies for the operation of the notified body;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe supervision of implementation of the procedures, policies and quality management systems of the notified body;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe supervision of the notified body's finances;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe activities and decisions taken by the notified body, including contractual agreements;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe delegation of authority to personnel and/or committees, where necessary, for the performance of defined activities;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe interaction with the authority responsible for notified bodies and the obligations regarding communications with other competent authorities, the Commission and other notified bodies.\n\n\n\n\n1.2.\u00a0\u00a0\u00a0Independence and impartiality\n1.2.1.\u00a0\u00a0\u00a0The notified body shall be a third-party body that is independent of the manufacturer of the device in relation to which it performs conformity assessment activities. The notified body shall also be independent of any other economic operator having an interest in the device as well as of any competitors of the manufacturer. This does not preclude the notified body from carrying out conformity assessment activities for competing manufacturers.\n1.2.2.\u00a0\u00a0\u00a0The notified body shall be organised and operated so as to safeguard the independence, objectivity and impartiality of its activities. The notified body shall document and implement a structure and procedures for safeguarding impartiality and for promoting and applying the principles of impartiality throughout its organisation, personnel and assessment activities. Such procedures shall provide for the identification, investigation and resolution of any case in which a conflict of interest may arise, including involvement in consultancy services in the field of devices prior to taking up employment with the notified body. The investigation, outcome and its resolution shall be documented.\n1.2.3.\u00a0\u00a0\u00a0The notified body, its top-level management and the personnel responsible for carrying out the conformity assessment tasks shall not:\n\n\n\n\n\n\n(a)\n\n\nbe the designer, manufacturer, supplier, installer, purchaser, owner or maintainer of devices which they assess, nor the authorised representative of any of those parties. Such restriction shall not preclude the purchase and use of assessed devices that are necessary for the operations of the notified body and the conduct of the conformity assessment, or the use of such devices for personal purposes;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nbe involved in the design, manufacture or construction, marketing, installation and use, or maintenance of the devices for which they are designated, nor represent the parties engaged in those activities;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nengage in any activity that may conflict with their independence of judgement or integrity in relation to conformity assessment activities for which they are designated;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\noffer or provide any service which may jeopardise the confidence in their independence, impartiality or objectivity. In particular, they shall not offer or provide consultancy services to the manufacturer, its authorised representative, a supplier or a commercial competitor as regards the design, construction, marketing or maintenance of devices or processes under assessment, and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nbe linked to any organisation which itself provides consultancy services as referred to in point\u00a0(d). Such restriction does not preclude general training activities that are not client specific and that relate to regulation of devices or to related standards.\n\n\n\n\n1.2.4.\u00a0\u00a0\u00a0Involvement in consultancy services in the field of devices prior to taking up employment with a notified body shall be fully documented at the time of employment and potential conflicts of interest shall be monitored and resolved in accordance with this Annex. Personnel who were formerly employed by a specific client, or provided consultancy services in the field of devices to that specific client prior to taking up employment with a notified body, shall not be assigned for conformity assessment activities for that specific client or companies belonging to the same group for a period of three years.\n1.2.5.\u00a0\u00a0\u00a0The impartiality of notified bodies, of their top-level management and of the assessment personnel shall be guaranteed. The level of the remuneration of the top-level management and assessment personnel of a notified body and subcontractors, involved in assessment activities shall not depend on the results of the assessments. Notified bodies shall make publicly available the declarations of interest of their top-level management.\n1.2.6.\u00a0\u00a0\u00a0If a notified body is owned by a public entity or institution, independence and absence of any conflict of interest shall be ensured and documented between, on the one hand, the authority responsible for notified bodies and/or the competent authority and, on the other hand, the notified body.\n1.2.7.\u00a0\u00a0\u00a0The notified body shall ensure and document that the activities of its subsidiaries or subcontractors, or of any associated body, including the activities of its owners do not affect its independence, impartiality or the objectivity of its conformity assessment activities.\n1.2.8.\u00a0\u00a0\u00a0The notified body shall operate in accordance with a set of consistent, fair and reasonable terms and conditions, taking into account the interests of small and medium-sized enterprises as defined in Recommendation\u00a02003/361/EC in relation to fees.\n1.2.9.\u00a0\u00a0\u00a0The requirements laid down in this Section\u00a0in no way preclude exchanges of technical information and regulatory guidance between a notified body and a manufacturer applying for conformity assessment.\n1.3.\u00a0\u00a0\u00a0Confidentiality\n1.3.1.\u00a0\u00a0\u00a0The notified body shall have documented procedures in place ensuring that its personnel, committees, subsidiaries, subcontractors, and any associated body or personnel of external bodies respect the confidentiality of the information which comes into its possession during the performance of conformity assessment activities, except when disclosure is required by law.\n1.3.2.\u00a0\u00a0\u00a0The personnel of a notified body shall observe professional secrecy in carrying out their tasks under this Regulation or any provision of national law giving effect to it, except in relation to the authorities responsible for notified bodies, competent authorities for medical devices in the Member\u00a0States or the Commission. Proprietary rights shall be protected. The notified body shall have documented procedures in place in respect of the requirements of this Section.\n1.4.\u00a0\u00a0\u00a0Liability\n1.4.1.\u00a0\u00a0\u00a0The notified body shall take out appropriate liability insurance for its conformity assessment activities, unless liability is assumed by the Member\u00a0State in question in accordance with national law or that Member\u00a0State is directly responsible for the conformity assessment.\n1.4.2.\u00a0\u00a0\u00a0The scope and overall financial value of the liability insurance shall correspond to the level and geographic scope of activities of the notified body and be commensurate with the risk profile of the devices certified by the notified body. The liability insurance shall cover cases where the notified body may be obliged to withdraw, restrict or suspend certificates.\n1.5.\u00a0\u00a0\u00a0Financial requirements\nThe notified body shall have at its disposal the financial resources required to conduct its conformity assessment activities within its scope of designation and related business operations. It shall document and provide evidence of its financial capacity and its long-term economic viability, taking into account, where relevant, any specific circumstances during an initial start-up phase.\n1.6.\u00a0\u00a0\u00a0Participation in coordination activities\n1.6.1.\u00a0\u00a0\u00a0The notified body shall participate in, or ensure that its assessment personnel is informed of, any relevant standardisation activities and in the activities of the notified body coordination group referred to in Article\u00a049 and that its assessment and decision-making personnel are informed of all relevant legislation, guidance and best practice documents adopted in the framework of this Regulation.\n1.6.2.\u00a0\u00a0\u00a0The notified body shall take into consideration guidance and best practice documents.\n2.\u00a0\u00a0\u00a0QUALITY MANAGEMENT REQUIREMENTS\n2.1.\u00a0\u00a0\u00a0The notified body shall establish, document, implement, maintain and operate a quality management system that is appropriate to the nature, area and scale of its conformity assessment activities and is capable of supporting and demonstrating the consistent fulfilment of the requirements of this Regulation.\n2.2.\u00a0\u00a0\u00a0The quality management system of the notified body shall address at least the following:\n\n\n\n\n\n\n\u2014\n\n\nmanagement system structure and documentation, including policies and objectives for its activities;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npolicies for assignment of activities and responsibilities to personnel;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nassessment and decision-making processes in accordance with the tasks, responsibilities and role of the notified body's personnel and top-level management;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe planning, conduct, evaluation and, if necessary, adaptation of its conformity assessment procedures;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncontrol of documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncontrol of records;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmanagement reviews;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninternal audits;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncorrective and preventive actions;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncomplaints and appeals; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncontinuous training.\n\n\n\n\nWhere documents are used in various languages, the notified body shall ensure and control that they have the same content.\n2.3.\u00a0\u00a0\u00a0The top-level management of the notified body shall ensure that the quality management system is fully understood, implemented and maintained throughout the notified body organisation including subsidiaries and subcontractors involved in conformity assessment activities pursuant to this Regulation.\n2.4.\u00a0\u00a0\u00a0The notified body shall require all personnel to formally commit themselves by a signature or equivalent to comply with the procedures defined by the notified body. That commitment shall cover aspects relating to confidentiality and to independence from commercial and other interests, and any existing or prior association with clients. The personnel shall be required to complete written statements indicating their compliance with confidentiality, independence and impartiality principles.\n3.\u00a0\u00a0\u00a0RESOURCE REQUIREMENTS\n3.1.\u00a0\u00a0\u00a0General\n3.1.1.\u00a0\u00a0\u00a0Notified bodies shall be capable of carrying out all the tasks falling to them under this Regulation with the highest degree of professional integrity and the requisite competence in the specific field, whether those tasks are carried out by notified bodies themselves or on their behalf and under their responsibility.\nIn particular, notified bodies shall have the necessary personnel and possess or have access to all equipment, facilities and competence needed to perform properly the technical, scientific and administrative tasks entailed in the conformity assessment activities in relation to which they have been designated.\nSuch requirement presupposes at all times and for each conformity assessment procedure and each type of devices in relation to which they have been designated, that the notified body has permanent availability of sufficient administrative, technical and scientific personnel who possess experience and knowledge relating to the relevant devices and the corresponding technologies. Such personnel shall be in sufficient numbers to ensure that the notified body in question can perform the conformity assessment tasks, including the assessment of the medical functionality, clinical evaluations and the performance and safety of devices, for which it has been designated, having regard to the requirements of this Regulation, in particular, those set out in Annex\u00a0I.\nA notified body's cumulative competences shall be such as to enable it to assess the types of devices for which it is designated. The notified body shall have sufficient internal competence to critically evaluate assessments conducted by external expertise. Tasks which a notified body is precluded from subcontracting are set out in Section\u00a04.1.\nPersonnel involved in the management of the operation of a notified body's conformity assessment activities for devices shall have appropriate knowledge to set up and operate a system for the selection of assessment and verification staff, for verification of their competence, for authorisation and allocation of their tasks, for organisation of their initial and ongoing training and for the assignment of their duties and the monitoring of those staff, in order to ensure that personnel who carry out and perform assessment and verification operations are competent to fulfil the tasks required of them.\nThe notified body shall identify at least one individual within its top-level management as having overall responsibility for all conformity assessment activities in relation to devices.\n3.1.2.\u00a0\u00a0\u00a0The notified body shall ensure that personnel involved in conformity assessment activities maintain their qualification and expertise by implementing a system for exchange of experience and a continuous training and education programme.\n3.1.3.\u00a0\u00a0\u00a0The notified body shall clearly document the extent and limits of duties and responsibilities and the level of authorisation of the personnel, including any subcontractors and external experts, involved in conformity assessment activities and inform those personnel accordingly.\n3.2.\u00a0\u00a0\u00a0Qualification criteria in relation to personnel\n3.2.1.\u00a0\u00a0\u00a0The Notified Body shall establish and document qualification criteria and procedures for selection and authorisation of persons involved in conformity assessment activities, including as regards knowledge, experience and other competence required, and the required initial and ongoing training. The qualification criteria shall address the various functions within the conformity assessment process, such as auditing, product evaluation or testing, technical documentation review and decision-making, as well as the devices, technologies and areas, such as biocompatibility, sterilisation, tissues and cells of human and animal origin and clinical evaluation, covered by the scope of designation.\n3.2.2.\u00a0\u00a0\u00a0The qualification criteria referred to in Section\u00a03.2.1 shall refer to the scope of a notified body's designation in accordance with the scope description used by the Member\u00a0State for the notification referred to in Article\u00a042(3), providing a sufficient level of detail for the required qualification within the subdivisions of the scope description.\nSpecific qualification criteria shall be defined at least for the assessment of:\n\n\n\n\n\n\n\u2014\n\n\nthe pre-clinical evaluation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclinical evaluation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntissues and cells of human and animal origin,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nfunctional safety,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsoftware,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npackaging,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndevices that incorporate as an integral part a medicinal product,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndevices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe different types of sterilisation processes.\n\n\n\n\n3.2.3.\u00a0\u00a0\u00a0The personnel responsible for establishing qualification criteria and for authorising other personnel to perform specific conformity assessment activities shall be employed by the notified body itself and shall not be external experts or subcontracted. They shall have proven knowledge and experience in all of the following:\n\n\n\n\n\n\n\u2014\n\n\nUnion devices legislation and relevant guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe conformity assessment procedures provided for in this Regulation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na broad base of knowledge of device technologies and the design and manufacture of devices;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe notified body's quality management system, related procedures and the required qualification criteria;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntraining relevant to personnel involved in conformity assessment activities in relation to devices;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nadequate experience in conformity assessments under this Regulation or previously applicable law within a notified body.\n\n\n\n\n3.2.4.\u00a0\u00a0\u00a0The notified body shall have permanent availability of personnel with relevant clinical expertise and where possible such personnel shall be employed by the notified body itself. Such personnel shall be integrated throughout the notified body's assessment and decision-making process in order to:\n\n\n\n\n\n\n\u2014\n\n\nidentify when specialist input is required for the assessment of the clinical evaluation conducted by the manufacturer and identify appropriately qualified experts;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriately train external clinical experts in the relevant requirements of this Regulation, CS, guidance and harmonised standards and ensure that the external clinical experts are fully aware of the context and implications of their assessment and the advice they provide;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbe able to review and scientifically challenge the clinical data contained within the clinical evaluation, and any associated clinical investigations, and appropriately guide external clinical experts in the assessment of the clinical evaluation presented by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbe able to scientifically evaluate and, if necessary, challenge the clinical evaluation presented, and the results of the external clinical experts' assessment of the manufacturer's clinical evaluation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbe able to ascertain the comparability and consistency of the assessments of clinical evaluations conducted by clinical experts;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbe able to make an assessment of the manufacturer's clinical evaluation and a clinical judgement of the opinion provided by any external expert and make a recommendation to the notified body's decision maker; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbe able to draw up records and reports demonstrating that the relevant conformity assessment activities have been appropriately carried out.\n\n\n\n\n3.2.5.\u00a0\u00a0\u00a0The personnel responsible for carrying out product-related reviews (product reviewers), such as technical documentation reviews or type examination, including aspects such as clinical evaluation, biological safety, sterilisation and software validation, shall have all of the following proven qualifications:\n\n\n\n\n\n\n\u2014\n\n\nsuccessful completion of a university or a technical college degree or equivalent qualification in relevant studies, e.g. medicine, pharmacy, engineering or other relevant sciences;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nfour years' professional experience in the field of healthcare products or related activities, such as in manufacturing, auditing or research, of which two years shall be in the design, manufacture, testing or use of the device or technology to be assessed or related to the scientific aspects to be assessed;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nknowledge of device legislation, including the general safety and performance requirements set out in Annex\u00a0I;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge and experience of relevant harmonised standards, CS and guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge and experience of risk management and related device standards and guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge and experience of clinical evaluation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge of the devices which they are assessing;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge and experience of the conformity assessment procedures laid down in Annexes\u00a0IX to\u00a0XI, in particular of the aspects of those procedures for which they are responsible, and adequate authorisation for carrying out those assessments;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe ability to draw up records and reports demonstrating that the relevant conformity assessment activities have been appropriately carried out.\n\n\n\n\n3.2.6.\u00a0\u00a0\u00a0The personnel responsible for carrying out audits of the manufacturer's quality management system (site auditors) shall have all of the following proven qualifications:\n\n\n\n\n\n\n\u2014\n\n\nsuccessful completion of a university or a technical college degree or equivalent qualification in relevant studies, such as medicine, pharmacy, engineering or other relevant sciences;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nfour years' professional experience in the field of healthcare products or related activities, such as in manufacturing, auditing or research, of which two years shall be in the area of quality management;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge of devices legislation as well as related harmonised standards, CS and guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge and experience of risk management and related device standards and guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge of quality management systems and related standards and guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge and experience of the conformity assessment procedures laid down in Annexes\u00a0IX to\u00a0XI, in particular of the aspects of those procedures for which they are responsible, and adequate authorisation for carrying out those audits;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntraining in auditing techniques enabling them to challenge quality management systems;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe ability to draw up records and reports demonstrating that the relevant conformity assessment activities have been appropriately carried out.\n\n\n\n\n3.2.7.\u00a0\u00a0\u00a0The personnel with overall responsibility for final reviews and decision-making on certification shall be employed by the notified body itself and shall not be external experts or be subcontracted. Those personnel shall, as a group, have proven knowledge and comprehensive experience of all of the following:\n\n\n\n\n\n\n\u2014\n\n\ndevices legislation and relevant guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe device conformity assessments relevant to this Regulation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe types of qualifications, experience and expertise relevant to device conformity assessment;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na broad base of knowledge of device technologies, including sufficient experience of conformity assessment of devices being reviewed for certification, the device industry and the design and manufacture of devices;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe notified body's quality management system, related procedures and the required qualifications for personnel involved;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe ability to draw up records and reports demonstrating that the conformity assessment activities have been appropriately carried out.\n\n\n\n\n3.3.\u00a0\u00a0\u00a0Documentation of qualification, training and authorisation of personnel\n3.3.1.\u00a0\u00a0\u00a0The notified body shall have a procedure in place to fully document the qualification of each member of personnel involved in conformity assessment activities and the satisfaction of the qualification criteria referred to in Section\u00a03.2. Where in exceptional circumstances the fulfilment of the qualification criteria set out in Section\u00a03.2. cannot be fully demonstrated, the notified body shall justify to the authority responsible for notified bodies the authorisation of those members of personnel to carry out specific conformity assessment activities.\n3.3.2.\u00a0\u00a0\u00a0For all of its personnel referred to in Sections 3.2.3 to 3.2.7, the notified body shall establish and maintain up to date:\n\n\n\n\n\n\n\u2014\n\n\na matrix detailing the authorisations and responsibilities of the personnel in respect of conformity assessment activities; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nrecords attesting to the required knowledge and experience for the conformity assessment activity for which they are authorised. The records shall contain a rationale for defining the scope of the responsibilities for each of the assessment personnel and records of the conformity assessment activities carried out by each of them.\n\n\n\n\n3.4.\u00a0\u00a0\u00a0Subcontractors and external experts\n3.4.1.\u00a0\u00a0\u00a0Notified bodies may, without prejudice to Section\u00a03.2, subcontract certain clearly defined component parts of a conformity assessment activity.\nThe subcontracting of the auditing of quality management systems or of product related reviews as a whole shall not be permitted; nevertheless parts of those activities may be conducted by subcontractors and external auditors and experts working on behalf of the notified body. The notified body in question shall retain full responsibility for being able to produce appropriate evidence of the competence of subcontractors and experts to fulfil their specific tasks, for making a decision based on a subcontractor's assessment and for the work conducted by subcontractors and experts on its behalf.\nThe following activities may not be subcontracted by notified bodies:\n\n\n\n\n\n\n\u2014\n\n\nreview of the qualifications and monitoring of the performance of external experts;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nauditing and certification activities where the subcontracting in question is to auditing or certification organisations;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nallocation of work to external experts for specific conformity assessment activities; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nfinal review and decision making functions.\n\n\n\n\n3.4.2.\u00a0\u00a0\u00a0Where a notified body subcontracts certain conformity assessment activities either to an organisation or an individual, it shall have a policy describing the conditions under which subcontracting may take place, and shall ensure that:\n\n\n\n\n\n\n\u2014\n\n\nthe subcontractor meets the relevant requirements of this Annex;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsubcontractors and external experts do not further subcontract work to organisations or personnel; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe natural or legal person that applied for conformity assessment has been informed of the requirements referred to in the first and second indent.\n\n\n\n\nAny subcontracting or consultation of external personnel shall be properly documented, shall not involve any intermediaries and shall be subject to a written agreement covering, among other things, confidentiality and conflicts of interest. The notified body in question shall take full responsibility for the tasks performed by subcontractors.\n3.4.3.\u00a0\u00a0\u00a0Where subcontractors or external experts are used in the context of a conformity assessment, in particular regarding novel, invasive and implantable devices or technologies, the notified body in question shall have internal competence in each product area for which it is designated that is adequate for the purpose of leading the overall conformity assessment, verifying the appropriateness and validity of expert opinions and making decisions on certification.\n3.5.\u00a0\u00a0\u00a0Monitoring of competences, training and exchange of experience\n3.5.1.\u00a0\u00a0\u00a0The notified body shall establish procedures for the initial evaluation and on-going monitoring of the competence, conformity assessment activities and performance of all internal and external personnel, and subcontractors, involved in conformity assessment activities.\n3.5.2.\u00a0\u00a0\u00a0Notified bodies shall review at regular intervals, the competence of their personnel, identify training needs and draw up a training plan to maintain the required level of qualification and knowledge of individual personnel. That review shall at a minimum, verify that personnel:\n\n\n\n\n\n\n\u2014\n\n\nare aware of Union and national law in force on devices, relevant harmonised standards, CS, guidance documents and the results of the coordination activities referred to in Section\u00a01.6; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntake part in the internal exchange of experience and the continuous training and education programme referred to in Section\u00a03.1.2.\n\n\n\n\n4.\u00a0\u00a0\u00a0PROCESS REQUIREMENTS\n4.1.\u00a0\u00a0\u00a0General\nThe notified body shall have in place documented processes and sufficiently detailed procedures for the conduct of each conformity assessment activity for which it is designated, comprising the individual steps from pre-application activities up to decision making and surveillance and taking into account, when necessary, the respective specificities of the devices.\nThe requirements laid down in Sections 4.3, 4.4, 4.7 and 4.8 shall be fulfilled as part of the internal activities of notified bodies and shall not be subcontracted.\n4.2.\u00a0\u00a0\u00a0Notified body quotations and pre-application activities\nThe notified body shall:\n\n\n\n\n\n\n(a)\n\n\npublish a publicly available description of the application procedure by which manufacturers can obtain certification from it. That description shall include which languages are acceptable for submission of documentation and for any related correspondence;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nhave documented procedures relating to, and documented details about, fees charged for specific conformity assessment activities and any other financial conditions relating to notified bodies' assessment activities for devices;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nhave documented procedures in relation to advertising of their conformity assessment services. Those procedures shall ensure that advertising or promotional activities in no way imply or are capable of leading to an inference that their conformity assessment will offer manufacturers earlier market access or be quicker, easier or less stringent than that of other notified bodies;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nhave documented procedures requiring the review of pre-application information, including the preliminary verification that the product is covered by this Regulation and its classification, prior to issuing any quotation to the manufacturer relating to a specific conformity assessment; and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nensure that all contracts relating to the conformity assessment activities covered by this Regulation are concluded directly between the manufacturer and the notified body and not with any other organisation.\n\n\n\n\n4.3.\u00a0\u00a0\u00a0Application review and contract\nThe notified body shall require a formal application signed by a manufacturer or an authorised representative containing all of the information and the manufacturer's declarations required by the relevant conformity assessment as referred to in Annexes\u00a0IX to\u00a0XI.\nThe contract between a notified body and a manufacturer shall take the form of a written agreement signed by both parties. It shall be kept by the notified body. This contract shall have clear terms and conditions and contain obligations that enable the notified body to act as required under this Regulation, including an obligation on the manufacturer to inform the notified body of vigilance reports, the right of the notified body to suspend, restrict or withdraw certificates issued and the duty of the notified body to fulfil its information obligations.\nThe notified body shall have documented procedures to review applications, addressing:\n\n\n\n\n\n\n(a)\n\n\nthe completeness of those applications with respect to the requirements of the relevant conformity assessment procedure, as referred to in the corresponding Annex, under which approval has been sought,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe verification of the qualification of products covered by those applications as devices and their respective classifications,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nwhether the conformity assessment procedures chosen by the applicant are applicable to the device in question under this Regulation,\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe ability of the notified body to assess the application based on its designation, and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe availability of sufficient and appropriate resources.\n\n\n\n\nThe outcome of each review of an application shall be documented. Refusals or withdrawals of applications shall be notified to the electronic system referred to in Article\u00a057 and shall be accessible to other notified bodies.\n4.4.\u00a0\u00a0\u00a0Allocation of resources\nThe notified body shall have documented procedures to ensure that all conformity assessment activities are conducted by appropriately authorised and qualified personnel who are sufficiently experienced in the evaluation of the devices, systems and processes and related documentation that are subject to conformity assessment.\nFor each application, the notified body shall determine the resources needed and identify one individual responsible for ensuring that the assessment of that application is conducted in accordance with the relevant procedures and for ensuring that the appropriate resources including personnel are utilised for each of the tasks of the assessment. The allocation of tasks required to be carried out as part of the conformity assessment and any changes subsequently made to this allocation shall be documented.\n4.5.\u00a0\u00a0\u00a0Conformity assessment activities\n4.5.1.\u00a0\u00a0\u00a0General\nThe notified body and its personnel shall carry out the conformity assessment activities with the highest degree of professional integrity and the requisite technical and scientific competence in the specific fields.\nThe notified body shall have expertise, facilities and documented procedures that are sufficient to effectively conduct the conformity assessment activities for which the notified body in question is designated, taking account of the relevant requirements set out in Annexes\u00a0IX to XI, and in particular all of the following requirements:\n\n\n\n\n\n\n\u2014\n\n\nappropriately plan the conduct of each individual project,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure that the composition of the assessment teams is such that there is sufficient experience in relation to the technology concerned, and that there is continuous objectivity and independence, and to provide for rotation of the members of the assessment team at appropriate intervals,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nspecify the rationale for fixing time limits for completion of conformity assessment activities,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nassess the manufacturer's technical documentation and the solutions adopted to meet the requirements laid down in Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreview the manufacturer's procedures and documentation relating to the evaluation of pre-clinical aspects,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreview the manufacturer's procedures and documentation relating to clinical evaluation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\naddress the interface between the manufacturer's risk management process and its appraisal and analysis of the pre-clinical and clinical evaluation and to evaluate their relevance for the demonstration of conformity with the relevant requirements in Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncarry out the specific procedures referred to in Sections 5.2 to 5.4 of Annex\u00a0IX,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nin the case of class IIa or class IIb devices, assess the technical documentation of devices selected on a representative basis,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nplan and periodically carry out appropriate surveillance audits and assessments, carry out or request certain tests to verify the proper functioning of the quality management system and to perform unannounced on site audits,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nrelating to the sampling of devices, verify that the manufactured device is in conformity with the technical documentation; such requirements shall define the relevant sampling criteria and testing procedure prior to sampling,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nevaluate and verify a manufacturer's compliance with relevant Annexes.\n\n\n\n\nThe notified body shall, where relevant, take into consideration available CS, guidance and best practice documents and harmonised standards, even if the manufacturer does not claim to be in compliance.\n4.5.2.\u00a0\u00a0\u00a0Quality management system auditing\n\n\n\n\n\n\n(a)\n\n\nAs part of the assessment of the quality management system, a notified body shall prior to an audit and in accordance with its documented procedures:\n\n\n\n\n\n\n\u2014\n\n\nassess the documentation submitted in accordance with the relevant conformity assessment Annex, and draw up an audit programme which clearly identifies the number and sequence of activities required to demonstrate complete coverage of a manufacturer's quality management system and to determine whether it meets the requirements of this Regulation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nidentify links between, and allocation of responsibilities among, the various manufacturing sites, and identify relevant suppliers and/or subcontractors of the manufacturer, and consider the need to specifically audit any of those suppliers or subcontractors or both,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclearly define, for each audit identified in the audit programme, the objectives, criteria and scope of the audit, and draw up an audit plan that adequately addresses and takes account of the specific requirements for the devices, technologies and processes involved,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndraw up and keep up to date, for class IIa and class IIb devices, a sampling plan for the assessment of technical documentation as referred to in Annexes\u00a0II and III covering the range of such devices covered by the manufacturer's application. That plan shall ensure that all devices covered by the certificate are sampled over the period of validity of the certificate, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nselect and assign appropriately qualified and authorised personnel for conducting the individual audits. The respective roles, responsibilities and authorities of the team members shall be clearly defined and documented.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nBased on the audit programme it has drawn up, the notified body shall, in accordance with its documented procedures:\n\n\n\n\n\n\n\u2014\n\n\naudit the manufacturer's quality management system, in order to verify that the quality management system ensures that the devices covered conform to the relevant provisions of this Regulation which apply to devices at every stage, from design through final quality control to ongoing surveillance, and shall determine whether the requirements of this Regulation are met,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbased on relevant technical documentation and in order to determine whether the manufacturer meets the requirements referred to in the relevant conformity assessment Annex, review and audit the manufacturer's processes and subsystems, in particular for:\n\n\n\n\n\n\n\u2014\n\n\ndesign and development,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nproduction and process controls,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nproduct documentation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npurchasing controls including verification of purchased devices,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncorrective and preventive actions, including for post-market surveillance, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nPMCF,\n\n\n\n\nand review and audit requirements and provisions adopted by the manufacturer, including those in relation to fulfilling the general safety and performance requirements set out in Annex\u00a0I.\nThe documentation shall be sampled in such a manner as to reflect the risks associated with the intended use of the device, the complexity of the manufacturing technologies, the range and classes of devices produced and any available post-market surveillance information,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif not already covered by the audit programme, audit the control of processes on the premises of the manufacturer's suppliers, when the conformity of finished devices is significantly influenced by the activity of suppliers and, in particular when the manufacturer cannot demonstrate sufficient control over its suppliers,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nconduct assessments of the technical documentation based on its sampling plan and taking account of Sections 4.5.4. and\u00a04.5.5. for pre-clinical and clinical evaluations, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe notified body shall ensure that audit findings are appropriately and consistently classified in accordance with the requirements of this Regulation and with relevant standards, or with best practice documents developed or adopted by the MDCG.\n\n\n\n\n\n\n\n\n4.5.3.\u00a0\u00a0\u00a0Product verification\nAssessment of the technical documentation\nFor assessment of the technical documentation conducted in accordance with Chapter\u00a0II of Annex\u00a0IX, notified bodies shall have sufficient expertise, facilities and documented procedures for:\n\n\n\n\n\n\n\u2014\n\n\nthe allocation of appropriately qualified and authorised personnel for the examination of individual aspects such as use of the device, biocompatibility, clinical evaluation, risk management, and sterilisation, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe assessment of conformity of the design with this Regulation, and for taking account of Sections 4.5.4. to\u00a04.5.6. That assessment shall include examination of the implementation by manufacturers of incoming, in-process and final checks and the results thereof. If further tests or other evidence is required for the assessment of conformity with the requirements of this Regulation, the notified body in question shall carry out adequate physical or laboratory tests in relation to the device or request the manufacturer to carry out such tests.\n\n\n\n\nType-examinations\nThe notified body shall have documented procedures, sufficient expertise and facilities for the type-examination of devices in accordance with Annex\u00a0X including the capacity to:\n\n\n\n\n\n\n\u2014\n\n\nexamine and assess the technical documentation taking account of Sections 4.5.4. to\u00a04.5.6., and verify that the type has been manufactured in conformity with that documentation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nestablish a test plan identifying all relevant and critical parameters which need to be tested by the notified body or under its responsibility;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndocument its rationale for the selection of those parameters;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncarry out the appropriate examinations and tests in order to verify that the solutions adopted by the manufacturer meet the general safety and performance requirements set out in Annex\u00a0I. Such examinations and tests shall include all tests necessary to verify that the manufacturer has in fact applied the relevant standards it has opted to use;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nagree with the applicant as to where the necessary tests will be performed if they are not to be carried out directly by the notified body; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nassume full responsibility for test results. Test reports submitted by the manufacturer shall only be taken into account if they have been issued by conformity assessment bodies which are competent and independent of the manufacturer.\n\n\n\n\nVerification by examination and testing of every product\nThe notified body shall:\n\n\n\n\n\n\n(a)\n\n\nhave documented procedures, sufficient expertise and facilities for the verification by examination and testing of every product in accordance with Part B of Annex\u00a0XI;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nestablish a test plan identifying all relevant and critical parameters which need to be tested by the notified body or under its responsibility in order to:\n\n\n\n\n\n\n\u2014\n\n\nverify, for class IIb devices, the conformity of the device with the type described in the EU type-examination certificate and with the requirements of this Regulation which apply to those devices,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nconfirm, for class IIa devices, the conformity with the technical documentation referred to in Annexes\u00a0II and III and with the requirements of this Regulation which apply to those devices;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\ndocument its rationale for the selection of the parameters referred to in point\u00a0(b);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nhave documented procedures to carry out the appropriate assessments and tests in order to verify the conformity of the device with the requirements of this Regulation by examining and testing every product as specified in Section\u00a015 of Annex\u00a0XI;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nhave documented procedures providing for the reaching of an agreement with the applicant concerning when and where necessary tests that are not to be carried out by the notified body itself are to be performed; and\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nassume full responsibility for test results in accordance with documented procedures; test reports submitted by the manufacturer shall only be taken into account if they have been issued by conformity assessment bodies which are competent and independent of the manufacturer.\n\n\n\n\n4.5.4.\u00a0\u00a0\u00a0Pre-clinical evaluation assessment\nThe notified body shall have documented procedures in place for the review of the manufacturer's procedures and documentation relating to the evaluation of pre-clinical aspects. The notified body shall examine, validate and verify that the manufacturer's procedures and documentation adequately address:\n\n\n\n\n\n\n(a)\n\n\nthe planning, conduct, assessment, reporting and, where appropriate, updating of the pre-clinical evaluation, in particular of\n\n\n\n\n\n\n\u2014\n\n\nthe scientific pre-clinical literature search, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe pre-clinical testing, for example laboratory testing, simulated use testing, computer modelling, the use of animal models,\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe nature and duration of body contact and the specific associated biological risks,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe interface with the risk management process, and\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe appraisal and analysis of the available pre-clinical data and its relevance with regard to demonstrating conformity with the relevant requirements in Annex\u00a0I.\n\n\n\n\nThe notified body's assessment of pre-clinical evaluation procedures and documentation shall address the results of literature searches and all validation, verification and testing performed and conclusions drawn, and shall typically include considering the use of alternative materials and substances and take account of the packaging, stability, including shelf life, of the finished device. Where no new testing has been undertaken by a manufacturer or where there are deviations from procedures, the notified body in question shall critically examine the justification presented by the manufacturer.\n4.5.5.\u00a0\u00a0\u00a0Clinical evaluation assessment\nThe notified body shall have documented procedures in place relating to the assessment of a manufacturer's procedures and documentation relating to clinical evaluation both for initial conformity assessment and on an ongoing basis. The notified body shall examine, validate and verify that manufacturers' procedures and documentation adequately address:\n\n\n\n\n\n\n\u2014\n\n\nthe planning, conduct, assessment, reporting and updating of the clinical evaluation as referred to in Annex\u00a0XIV,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npost-market surveillance and PMCF,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe interface with the risk management process,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe appraisal and analysis of the available data and its relevance with regard to demonstrating conformity with the relevant requirements in Annex\u00a0I, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe conclusions drawn with regard to the clinical evidence and drawing up of the clinical evaluation report.\n\n\n\n\nThese procedures referred to in the first paragraph\u00a0shall take into consideration available CS, guidance and best practice documents.\nThe notified body's assessment of clinical evaluations as referred to in Annex\u00a0XIV shall cover:\n\n\n\n\n\n\n\u2014\n\n\nthe intended use specified by the manufacturer and claims for the device defined by it,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe planning of the clinical evaluation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe methodology for the literature search,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nrelevant documentation from the literature search,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe clinical investigation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nvalidity of equivalence claimed in relation to other devices, the demonstration of equivalence, the suitability and conclusions data from equivalent and similar devices,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npost-market surveillance and PMCF,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe clinical evaluation report, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\njustifications in relation to non-performance of clinical investigations or PMCF.\n\n\n\n\nIn relation to clinical data from clinical investigations included within the clinical evaluation, the notified body in question shall ensure that the conclusions drawn by the manufacturer are valid in the light of the approved clinical investigation plan.\nThe notified body shall ensure that the clinical evaluation adequately addresses the relevant safety and performance requirements provided for in Annex\u00a0I, that it is appropriately aligned with the risk management requirements, that it is conducted in accordance with Annex\u00a0XIV and that it is appropriately reflected in the information provided relating to the device.\n4.5.6.\u00a0\u00a0\u00a0Specific Procedures\nThe notified body shall have documented procedures, sufficient expertise and facilities for the procedures referred to in Sections 5 and 6 of Annex\u00a0IX, Section\u00a06 of Annex\u00a0X and Section\u00a016 of Annex\u00a0XI, for which they are designated.\nIn the case of devices manufactured utilising tissues or cells of animal origin or their derivatives, such as from TSE susceptible species, as referred to in Regulation\u00a0(EU)\u00a0No\u00a0722/2012, the notified body shall have documented procedures in place that fulfil the requirements laid down in that Regulation, including for the preparation of a summary evaluation report for the relevant competent authority.\n4.6.\u00a0\u00a0\u00a0Reporting\nThe notified body shall:\n\n\n\n\n\n\n\u2014\n\n\nensure that all steps of the conformity assessment are documented so that the conclusions of the assessment are clear and demonstrate compliance with the requirements of this Regulation and can represent objective evidence of such compliance to persons that are not themselves involved in the assessment, for example personnel in designating authorities,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure that records that are sufficient to provide a discernible audit trail are available for quality management system audits,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclearly document the conclusions of its assessment of clinical evaluation in a clinical evaluation assessment report, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nfor each specific project, provide a detailed report which shall be based on a standard format containing a minimum set of elements determined by the MDCG.\n\n\n\n\nThe report of the notified body shall:\n\n\n\n\n\n\n\u2014\n\n\nclearly document the outcome of its assessment and draw clear conclusions from the verification of the manufacturer's conformity with the requirements of this Regulation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmake a recommendation for a final review and for a final decision to be taken by the notified body; this recommendation shall be signed off by the member of personnel responsible in the notified body, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbe provided to the manufacturer in question.\n\n\n\n\n4.7.\u00a0\u00a0\u00a0Final review\nThe notified body shall prior to making a final decision:\n\n\n\n\n\n\n\u2014\n\n\nensure that the personnel assigned for the final review and decision-making on specific projects are appropriately authorised and are different from the personnel who have conducted the assessments,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nverify that the report or reports and supporting documentation needed for decision making, including concerning resolution of non-conformities noted during assessment, are complete and sufficient with respect to the scope of the application, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nverify whether there are any unresolved non-conformities preventing issuance of a certificate.\n\n\n\n\n4.8.\u00a0\u00a0\u00a0Decisions and Certifications\nThe notified body shall have documented procedures for decision-making including as regards the allocation of responsibilities for the issuance, suspension, restriction and withdrawal of certificates. Those procedures shall include the notification requirements laid down in Chapter V of this Regulation. The procedures shall allow the notified body in question to:\n\n\n\n\n\n\n\u2014\n\n\ndecide, based on the assessment documentation and additional information available, whether the requirements of this Regulation are fulfilled,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndecide, based on the results of its assessment of the clinical evaluation and risk management, whether the post-market surveillance plan, including the PMCF plan, is adequate,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndecide on specific milestones for further review by the notified body of the up to date clinical evaluation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndecide whether specific conditions or provisions need to be defined for the certification,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndecide, based on the novelty, risk classification, clinical evaluation and conclusions from the risk analysis of the device, on a period of certification not exceeding five\u00a0years,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclearly document decision making and approval steps including approval by signature of the members of personnel responsible,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclearly document responsibilities and mechanisms for communication of decisions, in particular, where the final signatory of a certificate differs from the decision maker or decision makers or does not fulfil the requirements laid down in Section\u00a03.2.7,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nissue a certificate or certificates in accordance with the minimum requirements laid down in Annex\u00a0XII for a period of validity not exceeding five years and shall indicate whether there are specific conditions or limitations associated with the certification,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nissue a certificate or certificates for the applicant alone and shall not issue certificates covering multiple entities, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure that the manufacturer is notified of the outcome of the assessment and the resultant decision and that they are entered into the electronic system referred to in Article\u00a057.\n\n\n\n\n4.9.\u00a0\u00a0\u00a0Changes and modifications\nThe notified body shall have documented procedures and contractual arrangements with manufacturers in place relating to the manufacturers' information obligations and the assessment of changes to:\n\n\n\n\n\n\n\u2014\n\n\nthe approved quality management system or systems or to the product-range covered,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe approved design of a device,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe intended use of or claims made for the device,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe approved type of a device, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nany substance incorporated in or utilised for the manufacturing of a device and being subject to the specific procedures in accordance with Section\u00a04.5.6.\n\n\n\n\nThe procedures and contractual arrangements referred to in the first paragraph\u00a0shall include measures for checking the significance of the changes referred to in the first paragraph.\nIn accordance with its documented procedures, the notified body in question shall:\n\n\n\n\n\n\n\u2014\n\n\nensure that manufacturers submit for prior approval plans for changes as referred to in the first paragraph\u00a0and relevant information relating to such changes,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nassess the changes proposed and verify whether, after these changes, the quality management system, or the design of a device or type of a device, still meets the requirements of this Regulation, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nnotify the manufacturer of its decision and provide a report or as applicable a supplementary report, which shall contain the justified conclusions of its assessment.\n\n\n\n\n4.10.\u00a0\u00a0\u00a0Surveillance activities and post-certification monitoring\nThe notified body shall have documented procedures:\n\n\n\n\n\n\n\u2014\n\n\ndefining how and when surveillance activities of manufacturers are to be conducted. Those procedures shall include arrangements for unannounced on-site audits of manufacturers and, where applicable, subcontractors and suppliers carrying out product tests and the monitoring of compliance with any conditions binding manufacturers and associated with certification decisions, such as updates to clinical data at defined intervals,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nfor screening relevant sources of scientific and clinical data and post-market information relating to the scope of their designation. Such information shall be taken into account in the planning and conduct of surveillance activities, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nto review vigilance data to which they have access under Article\u00a092(2) in order to estimate its impact, if any, on the validity of existing certificates. The results of the evaluation and any decisions taken shall be thoroughly documented.\n\n\n\n\nThe notified body in question shall, upon receipt of information about vigilance cases from a manufacturer or competent authorities, decide which of the following options to apply:\n\n\n\n\n\n\n\u2014\n\n\nnot to take action on the basis that the vigilance case is clearly not related to the certification granted,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nobserve the manufacturer's and competent authority's activities and the results of the manufacturer's investigation so as to determine whether the certification granted is at risk or whether adequate corrective action has been taken,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nperform extraordinary surveillance measures, such as document reviews, short-notice or unannounced audits and product testing, where it is likely that the certification granted is at risk,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nincrease the frequency of surveillance audits,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreview specific products or processes on the occasion of the next audit of the manufacturer, or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntake any other relevant measure.\n\n\n\n\nIn relation to surveillance audits of manufacturers, the notified body shall have documented procedures to:\n\n\n\n\n\n\n\u2014\n\n\nconduct surveillance audits of the manufacturer on at least an annual basis which shall be planned and conducted in line with the relevant requirements in Section\u00a04.5,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure adequate assessment of the manufacturer's documentation on, and application of the provisions on, vigilance, the post-market surveillance, and PMCF,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsample and test devices and technical documentation, during audits, according to pre-defined sampling criteria and testing procedures to ensure that the manufacturer continuously applies the approved quality management system,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure that the manufacturer complies with the documentation and information obligations laid down in the relevant Annexes\u00a0and that its procedures take into account best practices in the implementation of quality management systems,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure that the manufacturer does not use quality management system or device approvals in a misleading manner,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ngather sufficient information to determine if the quality management system continues to comply with the requirements of this Regulation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nask the manufacturer, if non-conformities are detected, for corrections, corrective actions and, where applicable, preventive actions, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwhere necessary, impose specific restrictions on the relevant certificate, or suspend or withdraw it.\n\n\n\n\nThe notified body shall, if listed as part of the conditions for certification:\n\n\n\n\n\n\n\u2014\n\n\nconduct an in-depth review of the clinical evaluation as most recently updated by the manufacturer based on the manufacturer's post-market surveillance, on its PMCF and on clinical literature relevant to the condition being treated with the device or on clinical literature relevant to similar devices,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclearly document the outcome of the in-depth review and address any specific concerns to the manufacturer or impose any specific conditions on it, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure that the clinical evaluation as most recently updated, is appropriately reflected in the instructions for use and, where applicable, the summary of safety and performance.\n\n\n\n\n4.11.\u00a0\u00a0\u00a0Re-certification\nThe notified body shall have documented procedures in place relating to the re-certification reviews and the renewal of certificates. Re-certification of approved quality management systems or EU technical documentation assessment certificates or EU type-examination certificates shall occur at least every five years.\nThe notified body shall have documented procedures relating to renewals of EU technical documentation assessment certificates and EU type-examination certificates and those procedures shall require the manufacturer in question to submit a summary of changes and scientific findings for the device, including:\n\n\n\n\n\n\n(a)\n\n\nall changes to the originally approved device, including changes not yet notified,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nexperience gained from post-market surveillance,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nexperience from risk management,\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nexperience from updating the proof of compliance with the general safety and performance requirements set out in Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nexperience from reviews of the clinical evaluation, including the results of any clinical investigations and PMCF,\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nchanges to the requirements, to components of the device or to the scientific or regulatory environment,\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nchanges to applied or new harmonised standards, CS or equivalent documents, and\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nchanges in medical, scientific and technical knowledge, such as:\n\n\n\n\n\n\n\u2014\n\n\nnew treatments,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nchanges in test methods,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nnew scientific findings on materials and components, including findings on their biocompatibility,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nexperience from studies on comparable devices,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndata from registers and registries,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nexperience from clinical investigations with comparable devices.\n\n\n\n\n\n\n\n\nThe notified body shall have documented procedures to assess the information referred to in the second paragraph\u00a0and shall pay particular attention to clinical data from post-market surveillance and PMCF activities undertaken since the previous certification or re-certification, including appropriate updates to manufacturers' clinical evaluation reports.\nFor the decision on re-certification, the notified body in question shall use the same methods and principles as for the initial certification decision. If necessary, separate forms shall be established for re-certification taking into account the steps taken for certification such as application and application review.\n\n\n\n\n\nANNEX\u00a0VIII\n\nCLASSIFICATION RULES\n\nCHAPTER I\n\nDEFINITIONS SPECIFIC TO CLASSIFICATION RULES\n\n1.\u00a0\u00a0\u00a0DURATION OF USE\n1.1.\u00a0\u00a0\u00a0\n                     \u2018Transient\u2019 means normally intended for continuous use for less than 60 minutes.\n1.2.\u00a0\u00a0\u00a0\n                     \u2018Short term\u2019 means normally intended for continuous use for between 60 minutes and 30\u00a0days.\n1.3.\u00a0\u00a0\u00a0\n                     \u2018Long term\u2019 means normally intended for continuous use for more than 30 days.\n2.\u00a0\u00a0\u00a0INVASIVE AND ACTIVE DEVICES\n2.1.\u00a0\u00a0\u00a0\n                     \u2018Body orifice\u2019 means any natural opening in the body, as well as the external surface of the eyeball, or any permanent artificial opening, such as a stoma.\n2.2.\u00a0\u00a0\u00a0\n                     \u2018Surgically invasive device\u2019 means:\n\n\n\n\n\n\n(a)\n\n\nan invasive device which penetrates inside the body through the surface of the body, including through mucous membranes of body orifices with the aid or in the context of a surgical operation; and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\na device which produces penetration other than through a body orifice.\n\n\n\n\n2.3.\u00a0\u00a0\u00a0\n                     \u2018Reusable surgical instrument\u2019 means an instrument intended for surgical use in cutting, drilling, sawing, scratching, scraping, clamping, retracting, clipping or similar procedures, without a connection to an active device and which is intended by the manufacturer to be reused after appropriate procedures such as cleaning, disinfection and sterilisation have been carried out.\n2.4.\u00a0\u00a0\u00a0\n                     \u2018Active therapeutic device\u2019 means any active device used, whether alone or in combination with other devices, to support, modify, replace or restore biological functions or structures with a view to treatment or alleviation of an illness, injury or disability.\n2.5.\u00a0\u00a0\u00a0\n                     \u2018Active device intended for diagnosis and monitoring\u2019 means any active device used, whether alone or in combination with other devices, to supply information for detecting, diagnosing, monitoring or treating physiological conditions, states of health, illnesses or congenital deformities.\n2.6.\u00a0\u00a0\u00a0\n                     \u2018Central circulatory system\u2019 means the following blood vessels: arteriae pulmonales, aorta ascendens, arcus aortae, aorta descendens to the bifurcatio aortae, arteriae coronariae, arteria carotis communis, arteria carotis externa, arteria carotis interna, arteriae cerebrales, truncus brachiocephalicus, venae cordis, venae pulmonales, vena cava superior and vena cava inferior.\n2.7.\u00a0\u00a0\u00a0\n                     \u2018Central nervous system\u2019 means the brain, meninges and spinal cord.\n2.8.\u00a0\u00a0\u00a0\n                     \u2018Injured skin or mucous membrane\u2019 means an area of skin or a mucous membrane presenting a pathological change or change following disease or a wound.\nCHAPTER II\n\nIMPLEMENTING RULES\n\n3.1.\u00a0\u00a0\u00a0Application of the classification rules shall be governed by the intended purpose of the devices.\n3.2.\u00a0\u00a0\u00a0If the device in question is intended to be used in combination with another device, the classification rules shall apply separately to each of the devices. Accessories for a medical device and for a product listed in Annex\u00a0XVI shall be classified in their own right separately from the device with which they are used.\n3.3.\u00a0\u00a0\u00a0Software, which drives a device or influences the use of a device, shall fall within the same class as the device.\nIf the software is independent of any other device, it shall be classified in its own right.\n3.4.\u00a0\u00a0\u00a0If the device is not intended to be used solely or principally in a specific part of the body, it shall be considered and classified on the basis of the most critical specified use.\n3.5.\u00a0\u00a0\u00a0If several rules, or if, within the same rule, several sub-rules, apply to the same device based on the device's intended purpose, the strictest rule and sub-rule resulting in the higher classification shall apply.\n3.6.\u00a0\u00a0\u00a0In calculating the duration referred to in Section\u00a01, continuous use shall mean:\n\n\n\n\n\n\n(a)\n\n\nthe entire duration of use of the same device without regard to temporary interruption of use during a procedure or temporary removal for purposes such as cleaning or disinfection of the device. Whether the interruption of use or the removal is temporary shall be established in relation to the duration of the use prior to and after the period when the use is interrupted or the device removed; and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe accumulated use of a device that is intended by the manufacturer to be replaced immediately with another of the same type.\n\n\n\n\n3.7.\u00a0\u00a0\u00a0A device is considered to allow direct diagnosis when it provides the diagnosis of the disease or condition in question by itself or when it provides decisive information for the diagnosis.\nCHAPTER III\n\nCLASSIFICATION RULES\n\n4.\u00a0\u00a0\u00a0NON-INVASIVE DEVICES\n4.1.\u00a0\u00a0\u00a0Rule 1\nAll non-invasive devices are classified as class I, unless one of the rules set out hereinafter applies.\n4.2.\u00a0\u00a0\u00a0Rule 2\nAll non-invasive devices intended for channelling or storing blood, body liquids, cells or tissues, liquids or gases for the purpose of eventual infusion, administration or introduction into the body are classified as class IIa:\n\n\n\n\n\n\n\u2014\n\n\nif they may be connected to a class\u00a0IIa, class\u00a0IIb or class\u00a0III active device; or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif they are intended for use for channelling or storing blood or other body liquids or for storing organs, parts of organs or body cells and tissues, except for blood bags; blood bags are classified as class\u00a0IIb.\n\n\n\n\nIn all other cases, such devices are classified as class\u00a0I.\n4.3.\u00a0\u00a0\u00a0Rule 3\nAll non-invasive devices intended for modifying the biological or chemical composition of human tissues or cells, blood, other body liquids or other liquids intended for implantation or administration into the body are classified as class IIb, unless the treatment for which the device is used consists of filtration, centrifugation or exchanges of gas, heat, in which case they are classified as class\u00a0IIa.\nAll non-invasive devices consisting of a substance or a mixture of substances intended to be used in vitro in direct contact with human cells, tissues or organs taken from the human body or used in vitro with human embryos before their implantation or administration into the body are classified as class\u00a0III.\n4.4.\u00a0\u00a0\u00a0Rule 4\nAll non-invasive devices which come into contact with injured skin or mucous membrane are classified as:\n\n\n\n\n\n\n\u2014\n\n\nclass I if they are intended to be used as a mechanical barrier, for compression or for absorption of exudates;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIb if they are intended to be used principally for injuries to skin which have breached the dermis or mucous membrane and can only heal by secondary intent;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIa if they are principally intended to manage the micro-environment of injured skin or mucous membrane; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIa in all other cases.\n\n\n\n\nThis rule applies also to the invasive devices that come into contact with injured mucous membrane.\n5.\u00a0\u00a0\u00a0INVASIVE DEVICES\n5.1.\u00a0\u00a0\u00a0Rule 5\nAll invasive devices with respect to body orifices, other than surgically invasive devices, which are not intended for connection to an active device or which are intended for connection to a class I active device are classified as:\n\n\n\n\n\n\n\u2014\n\n\nclass I if they are intended for transient use;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass IIa if they are intended for short-term use, except if they are used in the oral cavity as far as the pharynx, in an ear canal up to the ear drum or in the nasal cavity, in which case they are classified as class I; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIb if they are intended for long-term use, except if they are used in the oral cavity as far as the pharynx, in an ear canal up to the ear drum or in the nasal cavity and are not liable to be absorbed by the mucous membrane, in which case they are classified as class\u00a0IIa.\n\n\n\n\nAll invasive devices with respect to body orifices, other than surgically invasive devices, intended for connection to a class\u00a0IIa, class\u00a0IIb or class\u00a0III active device, are classified as class\u00a0IIa.\n5.2.\u00a0\u00a0\u00a0Rule 6\nAll surgically invasive devices intended for transient use are classified as class\u00a0IIa unless they:\n\n\n\n\n\n\n\u2014\n\n\nare intended specifically to control, diagnose, monitor or correct a defect of the heart or of the central circulatory system through direct contact with those parts of the body, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare reusable surgical instruments, in which case they are classified as class\u00a0I;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended specifically for use in direct contact with the heart or central circulatory system or the central nervous system, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to supply energy in the form of ionising radiation in which case they are classified as class\u00a0IIb;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nhave a biological effect or are wholly or mainly absorbed in which case they are classified as class\u00a0IIb; or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to administer medicinal products by means of a delivery system, if such administration of a medicinal product is done in a manner that is potentially hazardous taking account of the mode of application, in which case they are classified as class\u00a0IIb.\n\n\n\n\n5.3.\u00a0\u00a0\u00a0Rule 7\nAll surgically invasive devices intended for short-term use are classified as class IIa unless they:\n\n\n\n\n\n\n\u2014\n\n\nare intended specifically to control, diagnose, monitor or correct a defect of the heart or of the central circulatory system through direct contact with those parts of the body, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended specifically for use in direct contact with the heart or central circulatory system or the central nervous system, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to supply energy in the form of ionizing radiation in which case they are classified as class\u00a0IIb;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nhave a biological effect or are wholly or mainly absorbed in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to undergo chemical change in the body in which case they are classified as class\u00a0IIb, except if the devices are placed in the teeth; or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to administer medicines, in which case they are classified as class\u00a0IIb.\n\n\n\n\n5.4.\u00a0\u00a0\u00a0Rule 8\nAll implantable devices and long-term surgically invasive devices are classified as class\u00a0IIb unless they:\n\n\n\n\n\n\n\u2014\n\n\nare intended to be placed in the teeth, in which case they are classified as class\u00a0IIa;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to be used in direct contact with the heart, the central circulatory system or the central nervous system, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nhave a biological effect or are wholly or mainly absorbed, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to undergo chemical change in the body in which case they are classified as class\u00a0III, except if the devices are placed in the teeth;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to administer medicinal products, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare active implantable devices or their accessories, in which cases they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare breast implants or surgical meshes, in which cases they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare total or partial joint replacements, in which case they are classified as class\u00a0III, with the exception of ancillary components such as screws, wedges, plates and instruments; or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare spinal disc replacement implants or are implantable devices that come into contact with the spinal column, in which case they are classified as class\u00a0III with the exception of components such as screws, wedges, plates and instruments.\n\n\n\n\n6.\u00a0\u00a0\u00a0ACTIVE DEVICES\n6.1.\u00a0\u00a0\u00a0Rule 9\nAll active therapeutic devices intended to administer or exchange energy are classified as class IIa unless their characteristics are such that they may administer energy to or exchange energy with the human body in a potentially hazardous way, taking account of the nature, the density and site of application of the energy, in which case they are classified as class\u00a0IIb.\nAll active devices intended to control or monitor the performance of active therapeutic class IIb devices, or intended directly to influence the performance of such devices are classified as class\u00a0IIb.\nAll active devices intended to emit ionizing radiation for therapeutic purposes, including devices which control or monitor such devices, or which directly influence their performance, are classified as class\u00a0IIb.\nAll active devices that are intended for controlling, monitoring or directly influencing the performance of active implantable devices are classified as class\u00a0III.\n6.2.\u00a0\u00a0\u00a0Rule 10\nActive devices intended for diagnosis and monitoring are classified as class\u00a0IIa:\n\n\n\n\n\n\n\u2014\n\n\nif they are intended to supply energy which will be absorbed by the human body, except for devices intended to illuminate the patient's body, in the visible spectrum, in which case they are classified as class I;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif they are intended to image in vivo distribution of radiopharmaceuticals; or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif they are intended to allow direct diagnosis or monitoring of vital physiological processes, unless they are specifically intended for monitoring of vital physiological parameters and the nature of variations of those parameters is such that it could result in immediate danger to the patient, for instance variations in cardiac performance, respiration, activity of the central nervous system, or they are intended for diagnosis in clinical situations where the patient is in immediate danger, in which cases they are classified as class\u00a0IIb.\n\n\n\n\nActive devices intended to emit ionizing radiation and intended for diagnostic or therapeutic radiology, including interventional radiology devices and devices which control or monitor such devices, or which directly influence their performance, are classified as class\u00a0IIb.\n6.3.\u00a0\u00a0\u00a0Rule 11\nSoftware intended to provide information which is used to take decisions with diagnosis or therapeutic purposes is classified as class IIa, except if such decisions have an impact that may cause:\n\n\n\n\n\n\n\u2014\n\n\ndeath or an irreversible deterioration of a person's state of health, in which case it is in class\u00a0III; or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na serious deterioration of a person's state of health or a surgical intervention, in which case it is classified as class\u00a0IIb.\n\n\n\n\nSoftware intended to monitor physiological processes is classified as class\u00a0IIa, except if it is intended for monitoring of vital physiological parameters, where the nature of variations of those parameters is such that it could result in immediate danger to the patient, in which case it is classified as class\u00a0IIb.\nAll other software is classified as class\u00a0I.\n6.4.\u00a0\u00a0\u00a0Rule 12\nAll active devices intended to administer and/or remove medicinal products, body liquids or other substances to or from the body are classified as class\u00a0IIa, unless this is done in a manner that is potentially hazardous, taking account of the nature of the substances involved, of the part of the body concerned and of the mode of application in which case they are classified as class\u00a0IIb.\n6.5.\u00a0\u00a0\u00a0Rule 13\nAll other active devices are classified as class\u00a0I.\n7.\u00a0\u00a0\u00a0SPECIAL RULES\n7.1.\u00a0\u00a0\u00a0Rule 14\nAll devices incorporating, as an integral part, a substance which, if used separately, can be considered to be a medicinal product, as defined in point\u00a02 of Article\u00a01 of Directive\u00a02001/83/EC, including a medicinal product derived from human blood or human plasma, as defined in point\u00a010 of Article\u00a01 of that Directive, and that has an action ancillary to that of the devices, are classified as class\u00a0III.\n7.2.\u00a0\u00a0\u00a0Rule 15\nAll devices used for contraception or prevention of the transmission of sexually transmitted diseases are classified as class\u00a0IIb, unless they are implantable or long term invasive devices, in which case they are classified as class\u00a0III.\n7.3.\u00a0\u00a0\u00a0Rule 16\nAll devices intended specifically to be used for disinfecting, cleaning, rinsing or, where appropriate, hydrating contact lenses are classified as class\u00a0IIb.\nAll devices intended specifically to be used for disinfecting or sterilising medical devices are classified as class IIa, unless they are disinfecting solutions or washer-disinfectors intended specifically to be used for disinfecting invasive devices, as the end point of processing, in which case they are classified as class\u00a0IIb.\nThis rule does not apply to devices that are intended to clean devices other than contact lenses by means of physical action only.\n7.4.\u00a0\u00a0\u00a0Rule 17\nDevices specifically intended for recording of diagnostic images generated by X-ray radiation are classified as class\u00a0IIa.\n7.5.\u00a0\u00a0\u00a0Rule 18\nAll devices manufactured utilising tissues or cells of human or animal origin, or their derivatives, which are non-viable or rendered non-viable, are classified as class\u00a0III, unless such devices are manufactured utilising tissues or cells of animal origin, or their derivatives, which are non-viable or rendered non-viable and are devices intended to come into contact with intact skin only.\n7.6.\u00a0\u00a0\u00a0Rule 19\nAll devices incorporating or consisting of nanomaterial are classified as:\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0III if they present a high or medium potential for internal exposure;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIb if they present a low potential for internal exposure; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIa if they present a negligible potential for internal exposure.\n\n\n\n\n7.7.\u00a0\u00a0\u00a0Rule 20\nAll invasive devices with respect to body orifices, other than surgically invasive devices, which are intended to administer medicinal products by inhalation are classified as class\u00a0IIa, unless their mode of action has an essential impact on the efficacy and safety of the administered medicinal product or they are intended to treat life-threatening conditions, in which case they are classified as class\u00a0IIb.\n7.8.\u00a0\u00a0\u00a0Rule 21\nDevices that are composed of substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed by or locally dispersed in the human body are classified as:\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0III if they, or their products of metabolism, are systemically absorbed by the human body in order to achieve the intended purpose;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0III if they achieve their intended purpose in the stomach or lower gastrointestinal tract and they, or their products of metabolism, are systemically absorbed by the human body;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIa if they are applied to the skin or if they are applied in the nasal or oral cavity as far as the pharynx, and achieve their intended purpose on those cavities; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIb in all other cases.\n\n\n\n\n7.9.\u00a0\u00a0\u00a0Rule 22\nActive therapeutic devices with an integrated or incorporated diagnostic function which significantly determines the patient management by the device, such as closed loop systems or automated external defibrillators, are classified as class\u00a0III.\n\n\n\n\n\nANNEX IX\n\nCONFORMITY ASSESSMENT BASED ON A QUALITY MANAGEMENT SYSTEM AND ON ASSESSMENT OF TECHNICAL DOCUMENTATION\n\nCHAPTER I\n\nQUALITY MANAGEMENT SYSTEM\n\n1.\u00a0\u00a0\u00a0The manufacturer shall establish, document and implement a quality management system as described in Article\u00a010(9) and maintain its effectiveness throughout the life cycle of the devices concerned. The manufacturer shall ensure the application of the quality management system as specified in Section\u00a02 and shall be subject to audit, as laid down in Sections\u00a02.3 and 2.4, and to surveillance as specified in Section\u00a03.\n2.\u00a0\u00a0\u00a0Quality management system assessment\n2.1.\u00a0\u00a0\u00a0The manufacturer shall lodge an application for assessment of its quality management system with a notified body. The application shall include:\n\n\n\n\n\n\n\u2014\n\n\nthe name of the manufacturer and address of its registered place of business and any additional manufacturing site covered by the quality management system, and, if the manufacturer's application is lodged by its authorised representative, the name of the authorised representative and the address of the authorised representative's registered place of business,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nall relevant information on the device or group of devices covered by the quality management system,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na written declaration that no application has been lodged with any other notified body for the same device-related quality management system, or information about any previous application for the same device-related quality management system,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na draft of an EU declaration of conformity in accordance with Article\u00a019 and Annex\u00a0IV for the device model covered by the conformity assessment procedure,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation on the manufacturer's quality management system,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na documented description of the procedures in place to fulfil the obligations arising from the quality management system and required under this Regulation and the undertaking by the manufacturer in question to apply those procedures,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na description of the procedures in place to ensure that the quality management system remains adequate and effective, and the undertaking by the manufacturer to apply those procedures,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation on the manufacturer's post-market surveillance system and, where applicable, on the PMCF plan, and the procedures put in place to ensure compliance with the obligations resulting from the provisions on vigilance set out in Articles\u00a087 to\u00a092,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na description of the procedures in place to keep up to date the post-market surveillance system, and, where applicable, the PMCF plan, and the procedures ensuring compliance with the obligations resulting from the provisions on vigilance set out in Articles\u00a087 to 92, as well as the undertaking by the manufacturer to apply those procedures,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndocumentation on the clinical evaluation plan, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na description of the procedures in place to keep up to date the clinical evaluation plan, taking into account the state of the art.\n\n\n\n\n2.2.\u00a0\u00a0\u00a0Implementation of the quality management system shall ensure compliance with this Regulation. All the elements, requirements and provisions adopted by the manufacturer for its quality management system shall be documented in a systematic and orderly manner in the form of a quality manual and written policies and procedures such as quality programmes, quality plans and quality records.\nMoreover, the documentation to be submitted for the assessment of the quality management system shall include an adequate description of, in particular:\n\n\n\n\n\n\n(a)\n\n\nthe manufacturer's quality objectives;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe organisation of the business and in particular:\n\n\n\n\n\n\n\u2014\n\n\nthe organisational structures with the assignment of staff responsibilities in relation to critical procedures, the responsibilities of the managerial staff and their organisational authority,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe methods of monitoring whether the operation of the quality management system is efficient and in particular the ability of that system to achieve the desired design and device quality, including control of devices which fail to conform,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwhere the design, manufacture and/or final verification and testing of the devices, or parts of any of those processes, is carried out by another party, the methods of monitoring the efficient operation of the quality management system and in particular the type and extent of control applied to the other party, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwhere the manufacturer does not have a registered place of business in a Member\u00a0State, the draft mandate for the designation of an authorised representative and a letter of intention from the authorised representative to accept the mandate;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe procedures and techniques for monitoring, verifying, validating and controlling the design of the devices and the corresponding documentation as well as the data and records arising from those procedures and techniques. Those procedures and techniques shall specifically cover:\n\n\n\n\n\n\n\u2014\n\n\nthe strategy for regulatory compliance, including processes for identification of relevant legal requirements, qualification, classification, handling of equivalence, choice of and compliance with conformity assessment procedures,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nidentification of applicable general safety and performance requirements and solutions to fulfil those requirements, taking applicable CS and, where opted for, harmonised standards or other adequate solutions into account,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nrisk management as referred to in Section\u00a03 of Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe clinical evaluation, pursuant to Article\u00a061 and Annex\u00a0XIV, including post-market clinical follow-up,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsolutions for fulfilling the applicable specific requirements regarding design and construction, including appropriate pre-clinical evaluation, in particular the requirements of Chapter II of Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsolutions for fulfilling the applicable specific requirements regarding the information to be supplied with the device, in particular the requirements of Chapter III of Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe device identification procedures drawn up and kept up to date from drawings, specifications or other relevant documents at every stage of manufacture, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmanagement of design or quality management system changes; and\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe verification and quality assurance techniques at the manufacturing stage and in particular the processes and procedures which are to be used, particularly as regards sterilisation and the relevant documents; and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe appropriate tests and trials which are to be carried out before, during and after manufacture, the frequency with which they are to take place, and the test equipment to be used; it shall be possible to trace back adequately the calibration of that test equipment.\n\n\n\n\nIn addition, the manufacturer shall grant the notified body access to the technical documentation referred to in Annexes\u00a0II and III.\n2.3.\u00a0\u00a0\u00a0Audit\nThe notified body shall audit the quality management system to determine whether it meets the requirements referred to in Section\u00a02.2. Where the manufacturer uses a harmonised standard or CS related to a quality management system, the notified body shall assess conformity with those standards or CS. The notified body shall assume that a quality management system which satisfies the relevant harmonised standards or CS conforms to the requirements covered by those standards or CS, unless it duly substantiates not doing so.\nThe audit team of the notified body shall include at least one member with past experience of assessments of the technology concerned in accordance with Sections 4.3. to 4.5. of Annex\u00a0VII. In circumstances where such experience is not immediately obvious or applicable, the notified body shall provide a documented rationale for the composition of that team. The assessment procedure shall include an audit on the manufacturer's premises and, if appropriate, on the premises of the manufacturer's suppliers and/or subcontractors to verify the manufacturing and other relevant processes.\nMoreover, in the case of class IIa and class IIb devices, the quality management system assessment shall be accompanied by the assessment of technical documentation for devices selected on a representative basis in accordance with Sections 4.4 to 4.8. In choosing representative samples, the notified body shall take into account the published guidance developed by the MDCG pursuant to Article\u00a0105 and in particular the novelty of the technology, similarities in design, technology, manufacturing and sterilisation methods, the intended purpose and the results of any previous relevant assessments such as with regard to physical, chemical, biological or clinical properties, that have been carried out in accordance with this Regulation. The notified body in question shall document its rationale for the samples taken.\nIf the quality management system conforms to the relevant provisions of this Regulation, the notified body shall issue an EU quality management system certificate. The notified body shall notify the manufacturer of its decision to issue the certificate. The decision shall contain the conclusions of the audit and a reasoned report.\n2.4.\u00a0\u00a0\u00a0The manufacturer in question shall inform the notified body which approved the quality management system of any plan for substantial changes to the quality management system, or the device-range covered. The notified body shall assess the changes proposed, determine the need for additional audits and verify whether after those changes the quality management system still meets the requirements referred to in Section\u00a02.2. It shall notify the manufacturer of its decision which shall contain the conclusions of the assessment, and where applicable, conclusions of additional audits. The approval of any substantial change to the quality management system or the device-range covered shall take the form of a supplement to the EU quality management system certificate.\n3.\u00a0\u00a0\u00a0Surveillance assessment applicable to class IIa, class IIb and class III devices\n3.1.\u00a0\u00a0\u00a0The aim of surveillance is to ensure that the manufacturer duly fulfils the obligations arising from the approved quality management system.\n3.2.\u00a0\u00a0\u00a0The manufacturer shall give authorisation to the notified body to carry out all the necessary audits, including on-site audits, and supply it with all relevant information, in particular:\n\n\n\n\n\n\n\u2014\n\n\nthe documentation on its quality management system,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndocumentation on any findings and conclusions resulting from the application of the post-market surveillance plan, including the PMCF plan, for a representative sample of devices, and of the provisions on vigilance set out in Articles\u00a087 to 92,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe data stipulated in the part of the quality management system relating to design, such as the results of analyses, calculations, tests and the solutions adopted regarding the risk-management as referred to in Section\u00a04 of Annex\u00a0I, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe data stipulated in the part of the quality management system relating to manufacture, such as quality control reports and test data, calibration data, and records on the qualifications of the personnel concerned.\n\n\n\n\n3.3.\u00a0\u00a0\u00a0Notified bodies shall periodically, at least once every 12 months, carry out appropriate audits and assessments to make sure that the manufacturer in question applies the approved quality management system and the post-market surveillance plan. Those audits and assessments shall include audits on the premises of the manufacturer and, if appropriate, of the manufacturer's suppliers and/or subcontractors. At the time of such on-site audits, the notified body shall, where necessary, carry out or ask for tests in order to check that the quality management system is working properly. It shall provide the manufacturer with a surveillance audit report and, if a test has been carried out, with a test report.\n3.4.\u00a0\u00a0\u00a0The notified body shall randomly perform at least once every five years unannounced audits on the site of the manufacturer and, where appropriate, of the manufacturer's suppliers and/or subcontractors, which may be combined with the periodic surveillance assessment referred to in Section\u00a03.3. or be performed in addition to that surveillance assessment. The notified body shall establish a plan for such unannounced on-site audits but shall not disclose it to the manufacturer.\nWithin the context of such unannounced on-site audits, the notified body shall test an adequate sample of the devices produced or an adequate sample from the manufacturing process to verify that the manufactured device is in conformity with the technical documentation, with the exception of the devices referred to in the second subparagraph\u00a0of Article\u00a052(8). Prior to unannounced on-site audits, the notified body shall specify the relevant sampling criteria and testing procedure.\nInstead of, or in addition to, sampling referred to in the second paragraph, the notified body shall take samples of devices from the market to verify that the manufactured device is in conformity with the technical documentation, with the exception of the devices referred to in the second subparagraph\u00a0of Article\u00a052(8). Prior to the sampling, the notified body in question shall specify the relevant sampling criteria and testing procedure.\nThe notified body shall provide the manufacturer in question with an on-site audit report which shall include, if applicable, the result of the sample test.\n3.5.\u00a0\u00a0\u00a0In the case of class IIa and class IIb devices, the surveillance assessment shall also include an assessment of the technical documentation as referred to in Sections 4.4 to 4.8 for the device or devices concerned on the basis of further representative samples chosen in accordance with the rationale documented by the notified body in accordance with the second paragraph\u00a0of Section\u00a02.3.\nIn the case of class III devices, the surveillance assessment shall also include a test of the approved parts and/or materials that are essential for the integrity of the device, including, where appropriate, a check that the quantities of produced or purchased parts and/or materials correspond to the quantities of finished devices.\n3.6.\u00a0\u00a0\u00a0The notified body shall ensure that the composition of the assessment team is such that there is sufficient experience with the evaluation of the devices, systems and processes concerned, continuous objectivity and neutrality; this shall include a rotation of the members of the assessment team at appropriate intervals. As a general rule, a lead auditor shall neither lead nor attend audits for more than three consecutive years in respect of the same manufacturer.\n3.7.\u00a0\u00a0\u00a0If the notified body finds a divergence between the sample taken from the devices produced or from the market and the specifications laid down in the technical documentation or the approved design, it shall suspend or withdraw the relevant certificate or impose restrictions on it.\nCHAPTER II\n\nASSESSMENT OF THE TECHNICAL DOCUMENTATION\n\n4.\u00a0\u00a0\u00a0Assessment of the technical documentation applicable to class III devices and to the class\u00a0IIb devices referred to in the second subparagraph\u00a0of Article\u00a052(4)\n4.1.\u00a0\u00a0\u00a0In addition to the obligations laid down in Section\u00a02, the manufacturer shall lodge with the notified body an application for assessment of the technical documentation relating to the device which it plans to place on the market or put into service and which is covered by the quality management system referred to in Section\u00a02.\n4.2.\u00a0\u00a0\u00a0The application shall describe the design, manufacture and performance of the device in question. It shall include the technical documentation as referred to in Annexes\u00a0II and III.\n4.3.\u00a0\u00a0\u00a0The notified body shall examine the application by using staff, employed by it, with proven knowledge and experience regarding the technology concerned and its clinical application. The notified body may require the application to be completed by having further tests carried out or requesting further evidence to be provided to allow assessment of conformity with the relevant requirements of the Regulation. The notified body shall carry out adequate physical or laboratory tests in relation to the device or request the manufacturer to carry out such tests.\n4.4.\u00a0\u00a0\u00a0The notified body shall review the clinical evidence presented by the manufacturer in the clinical evaluation report and the related clinical evaluation that was conducted. The notified body shall employ device reviewers with sufficient clinical expertise and, if necessary, use external clinical experts with direct and current experience relating to the device in question or the clinical condition in which it is utilised, for the purposes of that review.\n4.5.\u00a0\u00a0\u00a0The notified body shall, in circumstances in which the clinical evidence is based partly or totally on data from devices which are claimed to be equivalent to the device under assessment, assess the suitability of using such data, taking into account factors such as new indications and innovation. The notified body shall clearly document its conclusions on the claimed equivalence, and on the relevance and adequacy of the data for demonstrating conformity. For any characteristic of the device claimed as innovative by the manufacturer or for new indications, the notified body shall assess to what extent specific claims are supported by specific pre-clinical and clinical data and risk analysis.\n4.6.\u00a0\u00a0\u00a0The notified body shall verify that the clinical evidence and the clinical evaluation are adequate and shall verify the conclusions drawn by the manufacturer on the conformity with the relevant general safety and performance requirements. That verification shall include consideration of the adequacy of the benefit-risk determination, the risk management, the instructions for use, the user training and the manufacturer's post-market surveillance plan, and include a review of the need for, and the adequacy of, the PMCF plan proposed, where applicable.\n4.7.\u00a0\u00a0\u00a0Based on its assessment of the clinical evidence, the notified body shall consider the clinical evaluation and the benefit-risk determination, and whether specific milestones need to be defined to allow the notified body to review updates to the clinical evidence that result from post-market surveillance and PMCF data.\n4.8.\u00a0\u00a0\u00a0The notified body shall clearly document the outcome of its assessment in the clinical evaluation assessment report.\n4.9.\u00a0\u00a0\u00a0The notified body shall provide the manufacturer with a report on the technical documentation assessment, including a clinical evaluation assessment report. If the device conforms to the relevant provisions of this Regulation, the notified body shall issue an EU\u00a0technical documentation assessment certificate. The certificate shall contain the conclusions of the technical documentation assessment, the conditions of the certificate's validity, the data needed for identification of the approved design, and, where appropriate, a description of the intended purpose of the device.\n4.10.\u00a0\u00a0\u00a0Changes to the approved device shall require approval from the notified body which issued the EU technical documentation assessment certificate where such changes could affect the safety and performance of the device or the conditions prescribed for use of the device. Where the manufacturer plans to introduce any of the above-mentioned changes it shall inform the notified body which issued the EU technical documentation assessment certificate thereof. The notified body shall assess the planned changes and decide whether the planned changes require a new conformity assessment in accordance with Article\u00a052 or whether they could be addressed by means of a supplement to the EU technical documentation assessment certificate. In the latter case, the notified body shall assess the changes, notify the manufacturer of its decision and, where the changes are approved, provide it with a supplement to the EU technical documentation assessment certificate.\n5.\u00a0\u00a0\u00a0Specific additional procedures\n5.1.\u00a0\u00a0\u00a0Assessment procedure for certain class III and class IIb devices\n\n\n\n\n\n\n(a)\n\n\nFor class III implantable devices, and for class IIb active devices intended to administer and/or remove a medicinal product as referred to in Section\u00a06.4. of Annex\u00a0VIII (Rule\u00a012), the notified body shall, having verified the quality of clinical data supporting the clinical evaluation report of the manufacturer referred to in Article\u00a061(12), prepare a clinical evaluation assessment report which sets out its conclusions concerning the clinical evidence provided by the manufacturer, in particular concerning the benefit-risk determination, the consistency of that evidence with the intended purpose, including the medical indication or indications and the PMCF plan referred to in Article\u00a010(3) and Part B of Annex\u00a0XIV.\nThe notified body shall transmit its clinical evaluation assessment report, along with the manufacturer's clinical evaluation documentation, referred to in points (c) and (d) of Section\u00a06.1 of Annex\u00a0II, to the Commission.\nThe Commission shall immediately transmit those documents to the relevant expert panel referred to in Article\u00a0106.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nThe notified body may be requested to present its conclusions as referred to in point\u00a0(a) to the expert panel concerned.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nThe expert panel shall decide, under the supervision of the Commission, on the basis of all of the following criteria:\n\n\n\n\n\n\n(i)\n\n\nthe novelty of the device or of the related clinical procedure involved, and the possible major clinical or health impact thereof;\n\n\n\n\n\n\n\n\n\n\n(ii)\n\n\na significantly adverse change in the benefit-risk profile of a specific category or group of devices due to scientifically valid health concerns in respect of components or source material or in respect of the impact on health in the case of failure of the device;\n\n\n\n\n\n\n\n\n\n\n(iii)\n\n\na significantly increased rate of serious incidents reported in accordance with Article\u00a087 in respect of a specific category or group of devices,\n\n\n\n\nwhether to provide a scientific opinion on the clinical evaluation assessment report of the notified body based on the clinical evidence provided by the manufacturer, in particular concerning the benefit-risk determination, the consistency of that evidence with the medical indication or indications and the PMCF plan. That scientific opinion shall be provided within a period of 60 days, starting on the day of receipt of the documents from the Commission as referred to in point\u00a0(a). The reasons for the decision to provide a scientific opinion on the basis of the criteria in points (i), (ii) and (iii) shall be included in the scientific opinion. Where the information submitted is not sufficient for the expert panel to reach a conclusion, this shall be stated in the scientific opinion.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nThe expert panel may decide, under the supervision of the Commission, on the basis of the criteria laid down in point\u00a0(c) not to provide a scientific opinion, in which case it shall inform the notified body as soon as possible and in any event within 21\u00a0days of receipt of the documents as referred to in point\u00a0(a) from the Commission. The expert panel shall within that time limit provide the notified body and the Commission with the reasons for its decision, whereupon the notified body may proceed with the certification procedure of that device.\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nThe expert panel shall within 21 days of receipt of the documents from the Commission notify the Commission, through Eudamed whether it intends to provide a scientific opinion, pursuant to point\u00a0(c), or whether it intends not to provide a scientific opinion, pursuant to point\u00a0(d).\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nWhere no opinion has been delivered within a period of 60 days, the notified body may proceed with the certification procedure of the device in question.\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nThe notified body shall give due consideration to the views expressed in the scientific opinion of the expert panel. Where the expert panel finds that the level of clinical evidence is not sufficient or otherwise gives rise to serious concerns about the benefit-risk determination, the consistency of that evidence with the intended purpose, including the medical indication(s), and with the PMCF plan, the notified body shall, if necessary, advise the manufacturer to restrict the intended purpose of the device to certain groups of patients or certain medical indications and/or to impose a limit on the duration of validity of the certificate, to undertake specific PMCF studies, to adapt the instructions for use or the summary of safety and performance, or to impose other restrictions in its conformity assessment report, as appropriate. The notified body shall provide a full justification where it has not followed the advice of the expert panel in its conformity assessment report and the Commission shall without prejudice to Article\u00a0109 make both the scientific opinion of the expert panel and the written justification provided by the notified body publicly available via Eudamed.\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nThe Commission, after consultation with the Member\u00a0States and relevant scientific experts shall provide guidance for expert panels for consistent interpretation of the criteria in point\u00a0(c) before 26 May 2020.\n\n\n\n\n5.2.\u00a0\u00a0\u00a0Procedure in the case of devices incorporating a medicinal substance\n\n\n\n\n\n\n(a)\n\n\nWhere a device incorporates, as an integral part, a substance which, if used separately, may be considered to be a medicinal product within the meaning of point\u00a02 of Article\u00a01 of Directive\u00a02001/83/EC, including a medicinal product derived from human blood or human plasma and that has an action ancillary to that of the device, the quality, safety and usefulness of the substance shall be verified by analogy with the methods specified in Annex\u00a0I to Directive\u00a02001/83/EC.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nBefore issuing an EU technical documentation assessment certificate, the notified body shall, having verified the usefulness of the substance as part of the device and taking account of the intended purpose of the device, seek a scientific opinion from one of the competent authorities designated by the Member\u00a0States in accordance with Directive\u00a02001/83/EC or from the EMA, either of which to be referred to in this Section\u00a0as \u2018the medicinal products authority consulted\u2019 depending on which has been consulted under this point, on the quality and safety of the substance including the benefit or risk of the incorporation of the substance into the device. Where the device incorporates a human blood or plasma derivative or a substance that, if used separately, may be considered to be a medicinal product falling exclusively within the scope of the Annex to Regulation (EC)\u00a0No\u00a0726/2004, the notified body shall seek the opinion of the EMA.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nWhen issuing its opinion, the medicinal products authority consulted shall take into account the manufacturing process and the data relating to the usefulness of incorporation of the substance into the device as determined by the notified body.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nThe medicinal products authority consulted shall provide its opinion to the notified body within 210 days of receipt of all the necessary documentation.\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nThe scientific opinion of the medicinal products authority consulted, and any possible update of that opinion, shall be included in the documentation of the notified body concerning the device. The notified body shall give due consideration to the views expressed in the scientific opinion when making its decision. The notified body shall not deliver the certificate if the scientific opinion is unfavourable and shall convey its final decision to the medicinal products authority consulted.\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nBefore any change is made with respect to an ancillary substance incorporated in a device, in particular related to its manufacturing process, the manufacturer shall inform the notified body of the changes. That notified body shall seek the opinion of the medicinal products authority consulted, in order to confirm that the quality and safety of the ancillary substance remain unchanged. The medicinal products authority consulted shall take into account the data relating to the usefulness of incorporation of the substance into the device as determined by the notified body, in order to ensure that the changes have no negative impact on the risk or benefit previously established concerning the incorporation of the substance into the device. The medicinal products authority consulted shall provide its opinion within 60 days after receipt of all the necessary documentation regarding the changes. The notified body shall not deliver the supplement to the EU technical documentation assessment certificate if the scientific opinion provided by the medicinal products authority consulted is unfavourable. The notified body shall convey its final decision to the medicinal products authority consulted.\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nWhere the medicinal products authority consulted obtains information on the ancillary substance, which could have an impact on the risk or benefit previously established concerning the incorporation of the substance into the device, it shall advise the notified body as to whether this information has an impact on the risk or benefit previously established concerning the incorporation of the substance into the device. The notified body shall take that advice into account in reconsidering its assessment of the conformity assessment procedure.\n\n\n\n\n5.3.\u00a0\u00a0\u00a0Procedure in the case of devices manufactured utilising, or incorporating, tissues or cells of human or animal origin, or their derivatives, that are non-viable or rendered non-viable\n5.3.1.\u00a0\u00a0\u00a0Tissues or cells of human origin or their derivatives\n\n\n\n\n\n\n(a)\n\n\nFor devices manufactured utilising derivatives of tissues or cells of human origin that are covered by this Regulation in accordance with point\u00a0(g) of Article\u00a01(6) and for devices that incorporate, as an integral part, tissues or cells of human origin, or their derivatives, covered by Directive\u00a02004/23/EC, that have an action ancillary to that of the device, the notified body shall, prior to issuing an EU technical documentation assessment certificate, seek a scientific opinion from one of the competent authorities designated by the Member\u00a0States in accordance with Directive\u00a02004/23/EC (\u2018human tissues and cells competent authority\u2019) on the aspects relating to the donation, procurement and testing of tissues or cells of human origin or their derivatives. The notified body shall submit a summary of the preliminary conformity assessment which provides, among other things, information about the non-viability of the human tissues or cells in question, their donation, procurement and testing and the risk or benefit of the incorporation of the tissues or cells of human origin or their derivatives into the device.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nWithin 120 days of receipt of all the necessary documentation, the human tissues and cells competent authority shall provide to the notified body its opinion.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nThe scientific opinion of the human tissues and cells competent authority, and any possible update, shall be included in the documentation of the notified body concerning the device. The notified body shall give due consideration to the views expressed in the scientific opinion of the human tissues and cells competent authority when making its decision. The notified body shall not deliver the certificate if that scientific opinion is unfavourable. It shall convey its final decision to the human tissues and cells competent authority concerned.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nBefore any change is made with respect to non-viable tissues or cells of human origin or their derivatives incorporated in a device, in particular relating to their donation, testing or procurement, the manufacturer shall inform the notified body of the intended changes. The notified body shall consult the authority that was involved in the initial consultation, in order to confirm that the quality and safety of the tissues or cells of human origin or their derivatives incorporated in the device are maintained. The human tissues and cells competent authority concerned shall take into account the data relating to the usefulness of incorporation of the tissues or cells of human origin or their derivatives into the device as determined by the notified body, in order to ensure that the changes have no negative impact on the established benefit-risk ratio of the addition of the tissues or cells of human origin or their derivatives in the device. It shall provide its opinion within 60\u00a0days of receipt of all the necessary documentation regarding the intended changes. The notified body shall not deliver a supplement to the EU technical documentation assessment certificate if the scientific opinion is unfavourable and shall convey its final decision to the human tissues and cells competent authority concerned.\n\n\n\n\n5.3.2.\u00a0\u00a0\u00a0Tissues or cells of animal origin or their derivatives\nIn the case of devices manufactured utilising animal tissue which is rendered non-viable or utilising non-viable products derived from animal tissue, as referred to in Regulation\u00a0(EU)\u00a0No\u00a0722/2012, the notified body shall apply the relevant requirements laid down in that Regulation.\n5.4.\u00a0\u00a0\u00a0Procedure in the case of devices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body\n\n\n\n\n\n\n(a)\n\n\nThe quality and safety of devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed by, or locally dispersed in, the human body, shall be verified where applicable and only in respect of the requirements not covered by this Regulation, in accordance with the relevant requirements laid down in Annex\u00a0I to Directive\u00a02001/83/EC for the evaluation of absorption, distribution, metabolism, excretion, local tolerance, toxicity, interaction with other devices, medicinal products or other substances and potential for adverse reactions.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nIn addition, for devices, or their products of metabolism, that are systemically absorbed by the human body in order to achieve their intended purpose, the notified body shall seek a scientific opinion from one of the competent authorities designated by the Member\u00a0States in accordance with Directive\u00a02001/83/EC or from the EMA, either of which to be referred to in this Section\u00a0as \u2018the medicinal products authority consulted\u2019 depending on which has been consulted under this point, on the compliance of the device with the relevant requirements laid down in Annex\u00a0I to Directive\u00a02001/83/EC.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nThe opinion of the medicinal products authority consulted shall be drawn up within 150\u00a0days of receipt of all the necessary documentation.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nThe scientific opinion of the medicinal products authority consulted, and any possible update, shall be included in the documentation of the notified body concerning the device. The notified body shall give due consideration to the views expressed in the scientific opinion when making its decision and shall convey its final decision to the medicinal products authority consulted.\n\n\n\n\n6.\u00a0\u00a0\u00a0Batch verification in the case of devices incorporating, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma as referred to in Article\u00a01(8)\nUpon completing the manufacture of each batch of devices that incorporate, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma as referred to in the first subparagraph\u00a0of Article\u00a01(8), the manufacturer shall inform the notified body of the release of the batch of devices and send it the official certificate concerning the release of the batch of human blood or plasma derivative used in the device, issued by a Member\u00a0State laboratory or a laboratory designated for that purpose by a Member\u00a0State in accordance with Article\u00a0114(2) of Directive\u00a02001/83/EC.\nCHAPTER III\n\nADMINISTRATIVE PROVISIONS\n\n7.\u00a0\u00a0\u00a0The manufacturer or, where the manufacturer does not have a registered place of business in a Member\u00a0State, its authorised representative shall, for a period ending no sooner than 10 years, and in the case of implantable devices no sooner than 15 years, after the last device has been placed on the market, keep at the disposal of the competent authorities:\n\n\n\n\n\n\n\u2014\n\n\nthe EU declaration of conformity,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation referred to in the fifth indent of Section\u00a02.1 and in particular the data and records arising from the procedures referred to in point\u00a0(c) of the second paragraph\u00a0of Section\u00a02.2,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation on the changes referred to in Section\u00a02.4,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation referred to in Section\u00a04.2, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe decisions and reports from the notified body as referred to in this Annex.\n\n\n\n\n8.\u00a0\u00a0\u00a0Each Member\u00a0State shall require that the documentation referred to in Section\u00a07 is kept at the disposal of competent authorities for the period indicated in that Section\u00a0in case a manufacturer, or its authorised representative, established within its territory goes bankrupt or ceases its business activity prior to the end of that period.\n\n\n\n\n\nANNEX\u00a0X\n\nCONFORMITY ASSESSMENT BASED ON TYPE-EXAMINATION\n\n1.\u00a0\u00a0\u00a0EU type-examination is the procedure whereby a notified body ascertains and certifies that a device, including its technical documentation and relevant life cycle processes and a corresponding representative sample of the device production envisaged, fulfils the relevant provisions of this Regulation.\n2.\u00a0\u00a0\u00a0Application\nThe manufacturer shall lodge an application for assessment with a notified body. The application shall include:\n\n\n\n\n\n\n\u2014\n\n\nthe name of the manufacturer and address of the registered place of business of the manufacturer and, if the application is lodged by the authorised representative, the name of the authorised representative and the address of its registered place of business,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe technical documentation referred to in Annexes\u00a0II and III. The applicant shall make a representative sample of the device production envisaged (\u2018type\u2019) available to the notified body. The notified body may request other samples as necessary, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na written declaration that no application has been lodged with any other notified body for the same type, or information about any previous application for the same type that was refused by another notified body or was withdrawn by the manufacturer or its authorised representative before that other notified body made its final assessment.\n\n\n\n\n3.\u00a0\u00a0\u00a0Assessment\nThe notified body shall:\n\n\n\n\n\n\n(a)\n\n\nexamine the application by using staff with proven knowledge and experience regarding the technology concerned and its clinical application. The notified body may require the application to be completed by having further tests carried out or requesting further evidence to be provided to allow assessment of conformity with the relevant requirements of this Regulation. The notified body shall carry out adequate physical or laboratory tests in relation to the device or request the manufacturer to carry out such tests;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nexamine and assess the technical documentation for conformity with the requirements of this Regulation that are applicable to the device and verify that the type has been manufactured in conformity with that documentation; it shall also record the items designed in conformity with the applicable standards referred to in Article\u00a08 or with applicable CS, and record the items not designed on the basis of the relevant standards referred to in Article\u00a08 or of the relevant CS;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nreview the clinical evidence presented by the manufacturer in the clinical evaluation report in accordance with Section\u00a04 of Annex\u00a0XIV. The notified body shall employ device reviewers with sufficient clinical expertise and, if necessary, use external clinical experts with direct and current experience relating to the device in question or to the clinical condition in which it is utilised, for the purposes of that review;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nin circumstances in which the clinical evidence is based partly or totally on data from devices which are claimed to be similar or equivalent to the device under assessment, assess the suitability of using such data, taking into account factors such as new indications and innovation. The notified body shall clearly document its conclusions on the claimed equivalence, and on the relevance and adequacy of the data for demonstrating conformity;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nclearly document the outcome of its assessment in a pre-clinical and clinical evaluation assessment report as part of the EU type examination report referred to in point\u00a0(i);\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\ncarry out or arrange for the appropriate assessments and the physical or laboratory tests necessary to verify whether the solutions adopted by the manufacturer meet the general safety and performance requirements laid down in this Regulation, in the event that the standards referred to in Article\u00a08 or the CS have not been applied. Where the device has to be connected to another device or devices in order to operate as intended, proof shall be provided that it conforms to the general safety and performance requirements when connected to any such device or devices having the characteristics specified by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\ncarry out or arrange for the appropriate assessments and the physical or laboratory tests necessary to verify whether, in the event that the manufacturer has chosen to apply the relevant harmonised standards, those standards have actually been applied;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nagree with the applicant on the place where the necessary assessments and tests are to be carried out; and\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\ndraw up an EU type-examination report on the results of the assessments and tests carried out under points (a) to (g).\n\n\n\n\n4.\u00a0\u00a0\u00a0Certificate\nIf the type conforms to this Regulation, the notified body shall issue an EU\u00a0type-examination certificate. The certificate shall contain the name and address of the manufacturer, the conclusions of the type examination assessment, the conditions of the certificate's validity and the data needed for identification of the type approved. The certificate shall be drawn up in accordance with Annex\u00a0XII. The relevant parts of the documentation shall be annexed to the certificate and a copy kept by the notified body.\n5.\u00a0\u00a0\u00a0Changes to the type\n5.1.\u00a0\u00a0\u00a0The applicant shall inform the notified body which issued the EU type-examination certificate of any planned change to the approved type or of its intended purpose and conditions of use.\n5.2.\u00a0\u00a0\u00a0Changes to the approved device including limitations of its intended purpose and conditions of use shall require approval from the notified body which issued the EU\u00a0type-examination certificate where such changes may affect conformity with the general safety and performance requirements or with the conditions prescribed for use of the product. The notified body shall examine the planned changes, notify the manufacturer of its decision and provide him with a supplement to the EU type-examination report. The approval of any change to the approved type shall take the form of a supplement to the EU\u00a0type-examination certificate.\n5.3.\u00a0\u00a0\u00a0Changes to the intended purpose and conditions of use of the approved device, with the exception of limitations of the intended purpose and conditions of use, shall necessitate a new application for a conformity assessment.\n6.\u00a0\u00a0\u00a0Specific additional procedures\nSection\u00a05 of Annex\u00a0IX shall apply with the proviso that any reference to an EU technical documentation assessment certificate shall be understood as a reference to an EU\u00a0type-examination certificate.\n7.\u00a0\u00a0\u00a0Administrative provisions\nThe manufacturer or, where the manufacturer does not have a registered place of business in a Member\u00a0State, its authorised representative shall, for a period ending no sooner than 10 years, and in the case of implantable devices no sooner than 15 years, after the last device has been placed on the market, keep at the disposal of the competent authorities:\n\n\n\n\n\n\n\u2014\n\n\nthe documentation referred to in the second indent of Section\u00a02,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation on the changes referred to in Section\u00a05, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncopies of EU type-examination certificates, scientific opinions and reports and their additions/supplements.\n\n\n\n\nSection\u00a08 of Annex\u00a0IX shall apply.\n\n\n\n\n\nANNEX\u00a0XI\n\nCONFORMITY ASSESSMENT BASED ON PRODUCT CONFORMITY VERIFICATION\n\n1.\u00a0\u00a0\u00a0The objective of the conformity assessment based on product conformity verification is to ensure that devices conform to the type for which an EU type-examination certificate has been issued, and that they meet the provisions of this Regulation which apply to them.\n2.\u00a0\u00a0\u00a0Where an EU type-examination certificate has been issued in accordance with Annex\u00a0X, the manufacturer may either apply the procedure set out in Part A (production quality assurance) or the procedure set out in Part B (product verification) of this Annex.\n3.\u00a0\u00a0\u00a0By way of derogation from Sections 1 and 2 above, the procedures in this Annex\u00a0coupled with the drawing up of technical documentation as set out in Annexes\u00a0II and III may also be applied by manufacturers of class IIa devices.\nPART A\n\nPRODUCTION QUALITY ASSURANCE\n\n4.\u00a0\u00a0\u00a0The manufacturer shall ensure that the quality management system approved for the manufacture of the devices concerned is implemented, shall carry out a final verification, as specified in Section\u00a06, and shall be subject to the surveillance referred to in Section\u00a07.\n5.\u00a0\u00a0\u00a0When the manufacturer fulfils the obligations laid down in Section\u00a04, it shall draw up and keep an EU declaration of conformity in accordance with Article\u00a019 and Annex\u00a0IV for the device covered by the conformity assessment procedure. By issuing an EU declaration of conformity, the manufacturer shall be deemed to ensure and to declare that the device concerned conforms to the type described in the EU type-examination certificate and meets the requirements of this Regulation which apply to the device.\n6.\u00a0\u00a0\u00a0Quality management system\n6.1.\u00a0\u00a0\u00a0The manufacturer shall lodge an application for assessment of its quality management system with a notified body. The application shall include:\n\n\n\n\n\n\n\u2014\n\n\nall elements listed in Section\u00a02.1 of Annex\u00a0IX,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe technical documentation referred to in Annexes\u00a0II and III for the types approved, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na copy of the EU type-examination certificates referred to in Section\u00a04 of Annex\u00a0X; if the EU type-examination certificates have been issued by the same notified body with which the application is lodged, a reference to the technical documentation and its updates and the certificates issued shall also be included in the application.\n\n\n\n\n6.2.\u00a0\u00a0\u00a0Implementation of the quality management system shall be such as to ensure that there is compliance with the type described in the EU type-examination certificate and with the provisions of this Regulation which apply to the devices at each stage. All the elements, requirements and provisions adopted by the manufacturer for its quality management system shall be documented in a systematic and orderly manner in the form of a quality manual and written policies and procedures, such as quality programmes, quality plans and quality records.\nThat documentation shall, in particular, include an adequate description of all elements listed in points (a), (b), (d) and (e) of Section\u00a02.2 of Annex\u00a0IX.\n6.3.\u00a0\u00a0\u00a0The first and second paragraph\u00a0of Section\u00a02.3 of Annex\u00a0IX shall apply.\nIf the quality management system is such that it ensures that the devices conform to the type described in the EU type-examination certificate and that it conforms to the relevant provisions of this Regulation, the notified body shall issue an EU quality assurance certificate. The notified body shall notify the manufacturer of its decision to issue the certificate. That decision shall contain the conclusions of the notified body's audit and a reasoned assessment.\n6.4.\u00a0\u00a0\u00a0Section\u00a02.4 of Annex\u00a0IX shall apply.\n7.\u00a0\u00a0\u00a0Surveillance\nSection\u00a03.1, the first, second and fourth indents of Section\u00a03.2, Sections\u00a03.3, 3.4, 3.6 and 3.7 of Annex\u00a0IX shall apply.\nIn the case of class III devices, surveillance shall also include a check that the quantities of produced or purchased raw material or crucial components approved for the type and correspond to the quantities of finished devices.\n8.\u00a0\u00a0\u00a0Batch verification in the case of devices incorporating, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma referred to in Article\u00a01(8).\nUpon completing the manufacture of each batch of devices that incorporate, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma referred to in the first subparagraph\u00a0of Article\u00a01(8), the manufacturer shall inform the notified body of the release of the batch of devices and send it the official certificate concerning the release of the batch of human blood or plasma derivative used in the device, issued by a Member\u00a0State laboratory or a laboratory designated for that purpose by a Member\u00a0State in accordance with Article\u00a0114(2) of Directive\u00a02001/83/EC.\n9.\u00a0\u00a0\u00a0Administrative provisions\nThe manufacturer or, where the manufacturer does not have a registered place of business in a Member\u00a0State, its authorised representative shall, for a period ending no sooner than 10 years, and in the case of implantable devices no sooner than 15 years, after the last device has been placed on the market, keep at the disposal of the competent authorities:\n\n\n\n\n\n\n\u2014\n\n\nthe EU declaration of conformity,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation referred to in the fifth indent of Section\u00a02.1 of Annex\u00a0IX,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation referred to in the eighth indent of Section\u00a02.1 of Annex\u00a0IX, including the EU type-examination certificate referred to in Annex\u00a0X,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation on the changes referred to in Section\u00a02.4 of Annex\u00a0IX, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe decisions and reports from the notified body as referred to in Sections 2.3, 3.3 and 3.4 of Annex\u00a0IX.\n\n\n\n\nSection\u00a08 of Annex\u00a0IX shall apply.\n10.\u00a0\u00a0\u00a0Application to class IIa devices\n10.1.\u00a0\u00a0\u00a0By way of derogation from Section\u00a05, by virtue of the EU declaration of conformity the manufacturer shall be deemed to ensure and to declare that the class IIa devices in question are manufactured in conformity with the technical documentation referred to in Annexes\u00a0II and III and meet the requirements of this Regulation which apply to them.\n10.2.\u00a0\u00a0\u00a0For class IIa devices the notified body shall assess, as part of the assessment referred to in Section\u00a06.3, whether the technical documentation as referred to in Annexes\u00a0II and III for the devices selected on a representative basis is compliant with this Regulation.\nIn choosing a representative sample or samples of devices, the notified body shall take into account the novelty of the technology, similarities in design, technology, manufacturing and sterilisation methods, the intended use and the results of any previous relevant assessments (e.g. with regard to physical, chemical, biological or clinical properties) that have been carried out in accordance with this Regulation. The notified body shall document its rationale for the sample or samples of devices taken.\n10.3.\u00a0\u00a0\u00a0Where the assessment under Section\u00a010.2. confirms that the class IIa devices in question conform to the technical documentation referred to in Annexes\u00a0II and III and meet the requirements of this Regulation which apply to them, the notified body shall issue a certificate pursuant to this Part of this Annex.\n10.4.\u00a0\u00a0\u00a0Samples additional to those taken for the initial conformity assessment of devices shall be assessed by the notified body as part of the surveillance assessment referred to in Section\u00a07.\n10.5.\u00a0\u00a0\u00a0By way of derogation from Section\u00a06, the manufacturer or its authorised representative shall, for a period ending no sooner than 10 years after the last device has been placed on the market, keep at the disposal of the competent authorities:\n\n\n\n\n\n\n\u2014\n\n\nthe EU declaration of conformity,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe technical documentation referred to in Annexes\u00a0II and III, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe certificate referred to in Section\u00a010.3.\n\n\n\n\nSection\u00a08 of Annex\u00a0IX shall apply.\nPART B\n\nPRODUCT VERIFICATION\n\n11.\u00a0\u00a0\u00a0Product verification shall be understood to be the procedure whereby after examination of every manufactured device, the manufacturer, by issuing an EU declaration of conformity in accordance with Article\u00a019 and Annex\u00a0IV, shall be deemed to ensure and to declare that the devices which have been subject to the procedure set out in Sections 14 and 15 conform to the type described in the EU type-examination certificate and meet the requirements of this Regulation which apply to them.\n12.\u00a0\u00a0\u00a0The manufacturer shall take all the measures necessary to ensure that the manufacturing process produces devices which conform to the type described in the EU type-examination certificate and to the requirements of the Regulation which apply to them. Prior to the start of manufacture, the manufacturer shall prepare documents defining the manufacturing process, in particular as regards sterilisation where necessary, together with all routine, pre-established procedures to be implemented to ensure homogeneous production and, where appropriate, conformity of the devices with the type described in the EU\u00a0type-examination certificate and with the requirements of this Regulation which apply to them.\nIn addition, for devices placed on the market in a sterile condition, and only for those aspects of the manufacturing process designed to secure and maintain sterility, the manufacturer shall apply the provisions of Sections 6 and 7.\n13.\u00a0\u00a0\u00a0The manufacturer shall undertake to institute and keep up to date a post-market surveillance plan, including a PMCF plan, and the procedures ensuring compliance with the obligations of the manufacturer resulting from the provisions on vigilance and post-market surveillance system set out in Chapter VII.\n14.\u00a0\u00a0\u00a0The notified body shall carry out the appropriate examinations and tests in order to verify the conformity of the device with the requirements of the Regulation by examining and testing every product as specified in Section\u00a015.\nThe examinations and tests referred to in the first paragraph\u00a0of this Section\u00a0shall not apply to aspects of the manufacturing process designed to secure sterility.\n15.\u00a0\u00a0\u00a0Verification by examination and testing of every product\n15.1.\u00a0\u00a0\u00a0Every device shall be examined individually and the appropriate physical or laboratory tests as defined in the relevant standard or standards referred to in Article\u00a08, or equivalent tests and assessments, shall be carried out in order to verify, where appropriate, the conformity of the devices with the type described in the EU type-examination certificate and with the requirements of this Regulation which apply to them.\n15.2.\u00a0\u00a0\u00a0The notified body shall affix, or have affixed, its identification number to each approved device and shall draw up an EU product verification certificate relating to the tests and assessments carried out.\n16.\u00a0\u00a0\u00a0Batch verification in the case of devices incorporating, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma referred to in Article\u00a01(8).\nUpon completing the manufacture of each batch of devices that incorporate, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma referred to in the first subparagraph\u00a0of Article\u00a01(8), the manufacturer shall inform the notified body of the release of the batch of devices and send it the official certificate concerning the release of the batch of human blood or plasma derivative used in the device, issued by a Member\u00a0State laboratory or a laboratory designated for that purpose by a Member\u00a0State in accordance with Article\u00a0114(2) of Directive\u00a02001/83/EC.\n17.\u00a0\u00a0\u00a0Administrative provisions\nThe manufacturer or its authorised representative shall, for a period ending no sooner than 10 years, and in the case of implantable devices no sooner than 15 years, after the last device has been placed on the market, keep at the disposal of the competent authorities:\n\n\n\n\n\n\n\u2014\n\n\nthe EU declaration of conformity,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation referred to in Section\u00a012,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe certificate referred to in Section\u00a015.2, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe EU type-examination certificate referred to in Annex\u00a0X.\n\n\n\n\nSection\u00a08 of Annex\u00a0IX shall apply.\n18.\u00a0\u00a0\u00a0Application to class IIa devices\n18.1.\u00a0\u00a0\u00a0By way of derogation from Section\u00a011, by virtue of the EU declaration of conformity the manufacturer shall be deemed to ensure and to declare that the class IIa devices in question are manufactured in conformity with the technical documentation referred to in Annexes\u00a0II and III and meet the requirements of this Regulation which apply to them.\n18.2.\u00a0\u00a0\u00a0The verification conducted by the notified body in accordance with Section\u00a014 is intended to confirm the conformity of the class IIa devices in question with the technical documentation referred to in Annexes\u00a0II and III and with the requirements of this Regulation which apply to them.\n18.3.\u00a0\u00a0\u00a0If the verification referred to in Section\u00a018.2 confirms that the class IIa devices in question conform to the technical documentation referred to in Annexes\u00a0II and III and meet the requirements of this Regulation which apply to them, the notified body shall issue a certificate pursuant to this Part of this Annex.\n18.4.\u00a0\u00a0\u00a0By way of derogation from Section\u00a017, the manufacturer or its authorised representative shall, for a period ending no sooner than 10 years after the last device has been placed on the market, keep at the disposal of the competent authorities:\n\n\n\n\n\n\n\u2014\n\n\nthe EU declaration of conformity,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe technical documentation referred to in Annexes\u00a0II and III, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe certificate referred to in Section\u00a018.3.\n\n\n\n\nSection\u00a08 of Annex\u00a0IX shall apply.\n\n\n\n\n\nANNEX XII\n\nCERTIFICATES ISSUED BY A NOTIFIED BODY\n\nCHAPTER I\n\nGENERAL REQUIREMENTS\n\n\n\n\n\n\n\n\n\n1.\n\n\nCertificates shall be drawn up in one of the official languages of the Union.\n\n\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nEach certificate shall refer to only one conformity assessment procedure.\n\n\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nCertificates shall only be issued to one manufacturer. The name and address of the manufacturer included in the certificate shall be the same as that registered in the electronic system referred to in Article\u00a030.\n\n\n\n\n\n\n\n\n\n\n\n\n4.\n\n\nThe scope of the certificates shall unambiguously identify the device or devices covered:\n\n\n\n\n\n\n(a)\n\n\nEU technical documentation assessment certificates, EU type-examination certificates and EU product verification certificates shall include a clear identification, including the name, model and type, of the device or devices, the intended purpose, as included by the manufacturer in the instructions for use and in relation to which the device has been assessed in the conformity assessment procedure, risk classification and the Basic UDI-DI as referred to in Article\u00a027(6);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nEU quality management system certificates and EU quality assurance certificates shall include the identification of the devices or groups of devices, the risk classification, and, for class IIb devices, the intended purpose.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n5.\n\n\nThe notified body shall be able to demonstrate on request, which (individual) devices are covered by the certificate. The notified body shall set up a system that enables the determination of the devices, including their classification, covered by the certificate.\n\n\n\n\n\n\n\n\n\n\n\n\n6.\n\n\nCertificates shall contain, if applicable, a note that, for the placing on the market of the device or devices it covers, another certificate issued in accordance with this Regulation is required.\n\n\n\n\n\n\n\n\n\n\n\n\n7.\n\n\nEU quality management system certificates and EU quality assurance certificates for class\u00a0I devices for which the involvement of a notified body is required pursuant to Article\u00a052(7) shall include a statement that the audit by the notified body of the quality management system was limited to the aspects required under that paragraph.\n\n\n\n\n\n\n\n\n\n\n\n\n8.\n\n\nWhere a certificate is supplemented, modified or re-issued, the new certificate shall contain a reference to the preceding certificate and its date of issue with identification of the changes.\n\n\n\n\nCHAPTER II\n\nMINIMUM CONTENT OF THE CERTIFICATES\n\n\n\n\n\n\n\n1.\n\n\nname, address and identification number of the notified body;\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nname and address of the manufacturer and, if applicable, of the authorised representative;\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nunique number identifying the certificate;\n\n\n\n\n\n\n\n\n\n\n4.\n\n\nif already issued, the SRN of the manufacturer referred to in to Article\u00a031(2);\n\n\n\n\n\n\n\n\n\n\n5.\n\n\ndate of issue;\n\n\n\n\n\n\n\n\n\n\n6.\n\n\ndate of expiry;\n\n\n\n\n\n\n\n\n\n\n7.\n\n\ndata needed for the unambiguous identification of the device or devices where applicable as specified in Section\u00a04 of Part I;\n\n\n\n\n\n\n\n\n\n\n8.\n\n\nif applicable, reference to any previous certificate as specified in Section\u00a08 of Chapter I;\n\n\n\n\n\n\n\n\n\n\n9.\n\n\nreference to this Regulation and the relevant Annex\u00a0in accordance with which the conformity assessment has been carried out;\n\n\n\n\n\n\n\n\n\n\n10.\n\n\nexaminations and tests performed, e.g. reference to relevant CS, harmonised standards, test reports and audit report(s);\n\n\n\n\n\n\n\n\n\n\n11.\n\n\nif applicable, reference to the relevant parts of the technical documentation or other certificates required for the placing on the market of the device or devices covered;\n\n\n\n\n\n\n\n\n\n\n12.\n\n\nif applicable, information about the surveillance by the notified body;\n\n\n\n\n\n\n\n\n\n\n13.\n\n\nconclusions of the notified body's conformity assessment with regard to the relevant Annex;\n\n\n\n\n\n\n\n\n\n\n14.\n\n\nconditions for or limitations to the validity of the certificate;\n\n\n\n\n\n\n\n\n\n\n15.\n\n\nlegally binding signature of the notified body in accordance with the applicable national law.\n\n\n\n\n\n\n\n\n\nANNEX XIII\n\nPROCEDURE FOR CUSTOM-MADE DEVICES\n\n\n\n\n\n\n\n\n\n1.\n\n\nFor custom-made devices, the manufacturer or its authorised representative shall draw up a statement containing all of the following information:\n\n\n\n\n\n\n\u2014\n\n\nthe name and address of the manufacturer, and of all manufacturing sites,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif applicable, the name and address of the authorised representative,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndata allowing identification of the device in question,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na statement that the device is intended for exclusive use by a particular patient or user, identified by name, an acronym or a numerical code,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe name of the person who made out the prescription and who is authorised by national law by virtue of their professional qualifications to do so, and, where applicable, the name of the health institution concerned,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe specific characteristics of the product as indicated by the prescription,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na statement that the device in question conforms to the general safety and performance requirements set out in Annex\u00a0I and, where applicable, indicating which general safety and performance requirements have not been fully met, together with the grounds,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwhere applicable, an indication that the device contains or incorporates a medicinal substance, including a human blood or plasma derivative, or tissues or cells of human origin, or of animal origin as referred to in Regulation\u00a0(EU)\u00a0No\u00a0722/2012.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nThe manufacturer shall undertake to keep available for the competent national authorities documentation that indicates its manufacturing site or sites and allows an understanding to be formed of the design, manufacture and performance of the device, including the expected performance, so as to allow assessment of conformity with the requirements of this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nThe manufacturer shall take all the measures necessary to ensure that the manufacturing process produces devices which are manufactured in accordance with the documentation referred to in Section\u00a02.\n\n\n\n\n\n\n\n\n\n\n\n\n4.\n\n\nThe statement referred to in the introductory part of Section\u00a01 shall be kept for a period of at least 10 years after the device has been placed on the market. In the case of implantable devices, the period shall be at least 15 years.\nSection\u00a08 of Annex\u00a0IX shall apply.\n\n\n\n\n\n\n\n\n\n\n\n\n5.\n\n\nThe manufacturer shall review and document experience gained in the post-production phase, including from PMCF as referred to in Part B of Annex\u00a0XIV, and implement appropriate means to apply any necessary corrective action, In that context, it shall report in accordance with Article\u00a087(1) to the competent authorities any serious incidents or field safety corrective actions or both as soon as it learns of them.\n\n\n\n\n\n\n\n\n\nANNEX XIV\n\nCLINICAL EVALUATION AND POST-MARKET CLINICAL FOLLOW-UP\n\nPART A\n\nCLINICAL EVALUATION\n\n1.\u00a0\u00a0\u00a0To plan, continuously conduct and document a clinical evaluation, manufacturers shall:\n\n\n\n\n\n\n(a)\n\n\nestablish and update a clinical evaluation plan, which shall include at least:\n\n\n\n\n\n\n\u2014\n\n\nan identification of the general safety and performance requirements that require support from relevant clinical data;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na specification of the intended purpose of the device;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na clear specification of intended target groups with clear indications and contra-indications;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na detailed description of intended clinical benefits to patients with relevant and specified clinical outcome parameters;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na specification of methods to be used for examination of qualitative and quantitative aspects of clinical safety with clear reference to the determination of residual risks and side-effects;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nan indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nan indication how benefit-risk issues relating to specific components such as use of pharmaceutical, non-viable animal or human tissues, are to be addressed; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na clinical development plan indicating progression from exploratory investigations, such as first-in-man studies, feasibility and pilot studies, to confirmatory investigations, such as pivotal clinical investigations, and a PMCF as referred to in Part B of this Annex\u00a0with an indication of milestones and a description of potential acceptance criteria;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nidentify available clinical data relevant to the device and its intended purpose and any gaps in clinical evidence through a systematic scientific literature review;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nappraise all relevant clinical data by evaluating their suitability for establishing the safety and performance of the device;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\ngenerate, through properly designed clinical investigations in accordance with the clinical development plan, any new or additional clinical data necessary to address outstanding issues; and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nanalyse all relevant clinical data in order to reach conclusions about the safety and clinical performance of the device including its clinical benefits.\n\n\n\n\n2.\u00a0\u00a0\u00a0The clinical evaluation shall be thorough and objective, and take into account both favourable and unfavourable data. Its depth and extent shall be proportionate and appropriate to the nature, classification, intended purpose and risks of the device in question, as well as to the manufacturer's claims in respect of the device.\n3.\u00a0\u00a0\u00a0A clinical evaluation may be based on clinical data relating to a device for which equivalence to the device in question can be demonstrated. The following technical, biological and clinical characteristics shall be taken into consideration for the demonstration of equivalence:\n\n\n\n\n\n\n\u2014\n\n\nTechnical: the device is of similar design; is used under similar conditions of use; has similar specifications and properties including physicochemical properties such as intensity of energy, tensile strength, viscosity, surface characteristics, wavelength and software algorithms; uses similar deployment methods, where relevant; has similar principles of operation and critical performance requirements;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nBiological: the device uses the same materials or substances in contact with the same human tissues or body fluids for a similar kind and duration of contact and similar release characteristics of substances, including degradation products and leachables;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nClinical: the device is used for the same clinical condition or purpose, including similar severity and stage of disease, at the same site in the body, in a similar population, including as regards age, anatomy and physiology; has the same kind of user; has similar relevant critical performance in view of the expected clinical effect for a specific intended purpose.\n\n\n\n\nThe characteristics listed in the first paragraph\u00a0shall be similar to the extent that there would be no clinically significant difference in the safety and clinical performance of the device. Considerations of equivalence shall be based on proper scientific justification. It shall be clearly demonstrated that manufacturers have sufficient levels of access to the data relating to devices with which they are claiming equivalence in order to justify their claims of equivalence.\n4.\u00a0\u00a0\u00a0The results of the clinical evaluation and the clinical evidence on which it is based shall be documented in a clinical evaluation report which shall support the assessment of the conformity of the device.\nThe clinical evidence together with non-clinical data generated from non-clinical testing methods and other relevant documentation shall allow the manufacturer to demonstrate conformity with the general safety and performance requirements and shall be part of the technical documentation for the device in question.\nBoth favourable and unfavourable data considered in the clinical evaluation shall be included in the technical documentation.\nPART B\n\nPOST-MARKET CLINICAL FOLLOW-UP\n\n5.\u00a0\u00a0\u00a0PMCF shall be understood to be a continuous process that updates the clinical evaluation referred to in Article\u00a061 and Part A of this Annex\u00a0and shall be addressed in the manufacturer's post-market surveillance plan. When conducting PMCF, the manufacturer shall proactively collect and evaluate clinical data from the use in or on humans of a device which bears the CE marking and is placed on the market or put into service within its intended purpose as referred to in the relevant conformity assessment procedure, with the aim of confirming the safety and performance throughout the expected lifetime of the device, of ensuring the continued acceptability of identified risks and of detecting emerging risks on the basis of factual evidence.\n6.\u00a0\u00a0\u00a0PMCF shall be performed pursuant to a documented method laid down in a PMCF plan.\n6.1.\u00a0\u00a0\u00a0The PMCF plan shall specify the methods and procedures for proactively collecting and evaluating clinical data with the aim of:\n\n\n\n\n\n\n(a)\n\n\nconfirming the safety and performance of the device throughout its expected lifetime,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nidentifying previously unknown side-effects and monitoring the identified side-effects and contraindications,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nidentifying and analysing emergent risks on the basis of factual evidence,\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nensuring the continued acceptability of the benefit-risk ratio referred to in Sections\u00a01 and 9 of Annex\u00a0I, and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nidentifying possible systematic misuse or off-label use of the device, with a view to verifying that the intended purpose is correct.\n\n\n\n\n6.2.\u00a0\u00a0\u00a0The PMCF plan shall include at least:\n\n\n\n\n\n\n(a)\n\n\nthe general methods and procedures of the PMCF to be applied, such as gathering of clinical experience gained, feedback from users, screening of scientific literature and of other sources of clinical data;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe specific methods and procedures of PMCF to be applied, such as evaluation of suitable registers or PMCF studies;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\na rationale for the appropriateness of the methods and procedures referred to in points (a) and (b);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\na reference to the relevant parts of the clinical evaluation report referred to in Section\u00a04 and to the risk management referred to in Section\u00a03 of Annex\u00a0I;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe specific objectives to be addressed by the PMCF;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nan evaluation of the clinical data relating to equivalent or similar devices;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nreference to any relevant CS, harmonised standards when used by the manufacturer, and relevant guidance on PMCF; and\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\na detailed and adequately justified time schedule for PMCF activities (e.g. analysis of PMCF data and reporting) to be undertaken by the manufacturer.\n\n\n\n\n7.\u00a0\u00a0\u00a0The manufacturer shall analyse the findings of the PMCF and document the results in a PMCF evaluation report that shall be part of the clinical evaluation report and the technical documentation.\n8.\u00a0\u00a0\u00a0The conclusions of the PMCF evaluation report shall be taken into account for the clinical evaluation referred to in Article\u00a061 and Part A of this Annex\u00a0and in the risk management referred to in Section\u00a03 of Annex\u00a0I. If, through the PMCF, the need for preventive and/or corrective measures has been identified, the manufacturer shall implement them.\n\n\n\n\n\nANNEX XV\n\nCLINICAL INVESTIGATIONS\n\nCHAPTER I\n\nGENERAL REQUIREMENTS\n\n1.\u00a0\u00a0\u00a0Ethical principles\nEach step in the clinical investigation, from the initial consideration of the need for and justification of the study to the publication of the results, shall be carried out in accordance with recognised ethical principles.\n2.\u00a0\u00a0\u00a0Methods\n2.1.\u00a0\u00a0\u00a0Clinical investigations shall be performed on the basis of an appropriate plan of investigation reflecting the latest scientific and technical knowledge and defined in such a way as to confirm or refute the manufacturer's claims regarding the safety, performance and aspects relating to benefit-risk of devices as referred to in Article\u00a062(1); the clinical investigations shall include an adequate number of observations to guarantee the scientific validity of the conclusions. The rationale for the design and chosen statistical methodology shall be presented as further described in Section\u00a03.6 of Chapter II of this Annex.\n2.2.\u00a0\u00a0\u00a0The procedures used to perform the clinical investigation shall be appropriate to the device under investigation.\n2.3.\u00a0\u00a0\u00a0The research methodologies used to perform the clinical investigation shall be appropriate to the device under investigation.\n2.4.\u00a0\u00a0\u00a0Clinical investigations shall be performed in accordance with the clinical investigation plan by a sufficient number of intended users and in a clinical environment that is representative of the intended normal conditions of use of the device in the target patient population. Clinical investigations shall be in line with the clinical evaluation plan as referred to in Part\u00a0A of Annex\u00a0XIV.\n2.5.\u00a0\u00a0\u00a0All the appropriate technical and functional features of the device, in particular those involving safety and performance, and their expected clinical outcomes shall be appropriately addressed in the investigational design. A list of the technical and functional features of the device and the related expected clinical outcomes shall be provided.\n2.6.\u00a0\u00a0\u00a0The endpoints of the clinical investigation shall address the intended purpose, clinical benefits, performance and safety of the device. The endpoints shall be determined and assessed using scientifically valid methodologies. The primary endpoint shall be appropriate to the device and clinically relevant.\n2.7.\u00a0\u00a0\u00a0Investigators shall have access to the technical and clinical data regarding the device. Personnel involved in the conduct of an investigation shall be adequately instructed and trained in the proper use of the investigational device, and as regards the clinical investigation plan and good clinical practice. This training shall be verified and where necessary arranged by the sponsor and documented appropriately.\n2.8.\u00a0\u00a0\u00a0The clinical investigation report, signed by the investigator, shall contain a critical evaluation of all the data collected during the clinical investigation, and shall include any negative findings.\nCHAPTER II\n\nDOCUMENTATION REGARDING THE APPLICATION FOR CLINICAL INVESTIGATION\n\nFor investigational devices covered by Article\u00a062, the sponsor shall draw up and submit the application in accordance with Article\u00a070 accompanied by the following documents:\n1.\u00a0\u00a0\u00a0Application form\nThe application form shall be duly filled in, containing information regarding:\n\n\n\n\n\n\n1.1.\n\n\nname, address and contact details of the sponsor and, if applicable, name, address and contact details of its contact person or legal representative in accordance with Article\u00a062(2) established in the Union;\n\n\n\n\n\n\n\n\n\n\n1.2.\n\n\nif different from those in Section\u00a01.1, name, address and contact details of the manufacturer of the device intended for clinical investigation and, if applicable, of its authorised representative;\n\n\n\n\n\n\n\n\n\n\n1.3.\n\n\ntitle of the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n1.4.\n\n\nstatus of the clinical investigation application (i.e. first submission, resubmission, significant amendment);\n\n\n\n\n\n\n\n\n\n\n1.5.\n\n\ndetails and/or reference to the clinical evaluation plan;\n\n\n\n\n\n\n\n\n\n\n1.6.\n\n\nIf the application is a resubmission with regard to a device for which an application has been already submitted, the date or dates and reference number or numbers of the earlier application or in the case of significant amendment, reference to the original application. The sponsor shall identify all of the changes from the previous application together with a rationale for those changes, in particular, whether any changes have been made to address conclusions of previous competent authority or ethics committee reviews;\n\n\n\n\n\n\n\n\n\n\n1.7.\n\n\nif the application is submitted in parallel with an application for a clinical trial in accordance with Regulation\u00a0(EU)\u00a0No\u00a0536/2014, reference to the official registration number of the clinical trial;\n\n\n\n\n\n\n\n\n\n\n1.8.\n\n\nidentification of the Member\u00a0States and third countries in which the clinical investigation is to be conducted as part of a multicentre or multinational study at the time of application;\n\n\n\n\n\n\n\n\n\n\n1.9.\n\n\na brief description of the investigational device, its classification and other information necessary for the identification of the device and device type;\n\n\n\n\n\n\n\n\n\n\n1.10.\n\n\ninformation as to whether the device incorporates a medicinal substance, including a human blood or plasma derivative or whether it is manufactured utilising non-viable tissues or cells of human or animal origin, or their derivatives;\n\n\n\n\n\n\n\n\n\n\n1.11.\n\n\nsummary of the clinical investigation plan including the objective or objectives of the clinical investigation, the number and gender of subjects, criteria for subject selection, whether there are subjects under 18 years of age, design of the investigation such as controlled and/or randomised studies, planned dates of commencement and of completion of the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n1.12.\n\n\nif applicable, information regarding a comparator device, its classification and other information necessary for the identification of the comparator device;\n\n\n\n\n\n\n\n\n\n\n1.13.\n\n\nevidence from the sponsor that the clinical investigator and the investigational site are capable of conducting the clinical investigation in accordance with the clinical investigation plan;\n\n\n\n\n\n\n\n\n\n\n1.14.\n\n\ndetails of the anticipated start date and duration of the investigation;\n\n\n\n\n\n\n\n\n\n\n1.15.\n\n\ndetails to identify the notified body, if already involved at the stage of application for a clinical investigation;\n\n\n\n\n\n\n\n\n\n\n1.16.\n\n\nconfirmation that the sponsor is aware that the competent authority may contact the ethics committee that is assessing or has assessed the application; and\n\n\n\n\n\n\n\n\n\n\n1.17.\n\n\nthe statement referred to in Section\u00a04.1.\n\n\n\n\n2.\u00a0\u00a0\u00a0Investigator's Brochure\nThe investigator's brochure (IB) shall contain the clinical and non-clinical information on the investigational device that is relevant for the investigation and available at the time of application. Any updates to the IB or other relevant information that is newly available shall be brought to the attention of the investigators in a timely manner. The IB shall be clearly identified and contain in particular the following information:\n\n\n\n\n\n\n2.1.\n\n\nIdentification and description of the device, including information on the intended purpose, the risk classification and applicable classification rule pursuant to Annex\u00a0VIII, design and manufacturing of the device and reference to previous and similar generations of the device.\n\n\n\n\n\n\n\n\n\n\n2.2.\n\n\nManufacturer's instructions for installation, maintenance, maintaining hygiene standards and for use, including storage and handling requirements, as well as, to the extent that such information is available, information to be placed on the label, and instructions for use to be provided with the device when placed on the market. In addition, information relating to any relevant training required.\n\n\n\n\n\n\n\n\n\n\n2.3.\n\n\nPre-clinical evaluation based on relevant pre-clinical testing and experimental data, in particular regarding in-design calculations, in vitro tests, ex vivo tests, animal tests, mechanical or electrical tests, reliability tests, sterilisation validation, software verification and validation, performance tests, evaluation of biocompatibility and biological safety, as applicable.\n\n\n\n\n\n\n\n\n\n\n2.4.\n\n\nExisting clinical data, in particular:\n\n\n\n\n\n\n\u2014\n\n\nfrom relevant scientific literature available relating to the safety, performance, clinical benefits to patients, design characteristics and intended purpose of the device and/or of equivalent or similar devices;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nother relevant clinical data available relating to the safety, performance, clinical benefits to patients, design characteristics and intended purpose of equivalent or similar devices of the same manufacturer, including length of time on the market and a review of performance, clinical benefit and safety-related issues and any corrective actions taken.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n2.5.\n\n\nSummary of the benefit-risk analysis and the risk management, including information regarding known or foreseeable risks, any undesirable effects, contraindications and warnings.\n\n\n\n\n\n\n\n\n\n\n2.6.\n\n\nIn the case of devices that incorporate a medicinal substance, including a human blood or plasma derivative or devices manufactured utilising non-viable tissues or cells of human or animal origin, or their derivatives, detailed information on the medicinal substance or on the tissues, cells or their derivatives, and on the compliance with the relevant general safety and performance requirements and the specific risk management in relation to the substance or tissues, cells or their derivatives, as well as evidence for the added value of incorporation of such constituents in relation to the clinical benefit and/or safety of the device.\n\n\n\n\n\n\n\n\n\n\n2.7.\n\n\nA list detailing the fulfilment of the relevant general safety and performance requirements set out in Annex\u00a0I, including the standards and CS applied, in full or in part, as well as a description of the solutions for fulfilling the relevant general safety and performance requirements, in so far as those standards and CS have not or have only been partly fulfilled or are lacking.\n\n\n\n\n\n\n\n\n\n\n2.8.\n\n\nA detailed description of the clinical procedures and diagnostic tests used in the course of the clinical investigation and in particular information on any deviation from normal clinical practice.\n\n\n\n\n3.\u00a0\u00a0\u00a0Clinical Investigation Plan\nThe clinical investigation plan (CIP) shall set out the rationale, objectives, design methodology, monitoring, conduct, record-keeping and the method of analysis for the clinical investigation. It shall contain in particular the information as laid down in this Annex. If part of this information is submitted in a separate document, it shall be referenced in the CIP.\n3.1.\u00a0\u00a0\u00a0General\n3.1.1.\u00a0\u00a0\u00a0Single identification number of the clinical investigation, as referred to in Article\u00a070(1).\n3.1.2.\u00a0\u00a0\u00a0Identification of the sponsor \u2014 name, address and contact details of the sponsor and, where applicable, the name, address and contact details of the sponsor's contact person or legal representative in accordance with Article\u00a062(2) established in the Union.\n3.1.3.\u00a0\u00a0\u00a0Information on the principal investigator at each investigational site, the coordinating investigator for the investigation, the address details for each investigational site and the emergency contact details for the principal investigator at each site. The roles, responsibilities and qualifications of the various kinds of investigators shall be specified in the CIP.\n3.1.4.\u00a0\u00a0\u00a0A brief description of how the clinical investigation is financed and a brief description of the agreement between the sponsor and the site.\n3.1.5.\u00a0\u00a0\u00a0Overall synopsis of the clinical investigation, in an official Union language determined by the Member\u00a0State concerned.\n3.2.\u00a0\u00a0\u00a0Identification and description of the device, including its intended purpose, its manufacturer, its traceability, the target population, materials coming into contact with the human body, the medical or surgical procedures involved in its use and the necessary training and experience for its use, background literature review, the current state of the art in clinical care in the relevant field of application and the proposed benefits of the new device.\n3.3.\u00a0\u00a0\u00a0Risks and clinical benefits of the device to be examined, with justification of the corresponding expected clinical outcomes in the clinical investigation plan.\n3.4.\u00a0\u00a0\u00a0Description of the relevance of the clinical investigation in the context of the state of the art of clinical practice.\n3.5.\u00a0\u00a0\u00a0Objectives and hypotheses of the clinical investigation.\n3.6.\u00a0\u00a0\u00a0Design of the clinical investigation with evidence of its scientific robustness and validity.\n3.6.1.\u00a0\u00a0\u00a0General information such as type of investigation with rationale for choosing it, for its endpoints and for its variables as set out in the clinical evaluation plan.\n3.6.2.\u00a0\u00a0\u00a0Information on the investigational device, on any comparator and on any other device or medication to be used in the clinical investigation.\n3.6.3.\u00a0\u00a0\u00a0Information on subjects, selection criteria, size of investigation population, representativeness of investigation population in relation to target population and, if applicable, information on vulnerable subjects involved such as children, pregnant women, immuno-compromised or, elderly subjects.\n3.6.4.\u00a0\u00a0\u00a0Details of measures to be taken to minimise bias, such as randomisation, and management of potential confounding factors.\n3.6.5.\u00a0\u00a0\u00a0Description of the clinical procedures and diagnostic methods relating to the clinical investigation and in particular highlighting any deviation from normal clinical practice.\n3.6.6.\u00a0\u00a0\u00a0Monitoring plan.\n3.7.\u00a0\u00a0\u00a0Statistical considerations, with justification, including a power calculation for the sample size, if applicable.\n3.8.\u00a0\u00a0\u00a0Data management.\n3.9.\u00a0\u00a0\u00a0Information about any amendments to the CIP.\n3.10.\u00a0\u00a0\u00a0Policy regarding follow-up and management of any deviations from the CIP at the investigational site and clear prohibition of use of waivers from the CIP.\n3.11.\u00a0\u00a0\u00a0Accountability regarding the device, in particular control of access to the device, follow-up in relation to the device used in the clinical investigation and the return of unused, expired or malfunctioning devices.\n3.12.\u00a0\u00a0\u00a0Statement of compliance with the recognised ethical principles for medical research involving humans, and the principles of good clinical practice in the field of clinical investigations of devices, as well as with the applicable regulatory requirements.\n3.13.\u00a0\u00a0\u00a0Description of the Informed consent process.\n3.14.\u00a0\u00a0\u00a0Safety reporting, including definitions of adverse events and serious adverse events, device deficiencies, procedures and timelines for reporting.\n3.15.\u00a0\u00a0\u00a0Criteria and procedures for follow-up of subjects following the end, temporary halt or early termination of an investigation, for follow-up of subjects who have withdrawn their consent and procedures for subjects lost to follow-up.\u00a0Such procedures shall for implantable devices, cover as a minimum traceability.\n3.16.\u00a0\u00a0\u00a0A description of the arrangements for taking care of the subjects after their participation in the clinical investigation has ended, where such additional care is necessary because of the subjects' participation in the clinical investigation and where it differs from that normally expected for the medical condition in question.\n3.17.\u00a0\u00a0\u00a0Policy as regards the establishment of the clinical investigation report and publication of results in accordance with the legal requirements and the ethical principles referred to in Section\u00a01 of Chapter I.\n3.18.\u00a0\u00a0\u00a0List of the technical and functional features of the device, with specific mention of those covered by the investigation.\n3.19.\u00a0\u00a0\u00a0Bibliography.\n4.\u00a0\u00a0\u00a0Other information\n4.1.\u00a0\u00a0\u00a0A signed statement by the natural or legal person responsible for the manufacture of the investigational device that the device in question conforms to the general safety and performance requirements apart from the aspects covered by the clinical investigation and that, with regard to those aspects, every precaution has been taken to protect the health and safety of the subject.\n4.2.\u00a0\u00a0\u00a0Where applicable according to national law, copy of the opinion or opinions of the ethics committee or committees concerned. Where according to national law the opinion or opinions of the ethics committee or committees is not required at the time of the submission of the application, a copy of the opinion or opinions shall be submitted as soon as available.\n4.3.\u00a0\u00a0\u00a0Proof of insurance cover or indemnification of subjects in case of injury, pursuant to Article\u00a069 and the corresponding national law.\n4.4.\u00a0\u00a0\u00a0Documents to be used to obtain informed consent, including the patient information sheet and the informed consent document.\n4.5.\u00a0\u00a0\u00a0Description of the arrangements to comply with the applicable rules on the protection and confidentiality of personal data, in particular:\n\n\n\n\n\n\n\u2014\n\n\norganisational and technical arrangements that will be implemented to avoid unauthorised access, disclosure, dissemination, alteration or loss of information and personal data processed;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na description of measures that will be implemented to ensure confidentiality of records and personal data of subjects; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na description of measures that will be implemented in case of a data security breach in order to mitigate the possible adverse effects.\n\n\n\n\n4.6.\u00a0\u00a0\u00a0Full details of the available technical documentation, for example detailed risk analysis/management documentation or specific test reports, shall, upon request, be submitted to the competent authority reviewing an application.\nCHAPTER III\n\nOTHER OBLIGATIONS OF THE SPONSOR\n\n1.\u00a0\u00a0\u00a0The sponsor shall undertake to keep available for the competent national authorities any documentation necessary to provide evidence for the documentation referred to in Chapter\u00a0II of this Annex. If the sponsor is not the natural or legal person responsible for the manufacture of the investigational device, that obligation may be fulfilled by that person on behalf of the sponsor.\n2.\u00a0\u00a0\u00a0The Sponsor shall have an agreement in place to ensure that any serious adverse events or any other event as referred to in Article\u00a080(2) are reported by the investigator or investigators to the sponsor in a timely manner.\n3.\u00a0\u00a0\u00a0The documentation mentioned in this Annex\u00a0shall be kept for a period of at least 10 years after the clinical investigation with the device in question has ended, or, in the event that the device is subsequently placed on the market, at least 10 years after the last device has been placed on the market. In the case of implantable devices, the period shall be at least 15 years.\nEach Member\u00a0State shall require that this documentation is kept at the disposal of the competent authorities for the period referred to in the first subparagraph\u00a0in case the sponsor, or its contact person or legal representative as referred to in Article\u00a062(2) established within its territory, goes bankrupt or ceases its activity prior to the end of this period.\n4.\u00a0\u00a0\u00a0The Sponsor shall appoint a monitor that is independent from the investigational site to ensure that the investigation is conducted in accordance with the CIP, the principles of good clinical practice and this Regulation.\n5.\u00a0\u00a0\u00a0The Sponsor shall complete the follow-up of investigation subjects.\n6.\u00a0\u00a0\u00a0The Sponsor shall provide evidence that the investigation is being conducted in line with good clinical practice, for instance through internal or external inspection.\n7.\u00a0\u00a0\u00a0The Sponsor shall prepare a clinical investigation report which includes at least the following:\n\n\n\n\n\n\n\u2014\n\n\nCover/introductory page or pages indicating the title of the investigation, the investigational device, the single identification number, the CIP number and the details with signatures of the coordinating investigators and the principal investigators from each investigational site.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nDetails of the author and date of the report.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nA summary of the investigation covering the title, purpose of the investigation, description of the investigation, investigational design and methods used, the results of the investigation and conclusion of the investigation. The completion date of the investigation, and in particular details of early termination, temporary halts or suspensions of investigations.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nInvestigational device description, in particular clearly defined intended purpose.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nA summary of the clinical investigation plan covering objectives, design, ethical aspects, monitoring and quality measures, selection criteria, target patient populations, sample size, treatment schedules, follow-up duration, concomitant treatments, statistical plan, including hypothesis, sample size calculation and analysis methods, as well as a justification.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nResults of the clinical investigation covering, with rationale and justification, subject demographics, analysis of results related to chosen endpoints, details of subgroup analysis, as well as compliance with the CIP, and covering follow-up of missing data and of patients withdrawing from the clinical investigation, or lost to follow-up.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nSummary of serious adverse events, adverse device effects, device deficiencies and any relevant corrective actions.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nDiscussion and overall conclusions covering safety and performance results, assessment of risks and clinical benefits, discussion of clinical relevance in accordance with clinical state of the art, any specific precautions for specific patient populations, implications for the investigational device, limitations of the investigation.\n\n\n\n\n\n\n\n\n\nANNEX XVI\n\nLIST OF GROUPS OF PRODUCTS WITHOUT AN INTENDED MEDICAL PURPOSE REFERRED TO IN ARTICLE 1(2)\n\n\n\n\n\n\n\n\n\n1.\n\n\nContact lenses or other items intended to be introduced into or onto the eye.\n\n\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nProducts intended to be totally or partially introduced into the human body through surgically invasive means for the purpose of modifying the anatomy or fixation of body parts with the exception of tattooing products and piercings.\n\n\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nSubstances, combinations of substances, or items intended to be used for facial or other dermal or mucous membrane filling by subcutaneous, submucous or intradermal injection or other introduction, excluding those for tattooing.\n\n\n\n\n\n\n\n\n\n\n\n\n4.\n\n\nEquipment intended to be used to reduce, remove or destroy adipose tissue, such as equipment for liposuction, lipolysis or lipoplasty.\n\n\n\n\n\n\n\n\n\n\n\n\n5.\n\n\nHigh intensity electromagnetic radiation (e.g. infra-red, visible light and ultra-violet) emitting equipment intended for use on the human body, including coherent and non-coherent sources, monochromatic and broad spectrum, such as lasers and intense pulsed light equipment, for skin resurfacing, tattoo or hair removal or other skin treatment.\n\n\n\n\n\n\n\n\n\n\n\n\n6.\n\n\nEquipment intended for brain stimulation that apply electrical currents or magnetic or electromagnetic fields that penetrate the cranium to modify neuronal activity in the brain."}, {"title": "Guidance-on-Article-15-MDR-IVDR-Person-responsible-for-Regulatory-Compliance.pdf.txt", "text": "This document has been endorsed by the Medical Device Coordination Group (MDCG) \nestablished by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of \nrepresentatives of all Member States and it is chaired by a representative of the European \nCommi ssion.  \nThe document is not a European Commission document and it cannot be regarded as \nreflecting the official position of the European Commission. Any views expressed in this \ndocument are not legally binding and only the Court of Justice of the European Union can give \nbinding interpretations of Union law.  \n1 \n MDCG 2019- 7 \nGuidance  on Article 15 of the Medical Device Regulation (MDR) and \nin vitro Diagnostic Device Regulation (IVDR) regarding a \u2018person \nresponsible for regulatory compliance\u2019 (PRRC)  \nManufacturers1 (paragraph 1)  \n\u201cManufacturers shall have available within their organisation at least one person \nresponsible for regulatory compliance who possesses the requisite expertise in the \nfield of medical devices. The requisite expertise shall be demonstrated by either of the \nfollowing qualifications:   \n(a) a diploma, certificate or other evidence of formal qualification, awarded on \ncompletion of a university degree or of a course of study recognised as equivalent by \nthe Member State concerned, in law, medicine, pharmacy, engineering or another \nrelevant scientific discipline, and at least one year of professional experience in \nregulatory affairs or in quality management systems relating to medical devices;  \n(b) four years of professional experience in regulatory affairs or in quality management \nsystems relating to medical devices.  \nWithout prejudice to national provisions regarding professional qualifications, \nmanufacturers of custom -made devices may demonstrate the requisite expertise \nreferred to in the first subparagraph by having at least two years of professional \nexperience within a relevant field of manufacturing. \u201d \nClarification on qualifications  \nIt shall be noted that : \n- For the purpose of fulfilling the requirement laid down in point \u201c a\u201d of Article 15 \n(1), any qualification acquired outside the EU, including any university diplomas \nor certificates, should have been recognised by an EU Member State as \nequivalent to the EU corresponding qualification.  \n                                                           \n1  Enterprises which employ at least  50 persons and whose annual turnover and/or annual balance sheet total \nexceeds EUR 10 million (Commission Recommendation 2003/361/\u0395 C of 6 May 2003) . 2 \n - Professional experience in regulatory a ffairs or in quality management systems \nrelating to medical devices  should be related to the EU requirements in the field .  \nMeaning of \u201cwithin their organisation\u201d  \nThe person responsible for regulatory compliance (PRRC) appointed would need to \nbe an employee of the organisation.  \nOrganisations with more than one legal manufacturer  \nOrganisations with more than one legal manufacturer under the parent company would \nneed to ensure that each legal manufacturer has its own PRRC.2 \nCan the PRRC be located out side the EU?  \nAs to the location of the PRRC, it is important that a close linkage, of a permanent and \ncontinuous nature, is established between the PRRC and the manufacturing activities. \nFor this reason,  for manufacturers located outside the EU, it must be assumed that the \nPRRC should also be located outside the EU. On the other hand, for manufacturers \nlocated in the EU, it must be assumed that the PRRC should also be located in the EU.  \nMicro and small manufacturers3 (paragraph 2)  \n\u201cMicro and small enterpri ses within the meaning of Commission Recommendation \n2003/361/EC shall not be required to have the person responsible for regulatory \ncompliance within their organisation but shall have such person permanently \nand continuously at their disposal .\u201d \nMeaning of \u201cpermanently and continuously at their disposal\u201d  \nThe micro or small enterprise may subcontract the responsibilities of a person \nresponsible for regulatory compliance to a third party, so long as the qualification \ncriteria is met and the manufacturer can de monstrate and document how they can \nmeet their legal obligations. For example, the PRRC may be part of an external \norganisation, with which the manufacturer has established a contract lay ing down \nprovisions so as to ensure the permanent and continuous availability of that party. The \ncontract should mention the relevant person\u2019s qualifications allowing compliance with \npoints a and b of Article 15 (1).  \nCan the PRRC be located outside the EU?  \nFor micro or small enterpr ises located in the EU, it must be assumed that any person \nto be permanent ly and continuously at their  disposal should be also located in the EU . \n                                                           \n2  In the context of Article 15, the obligation for having available within the organisation at least one PRRC refers \nto the individual legal manufacturer.  \n3  Enterprises which employ fewer than  50 persons and whose annual turnover and/or annual balance sheet \ntotal does not exceed EUR 10 million (Commission Recommendation 2003/361/\u0395C of 6 May 2003) . 3 \n Authorised representatives (paragraph 6)  \n\u201cAuthorised representatives shall have permanently and continuously at their \ndisposal  at least one person responsible for regulatory compliance who possesses \nthe requisite expertise regarding the regulatory requirements for medical devices in the \nUnion. The requisite expertise shall be demonstrated by either of the followi ng \nqualifications:  \n(a) a diploma, certificate or other evidence of formal qualification, awarded on \ncompletion of a university degree or of a course of study recognised as equivalent by \nthe Member State concerned, in law, medicine, pharmacy, engineering or another \nrelevant scientific discipline, and at least one year of professional experience in \nregulatory affairs or in quality management systems relating to medical devices;  \n(b) four years of professional experience in regulatory affairs or in quality management \nsystems relating to medical devices. \u201d \nMeaning of \u201cpermanently and continuously at their disposal\u201d  \nThe authorised representative may subcontract the responsibilities of a person \nresponsible for regulatory compliance to a third party, so long as the qualification \ncriteria is met and the authorised representative can demonstrate and document how \nthey can meet their legal obligations. For example, the PRRC may be part of an \nexternal organisation with which the authorised representative has established e a \ncontract laying down provisions so as to ensure the permanent and continuous \navailability of that party.  The contract should mention the relevant person\u2019s \nqualifications allowing compliance with points a and b of Article 15 (1).  \nCan the PRRC be located outside the EU?  \nTaking into account that the Authorised Representative is located in the EU, it must be \nassumed that any person to be permanently and continuously at its disposal should be \nalso located in the EU . \nRoles and responsibilities of the person r esponsible for regulatory compliance \nwithin a manufacturer (paragraph 3)  \nFor the purpose of this position paper, the roles and responsibilities of a PRRC have \nbeen cross -referred to the roles and responsibilities of a manufacturer, as stated in \nArticle 10 of the MDR and IVDR. This paper does not interpret the roles and \nresponsibilities of a PRRC. We recommend that any guidance on post -market \nsurveillance, vigilance, clinical investigations and performance studies, created at a \nEuropean level, should cross -refer to Article 15, paragraph 3 to provide guidance on \nwhat a PRRC of a manufacturer would be expected to do in these areas.  \n  4 \n \u201cThe person responsible for regulatory compliance shall at least be responsible for \nensuring that:  \n(a) the conformity of the dev ices is appropriately checked, in accordance with the \nquality management system under which the devices are manufactured, before a \ndevice is released; \u201d  \nManufacturers \u201cof devices, other than investigational [performance study] devices, \nshall establish, document, implement, maintain, keep up to date and continually \nimprove a quality management system that shall ensure compliance with this \nRegulation in the most effective manner and in a manner that is proportionate to the \nrisk class and the type of device\u201d (Article 10(9) of the MDR and Article 10(8) of the \nIVDR).  \n\u201c(b) the technical documentation and the EU declaration of conformity are drawn up \nand kept up- to-date; \u201d \nManufacturers \u201c[of devices other than custom -made devices] shall draw up and keep \nup to date technical documentation for those devices\u201d (Article 10(4) of the MDR and \nIVDR) and \u201cshall draw up an EU declaration of conformity\u201d (Article 10(6) of the MDR \nand Article 10(5) of the IVDR).  \n\u201c(c) the post -market surveillance obligations are complied with in accordance with \nArticle 10(10) [Article 10(9) of the IVDR]; \u201d \nManufacturers \u201cof devices shall implement and keep up to date the post -market \nsurveillance system\u201d (Article 10(10) of the MDR and Article 10(9) of the IVDR).  \n\u201c(d) the reporting obligations ref erred to in Articles 87 to 91 [Article 82 and 86 of the \nIVDR] are fulfilled; \u201d \nManufacturers \u201cshall have a system for recording and reporting of incidents and field \nsafety corrective actions as described in Articles 87 and 88\u201d (Article 10(13) of the MDR \nand Article 10(12) of the IVDR).  \n\u201c(e) in the case of investigational devices, the statement referred to in Section 4.1 of \nChapter II of Annex XV [Section 4.1 of Annex XIV of the IVDR] is issued. \u201d \nManufacturers shall ensure that \u201ca signed statement by the natural or legal person \nresponsible for the manufacture of the investigational device [for performance study] \nthat the device in question conforms to the general safety and performance \nrequirements apart from the aspects covered by the clinical investigati on [performance \nstudy] and that, with regard to those aspects, every precaution has been taken to \nprotect the health and safety of the subject.\u201d  \n  5 \n Roles and responsibilities of the person responsible for regulatory compliance \nwithin an authorised represent ative (paragraph 3)  \nThe PRRC of an AR should be responsible for ensuring that the tasks of an AR  as \nspecified in the given mandate, in accordance with Article 11(3), are fulfilled. . \nCan one individual be the PRRC for a manufacturer and its authorised representative?  \nThe person responsible for regulatory compliance for an authorised representative and \nfor an 'outside EU' manufacturer cannot be the same person. There is a clear desire \nwithin the Regulations for the authorised representative to be adding an additional level \nof scrutiny and ensure that the supervision and control of the manufacture of devices, \nand the relevant post -market surveillance and vigilance activities  are adequately \neffected. If the two roles were conducted by the same person, the additional level of \nscrutiny would be undermined.  \nFor the same reason, the PRRC of a micro or small enterprise and the PRRC of the \nauthorised representative of that same enterprise shall not belong to the same external \norganisation."}, {"title": "md_mfr_stepbystep.pdf.txt", "text": "Implementation Model for\nMedical Devices  \nRegulation  \nStep by Step Guide\nMEDICAL DEVICES  CHANGE OF LEGISLATION\n1STEP  INTENTION / ACTION\nPre-assessmentBrief management to ensure a clear understanding of the importance and  \nbusiness implications of the MDR\nConsider organisational challenges: management awareness,  \nstaffing capability and availability, budget implications\nGAP analysis and actions  \nresulting from thisAssess impact on products, internal resources, organisation and budget\nCheck new classification rules (MDR Classes I, IIa, IIb and III) and confirm conformity \nassessment routes for existing and future products\nCheck the new definition of MD, particularly with respect to its expanded scope. \nThis also applies to products covered in Annex XVI\nReview the changes needed to existing technical documentation (Technical Files)\nReview and upgrade quality management system (QMS) (point 3 below)\nCheck the adequacy of available clinical evidence and risk  \nmanagement and identify any gaps (Article 61)\nReview product labelling (Annex I Chapter III)\nEnsure post-market surveillance (PMS) arrangements are adequate (Chapter VII \nSection 1)\nPrepare a post-market clinical follow-up plan (PMCF, Annex XIV Part B)\nGet ready for the new vigilance requirements (Chapter VII Section 2)\nEnsure the respect of traceability obligations (Chapter III) \nQuality Management  \nSystem (QMS)Review adequacy of QMS to meet standards and processes for medical devices \nunder the new Regulation\nBuild new regulatory requirements into the QMS\nIdentify/hire the person responsible for regulatory compliance within your  \norganisation (Article 15) and be sure it is adequately qualified and trained1\n2\n3What you need to know!\nInternal market, \nIndustry,  \nEntrepreneurship  \nand SMEs2Legal entitiesClarify how the company is affected: legal entities, obligation of economic  \noperators, organisational structures and resources\nConsider organisational challenges: management awareness, staffing capability \nand availability, budget implications\nEnsure product liability insurance is adequate\nPortfolioDo a cost/benefit analysis for your product portfolio; bear in mind costs for the \npossible upgrade of risk class of MDs and for the new procedures for conformity \nassessment as well as the costs for post-market surveillance and gaps in the \ntechnical documentation, and plan your transition to the MDR accordingly\nReview supply chain provisions, and clarify roles and responsibilities of business \npartners (authorised representatives, importers, distributors)\nMaster  \nimplementation planBuild a roadmap for implementation, including definition of sub-projects,  \nresource requirements and a steering group, and ensure overall responsibility for \nMDR implementation has been established\nGive special consideration to certificate expiry dates, bearing in mind the  \ntransitional period, transitional provisions and availability of your Notified Bodies\nNotified BodiesContact the selected Notified Bodies and determine their capacity and  \navailability to service the implementation plan\nRegulatory trainingEmpower and train staff through MDR implementation and transition workshops\nExecute master  \nimplementation planImplement the various sub-projects (clinical evaluation, technical documentation, \nrelation with other economic operators, Unique Device Identification, labelling,  \nregistration, post-market surveillance, vigilance, and reporting IT systems)\nEnsure a cross-functional project management team is in place to cover all \naspects of implementation\nEnsure overall and individual responsibilities for MDR implementation have been \nestablished\nReview efficiency and  \neffectivenessImplement regular meetings on project status and progress, discrepancy and \ngap analyses, risks, next steps and requirements\nHold regular progress reviews against the MDR implementation plan and include \nthese in the management review process\nNotified Body submissionDiscuss submission dates to avoid delays in the approval process\nOngoing monitoringActively monitor the still-developing European regulatory environment and \nguidelines expected in the coming months (check DG GROW web pages on  \nmedical devices and subscribe to the newsletter)\nEstablish a procedure for dealing with unannounced inspections from Notified Bodies\nRegularly review the MDR implementation plan, identifying and addressing key \nareas of risk4\n5\n6\n7\n8\n9\n10\n11\n12\n\u00a9 European Union, [2018]  Reuse is authorised provided the source is acknowledged.\nThe reuse policy of European Commission documents is regulated by Decision 2011/833/EU (OJ L 330, 14.12.2011, p. 39).\nET-03-18-103-EN-N\nISBN: 978-92-79-89702-3    DOI: 10.2873/66341"}, {"title": "MDCG 2019-8 v2 Implant guidance Card.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document                                               MDCG 2019-8 v2    \n \n \n \n       \n   MDCG 2019-8 v2  \nGuidance document \nImplant Card relating to the application  \n       of Article 18 Regulation (EU) 2017/745  \n       of the European Pa rliament and of the Council  \n       of 5 April 2017 on medical devices           \n \n             March 2020 \n \n \n  \n \nThis document has been endorsed b y the Medical Device Coordinat ion Group (MDCG) established by \nArticle 103 of Regulation (EU) 2017/745. The MDCG is composed o f representatives of all Member \nStates and it is chaired by a representative of the European Co mmission. \nThe document is not a European Commission document and it canno t be regarded as reflecting the \nofficial position of the European Commission. Any views express ed in this document are not legally \nbinding and only the Court of Justice of the European Union can  give binding interpretations of Union \nlaw. \n \n \n  Medical Devices: Guidance document \nImplant Card relating to the app lication of Article 18 Regulati on (EU) 2017/745 of the \nEuropean Parliament and of the Council of 5 April 2017 on medic al devices \n \n  List of Content \n \n1. Scope ............................................................................................................... 4  \n2. Purposes of the Implant Card ..................................................................... 4  \n3. Legal consideration on Implant Card design ........................................... 4  \n4. Information to be provided by the manufacturer on the Implant Card \nand information to be added by the health institution ........................... 5  \n5. Use of symbols .............................................................................................. 6  \n6. Language requirements on specific fields ................................................ 7  \n7. Benefits of an informativ e instruction leaflet ........................................... 7  \n8. Implant Card for implantable systems ...................................................... 7  \nAnnex I examples of principle designs of Implant Cards and leaflets ....... 8  \n \n  1. Scope \nThis document provides guidance for Memb er States, concerned industry and other \nstakeholders on a blueprint of an implant card (IC) required by the MDR (Regulation (EU) \n2017/745). It describes the intended use, cont ent and information to be provided by the \nmanufacturer together on the IC and a definition of fields to be completed by the implanting \nhealthcare institutions or healthcare provider s according to national law in Member States. \nWhereas the intended purpose and most of the da ta elements of the IC are already defined in \nArticle 18 of the MDR, this document contains the description of other data elements which must be completed by the healthcare institution or healthcare provider and which must be considered by the individual Member State wh en implementing Article 18 MDR as required\n1. \n2. Purposes of the Implant Card \nThe aim of introducing an IC has been to achieve three main objectives: \n1. Enable the patient to identify the impl anted devices and to get access to other \ninformation related to the implanted device (e.g. via EUDAMED, and other websites). \n2. Enable patients to identify themselves as persons requiring special care in relevant \nsituations e.g. security checks. \n3. Enabling e.g. emergency clinical staff or fi rst responder to be informed about special \ncare/needs for relevant patients in case of emergency situations. \n3. Legal consideration on Implant Card design \nArticle 18 MDR describes the requirements rega rding the IC which shall be provided by the \nmanufacturer together with the device. Wherea s Article 18 para 1a) describes the information \nwhich shall be provided by the manufacturer on the IC, Article 18 pa r a  2  l a y s  d o w n  t h e  \nobligation of Member States to require health in stitutions to provide the IC to the concerned \npatient. In accordance with Article 18, 1a) the manufact urer should provide th e following information \non the IC (preferably on the card itself or, alternatively, as stickers to be placed by the clinician): \n\u0081 Device name; \n\u0081 Serial number, lot number; \n\u0081 Unique device identification (UDI); \n\u0081 Name, address and the website of manufacturer; \n\u0081 Device type.\n2  \nArticle 18, 2 lays down that Member States shall require health institutions (or healthcare \nproviders) inter alia to make available the IC to the relevant patient. The IC should bear their \n                                                      \n1 This guidance doesn\u2019t include the patient information described in Ar ticle 18 para 1 (b-d) which might \nbe provided by the manufacturer by any means that allow rapid access to that information and that \nshall be stated in the language(s) determined by the concerned Member State.  \n2 In Article 18 1a) of the MDR, the term \u201cdevice model\u201d  is used. However, this term which is not defined \nin the MDR, is part of the UDI-DI related info r m a t i o n  t o  b e  p r o v i d e d  t o  E U D A M E D .  T o  a v o i d  \nduplication and in the context of the intended purpos e of the IC (to be used in situations requiring \nspecial care or in emergency situations), it is cons idered that reference to device model in the MDR for \nthe purpose of the IC shall be read as reference to device type, like \u201cpacemaker\u201d, \u201chip implant\u201d, etc. \nWhen the European Medical device nomenclature is made available, a \u201cstandardised\u201d set of terms of \nthis nomenclature should be recommended for use in relation to the field \u201cdevice type\u201d.  identity . For this purpose, the IC provided togeth er with the device should contain blank \nfields which shall be filled out by the health institution or healthcare provider, respectively. \nSince the establishment of (and the logistics behind) many different national IC designs is very \nexpensive and of no additional benefit, Member States should ensure that, in the context of \nnational implementation of Article 18 of the MD R, only the following information is required \nto be provided by the health institution or healthcare provider on the IC (together with the information provided by the manufacturer). Accordingly, a European or international \nblueprint for an IC which supports the purposes  described in Article 18, 2 should contain the \nfollowing blank fields: \n1. Name of the patient or patient ID; \n2. Name and address of the health institution or healthcare provider who performed the \nimplantation; \n3. Date of implantation. \nIn order to be fit for the purposes described in Article 18, the outer dimensions of the IC should \nbe the same as those of credit cards, ATM cards or ID cards (85.60 mm \u00d7 53.98 mm /3 3 \u20448 \u00d7 \n2 1\u20448  inches) and with a radius of 2.88\u20133.48 mm\n3. \n4. Information to be provided by the  manufacturer on the Implant \nCard and information to be adde d by the health institution \nThe manufacturer shall provide the following necessary information: \n1. Device name; \n2. Device type; \n3. Serial number or, where app licable, lot or batch number; \n4. Unique device identification (UDI); the UDI as AIDC4 format and the UDI-DI as HRI5 \n5. Name and address of the manufacturer of the medical device; \n6. Website of the manufacturer of the medical device. \nThe text provided on the IC and on the instru ction for completing the IC by the healthcare \ninstitution or healthcare provider must be legible and at least 2 millimetres high. \u2018Text\u2019 includes any: number, letter,  symbol, or  letter or number in a symbol.   \nIn addition, the manufacturer shou ld design the IC in a way that the following blank fields to \nbe filled out by the implanting healthcare institution or healthcare provider are available: \n1. Name of the patient or patient ID; \n2. Name and address of the healthcare inst itution which performed the implantation; \n3. Date of implantation. \n  \n                                                      \n3 Dimensions to conform to the standard ISO/IEC 7810 ID-1.  \n4 AIDC - Automatic identification and data capture format (e.g. linear or 2D-Barcodes)  \n5 HRI - Human readable interpretation   5. Use of symbols \nTo avoid national versions of the IC , the use of symbols is advisable.  \nThe following list contains symbols which have either been validated by users and have been \nsubmitted and accepted for inclusion in an upco ming international standard or already exist \nin the ISO database (Online Browsing Platform). The explanation of symbols on the IC should \nbe provided in a leaflet (see section  7) or  on the back of the IC, if space allows. \nArticle 18(1) lays down that the information provided in the IC shall be stated in the \nlanguage(s) determined by the concerned Member State. \nList of symbols recommended for use on the IC6: \n \n \n  \n Patient Name or patient ID\n \n \n \n \n Date of implantation  \n \n \n \n  Name and Address of the implanting healthcare \ninstitution/provide\nr  \n \n \n \n Name and Address of the manufacturer  \n Information website for patients  \n Device Name7 \n \n Serial Number  \n \n \n Lot Number/Batch Code  \n \n                                                      \n6 The symbols for patient name or patient ID, name and ad dress of the implanting healthcare institution/provider, \ndate of implantation, name and address of the manufacturer, serial number, lot number/batch code are already available and published in existing ISO standards. The symbols for device name, patient information website and \nUDI have been validated by users according to the ISO 15223-2 process. Note that the symbols listed here to indicate \nthe following terms: \u2018Device Name\u2019, \u2018Patient Name or Pati ent ID\u2019, \u2018Date of Implantation\u2019, \u2018Name and address of the \nimplanting healthcare institution/provider\u2019 on the implant card, are used in the ISO context to indicate \u2018Medical Device\u2019, \u2018Patient Identification\u2019, \u2018Date\u2019, \u2018Health Care Center or Doctor\u2019.   \n7 Please note that in the ISO context, the \u2018MD\u2019 symbol is used to identify that the product in question is a medical \ndevice. On the implant card, this symbol is used to indicate the device name.  \n \n UDI as AIDC format  \nUDI-DI information in a HRI format should  be introduced by the wording \u201cUDI-DI\u201d. \n6. Language requirements on specific fields \nDespite the nearly complete list of symbols for fields on the IC, there is currently no symbol \navailable for the required field \u201cDevice Type\u201d. \nThe lack of a symbol and the purpose of this field makes it necessary that the information on \nthe device type must be provided in the language accepted/required by the concerned \nMember State. \nThere are several possibilities available to provid e this information in the necessary languages, \ne.g. the information is already printed on the IC in the different languages or stickers are \nprovided with the IC and the healthcare professional selects the right one etc. \n7. Benefits of an informati ve instruction leaflet8 \nAs mentioned above (section 5), there is a need to provide, together with the IC, instructions \non how to complete the IC and to explain the us ed symbols. This information shall be stated \nin the language(s) determined by the concerned Member State. For this reason, the use of a leaflet, containing the relevant information, to be provided together with the IC and the \nimplantable device, is the recommended solution.  \nAs part of the risk management, the manufacturer has to investigate, by means of an \nergonomic analysis or ergonomic usability test procedure, if the provided instructions are \nsufficient to enable the health professional to complete the IC correctly. The instructions must reflect the solution chosen by the manufacturer (e .g. pre-printed IC, blank IC with sticker(s) to \nbe added, mixture of both). Special considerat ions might be needed when providing a system \nIC or an IC for a separate implantable compon ent, when there is not yet a common practice \n(standard) established.  \n8. Implant Card for implantable systems \nIf an implantable device contains implantable components which might be replaced by other \n(or the same) components, for example in case of a later revision, the manufacturers should \nconsider the use of a System IC. In Annex I to this guide an example is provided. \nW a y s  c o u l d  b e  e x p l o r e d  b y  r e l e v a n t  s t a k e h o l d e r s  t o  d e v e l o p  c o m m o n  r u l e s  o n  h o w  t h e  \nnecessary information to be placed on the Sy stem IC is delivered with the replaceable \ncomponent and how health professionals could en sure t hat  the  System  I C is  appropriately  \nupdated, when necessary. \n  \n                                                      \n8 This leaflet should not be confused with any possible vector of information referred to in points \u201cb\u201d, \u201cc\u201d and \u201cd\u201d \nof Article 18(1) of the MDR.  UDI Annex I examples of principle designs of Implant Cards and leaf lets \n \nGENERAL NOTE: All examples contained in this  Annex are to be intended as illustrative \nexamples only.9  \nThe basic shape of the IC shall be designed in  compliance with ISO/IEC 7810 ID-1 (credit card \nform). \nThe following pictures provide exam ples for individual device ICs.  \nExample 1: \n \nFront \u2013 Not to scale (handwritten text on pre-printed content) \n \n \n \n \n \n \n \n \n \nBack \u2013 Not to scale (blank \u2013 serial printed content in \nproduction) \n \n \n \n \n  \n                                                      \n9 Please note that this includes translations (into languages other than English) shown in Examples \nthroughout Annex 1, which are machine translated and not intended to be read as official translations \ninto EU languages. International Implant Card \nhttps://www.genericmed.com/patientimplantinfo John Smith\n27/05/2021\nABC Healthcare Center\n123 Medical Parkway, Cork, Ireland\nDr. H.C. Professional\nPM-5503  Pacer Advanced \nUDI-DI: (01)01865494261654  \nSN79856214  \nGenericmed \n500 Genericmed Place, Minneapolis, MN 55123 USA \nwww.genericmed.com \n \n \n \n    Example 2: \nBack \u2013 Not to scale (blank \u2013 batch/lot printed content in \nproduction) \n \n \n \n \n \n \n \n \n \n \n \n  PM-5503  Pacer Advanced \nUDI-DI: (01)03584124658462  \nGenericmed \n500 Genericmed Place, Minneapolis, MN 55123 USA \nwww.genericmed.com AO.582122\nExample 3 (suggested design of a foldable System IC): \nTo be able to represent medical device syst ems in one IC, the IC shall be available in \ncollapsible form.  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n     ABC Healthcare CenterInternational Implant Card \nwww.genericmed.com/patientimplantinfo John Smith \n27/05/2021 \n123 Medical Parkway\nDr. H.C. Professional\nGenericmed  \n500 Genericmed Place,  \nMinneapolis, MN 55123 USA \nwww.genericmed.com  \nCork, Ireland PM-5503 \nPacer Advanced Pacemaker \nUDI-DI: (01)85412654285216 \nSN65695452 \nGenericmed  \n500 Genericmed Place,  \nMinneapolis, MN 55123 USA \nwww.genericmed.com  PL-55-4 \nPacer Lead Pro Pacemaker Lead \nUDI-DI: (01)89654213882154 \nSN86223214 \n \nExamples of IC Leaflet  \nFront 1 (no stickers \u2013 preferred option) \n \nInstruction for completion (to be provided in the language(s) determined by the concerned member State(s)) \n1. Name of the patient or patient ID. To be f illed by the healthcare institution/provider. \n2. Date of implantation. To be filled by  the healthcare institution/provider. \n3. Name and address of the healthcare institutio n/provider. To be filled by the healthcare \ninstitution/provider. \n \n   \n \n \n  \nPM-5503  \nPacer Advanced  \n(01)8541265428\n5216  \nSN65695452 \nGenericmed  \n500 Genericmed Place,  \nMinneapolis, MN 55123 www.genericmed.com/patientimplantinfo \n \n \nFront 2 (sticker only for device type information) \n \nInstruction for completion (to be provided in the language(s) determined by the concerned member State(s)) \n1. Name of the patient or patient ID. To be f illed by the healthcare institution/provider. \n2. Date of implantation. To be filled by  the healthcare institution/provider. \n3. Name and address of the healthcare instit ution. To be filled by the healthcare \ninstitution/provider. \n5. Add sticker with device type in required language. \n  \n \n \n \n \n \n  \n   \n \n \n  \n \nStickers (to be detached and placed on the righ t place at the IC according to the numbers)  \n \n  \nPM-5503  \nPacer Advanced  \n(01)85412654285216 \nGenericmed  \n500 Genericmed Place,  \nMinneapolis, MN 55123 SN65695452 www.genericmed.com/patientimplantinfo \n5 \n \nFront 3 (stickers)  \n \nInstruction for completion (to be provided in the language(s) determined by the concerned member State(s)) \n1. Name of the patient or patient ID. To be f illed by the healthcare institution/provider. \n2. Date of implantation. To be filled by  the healthcare institution/provider. \n3. Name and address of the healthcare institutio n/provider. To be filled by the healthcare \ninstitution/provider. \n4. Manufacturer\u2019s information website.  \n5. Device type in required language.  \n6. Device name.  \n7. UDI-DI Code (HRI). \n8. UDI code (AIDC format). \n9. Serial number. \n10. Name and address of the \nmanufacturer of the implanted \nmedical device.  \n \nNOTE: Fields 4-10 might be filled \nwith stickers (though this is not the \npreferred solution) \n  \n \n \n  \n \n \nStickers (to be detached and plac ed on the right place at the IC  according to the numbers)  \n5, 6 \n \n9 \n \n    8           \n \n 7 2 081019001 002 4  \n10 \n \n4 \n \nBack  \n Explanation/ transl ation of symbols \n Patient Name or patient ID, \u0418\u043c\u0435 \u043d\u0430 \u043f\u0430\u0446\u0438\u0435\u043d\u0442\u0430 , Jm\u00e9no pacienta, Patientens navn, \nPatientenname, \u038c\u03bd\u03bf\u03bc\u03b1 \u03b1\u03c3\u03b8\u03b5\u03bd\u03bf\u03cd\u03c2 , Nombre del paciente, Patsiendi nimi, Potilaan nimi, \nNom du patient, Ime i prezime bolesnika, Imi \u0119 i nazwisko pacjenta, A beteg neve, \nNome del paziente, Paciento vardas ir pavard \u0117, Pacienta v \u0101rds, uzv\u0101rds, Naam pati\u00ebnt  \nPasientens navn, A beteg neve, Nome do doente, Nume pacient, Meno pacienta, Ime bolnika, Patientens namn \n Name and Address of the implanting healthcare institution/provide r , \u00e9tablissement \nsanitaire, centro de salud, struttura sanitaria, Gesundheitseinrichtung, \ngezondheidszorginstelling, plac\u00f3wka s\u0142u \u017cby zdrowia, \u0437\u0434\u0440\u0430\u0432\u043d\u043e  \u0437\u0430\u0432\u0435\u0434\u0435\u043d\u0438\u0435, vesel\u012bbas \napr\u016bpes iest\u0101de, \u03b5\u03b3\u03ba\u03b1\u03c4\u03ac\u03c3\u03c4\u03b1\u03c3\u03b7 \u03b3\u03b9\u03b1 \u03c4\u03b7\u03bd \u03c5\u03b3\u03b5\u03af\u03b1  \n Date of Implantation , \u0414\u0430\u0442\u0430  \u043d\u0430 \u0438\u043c\u043f\u043b\u0430\u043d\u0442\u0438\u0440\u0430\u043d\u0435, Datum implantace, Implanteringsdato, \nImplantationsdatum, \u0397\u03bc\u03b5\u03c1\u03bf\u03bc\u03b7\u03bd\u03af\u03b1  \u03b5\u03bc\u03c6\u03cd\u03c4\u03b5\u03c5\u03c3\u03b7\u03c2,  \nFecha de implantaci\u00f3n, Implanteerimiskuup\u00e4ev, Implantointip\u00e4iv\u00e4m\u00e4\u00e4r\u00e4, Date d\u2019implantation, Datum implantacije, Be\u00fcltet\u00e9s d\u00e1tuma, Data dell'impianto, Implantavimo data, Implant \u0113\u0161anas datums, \nImplantatiedatum, Data wszczepienia , Data do implante, Data implant \u0103rii, D\u00e1tum \nimplant\u00e1cie, Datum vsaditve \n Device Name, Nazwa urz \u0105dzenia medy \ncznego, N\u00e1zev zdravotnick\u00fdch prost \u0159edk\u016f, Medicinsk enhed, Name des \nMedizinprodukts, Nombre del dispositivo m\u00e9dico, Nom du dispositif m\u00e9dical, Orvosi eszk\u00f6z neve, Namn p\u00e5 medicinsk enhet, Ime medicinske naprave Nome do dispositivo m\u00e9dico \n \u03ba\u03b1\u03c4\u03b1\u03c3\u03ba\u03b5\u03c5\u03b1\u03c3\u03c4\u03ae\u03c2, Producent, Fabrikant, Produttore, Fabricante, Fa bricant, manufacturer, \nHersteller  \n Information website for patients , Webov\u00e1 str\u00e1nka s informacemi pro pacienta, \nInformationswebsite for patienten, Webseite mit Informationen f\u00fcr Patienten, Sitio web \ncon informaci\u00f3n para el paciente, Site d'in formations pour le patient, Inform\u00e1ci\u00f3s \nhonlap betegek sz\u00e1m\u00e1ra, Sito web con le informazioni per i pazienti, Website met informatie voor pati\u00ebnten, Strona internetowa z informacjami dla pacjenta \n \n Translation of serial number in required languages. \n \n Translation of LOT number in required languages. \n Explanation of unique device identi fier (UDI) in required languages. \n \n \nPlace to attach the  \nImplant card"}, {"title": "md_guidance-manufacturers_en.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document    MDCG  2019 -15 rev1   \n \n \n \n \n \n \n \n \n \nMDCG  2019 -15 rev.1  \n        GUIDANCE NOTES FOR MANUFACTURERS  \n        OF CLASS I MEDICAL DEVICES              \n \n             December   2019  \n July 2020 rev.1  \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) established by \nArticle 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member \nStates and it is chaired by a representative of the European Commission.  \nThe document is not a European Commission document and it cannot be regarded as reflecting the \nofficial position of the European Commission. Any views expressed in this doc ument are not legally \nbinding and only the Court of Justice of the European Union can give binding interpretations of Union \nlaw. \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n2 \n  \nMDCG 2019 -15 revision 1 changes  \nMDR postponement dates: from 2020 to 2021  \n \n \n \n \n \nGUIDANCE NOTES FOR MANUFACTURERS  \nOF CLASS I  MEDICAL DEVICES  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n3 \n Contents  \nList of acronyms  ................................ ................................ ................................ ................................ .... 4 \nForeword  ................................ ................................ ................................ ................................ ................  5 \nIntroduction  ................................ ................................ ................................ ................................ ...........  5 \nDefinitions  ................................ ................................ ................................ ................................ ..............  8 \nPlacing on the market of Class I medical devices: The necessary steps  ................................ .........  11 \n0) Integrate MDR  in the Quality Management System (QMS).  ................................ ..................  11 \n1) Confirm product as a medical device  ................................ ................................ ........................  11 \n2) Confirm product as a Class I medical device  ................................ ................................ ............  11 \n3) Procedures before placing on the market  ................................ ................................ ..................  12 \na) Meet the general safety and performance requirements  ................................ .......................  12 \nb) Conduct clinical evaluation  ................................ ................................ ................................ ... 12 \nc) Prepare technical documentation  ................................ ................................ ..........................  14 \nd) Request Notified Body involvement  ................................ ................................ .....................  16 \ne) Prepare Instructions for Use and Labelling  ................................ ................................ ...........  16 \n4) Check compliance with general obligations for manufacturers  ................................ ................  17 \n5) Draw -up the EU Declaration of Conformity  ................................ ................................ .............  18 \n6) Affix the CE marking  ................................ ................................ ................................ ................  18 \n7) Registration of devices and manufacturers in Eudamed  ................................ ...........................  19 \n8) Post Market Surveillance (PMS)  ................................ ................................ ...............................  20 \na) Review experience gained from Post -Market Surveillance  ................................ ..................  20 \nb) Vigilance  ................................ ................................ ................................ ...............................  20 \nc) Non conforming products  ................................ ................................ ................................ ..... 22 \n \n \n \n \n \n \n \n \n \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n4 \n List of acronyms  \nMDD \u2013 Medical Devices Directive  \nMDR \u2013 Medical Devices Regulation  \nFSCA \u2013 Field Safety Corrective Action  \nFSN - Field Safety Notice  \nUDI - Unique Device Identifier  \nSRN - Single Registration Number  \nNB - Notified Body  \nISO - International Organization for Standardization  \nIEC - International Electrotechnical Commission  \nCA \u2013 Competent Authority  \nPPE \u2013 Personal Protective Equipment  \nQMS - Quality Management System  \nIm \u2013 Class I devices with measuring function  \nIs \u2013 Class I sterile devices  \nIr \u2013 Class I reusable surgical instruments  \nDI \u2013 Device Identifier  \nEudamed - European database on medical devices  \nMD - Medical Device   \nCS - Common Specification   \nPMS \u2013 Post Market Surveillance  \nIFU \u2013 Instructions for use   \nPMCF - Post Market Clinical Follow -up   Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n5 \n Foreword  \nThese guidance notes do not aim to be a definitive interpretation of Regulation (EU) 2017/745 of the \nEuropean Parliament and of the Council of 5 April 2017 on medical devices (MDR) and are intended for  \nguidance purposes only.  \n \nIntroduction  \nThe purpose of this document is to provide guidance to manufacturers of Class I medical devices (other \nthan custom made devices) who place on the Union market medical devices (from now on referred to as \ndevices) under their name or trade mark, to help them meet the provi sions of the MDR.  This guidance \nshould also be applicable for situations when an importer, distributor or any other legal person assumes \nthe obligations incumbent on manufacturers, as per Article 16 (1), while not  covering the exception \nindicated by Artic le 16 (2).  \nThe MDR has changed the scope of the medical device legislation and it now extends its application to \nall economic operators in the supply chain (manufacturer, authorised representative, importer and \ndistributor) as well as a broadened range of products such as those specifically intended for the cleaning, \ndisinfection or sterilization of devices (Article 2 (1)) and products without an intended medical purpose \n(such as certain aesthetic products, as indicated in Annex XVI of the MDR). In addition , more emphasis \nis placed on a life -cycle approach to safety, backed up by clinical data and new requirements such as \ntransparency and traceability1. \nBefore placing a device on the market, the manufacturer will affix the CE mark in accordance with \nAnnex V and draw up the EU declaration of conformity, including all the information required by \nAnnex IV. Prior to that, the manufacturer will demonstrate conformity with the MDR and compliance \nwith the applicable general safety and performance requirements laid o ut in Annex I.  \nIn order to accomplish the abovementioned tasks, the manufacturer will carry out the following:   \n\uf02d Put in place a quality management system and a system for risk management according to Article \n10(2) and 10(9).  \n\uf02d Conduct a clinical evaluation i n accordance with Article 61, as established in Article 10(3) and \nAnnex XV.   \n\uf02d Conduct a conformity assessment according to Article 52(7). In specific cases ( sterile devices, \ndevices with measuring function, reusable surgical instruments ) defined in the referred Article, \nthe manufacturer will request the involvement of a Notified Body (NB).    \n\uf02d Draw up and keep up -to-date technical documentation related to devices as set out in Annexes II \nand III, in accordance with Article 10(4).  \n\uf02d Draw up an EU declaration of conformity in accordance with Article 19.  \n\uf02d Submit the required information to the electronic system for registration of economic operators \n(Eudamed) and comply with the registration obligation. The manufacturer will use the Single \nRegis tration Number (SRN) when applying to a NB for conformity assessment, if applicable and \nfor further accessing Eudamed2 in order to fulfil its obligations related to registration of the \ndevices.  \n\uf02d Register the device in Eudamed assigning the Basic UDI -DI to t he device, as defined in Part C of \nAnnex VI, and provide this to the UDI database together with the other core data elements \nreferred in Part B of Annex VI related to that device.  \n\uf02d Assign to the device and, if applicable, to all higher levels of packaging,  a UDI which will allow \nidentification and traceability.  \n                                                      \n1  More information can be found at  https://ec.europa.eu/health/md_sector/overview   \n2  Regarding all references to Eudamed in this document, please be advised that for the purposes of this guidance, obligations s trictly related to \nEudamed will only apply when it is fully functional and any u pdates will be published on the EU Commission webpage.    Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n6 \n \uf02d Ensure that the device is accompanied by the information needed to identify it and its \nmanufacturer, and any safety and performance information relevant to the user, or any other \nperson, as appropria te (Article 10(11)). This information, set out according to Section 23 of \nAnnex I, must be provided in an official Union language(s) determined by the Member State in \nwhich the device is made available to the user or patient. The particulars on the label w ill be \nindelible, easily legible and clearly comprehensible to the intended user or patient.   \n\uf02d Implement a post -market surveillance system in accordance with Article 83 (Article 10(10)) \nproportional to the risk class and appropriate for the type of device,  this includes additional \naspects to be taken into account in case of devices placed on the market in sterile condition, with \na measuring function or that are reusable surgical instruments. This system will be an integral \npart of the manufacturer's quality  management system based on a post -market surveillance plan \n(Article 84) , which will be part of the technical documentation specified in Annex III.  \n\uf02d Implement a system for recording and reporting incidents and field safety corrective actions as \ndescribed in  Articles 87 and 88 (Article 10(13)).  \n\uf02d Put measures in place to provide sufficient financial coverage in respect of their potential liability \nunder Directive 85/374/EEC3, without prejudice to more protective measures under national law. \nThese measures will be proportional to the risk class, type of device and the size of the enterprise \n(Article 10(16)).  \nFurther detail on the aforementioned list of obligations is provided in the chapter \u201cPlacing Class I \nmedical devices on the market \u201d.  \nFor devices placed on the market in a sterile condition, with a measuring function or which are reusable \nsurgical instruments, the manufacturer will apply the procedures set out in Chapters I and III of Annex \nIX, or in Part A of Annex XI which require a NB assessment, limited t o critical aspects such as those \nconcerning sterile condition, metrological requirements and the reuse of the device, as relevant, \naccording with Article 52 (7 a, b and c).  \n                                                      \n3  Council Directive 85/374/EEC of 25 July 1985 on the approximation of the laws, regulations and administrative provisions of t he Member \nStates concerning liability for defective products  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n7 \n  \nFigure 1. Illustration of the conformity procedures for  the assessment of Class I devices with and \nwithout NB involvement.  \nFor big and medium size enterprises, the manufacturer will have available within their organization at \nleast one person responsible for regulatory compliance4, as established by Article 15. Micro and small \nenterprises5 are required to have such person permanently and continuously at their disposal.  \nA manufacturer with a registered place of business outside the Union will designate a sole authorised \nrepresentative, at least per each gener ic device group, according to a written mandate. Such a mandate \nwill establish the tasks to be performed by the authorised representative. To enable the fulfilment of \nthese tasks, the manufacturer ensures that the authorised representative has the necessar y documentation \npermanently available and up -to date. The mandate will require the authorised representative to perform \nat least the tasks described in Article 11(3),  however the manufacturer cannot delegate its obligations \nlaid down in Article 10(1), (2),  (3), (4), (6), (7), (9), (10), (11) and (12). In case of the  change of \nauthorised representative, Article 12 establishes the minimum content of agreement to be addressed \nbetween the manufacturer, where practicable the outgoing authorised representative, a nd the incoming \nauthorised representative.  \nUpon request, the manufacturer will provide all the information and documentation necessary to \ndemonstrate conformity of the device to competent authorities and cooperate with them on any \ncorrective action. If th e manufacturer does not cooperate or does not provide the requested information \nor documentation, the competent authority (CA) can adopt restrictive measures.  \nThe manufacturer should periodically verify whether implementing and delegated acts, common \nspeci fications, technical standards and guidelines might be available on the European Commission \nwebsite6. Such documents might for example cover specific parts of legislation (e.g. classification of \n                                                      \n4  See the  relevant MDCG guidance on Article 15 of MDR and IVDR regarding a \"person responsible for regulatory compliance\" (PRRC)  \n5  See Commission Recommendation 2003/361/EC  \n6  https://ec.europa.eu/health/md_sector/overview     \nClass I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n8 \n medical devices, clinical evaluation) or specific requirement s regarding certain medical device \ntechnologies (e.g. software, 3D printing ) that can also be applicable for Class I devices.  \nDuring the transitional period, manufacturers might be tempted to refer to guidance documents \ndeveloped under the Directive 93/42/ EC. However, the old guidance documents, unless otherwise \nupdated in line with the MDR, may have only some limited indicative value under the MDR. For the \npurpose of the MDR, only the text of the Regulation is valid in law and sets out requirements not \nreflected in the old guidance. Hence, the MDR alone can be relied upon as a  legal basis . \nDefinitions  \nFor the complete list of definitions refer to Article 2 of the MDR. This is an excerpt of some definitions.  \nAccessory for a medical device - means an article  which, whilst not being itself a medical device, is \nintended by its manufacturer to be used together with one or several particular medical device(s) to \nspecifically enable the medical device(s) to be used in accordance with its/their intended  purpose(s)  or \nto specifically and directly assist the medical functionality of the medical device(s) in terms of its/their \nintended purpose(s) (Article 2(2)) . \nAuthorised representative - means any natural or legal person established within the Union who has \nreceived  and accepted a written mandate from a manufacturer, located outside the Union, to act on the \nmanufacturer's behalf in relation to specified tasks with regard to the latter's obligations under the MDR \n(Arti cle 2(32)). The designation of an authorised repre sentative will be in compliance with Article 11 \nand effective at least for all devices o f the same generic device group  (Article 11(2)) . \nAdverse event - means any untoward medical occurrence, unintended disease or injury or any untoward \nclinical signs, inc luding an abnormal laboratory finding, in subjects, users or other persons, in the \ncontext of a clinical investigation, whether or not related to the investigational device  (Article 2(57)) . \nBenefit -risk determination  - means the analysis of all assessments of benefit and risk of possible \nrelevance for the use of the device for the intended purpose, when used in accordance with the intended \npurpose given by the manufacturer (Article 2(24)) . \nClass I medical devices with  measuring function - are considered Class I medical devices which measure \nphysiological parameters or anatomical parameter  or energy, respectively, or volume of medicinal \nproducts, body liquids or other substances administered to or removed from the body and display or \nindicate its value in a unit of measurement (example: urine bags, non -active thermometers,  measuring \nspoons).   \nNote: According to section 15.2 of Annex I, measurements made by devices with a measuring function \nwill be expressed in legal un its7. \nCE marking of conformity or CE marking - means a marking by which a manufacturer indicates that a \ndevice is in conformity with the applicable requirements set out in the MDR and other applicable \nUnion harmonisation legislation providing for its affix ing (Article 2(43)) . \nNote: CE marking will be made in accordance with Annex V.  \nClinical evaluation - means a systematic and planned process to continuously generate, collect, analyse \nand assess the clinical data pertaining to a device in order to verify th e safety and performance, \nincluding clinical benefits, of the device when used as intended by the manufacturer. (Article 2(44)).  \nClinical data - means information concerning safety or performance that is generated from the use of a \ndevice and is sourced fr om the following:  \n\uf0b7 clinical investigation(s) of the device concerned,  \n                                                      \n7  In conformance to the provisions of Council Directive  80/181/EEC   Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n9 \n \uf0b7 clinical investigation(s) or other studies reported in scientific literature, of a device for which \nequivalence to the device in question can be demonstrated,  \n\uf0b7 reports published in peer re viewed scientific literature on other clinical experience of either the \ndevice in question or a device for which equivalence to the device in question can be \ndemonstrated,  \n\uf0b7 clinically relevant information coming from post -market surveillance, in particular the post -\nmarket clinical follow -up. (Article 2(48))  \nConformity Assessment \u2013 The process demonstrating whether the requirements of the MDR relating to a \ndevice have been fulfilled. (Article 2(40)). This process depends on the medical device classification, \naccording to the procedures described in the MDR, in particular Article 52 (7) applicable for class I \ndevices.  \nDistributor  - means any natural or legal person in the supply chain, other than the manufacturer or the \nimporter that makes a device available on  the market, up until the point of putting into service (Article \n2(34)) . \nEconomic operator  - means a manufacturer, an authorised representative, an importer, a distributor or \nthe person referre d to in Article 22(1) and 22(3)  (Article 2(35)) . \nField safety corrective action  - means corrective action taken by a manufacturer for technical or \nmedical reasons to prevent or reduce the risk of a serious incident in relation to a device made available \non the market (Article 2(68)) . \nField safety notice - means a com munication sent by a manufacturer to users or customers in relation to \na field safety corrective action  (Article 2(69)) . \nHarmonised standard - means a European standard as defined in point (1)(c) of Article 2 of Regulation \n(EU) N\u00b0 1025/20128, (as referred on the Article 2(70)) \u2013 means a European standard adopted on the basis \nof a request made by the Commission for the application of Union harmonisation legislation.  \nImporter  - means any natural or legal person established within the Union that places a devic e from a \nthird country on the Union market  (Article 2(33)).  \nIntended purpose/intended use - means the use for which a device is intended according to the data \nsupplied by the manufacturer on the label, in the instructions for use or in promotional or sales  materials \nor statements and as specified by the manufacturer in the clinical evaluation (Article 2(12)).  \nInstructions for use  - means the information provided by the manufacturer to inform the user of a device's \nintended purpose and proper use, and of any  precautions to be taken (Article 2(14)).  \nLabel  - means the written, printed or graphic information appearing either on the device itself, or on the \npackaging of each unit or on the packaging of multiple devices (Article 2(13)).  \nMedical device  - means any instrument, apparatus, appliance, software, implant, reagent, material or \nother article intended by the manufacturer to be used, alone or in combination, for human beings for one \nor more of the following specific medical purposes:  \n\u2012 diagnosis, prevention, m onitoring, prediction, prognosis, treatment or alleviation of disease,  \n\u2012 diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability,  \n\u2012 investigation, replacement or modification of the anatomy or of a physiological or path ological \nprocess or state,  \n\u2012 providing information by means of in vitro examination of specimens derived from the human \nbody, including organ, blood and tissue donations,  \n  \n                                                      \n8  Regulation  (EU) No 1025/2012 of the European Parliament and of the Council , of 25 October 2012 , on European standardization  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n10 \n and which does not achieve its principal intended action by pharmacological, immuno logical or \nmetabolic means, in or on the human body, but which may be assisted in its function by such means. \nThe following products shall also be deemed to be medical devices:  \n\u2012 devices for the control or support of conception;  \n\u2012 products specifically intended for the cleaning, disinfection or sterilisation of devices as referred to \nin Article 1(4) and of those referred to in the first paragraph of this point. (Article 2(1))  \nManufacturer -  means a natural or legal person who manufactures or fully refur bishes a device or has a \ndevice designed, manufactured or fully refurbished, and markets that device under its name or \ntrademark ; (Article 2(30)).  \nNotified Body - means a conformity assessment body designated in accordance with the MDR (Article \n2(42)).  \nPlacing on the market  - means the first making available of a device, other than an investigational device, \non the Union market (Article 2(28)).  \nPost-market surveillance - means all activities carried out by manufacturers in cooperation with other \neconomic op erators to institute and keep up to date a systematic procedure to proactively collect and \nreview experience gained from devices they place on the market, make available on the market or put into \nservice for the purpose of identifying any need to immediate ly apply any necessary corrective or \npreventive actions (Article 2(60)).  \nRisk - means the combination of the probability of occurrence of harm and the severity of that harm \n(Article 2(23)).  \nSerious incident  - means any incident that directly or indirectly led, might have led or might lead to any of \nthe following:  \n(a) the death of a patient, user or other person,  \n(b) the temporary or permanent serious deterioration of a patient's, user's or other person's state \nof health,  \n(c) a serious public health threat; ((Article 2( 65)) \nSerious public health threat -  means an event which could result in imminent risk of death, serious \ndeterioration in a person's state of health, or serious illness, that may require prompt remedial action, and \nthat may cause significant morbidity or mortality in humans, or that is unusual or unexpected for the \ngiven place and time (Article 2(66)) . \nUnique Device Identifier (UDI) - means a series of numeric or alphanumeric characters that is created \nthrough internationally accepted device identification  and coding standards and that allows unambiguous \nidentification of specific devices on the market (Article 2(15)).  \nUser - means any healthcare professional or lay person who uses a device  (Article 2(37)).  \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n11 \n Placing Class I medical devices on the market:  \nThe necessary steps  \nManufacturers that intend to place Class I medical devices on the market must guarantee compliance \nwith all the requirements below. Please note that some of the described requirements are inter -dependent \nand can be performed in a differe nt order than the one presented.  \nFor Class I devices already placed on the market in accordance with the MDD, the manufacturer will \nconduct a gap analysis in order to guarantee that all the necessary requirements outlined below are fully \ncompleted at the d ate of the application of MDR.  \n0) Integrate MDR in the Quality Management System (QMS).  \nThe applicable provisions of the MDR will be integrated into the QMS of the manufacturer. This will \nallow the correct assessment/decision to be made and  the proper documented evidence to be created, \nensuring compliance with the following requirements.  \n1) Confirm product as a medical device  \nConfirm that the product qualifies as a medical device as defined in Article 2(1) in accordance with its \nintended purpose and principal mode of action. If the manufacturer assigns several different intended \npurposes to their product, not all of which fall under the scope of the MDR, such a product qualifies as a \nmedical device only with respect to those intended medical purposes which are covered by Article 2(1). \nThis is applicable, for instance, for the case of examination gloves that are intended by the manufacturer \nto be used to protect the patient (medical purpose - MD) and also to protect the healthcare professional \n(protecti on purpose \u2013 PPE9). In that case the relevant requirements of both legislations will be applicable.  \nIn the case of accessories to medical devices, despite not being medical devices per se, they are covered \nby MDR provisions and fall under the term \u201cdevice\u201d  in the meaning of the MDR. However, accessories \nto devices covered by the MDR by virtue of its Annex XVI are not covered by the MDR.  \nFor borderline  products where such a determination could be difficult, please consult primarily the \ninformation10 available  on the European Commission website. Your CA may be able to provide \nguidance on where to find published information and regulatory requirements.  \n2) Confirm product as a Class I medical device  \nConsult Annex VIII of the MDR to confirm that the product is correc tly classified as Class I. It should be \nnoted that some Class I devices according to MDD will be reclassified under the MDR considering the \nnew classification rules of that annex, this is the case for most software (rule 11) and devices that are \ncomposed o f substances or of combination of substances (rule 21) . \nFor devices that were reclassified from Class I to higher risk classes by application of the MDR, the \npresent guideline cannot be applied.   \nThe application of the classification rules will be governe d by the intended purpose of the device and \n                                                      \n9  Directive 89/686/EEC is repealed with effect from 21 April 2018 by Regulation (EU) 2016/425  \n10  Guidelines available on  https://ec.europa.eu/health/md_sector/new_regulations/guidance_en   Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n12 \n their inherent risks linked to the duration of use, part of the body, whether it is active or not, whether it is \ninvasive or non -invasive.  \nIf more than one rule according to Annex VIII applies to the intended pur poses of the device, the highest \nclassification applies to the device, i.e. it must be classified on the basis of the most critical specified \nuse. \nFor classification issues, please primarily consult the information11 available on the European \nCommission web site. Your CA may be able to provide guidance on where to find published information \nand regulatory requirements.  \n3) Procedures before placing on the market  \na) Meet the general safety and performance requirements  \nThe devices will meet the general safety and per formance requirements  set out in Annex I of the MDR \nwhich apply to them, taking into account the purposes intended by their manufacturers.  \nParticular attention will be given to devices that are also machinery, within the meaning of Article 2(2), \npoint (a) , Machinery Directive 2006/42/EC12, where the relevant requirements of that directive will also \nbe covered given their specificity (according to Article 1(12)).  \nThe manufacturer will establish and implement a risk management system, which will allow for the  \nidentification and analysis of the hazards associated with each device, estimation and evaluation of the \nassociated risks, elimination or control of residual risks and evaluation of the adopted measures based on \nthe information collected from the post -market surveillance system.  \nThe risk management will be understood as a continuous iterative process throughout the entire lifecycle \nof a device, requiring regular systematic updating. To carry out this process the manufacturer can find \nsolutions in common sp ecifications, or in harmonised standards, published in the Official Journal of the \nEuropean Union, or in other referential materials. Where a harmonised standard exists but the \nmanufacturer is following other referential, the application of that referentia l should guarantee at least \nthe same level of safety and performance. Conformity with the relevant harmonized standards will \nprovide presumption of conformity with the requirements of the MDR covered by those standards or \nparts thereof.  Where common speci fications are available the manufacturer is obliged to follow them \nunless they can duly justify that they have adopted a solution at least with the same level of safety and \nperformance.  \nThe risk management, clinical evaluation processes and PMS will be inter-dependent and will be \nperiodically updated.  \nb) Conduct clinical evaluation  \nAll devices, regardless of risk classification, require a clinical evaluation as part of the technical \ndocumentation requirements of the MD R13. \nThe manufacturer will specify and justify the level of clinical evidence necessary to demonstrate \n                                                      \n11  Guidelines available on  https://ec.europa.eu/health/md_sector/new_regulations/guidance_en%20   \n12  Directive 2006/42/EC  of  the  European  Parliament  and  of  the  Council  of  17  May 2006  on  machinery, and amending \nDirective  95/16/EC (OJ  L 157, 9.6.2006,  p. 24) \n13  For further, see Annex II of the MDR  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n13 \n conformity with the relevant general safety and performance requirements described in Annex I. That \nlevel of clinical evidence will be appropriate in view of the characteristics of the device and its intended \npurpose. In order to do that, manufacturers will plan, conduct and document a clinical evaluation in \naccordance with Article 61 and Part A of Annex XIV.  \nGuidance on the process of conducting clinical eval uation is also available on the Commission website.14  \nConformity to Annex I requirements can only be assumed when the following items are aligned with each \nother:  \n\uf0b7 Risk management;  \n\uf0b7 The information materials supplied by the manufacturer, including:  \no labelling ,  \no instructions for use (where required),   \no available promotional materials,  \no any accompanying documents foreseen by the manufacturer;  \n\uf0b7 The clinical evaluation (the device description used for the clinical evaluation, other contents of the \nclinical evaluati on report);  \n\uf0b7 The available clinical data (such as results of clinical investigations, publications, Post Market \nSurveillance studies, clinical registries, etc.).  \nThe MDR reinforces the need to consider the following aspects when carrying out a clinical eval uation:  \n\u2022 Consideration of available alternative treatment options  is required as part of clinical \nevaluation for the MDR15. Whilst the existence of better alternative treatment options does not \ninfluence the compliance of the device with the MDR, the manufacturer needs to be able to \njustify the clinical benefit of using their device if alternatives are available.  \n\u2022 The incorpo ration of clinical data  obtained throughout the life cycle of the device from the \nmanufacturers post -market clinical follow -up plan and post -market surveillance plan to update \nthe clinic al evaluation and documentation16. \n\u2022 The acceptability of the benefit -risk ratio  must be based upon sufficient clinical data and  \nwill be continuously monitored and reassessed from clinical data collected through the post -\nmark et surveillance phase. The post -market surveillance plan should incorporate suitable \nindicators and thr eshold values to be used in this reassessment 17. \nIf available clinical data are not sufficient to demonstrate compliance with the MDR, further clinical \ndata will be obtained or generated by clinical investigations.  \nFor devices which are currently certifie d with respect to the Directive 93/42/EC, and for which the \navailable clinical data are not sufficient to demonstrate compliance with MDR, additional clinical data \nmay be obtained by post -market clinical follow -up studies of the device. Sometimes, even dat a from the \ngeneral post -market follow -up might suffice to close the gap18. \nNote : if a clinical investigation is required, then the Member State requires advance notification of the \nproposal and the provisions of Article 62 and Annex XV will be applicable.  \n                                                      \n14  https://ec.europa.eu/health/md_sector/new_regulations/guidance_en       \n15  MDR, Article 61(3)(c)  \n16  MDR, Article 61(11)  \n17  MDR, Article 61(1) and Annex III 1.1b  \n18  An MDCG guidance is intended to be published  on this matter including \u2018sufficient clinical da ta\u2019 in 2020 and will be availabl e at the EU \nCommission webpage  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n14 \n In duly justified and substantiated cases, some Class I devices manufacturers may exceptionally \ndemonstrate that the conformity with general safety and performance requirements based on clinical data \nis not deemed appropriate. Such a justification by the m anufacturer must be based upon an evaluation of \nevidence in accordance with Article 61(10).  \nThe clinical evaluation, risk management processes and PMS will be inter -dependent and will be \nperiodically updated.  \nc) Prepare technical documentation  \nThe manufactur er will draw up and keep up to date the technical documentation that demonstrates the \nconformity of their devices with the technical requirements of the MDR. This technical documentation \nmust be prepared according to Annex II and III and prior to drawing u p the EU declaration of \nconformity.  \nThe technical documentation  and, if applicable, its summary, will be drawn up and presented by the \nmanufacturer in a clear, organised, readily searchable and unambiguous manner.  \nThe manufacturer must make the technical d ocumentation available to the CA, the authorised \nrepresentative (when applicable) and NB (when applicable).  \nThe technical documentation will be prepared following review of the general safety and performance \nrequirements  and relevant technical provisions o f the MDR and, if applicable, of the Machinery \nDirective19 and will cover all the relevant aspects from Annex II and III, such as:  \n- Rationale for the  qualification as a medical device and  the risk class  attributed.  \n- Description and specification  - A general d escription of the device, including its intended \npurpose and intended users/patient population and, if applicable, accessories and variants of the \nproduct (for example trade names, model numbers, references, sizes). In addition , the Basic \nUDI-DI as per Par t C of Annex VI will be provided.  \n- Technical Specifications of the device - Specifications including details of raw materials, \ndrawings of components and/or master patterns and any quality control  procedures.  \n- Information to be supplied by the manufacturer - Labels on the device and packaging, such  as \nsingle  unit packaging,  sales  packaging,  transport packaging  in case of specific  management  \nconditions and instruction for use (if applicable),  in the languages determined by  the Member  \nStates  where  the device is envisaged to be sold.  \n- Reference to previous generations of the device and to similar devices  - Provide an overview of \nprevious generation(s) of the device and similar devices available on the market as ap plicable  \n- Design and manufacturing information \u2013 Information that allows the understanding of the \ndesign and manufacturing of a device, including the results of qualifications tests and design \ncalculations relevant to the intended use of the product, includ ing connections to other devices \nin order for it to operate as intended. If the manufacturer can provide information showing that \na safe design has been established for a number of years and that product has been performing \nas intended during that time suc h information is likely to be sufficient to cover this  \n                                                      \n19  According to Article 1 (12)  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n15 \n requirement. The identification of all sites, suppliers and sub -contractors, where design and \nmanufacturing activities are performed will also be included.  \n- General safety and performance requirements \u2013 information for the demonstration of \nconformity with the general safety and performance requirements, set out in Annex I. In order \nto do this, the manufacturer will refer to all the methods and solutions used for conformity \ndemonstration with each safety and performance requirement, including harmonised standards \nand/or common specifications (CS). The same applies for the requirements contained in the \nMachinery Directive.  \n- Demonstration of conformity  with the requirements set out in Annex I should typically be \npresented in the form of a checklist. This should list all requirements referred to in Annex I and \nspecify:  \n(1) the applicability of each requirement to the device,  \n(2) the solution adopted by the man ufacturer to comply with each applicable requirement,  \n(3) the reference to any possible CS or harmonized standards applied in full or in part and  \n(4) the reference to where to find evidence of the solution adopted in the technical \ndocumentation.  \nManufacturers wil l list the relevant harmonised standards (concerning for example sterilisation, \nlabelling and information to be supplied with the device, biocompatibility, specific groups of \nproducts) which have been applied in full or in part. If harmonised standards hav e not been \napplied in full, additional data will be required and provided detailing remaining solutions \nadopted to meet the concerned requirements.  \nInformation on standards harmonised under the MDR will be made available in the Official \nJournal of the Euro pean Union.  \nChanges on the harmonised standards used to demonstrate the conformity of device will be \nadequately taken into account in a timely manner.  \nPlease note that no standard harmonized under the Directive 93/42/EC, has ever covered all the \nrequirements of the Annex I to that Directive. Hence,  it is not likely that any one standard \nharmonized under the MDR will cover all the requirements of the Anne x I to the MDR. The \nscope of coverage is indicated in the so -called Annex Z to the European \u201cEN\u201d standard. The \nscope of coverage is never to be found in the ISO or IEC standard text.  \n- Benefit -risk analysis (sections 1 and 8 of Annex I) and Risk management ( section 3 of Annex I).  \n- Pre-clinical and Clinical evaluation data \u2013 Information to be provided on the results from pre -\nclinical and clinical evaluation.  \n- The post -market surveillance system  - The technical documentation on post -market surveillance \nto be dr awn up by the manufacturer in accordance with Articles 83 to 85 will be presented in a \nclear, organized, readily searchable and unambiguous manner. It shall address and cover the \nelements of point 1.1 of Annex III. The plan will cover  the post -market clini cal follow up plan as \nreferred to in part B of Annex XIV or a justification as to why it is not applicable. The PMS \nreport of article 85 shall be part of the technical documentation on post -market surveillance.  \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n16 \n - Records  - Manufacturers will keep the techn ical documentation, the EU declaration of \nconformity and, if applicable, a copy of any relevant certificate, including any amendments and \nsupplements, issued in accordance with Article 56, available for the competent authorities for a \nperiod of at least 10  years after the last device covered by the EU declaration of conformity has \nbeen placed on the market (Article 10(8)).  \nAvailability of documentation  \u2013 In case of request by the CA, the manufacturer will provide the required \ntechnical documentation in an official Union language determined by the Member State concerned \n(Article 10(14)).  \nd)  Request Notified Body involvement  \nIn the case of devices placed on the market in sterile condition, having a measuring function or being \nreusable surgical instruments, the manufacturer will apply the procedures set out in Chapters I and III of \nAnnex IX, or in Part A of Annex XI of MDR. This requires the involvement of a NB. In all other cases \nthe intervention of a NB is not required for Class I devices. If involvement of  the NB is needed it is \nlimited:  \n- In the case of devices placed on the market in sterile condition, to the aspects of manufacture \nconcerned with securing and maintaining sterile  conditions;  \n- In the case of devices with a measuring function, to the aspects of man ufacture concerned with \nthe conformity of the devices with the metrological  requirements;  \n- In the case of reusable surgical instruments20,  to the aspects relating to the reuse of the device, in \nparticular cleaning, disinfection, sterilization, maintenance a nd functional testing and the related \ninstructions for use.  \nManufacturers can choose any NB designated according to the MDR for the relevant codes and \ncorresponding types of devices as established by Regulation (EU) 2017/2185 (code MDS 1005 for \n\u201cDevices in  sterile condition\u201d, code MDS 1006 for \u201cReusable surgical instruments\u201d and code MDS 1010 \nfor \u201cDevices with a measuring function\u201d) . The list of designated NBs is available in the NANDO \ndatabase at the following link: http://ec.europa.eu/growth/tools -databases/nando/  \nPlease note that notification under the Directive 93/42/EC, become s void after the application of the MDR \non the 26 May 202 1.  Hence, it is necessary to consult the NANDO database for the MDR.  \ne) Prepare Instructions for Use and Labelling  \nEach device must be accompanied by any safety and performance information needed to use it safely \nand to identify the device as well as the manufacturer and/or the authorised representative, taking \naccount of the training and knowledge of the potential users. This information comprises the label, \ndevice packaging and the data in the instructions for use. By way of derogation to the general principles, \nno instructions for use are required for Class I de vices if they can be used properly and safely without \nsuch instruction. An exception is most likely posed for Class Ir devices as reprocessing (cleaning and \nsterilization) will require an instruction.  \nThe requirements regarding the information to be suppl ied with the device will be found in Annex I, \nChapter III (23). In the labelling and instructions for use as well as in promotional materials of the \ndevice, the manufacturer may not (Article 7):  \n                                                      \n20  Please also note that involvement of a Notified Body in the case of reusable surgical instruments is a new requirement under the MDR, which \ndid not exist under the MDD. Manufacturers of such products are advised to take this into consideration for their pl ans to meet the provisions \nof the MDR before its application on the 26 May 202 1. Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n17 \n - Ascribe functions and properties to the device which the devi ce does not have;  \n- Create a false impression regarding treatment or diagnosis, functions or properties which the \ndevice does not have;  \n- Fail to inform the user or the patient of a likely risk associated with the use of the device in line \nwith its intended purpose;  \n- Suggest uses for the device other than those stated to form part of the intended purpose for \nwhich the conformity assessment was carried out.  \nNational language requirements must be taken into account in relation to the labelling and instructions \nfor use. Versions of labelling  and IFU ( in each of the relevant national languages) will be included in the \ntechnical documentation.  \nNote : According to Article 16(2), a distributor or importer may provide a translation of the information \nprovided according to Section 23 of Annex I. The manufacturer will be informed about the intended \ntranslation and receive a copy 28 days prior to the date of making the device available in the respective \ncountry. It is advisable to perform a review of the translation, as a w rong or misleading translation can \ncause harm to patients or others, leading to possible liability of the manufacturer.  \nWhere appropriate, the information supplied by the manufacturer will take the form of internationally \nrecognised symbols. Any symbol or identification colour used will conform to harmonised standards or \ncommon specifications (CS). In areas for which no harmonised standards or CS exist, the symbols and \ncolours will be described in the documentation supplied with the device.  \nThe label should  have the indication that the product is a \u201cmedical device\u201d.  \n4) Check compliance with general obligations for manufacturers  \nBefore placing a device on the market, the manufacturer will make sure to comply with the general \nobligations for manufacturers as est ablished in Article 10.  \nSpecial attention will be given to the establishment of an appropriate QMS that will ensure compliance \nwith the MDR in the most effective manner, for example by means of an internal audit. The QMS will \nbe documented, implemented, m aintained, kept up to date and continually improved and will cover at \nleast the following aspects:  \na) a strategy for regulatory compliance;  \nb) identification of applicable general safety and performance requirements and exploration of \noptions to address those requirements;  \nc) responsibility of the management;  \nd) resource management, including selection and control of suppliers and sub -contractors;  \ne) risk management;  \nf) clinical evaluation, including post market clinical follow -up (PMCF);  \ng) product realisation, including planning, design, development, production and service provision;  \nh) verification of the UDI assignments;  \ni) setting -up, implementation and ma intenance of a post -market surveillance system;  \nj) handling communication with competent authorities, notified bodies, other economic operators, \ncustomers and/or other stakeholders;  \nk) processes for reporting of serious incidents and field safety corrective ac tions in the context of \nvigilance;  \nl) management of corrective and preventive actions and verification of their effectiveness;  \nm) processes for monitoring and measurement of output, data analysis and product improvement.  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n18 \n The QMS will be established at least in  parallel, if not prior to chapter 3 a) and 3 b) as described in this \nguidance note.  \nNatural or legal persons may claim compensation for damage caused by a defective device in \naccordance with applicable Union and national law. Therefore, manufacturers sha ll, in a manner that is \nproportionate to the risk class, type of device and size of the enterprise, have measures in place to \nprovide sufficient financial coverage in respect of their potential liability under Directive 85/374/EEC, \nwithout prejudice to mor e protective measures under national law.  \n5)  Draw -up the EU Declaration of Conformity  \nThe EU declaration of conformity, referred to in Article 19, is the procedure whereby the manufacturer, \nwho fulfils the obligations imposed by Article 52(7), declares that the devices concerned fulfil the \nrequirements of the MDR which apply to them. The declaration of conformity will contain as a \nminimum all information referred to in Annex IV and will be available to the CA.  \nThe manufacturer will continuously update the EU declaration of conformity and will translate it into an \nofficial union language or languages required by Member States in which the device is made available.  \nIf, in addition to the MDR, a device is covered by other Union legislation which also requires an EU \ndeclaration of conformity, the manufacturers will elaborate a single EU declaration of conformity where \nall the Union legislation applied to the product are referred to.  \nBy drawing up the EU declaration of conformity the manufacturer assumes the respon sibility for the \nregulatory compliance of the device with all Union legislation applicable to it.  \nBefore affixing a CE mark, for class Ir, Im and Is devices, the manufacturer will have an EC certificate \nissued by NB according to the Annex IX, Chapter I and III, or to Annex XI, Part A.  \n6)  Affix the CE marking  \nAll Class I medical devices placed on the mar ket will bear the CE marking of conformity, which will be \naffixed in a visible, legible and indelible form on the device or on its sterile packaging. Where such \naffixing is not possible or not warranted on account of the nature of the device, the CE markin g shall be \naffixed to the packaging. The CE marking shall also appear  on the instructions for use, as well as on any \nsales packaging.  \nIn the case of Class I medical devices placed on the market in a sterile condition and/or devices with \nmeasuring function  and/or reusable surgical instruments, the CE marking will be accompanied by the \nidentification number of the relevant NB.  \nIt is prohibited to affix marks which are likely to mislead third parties with regard to the meaning of the \nCE marking. Other additio nal marks may be affixed to the device, to the packaging or the instructions \nfor use, but must not impair the visibility or legibility of the CE marking.  \nThe CE marking format will be in compliance with Annex V. Where the device is very small the \nminimum d imensions of the CE mark may be waived.  \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n19 \n 7) Registration of devices and manufacturers in Eudamed  \nBefore placing a device on the market, the manufacturer of a Class I medical device will register the \ndevice in Eudamed.  \nIn order to register the device, the manufacturer will submit to the electronic system referred to in \nArticle 30 the information referred to in Section 1 of Part A of Annex VI, provided that they have not \nalready been registered in accordance with Article 31. In cases where the conformity ass essment \nprocedure requires the involvement of a NB pursuant to Article 52, the information referred to in \nSection 1 of Part A of Annex VI will be provided to that electronic system before applying to the NB.  \nAfter having verified the data about the manufac turer, the CA will validate it in Eudamed and the \nmanufacturer will obtain a SRN from said electronic system.  \nThe manufacturer will use the SRN when applying to a NB for conformity assessment and for accessing \nEudamed in order to fulfil its obligations und er Article 29.  \nNote: Authorised representatives and importers are also required to register to get an SRN in order to \naccess Eudamed and provide data, as appropriate  \nThe registration of a device in Eudamed by the manufacturer includes:  \n\uf0b7 Assignment of a UDI -DI (with a Basic UDI -DI) as defined in Part C of Annex VI to the device \n(in accordance with the rules of the issuing entity referred to in Article 27(2) and introduction of \nthe UDI -DI (with a Basic UDI -DI) to the UDI database together with the other core d ata elements \nreferred to in Part B of Annex VI related to that device.  \n\uf0b7 Entering, or if already provided, verifying in Eudamed the information referred to in Section 2 of \nPart A of Annex VI, with the exception of Section 2.2 thereof, and thereafter keeping the \ninformation updated.  \nIf the manufacturer has its devices designed or manufactured by another legal or natural person, the \ninformation on the identity of that person will be part of the information (Section 2.13 of Part A of \nAnnex VI) to be submitted to  Eudamed before the registration of the device.  \nNote 1  \u2013 The Unique Device Identification system will allow the identification and facilitate the \ntraceability of devices (as referred on Article 27). [Special attention will be given to point 11 of Article \n27]. \nNote 2  \u2013 The Basic UDI -DI as defined in Part C of Annex VI is the primary identifier of a device model. \nIt is the main key for records in the UDI database and is referenced in relevant certificates and EU \ndeclarations of conformity21. \nNote 3 \u2013 For Class I devices placed on the market according to MDD, afte r the date of application of \nMDR manufacturers will have in consideration the guidance documents applicable to legacy devices \ntimelines22 and registration in Eudamed23. \n                                                      \n21  For more information on the Basic UDI -DI, please refer to https://ec.europa.eu/docsroom/documents/28667   \n22  See at EU Commission webpage the relevant guidance on timelines for registration of device data elements in EUDAMED23  See at EU \nCommission webpage the relevant guidance on the registration of legacy devices in EUDAMED  \n23  See at EU Commission webpage the relevant guidance on the registration of legacy devices in EUDAMED  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n20 \n   Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n21 \n All devices including legacy devices of the manufacturer portfolio which are placed on the market or put \ninto service will have to be registered in Eudamed.  However, until Eudamed is fully functional the \nmanufacturer of a Class I medical device, or, where the manufacturer has no place of business in the EU, \nits authorised representative must  inform the CA of the country in which they have their registered place \nof business and provide a description of the device that is sufficient to identify it. The manufacturer or \nits authorised representative will contact their relevant CA for the required  procedures and forms \nrequired for such notifications. A fee might be applicable.  \n8) Post Market Surveillance (PMS)  \nAfter placing the Class I device on the market, the manufacturer will follow the next PMS steps:  \na) Review experience gained from Post -Market Sur veillance  \nThe manufacturer will put in place the required post market surveillance (PMS) system and actively \nkeep this PMS up to date in accordance with Article 83 of MDR. This includes actively and regularly \ncollecting the user experience from devices on the market, reviewing these and ensuring timely \nimplementation of any necessary corrective action, taking account of the nature and risks in relation to \nthe product.  In addition, there should be an evaluation of whether the intended benefits are achieved a nd \nwhether the benefit -risk profile stays positive.  The manufacturer will involve the distributors of the \ndevice and where applicable, the authorised representative and importers of the device in this system, in \norder to obtain the relevant  information from the market.  \nThis system will be part of the QMS, and be supported by the manufacturer\u2019s PMS plan, which must \naddress a range of information (Annex III), such as information from the vigilance context, information \nfrom trending and trend reporting, inf ormation and data on any undesirable side -effects, information \nfrom reports, complaints and incidents, provided by users and economic operators, related to the device. \nMoreover, the manufacturer will gather and assess the relevant information such as techn ical literature, \ndatabases, registers review and public information for the device itself as well as for similar devices \nalready present on the market.  \nA PMS report will be prepared according to Article 85, summarizing the results and conclusions of the \nanalysis of all of the data from the market. This report will be updated when necessary, for example  the \nintended benefits are not achieved or there is a change in the benefit -risk balance. The report can be \nrequested by the CA at any time.  \nData gathered from PMS system must be used to actively update the clinical evaluation, benefit -risk \ndetermination, improve risk management, as well as other technical documentation on a regular basis.  \nb) Vigilance   \nThe manufacturer is responsible for reporting all serious incidents and field safety corrective actions \n(FSCA) to the relevant CAs, according to Article 87 (1) of the MDR. After serious incident notification, \nthe manufacturer is obliged to make investigations, according to Article 89, which will include a risk \nassessment of the incident. If needed, a FSCA will be implemented in order to reduce the risk associated \nwith the use of the device.  \nThe manufacturer will involve the distributors of the device and, where applicable, the authorised \nrepresentative and import ers in the system, in order to obtain the information needed from the market, \nespecially for FSCA and issued field safety notices (FSN) to ensure that required actions are followed \nand completed in a timely manner.  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n22 \n When Eudamed is available, serious incide nts and FSCAs will be submitted via this electronic system \nonly.  \nManufacturers will report any serious incident immediately after they have established the causal \nrelationship between that incident and their device or that such a causal relationship is re asonably \npossible.  \nThe timeframe to report serious incidents must not exceed the following upper limits:  \n\uf0b7 In the event of a serious public health threat, a report will be submitted not later than 2 days \nafter becoming aware of the threat. (Article 87 (4))  \n\uf0b7 In the event of death or an unanticipated deterioration in a person\u2019s state of health a report will \nbe submitted not later than 10 days after becoming aware of the serious incident. (Article 87 \n(5)) \n\uf0b7 In all other cases not later than 15 days after becoming aware of the serious incident (Article 87 \n(3)) \nWhere necessary to ensure timely reporting of serious incidents, the manufacturer may submit an initial \nreport that is incomplete followed up by a complete report. If, after becoming aware of a potentially \nreportable incident, the manufacturer is uncertain about whether the incident is reportable, it shall \nnevertheless submit a report. Serious incidents will be reported only to the competent authority of the \ncountry in which the serious incident occurred via Eu damed.  \nThe manufacturer will provide a final report to that competent authority via Eudamed setting out its \nfindings from the investigation. The report will set out conclusions and - where relevant - indicate \ncorrective actions to be taken.  \nWhen the compet ent authority notifies a manufacturer of a suspected serious incident, communicated to \nthe competent authority by a healthcare professional, patient or user, the manufacturer is obliged to:  \n\uf0b7 submit a report of this serious incident to the notifying competen t authority via Eudamed within \nthe timeframes described above;  \n\uf0b7 submit an explanatory statement, to the competent authority, if the manufacturer believes the \nsuspected serious incident does not fulfil the reporting criteria.  \nIn case the competent authority disagrees with the explanatory statement provided by the manufacturer a \nreport of the serious incident may be required to be provided to the competent authority that does not \nagree via Eudamed by the manufacturer.  \nIf a FSCA is undertaken, manufacturers wil l without unnecessary delay report the field safety corrective \naction via Eudamed in advance of the carrying out of the FSCA unless urgency demands the \nmanufacturer to undertake the actions immediately.  \nManufacturers will ensure that the information relate d to the FSCA is brought without delay to the \nattention of users of the device in question by means of a FSN. Except in cases of urgency, the content \nof the draft FSN will be submitted to the evaluating competent authority or to the coordinating \ncompetent authority to allow it to make comments. Unless duly justified by the situation of the \nindividual Member State, the content of the field safety notice will be consistent in all Member States. \nManufacturers will also report the FSN(s) to Eudamed.  \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n23 \n The FSN w ill allow the correct identification of the manufacturer ( by including the, if issued, SRN), the \ndevice or devices affected (by including the relevant UDIs) and the FSN will explain, in a clear manner, \nwithout understating the level of risk, the reasons fo r the FSCA. This includes a clear reference to the \ndevice deficiency and the associated risks for patients, users or other persons and will clearly indicate all \naction to be taken by the users.  \nManufacturers will report by the means of a trend report to Eudamed any statistically significant \nincrease in the frequency or severity of incidents that are not serious incidents or that are expected \nundesirable side -effects, when it could have a significant impact on the benefit -risk analysis and which \nhave led o r may lead to risks to the health or safety of patients, users or other persons that are \nunacceptable when weighed against the intended benefits.  \nManufacturers will, if they exist, follow national provisions in the field of vigilance specifically in but \nnot limited to the case of field safety corrective actions:  \n\uf0b7 The allowed languages used to communicate with users by means of the Field Safety Notice.  \nManufacturers are asked to check if templates exist (on European Commission website) on any of the \nreporta ble forms and make sure that all the necessary information according to these templates is \nprovided. This will be only applicable until Eudamed is available.  \nManufacturers should keep concerned economic operators informed of reported serious incidents and \nFSCA activities.  \nc) Non-conforming  products  \nIf a manufacturer has reasons to believe that a device which they have placed on the market or put into \nservice is not in conformity with the MDR they will immediately take the necessary corrective action to \nbring t hat device into conformity, to withdraw it or to recall it, as appropriate. The manufacturer will \ninform the distributors of the device in question and, if applicable, the authorised representative and \nimporters. If the device presents a serious risk, the manufacturer will immediately inform the competent \nauthorities of the Member States in which the manufacturer made the device available and, where \napplicable, the notified body that issued a certificate for the device, in particular, of the non -compliance \nand of any corrective action taken."}, {"title": "mdcg_2019_3_rev1_cecp_en.pdf.txt", "text": "Medical Devices       \nMedical Device  Coordination Group Document   MDCG  201 9-3 Rev.1   \nPage 1 of 4 \n  \n \n \n \n \nMDCG  2019 -3 Rev. 1 \n Interpretation of Article 54(2)b     \n          \n \n \n April 2020  \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commission document and it cannot be regar ded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  \n \n  Medical Devices       \nMedical Device  Coordination Group Document   MDCG  201 9-3 Rev.1   \nPage 2 of 4 \n  \nMDCG 2019 -3 Rev. 1 changes  \nAddendum on procedural aspects  New \n \n \nInterpretation of Article 54(2)b  \nArticle 54(2) of the MDR lays down three criteria that exempt devices from the pre -\nmarket clinical evaluation consultation procedure with the involvement of expert \npanels. In particular that article states that:  \n\u201cThe procedure referred to in paragraph 1 shall not be required for the devices \nreferred to therein:  \n(a)  in the case of renewal of a certificate issued under this Regulation;  \n(b)  where the device has been designed by modifying a device already marketed by \nthe same manufacturer for the same intended purpose, provided that the \nmanufacturer has demonstrated to the satisfaction of the notified body that the \nmodifications do not ad versely affect the benefit -risk ratio of the device; or  \n(c) where the principles of the clinical evaluation of the device type or category have \nbeen addressed in a CS referred to in Article 9 and the notified body confirms that the \nclinical evaluation of the manufacturer for this device is in compliance with the \nrelevant CS for clinical evaluation of that kind of device\u201d.  \nInterpretation of point (b) of Article 54(2) is unclear, notably in relation to the \napplication of the word \u201cmarketed\u201d.  In fact, while in point \u201ca\u201d the co -legislator \nexplicitly indicates that the certificates referred to are those issued under the new \nRegulation, in point \u201cb\u201d there is no indication of whether a \u201cdevice already marketed\u201d \nrefers to devices already marketed under the Directi ves or the Regulations.  \nThis has raised questions from the public and from Member States.  \nAs we are about to launch the procedures for the establishment of expert panels, \nclarification of this issue is extremely urgent, notably due to its impact on the fu ture \nworkload of panels and hence on relevant budget and workload estimations.  \nThe following considerations seem to indicate that the expression \u201cdevice already \nmarketed\u201d cannot be intended to refer to a device already marketed uniquely under \nthe new Regu lation : \n\uf0b7 If the co -legislators had decided to restrict the application of point \u201cb\u201d to devices \nmarketed uniquely under the MDR, they would have explicitly stated so, as they \ndid for point \u201ca\u201d;  \n\uf0b7 Article 54, together with other Articles (such as Article 61(6) and Article 120(3)), \nwas written at the end of the negotiation process with a view to smoothen the  Medical Devices       \nMedical Device  Coordination Group Document   MDCG  201 9-3 Rev.1   \nPage 3 of 4 \n  \n \nimplementation of the new Regulation. Therefore the interpretation of the \nexemption should be understood in line with the spirit and intention of the co -\nlegislators.  \n \nIt has to be noted that, in respect to devices that have been marketed already under \nthe relevant Directives, the word \u201cmodification\u201d shall be meant as limited only to those \nmodifications needed in order to comply with the new legal requiremen ts introduced \nby the MDR1 2. \n \n \nAddendum - Procedural aspects  \n \nTogether with the application to be lodged under the applicable conformity \nassessment procedure, the manufacturer will provide the notified body with:  \n\uf0b7 a statement that it has marketed the device  in question for the same intended \npurpose under the relevant Directive,  \n\uf0b7 copy of the last issued certificate(s) together with the certificate history, and  \n\uf0b7 a description of the modifications introduced to comply with the MDR  \nAs part of its technical documen tation assessment according to the MDR, the notified \nbody will verify that the \u201cmodifications\u201d, as referred to in the main document, do not \nadversely affect the benefit -risk ratio. In particular, the notified body will verify:  \n\uf0b7 that the device in question h ad a valid certificate under the Directives,  \n\uf0b7 in case the certificate has been withdrawn, suspended3 or expired, if there is \nan impact on compliance with the general safety and performance \nrequirements, and  \n\uf0b7 that there is no pending assessment of changes fo r the device or outstanding \nnon-compliance.   \nIn addition, the notified body will verify the description of modifications provided and \nassess if these modifications are limited only to those needed in order to comply with \nthe new legal requirements introdu ced by the MDR. Limitations of the intended \npurpose of the device should not trigger the consultation procedure in accordance to \nArt. 54.  \n                                                            \n1  These devices will anyhow be subject to all applicable new MDR requirements, including those ones related \nto the clinical evaluation, and will need to be assessed by notified bodies against these new (and higher) \nrequirements. This aspect together with the increased notified bodies\u2019 oversight foreseen under MDR should \nguarantee a high standard of safety for these products.  \n2  From a practical perspective, u nder the scenario where those products had to be subject to clinical evaluation \nconsultation procedure with the involvement of expert panels, as a result of the application of criteria set in \nAnnex IX 5c, in most if not all of the cases, the panel would de cide not to give an opinion. Therefore , a very \nsignificant additional workload and financial burden would be created for an extremely limited added value.  \n3    Certificates for which the rationale for withdrawal or suspension is linked to lack of complian ce with essential   \nrequirements may adversely affect the benefit -risk ratio of the device and will require a clinical evaluation \nconsultation procedure.  Medical Devices       \nMedical Device  Coordination Group Document   MDCG  201 9-3 Rev.1   \nPage 4 of 4 \n  \n \nIn case that any of the abovementioned conditions are not fulfilled the notified body \nwill follow the consultation procedure in accordance to Art. 54.  \nThe assessment of the above conditions will be documented by the notified body in \naccordance with Section 4.6 of Annex VII in the clinical evaluation assessment report \nthat will be made available to competent authorities  in accordance with Art. 54 (1) \nand (3).  \n \n \nClarifications in respect to the applicability of Art. 54(2)b with regard to devices \nalready marketed under the MDR are to be provided in a separate guidance."}, {"title": "mdcg_2019_11_guidance_qualification_classification_software.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document   MDCG  2019-11    \n \n \n \n  \n \n \nMDCG  2019-11  \n        Guidance on Qualification and Classification  \n        of Software in Regulation (EU) 2017/745 \u2013 MDR  \n        and Regulation (EU) 2017/746 \u2013 IVDR    \n           \n \n           October   2019 \n \n \n  \n    \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member States and it is chaired by a representative of the European Commission. The document is not a European Commission document and it cannot be regarded as reflecting the official position of the European Commission. Any views expressed in this document are not legally binding and only the Court of Justice of the European Union can give binding interpretations of Union law.  \n \n   \nPage 1 of 28 \n   \nGuidance on Qualification and \nClassification of Software in \nRegulation (EU) 2017/745 \u2013 MDR and \nRegulation (EU) 2017/746 \u2013 IVDR \n \n Guidance on \nQualification and \nClassification of \nSoftware  \nOctober 201 9  \nPage 2 of 28 \n  \n \n \nTable of Contents \n \n 1.\n Scope and purpose of this document 3  \n2. Definitions and abbreviations 3  \n3. Qualification 6  \n3.1. Introduction to qualification criteria 6  \n3.2. Medical Device Software (MDSW)  7  \n3.3. \u2018Software  driving or influencing the use of a medical device\u2019 8  \n3.4. Qualification criteria of MDSW as an in vitro  diagnostic medical device 10  \n4. Classification of MDSW per MDR 2017/745 12  \n4.1. Implementing Rules 12  \n4.2. Classification Rules 12  \n5. Classification and implemen ting rules per IVDR 2017/746 15  \n5.1. Implementing Rules: 15  \n5.2. Classification Rules: 15  \n6. Considerations on placing on the market  and conformity asse ssment of MDSW 16  \n6.1. Option 1: as a medical device in its own right 16  \n6.2. Option 2: as an integral component/part of a device 17  \n7. Modules 17  \n8. Consideration of changes to an MDSW 18  \n9. Annex I: Illustrative examples of qualifica tion of software used in the healthcare \nenvironment 18  \n10. Annex II - Qualification examples of Medical Device Software (MDSW) according to \nFigures 1 and 2 24  \n11. Annex III - Usability of the IMDRF risk classification framework in the context of the \nMDR  26 \n12. Annex IV \u2013 Classification examples 27  \n \n \n  \nPage 3 of 28 \n 1. Scope and purpose of this document \nThis document, which primarily targets medical software manufacturers, defines the criteria for the \nqualification of software falling within the scope of the new medical devices regulations1 and provides \nguidance on the application of classification criteria for software under Regulation (EU) 2017/745 \u2013 \nMDR and Regulation (EU) 2017/746 \u2013 IVDR.2 The guidance also provides information related to \nplacing on the market. The classification criteria (classification rules) are set out in Annex VIII of the \nMedical Devices Regulation (EU) 2017/745 (MDR) and Annex VIII of the In vitro Diagnostic Medical Devices Regulation (EU) 2017/746 (IVDR).  \nThe criteria specified in this document shall also apply to applications (commonly referred to as apps), \nmay they be operating on a mobile phone, in the cloud or on other platforms. \n2. Definitions and abbreviations \nIntended purpose : \nAccording to Regulation (EU) 2017/745 \u2013 MDR, \u201cIntended purpose\u201d means the use for which a \ndevice is intended according to the data supplied by the manufacturer on the label, in the instructions \nfor use or in promotional or sales materials or statements and as specified by the manufacturer in the \nclinical evaluation;3 \nAccording to Regulation (EU) 2017/746 \u2013 IVDR, \u201cIntended purpose\u201d means the use for which a \ndevice is intended according to the data supplied by the manufacturer on the label, in the instructions for use or in promotional or sales materials or statements or as specified by the manufacturer in the \nperformance evaluation;\n4 \nAccessory: \nAccording to Regulation (EU) 2017/745 \u2013 MDR, \u201cAcc essory for a medical device\u201d means an article \nwhich, whilst not being itself a medical device, is intended by its manufacturer to be used together \nwith one or several particular medical device(s) to specifically enable the medical device(s) to be used in accordance with its/their intended purpose(s) or to specifically and directly assist the medical \nfunctionality of the medical device(s) in terms of its/their intended purpose(s);\n5 \nAccording to Regulation (EU) 2017/746 \u2013 IVDR, \u201cAccessory for an in vitro diagnostic medical \ndevice\u201d means an article which, whilst not being itself an in vitro diagnostic medical device, is \nintended by its manufacturer to be used together with one or several particular in vitro diagnostic \nmedical device(s) to specifically enable the in vitro diagnostic medical device(s) to be used in \naccordance with its/their intended purpose(s) or to specifically and directly assist the medical \nfunctionality of the in vitro diagnostic medical device(s) in terms of its/their intended purpose(s);6  \nNote:  Software accessory may be driving or influencing the use of a medical device.  \nNote:  Manufacturers must describe in the technical documentation accessories of a medical device or \nan in vitro diagnostic medical device which are intended to be used in combination with it; and in case \n                                                 \n1 The use of \u201cThe Medical Devices Regulations\u201d from here on out refers to both Regulation (EU) 2017/745 \u2013 MDR and \nRegulation (EU) 2017/746 \u2013 IVDR. \n2 It shall be noted that the term \u201cstandalone software\u201d which was used in the text of the medical device directives, is no \nlonger used in the context of the Medical Device Regulation. The rationale of the change is that software should be qualified and classified depending on its intended purpose uniquely, regardless of its location. \n3 Article 2(12) of Regulation (EU) 2017/745 \u2013 MDR  \n4 Article 2(12) of Regulation (EU) 2017/746 \u2013 IVDR  \n5 Article 2(2) of Regulation (EU) 2017/745 \u2013 MDR \n6 Article 2(4) of Regulation (EU) 2017/746 \u2013 IVDR   \nPage 4 of 28 \n of medical devices they must include in the instructions for use information allowing the selection of \nthe corresponding software and accessories.7 \n \nPlacing on the market: \nAccording to Regulation (EU) 2017/745 \u2013 MDR, \u201cPlacing on the market\u201d means the first making available of a device, other than an investigational device, on the Union market;\n8 \n \nAccording to Regulation (EU) 2017/746 \u2013 IVDR, \u201cPlacing on the market\u201d means the first making \navailable of a device, other than a device for performance study, on the Union market;9 \nPutting into service: \nAccording to Regulation (EU) 2017/745 \u2013 MDR, \u201cPut ting into service\u201d means the stage at which a \ndevice, other than an investigational device, has been made available to the final user as being ready \nfor use on the Union market for the first time for its intended purpose;10 \n \nAccording to Regulation (EU) 2017/746 \u2013 IVDR, \u201cPutti ng into service\u201d means the stage at which a \ndevice, other than a device for performance study, has been made available to the final user as being ready for use on the Union market for the first time for its intended purpose;\n11 \nMedical device : \n\u201cmedical device\u201d means any instrument, apparatus, appliance, software , implant, reagent, material or \nother article intended by the manufacturer to be used, alone or in combination, for human beings for \none or more of the following specific medical purposes: \n- diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease,  \n- diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability, \n- investigation, replacement or modification of the anatomy or of a physiological or \npathological process or state,  \n- providing information by means of in vitro examination of specimens derived from the human \nbody, including organ, blood and tissue donations,  \nand which does not achieve its principal intended action by pharmacological, immunological or \nmetabolic means, in or on the human body, but which may be assisted in its function by such means.  \nThe following products shall also be deemed to be medical devices:  \n- devices for the control or support of conception;  \n- products specifically intended for the cleaning, disinfection or sterilisation of devices as \nreferred to in Article 1(4) and of those referred to in the first paragraph of this point.12 \nActive medical device:  \n\u201cactive device\u201d means any device, the operation of which depends on a source of energy other than \nthat generated by the human body for that purpose, or by gravity, and which acts by changing the \ndensity of or converting that energy. Devices intended to transmit energy, substances or other elements \nbetween an active device and the patient, without any significant change, shall not be deemed to be active devices. Software shall also be deemed to be an active device;\n13 \n \n                                                 \n7 Article 32.2(c), Annex I, Chapter III Section 23.4(f), Annex II Section 1.1(h) of Regulation (EU) 2017/745 \u2013 MDRArticle \n29.2(c) and  Annex II Section 1.1(m) of Regulation (EU) 2017/746 \u2013 IVDR  \n8 Article 2(28) of Regulation (EU) 2017/745 \u2013 MDR \n9 Article 2(21) of Regulation (EU) 2017/746 \u2013 IVDR \n10 Article 2(29) of Regulation (EU) 2017/745 \u2013 MDR \n11 Article 2(22) of Regulation (EU) 2017/746 \u2013 IVDR \n12 Article 2(1) of Regulation (EU) 2017/745 \u2013 MDR \n13 Article 2(4) of Regulation (EU) 2017/745 \u2013 MDR   \nPage 5 of 28 \n In vitro  diagnostic medical device: \n\u201cIn vitro diagnostic medical device\u201d means any medical device which is a reagent, reagent product, \ncalibrator, control material, kit, instru ment, apparatus, piece of equipment, software  or system, \nwhether used alone or in combination, intended by the manufacturer to be used in vitro for the \nexamination of specimens, including blood and tissue donations, derived from the human body, solely \nor principally for the purpose of providing information on one or more of the following:  \n- concerning a physiological or pathological process or state;  \n- concerning congenital physical or mental impairments;  \n- concerning the predisposition to a medical condition or a disease;  \n- to determine the safety and compatibility with potential recipients;  \n- to predict treatment response or reactions;  \n- to define or monitoring therapeutic measures.  \nSpecimen receptacles shall also be deemed to be in vitro diagnostic medical devices;14 \n \nSoftware: \nFor the purpose of this guidance, \u201csoftware\u201d is defined as a set of instructions that processes input data \nand creates output data. \nInput data : \nAny data provided to software in order to obtain ou tput data after computation of this data can be \nconsidered as input data. Input data examples (non-exhaustive): \n- Data given through the use of a human data-input device such as a keyboard, mouse, stylus, or \ntouch screen; \n- Data given through speech recognition; \n- Digital document: formatted for general purpose such as Word file or pdf file or jpeg image, \nformatted for medical purpose such as DICOM file or ECG records or Electronic Health \nRecord, unformatted document. Note that digital documents have to be differentiated from \nsoftware able to read such documents; \n- Data received from/transmitted by devices. \nOutput data : \nAny data produced by a software can be considered  as an output data. Output data examples (non-\nexhaustive): \n- Screen display data (such as layout with number, characters, picture, graphics, etc.); \n- Print data (such as layout with number, characters, picture, graphics, etc.); \n- Audio data; \n- Digital document (formatted for a general purpose such as Word file or pdf file or jpeg image, \nor formatted for medical purpose such as DICOM file or ECG records or Electronic Health \nRecord, unformatted document). \n- Haptic buzzing as an alternative to audio sound \nSoftware driving or influencing the use of a device  \nSoftware which is intended to drive or influence the use of a (hardware) medical device and does not  \nhave or perform a medical purpose on its own , nor does it create information on its own  for one or \nmore of the medical purposes described in the definition of a medical device or an in vitro  diagnostic \nmedical device. This software can, but is not limited to:  \n(a) operate, modify the state of, or control the device either through an interface (e.g., software, \nhardware) or via the operator of this device \n(b)  or supply output related to the (hardware) functioning of that device \nNote:  Software driving or influencing the use of a (hardware) medical device may be qualified as an \naccessory for a (hardware) medical device.  \n                                                 \n14 Article 2(2) of Regulation (EU) 2017/746 \u2013 IVDR   \nPage 6 of 28 \n Medical Device Software (MDSW) \nMedical device software is software that is intended to be used, alone or in combination, for a purpose \nas specified in the definition of a \u201cmedical device\u201d in the medical devices regulation15 or in vitro  \ndiagnostic medical devices regulation.16 \n3. Qualification \n3.1. Introduction to qualification criteria \nThe purpose of this section is to clarify what software is in itself subject to the medical devices \nregulations.  \nSoftware must have a medical purpose on its own to be qualified as a medical device software \n(MDSW). It should be noted that the intended purpose as described by the manufacturer of the \nsoftware is relevant for the qualification and classification of any device. \nIn order to be qualified as medical device software, the product must first fulfil the definition of \nsoftware according to this guidance and the definiti on of a medical device according to Article 2(1) of \nRegulation (EU) 2017/745 \u2013 MDR. To be qualified as an in vitro  diagnostic medical device software, \nthe product must additionally fulfil the definition of an in vitro  diagnostic medical device according to \nArticle 2(2) of Regulati on (EU) 2017/746 \u2013 IVDR.  \nWhere a given product does not fall under the definition of a medical device, or is excluded by the \nscope of the Medical Devices Regulations, other Community and/or national legislation may be \napplicable. Software that does not meet th e definition of a medical device or an in vitro diagnostic \nmedical device (i.e. software that is not MDSW) but is intended by the manufacturer to be an \naccessory for a medical device, or an in vitro  diagnostic medical device, falls respectively under the \nscope of the Regulation (EU) 2017/745 \u2013 MDR or Regulation (EU) 2017/746 \u2013 IVDR. \nSoftware can directly control a (hardware)  medical device (e.g. radiotherapy treatment software), can \nprovide immediate decision-triggering information (e .g. blood glucose meter software), or can provide \nsupport for healthcare professionals (e.g. ECG interpretation software).  \nIt is important to clarify that not all software used within healthcare is qualified as a medical device. \nFor example, \u201cSimple search\u201d, which refers to the retrieval of records by matching record metadata \nagainst record search criteria or to the retrieval of information does not qualify as medical device \nsoftware (e.g. library functions).  \nHowever, software which is intended to process, an alyse, create or modify medical information may \nbe qualified as a medical device software if the creation or modification of that information is \ngoverned by a medical intended purpose. For example, the software which alters the representation of \ndata for a medical purpose would qualify as a medical device software. (e.g. \u201csearching image for \nfindings that support a clinical hypothesis as to th e diagnosis or evolution of therapy\u201d or \u201csoftware \nwhich locally amplifies the contrast of the finding on an image display so that it serves as a decision \nsupport or suggests an action to be taken by the user\u201d). However, altering the representation of data for \nembellishment/cosmetic or compatibility purposes does not readily qualify the software as medical \ndevice software.  \nSoftware intended for non-medical purposes (excludi ng MDR Annex XVI devices), such as invoicing \nor staff planning, does not qualify as a medical device software. These software do not fall under the \nMedical Devices Regulations. \n                                                 \n15 Article 2(1) of Regulation (EU) 2017/745 \u2013 MDR \n16 Article 2(2) of Regulation (EU) 2017/746 \u2013 IVDR   \nPage 7 of 28 \n A task such as e-mailing, web or voice messaging, data parsing, word processing, and back-up is by \nitself not considered as having a medical purpose. \nAdditionally, software may run on different operating systems or in virtual environments. These \noperating systems or virtual environments do not impact the qualification criteria. \nIt must be highlighted that the risk of harm to patients, users of the software, or any other person, \nrelated to the use of the software within healthcare, including a possible malfunction is not a criterion \non whether the software qualifies as a medical device.  \n3.2. Medical Device Software (MDSW)   \nMedical device software is software that is intended to be used, alone or in combination , for a \npurpose as specified in the definition of a \u201cmedical device\u201d in the MDR or IVDR, regardless of \nwhether the software is independent or driving or influencing the use of a device. \nNote 1:  MDSW may be independent , by having its own intended medical purpose and thus meeting \nthe definition of a medical device or in vitro  diagnostic medical device on its own (i.e. alone ) \nMDSW that uses maternal parameters such as ag e, concentration of serum markers and information \nobtained through foetal ultrasound examination for evaluating the risk of trisomy 21. \nMDSW that receives measurements from transrectal  ultrasound findings, age, and in vitro diagnostic \ninstruments and calculates a patient\u2019s risk of developing prostate cancer. \nMass Spectrometry MDSW intended to analyse LC-MS/MS data to be used for microorganism \nidentification and detection of antibiotic resistance. \nMDSW smartwatch app, which is intended to send alarm notifications to the user and/or health \npractitioner  when it recognises irregular heartbeats for the purpose of detecting cardiac arrhythmia. \nNote 2:  If the software drives or influences a (hardware) medical device and also has a medical \npurpose, then it is qualified as a MDSW \nMelanoma image analysis software intended to drive a near-infrared laser light scanner. \nMDSW intended to measure and transmit blood glucose levels, calculate insulin dose required and \ndrive the insulin pump to administer the calculated dosage (closed loop insulin delivery system). \nNote 3:  Software may be qualified as MDSW regardless of its location (e.g. operating in the cloud, on \na computer, on a mobile phone, or as an additional functionality on a hardware medical device). \nMDSW that is intended to operate a point of care test from a remote location.  \nNote 4:  MDSW may be intended to be used by healthcare professionals or laypersons (e.g. patients or \nother users).17, 18 \nMDSW that provides insulin dose recommendations to  a patient regardless of the method of delivery \nof the prescribed dose, whether via an insulin pump, insulin pen or insulin syringe. \n                                                 \n17 Where MDSW is intended to be used by a lay person, the manufacturer shall apply safety and performance requirements \noutlined in MDR Annex I. 22 and 23.4 (w); or IVDR Annex I. 9.4 and 20.4.2. \n18 MDSW which can be considered as an IVD for self-testing shall be considered as a device intended to be used by \nlaypersons.   \nPage 8 of 28 \n Manufacturers must ensure that all regulatory requirements for placing on the market and conformity \nassessment have been fulfilled. As set out in Article 7 of MDR and IVDR, this also entails that any claims, relating to the intended medical purpose of their MDSW are supported by clinical evidence. If \nthis is not the case, the software would not meet the requirements of the regulations and therefore may \nnot be CE marked as a medical device, nor present said claims.  \n3.3. \u2018Software  driving or influencing the use of a medical device\u2019  \nIs software intended to drive or influence the use of a (hardware)  medical device and does not  have or \nperform a medical purpose on its own , nor does it create information on its own  for one or more of the \nmedical purposes described in the definition of a medical device or an in vitro  diagnostic medical \ndevice. This software can, but is not limited to:  \na) operate, modify the state of, or control the device either through an interface (e.g., software, \nhardware) or via the operator of this device \nb)  or supply output related to the (hardware) functioning of that device \nNote:  Software that is driving or influencing the use of a medical device is covered by the medical \ndevices regulations either as a part/component of a device or as an accessory for a medical device. \n(refer to Figure 2, box 2).  \nSoftware that is intended to be used to operate a clinical chemistry analyser. \nSoftware with built-in electronic controls for IVD quality control procedures. These quality control \nprocedures are intended to provide users with assurance that the device is performing within \nspecifications. \nDecision steps for qualification of software as MDSW (Figure 1) \nDecision step 1 : if the product is software according to Section 2 (Definitions and Abbreviations) of \nthis guidance, then it may be a medical device software, proceed to decision step 2; if the product is \nnot software according to the definition of this guidance, then it is not covered by this guidance but \nmay still be covered by the Medical Devices Regulations. \nDecision step 2 : if the product is an MDR Annex XVI device, or is an accessory for a medical \ndevice19, or is software driving or influencing the use of a medical device, then it must be considered \nas part of that device in its regulatory process or independently if it is an accessory. If it is not, proceed \nto decision step 3. \nDecision step 3 : if the software does perform an action on data, or performs an action beyond storage, \narchival, communication20, simple search, lossless compression (i.e. using a compression procedure \nthat allows the exact reconstruction of the original data) then it may be a medical device software \n(Refer to section 3.1 for more guidance on these software functions) proceed to step 4. \n \nDecision step 4 : is the action for the benefit of individual patients?  \nExamples of software which are not considered as being for the benefit of individual patients are those \nwhich are intended only to aggregate population data, provide generic diagnostic or treatment \npathways (not directed to individual patients), scientific literature, medical atlases, models and \ntemplates as well as software intended only for epidemiological studies or registers. \n \nDecision step 5:  Is the software medical device software (MDSW) according to the definition of this \nguidance? \n                                                 \n19 According to Article 2(2) of the Medical Devices Regulation or In Vitro  Diagnostic Medical Devices Regulation. \n20 Communication: The flow of information from one point, known as the source, to another, the receiver; Source: IEEE \n610.10-1994.   \nPage 9 of 28 \n  \n  \n \nPage 10 of 28 \n 3.4. Qualification criteria of MDSW as an in vitro  diagnostic medical \ndevice \nMedical Device Software (MDSW) fulfilling the definition of an in vitro  diagnostic medical device \nfalls under the in vitro diagnostic medical devices Regulation (EU) 2017/746.  Provided that MDSW is \nintended specifically by its manufacturer to be used together with an in vitro diagnostic  medical device \nto enable it to be used in accordance with its in tended purpose, this MDSW falls under the scope of the \nin vitro  diagnostic medical devices regulation and shall be treated as an In Vitro  Diagnostic MDSW \n(IVD MDSW) in its own right.  \nIn cases when software is driving or influencing the use of a (hardware) device, the software should be \nconsidered as falling under the respective regulation of the driven or influenced (hardware) device.  \nSoftware that analyses and interprets the optical density delivered by an ELISA reader, line or spot \npattern of a blot.  Such software takes raw data outputs and use clinical algorithms for diagnostic \nand/or prognostic purposes, in which case it qualifies as IVD MDSW. \n \n \nDecision steps for qualification of MDSW as either a medical device or an in vitro  \ndiagnostic medical device (Figure 2) \nDecision Step 1: Does the  Medical Device Software (MDSW) provide information within the scope \nof the in vitro  diagnostic medical device definition? \nMDSW which provides information according to Re gulation (EU) 2017/746 \u2013 IVDR Article 2(2) (a) \nto (f) should qualify as In Vitro  Diagnostic Medical Device Software (IVD MDSW) \n(a) concerning a physiological or pathological process or state (by investigation of this process or \nstate); or \n(b) concerning congenital physical or mental impairments  \n(c) concerning the predisposition to a medical condition or a disease;  \n(d) to determine the safety and compatibility with potential recipients;  \n(e) to predict treatment response or reactions;  \n(f) to define or monitoring therapeutic measures. \nA MDSW which falls under the definition set out in EU Article 2 (1) of Regulation (EU) 2017/745 \u2013 \nMDR should qualify as Medical Device Software (MD MDSW). In specific, the following \nconsiderations should apply on the prov ision of information by software on: \n(g) diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease \n(h) diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability, \n(i) investigation, replacement or modification of the anatomy or of a physiological or \npathological process or state, \n(j) control or support of conception; \n(k) products specifically intended for the cleaning, disinfection or sterilization of devices as \nreferred to in Article 1(4) and Annex XVI products.  \nDecision Step 2 : Does the MDSW create information based on data obtained by in vitro  diagnostic \nmedical devices only?  \nIf the information provided is based on data obtained solely from  in vitro  diagnostic medical devices, \nthen the software is an in vitro  diagnostic medical device and is therefore an IVD MDSW. \nIf the data analysed is obtained from a combination of both in vitro  diagnostic medical devices and \nmedical devices, proceed to step 3.     \nPage 11 of 28 \n Decision Step 3 : Is the intended purpose substantially driven by data sources coming from in vitro  \ndiagnostic medical devices? If yes, then the appli cable legislation is Regulation (EU) 2017/746. If the \nintended purpose is substantially driven by data sources coming from medical devices, then the \napplicable legislation is Regulation (EU) 2017/745.  \n \nIn the condition where the intended purpose of the MDSW output data fulfils both the medical device \nand in vitro  diagnostic medical device definitions set out in the MDR and IVDR (refer to Decision \nStep 2), a weighting of the data sources based on the significance of the information21 in relation to \nfulfilling the intended purpose should be conducted to aid the manufacturer in determining which regulation to apply. \n \nAnnex II of this guidance offers some prescrip tive examples of how such a weighting may be \nperformed. \n \n \n \n                                                 \n21 A qualitative approach is intended to drive the weighting of data. The weighing aims to assess the contribution of each data \ntowards achieving the result.  \n \nPage 12 of 28 \n 4. Classification of MDSW per MDR 2017/745 \n4.1. Implementing Rules \nAll implementing rules in Annex VIII of Regulation (EU) 2017/745 shall be considered.  \nSpecial considerations on Implementing Rule 3.3 and 3.5:  \nThe first sentence of implementing rule 3.3  of Annex VIII clarifies the regime applicable to software \ndriving or influencing the use of a device:   \n\u2018Software, which drives or influences the use of a device, shall fall within the same class as the device\u2019  \nThe second sentence of implementing rule 3.3  of Annex VIII clarifies that the regime applicable to \nIndependent MDSW:  \n \u2018If software is independent of any other device, it shall be classified in its own right\u2019 \nThis rule should also be considered at least as an orientation for finding the correct (minimum) \nclassification of software which is placed on the market in combination with a (hardware) medical \ndevice. Therefore, Medical Device Software that both achieves its own intended purpose and also \ndrives or influences the use of a (hardware) device for a medical purpose is classified on its own, \nbased on the intended purpose achieved. In such a case, however, the risk class shall not be lower than \nthe risk class of the hardware medical device.  \nImplementing rule 3.5  of Annex VIII is relevant for all devices and states that  \n\u2018If several rules, or if, within the same rule, seve ral sub-rules, apply to the same device based on the \ndevice\u2019s intended purpose, the strictest rule and sub-rule resulting in higher classification will apply\u2019  \nMelanoma image analysis software intended to be used with a near-infrared laser light scanner , \nwhich is considered class IIa per Rule 10. The software \u201cdrives or influences the use of\u201d the near-\ninfrared laser light scanner as it is intended to take control of the scanner by letting it execute \nproprietary multi-exposure programs for the detection of melanoma. As such, implementing rule 3.3  \napplies. However, Rule 11 would also apply based on the intended medical purpose of the software \ne.g. cancer diagnosis. The MDSW would be classified as class III based on Rule 11 (see section \nClassification Rules) and per implementing rule 3.5  of Annex VIII. \n4.2. Classification Rules \nRules 9, 10 and 12 mainly categorise the risks related to the exchange of energy/substances between \nthe body and diagnostic or therapeutic active devices, taking into account the different healthcare \nsituations (condition of patients).  \nMDSW, in the majority of cases, does not (directly) relate to such risks. It relates to the consequences \nof indirect harm from failure to provide correct information.  \nTherefore, in line with Recital 5 of the Medical Device Regulation and international guidance from the \nIMDRF (International Medical Device Regulators Forum)22, Rule 11 was introduced into the MDR \nand is intended to address the risks related to the information provided by an active device, such as \nMDSW. Rule 11, in particular, describes and categorises the significance of the information provided \nby the active device to the healthcare decision (patient management) in combination with the healthcare situation (patient condition). \nAs software is defined as an active device, for the classification of active (hardware) devices, which \nalso includes MDSW providing information for patient management, Rules 9, 10, 11, 12, 13, 15 and \n                                                 \n22 IMDRF is a voluntary group of medical device regulators from around the world who have come together to build on the \nstrong foundational work of the Global Harmonization Task Force on Medical Devices (GHTF) and aims to accelerate international medical device regulatory harmonization and convergence.  \nPage 13 of 28 \n 22 of Annex VIII MDR 2017/ 745 should be considered. In line with implementation rule 3.5, the \nstrictest rule or sub-rule should hence apply. \nMDSW should be classified in the same way, rega rdless of the software's location or the type of \ninterconnection between the software and a (hardware) device.  \n4.2.1.  Rule 11 \u2013 Software for decisions with diagnosis or therapeutic purposes or \nsoftware intended to monitor  physiological processes  \nRule 11 states:  \nSoftware intended to provide information which is used to take decisions with diagnosis or \ntherapeutic purposes is classified as class IIa, except if such decisions have an impact that \nmay cause: \ndeath or an irreversible deterioration of a person's state of health, in which case it is in class \nIII; or \na serious deterioration of a person's state of health or a surgical intervention, in which case it \nis classified as class IIb.  \nSoftware intended to monitor physiological processes is classified as class IIa, except if it is \nintended for monitoring of vital physiological parameters, where the nature of variations of \nthose parameters is such that it could result in immediate danger to the patient, in which case \nit is classified as class IIb.  \nAll other software is classified as class I. \nThe text of Rule 11 can be divided into what are essentially three sub-rules that are applied depending \non the intended use/purpose of the MDSW: \n11a: (3 first paragraphs of Rule 11) intended to provide information which is used to take \ndecisions with diagnostic or therapeutic purposes; \n11b: (Paragraph 4 of Rule 11) intended to monitor physiological processes or parameters; \n11c: (Paragraph 5 of Rule 11) all other uses.  \nSub-rule 11a): \nThe wording \u201cintended to provide information which is used to take decisions with diagnosis or \ntherapeutic purposes\u201d describes, in very general terms, the \u201cmode of action\u201d which is characteristic of \nall MDSW.  Therefore, this sub-rule is generall y applicable to all MDSW (excluding those MDSW \nthat have no medical purpose). \nSub-rule 11a), states that MDSW (which is intende d to provide information which is used to take \ndecisions with diagnosis or therapeutic purposes) is classified as class IIa. \nThere are two exceptions from sub-rule 11a) that ar e mainly intended to apply a risk classification \nbased on the significance of the provided information and the potential impact of an (incorrect) \ndecision made using information from the MDSW.23 Accordingly, MDSW that is intended to provide \ninformation which is used to take decisions with diagnosis and therapeutic purposes, is at a higher risk \nclass where such decisions, if based on incorrect information from the MDSW, are reasonably likely to have an impact that may cause: \ni. death or an irreversible deterioration of a person's state of health, in which case it is in class III; \nii. serious deterioration of a person's state of health or surgical intervention, in which case it is \nclassified as class IIb. \n                                                 \n23 Compare IMDRF/SaMD WG/N12FINAL:2014 which states that there are two major factors that provide adequate \ndescription of the intended use of software: A. - Significance of  the information provided by the software to the healthcare \ndecision and B. - State of the healthcare situation or patient condition.   \nPage 14 of 28 \n The MDR contains several references to \u201cserious deterioration of a person\u2019s state of health\u201d and \n\u201csurgical intervention\u201d, notably in the vigilance or clinical investigation context. Further horizontal guidance could be provided in the future and will be available at: \nhttps://ec.europa.eu/growth/sectors/medical-devices/new-regulations/guidance_en    \nRule 11 was also introduced to mirror the regulatory guidance developed at international level and \nnotably in the context of the International Medi cal Device Regulators Forum (IMDRF). The IMDRF \nframework for risk categorisation of software as a medical device (SaMD) (\u201cIMDRF Risk \nFramework\u201d) categorises the risk of software based on the combination of the significance of the \ninformation provided by the software to the healthcare decision and the healthcare situation or patient condition. IMDRF also developed a table for assisting operators in identifying the appropriate risk \ncategory for their own product. \nSuch a table could provide operators placing MDSW on the EU market with some useful indications \non the risk class applicable to their products as a result of the application of Rule 11 of the MDR. For \nthis purpose, a table is provided in Annex III to this document which lists the IMDRF risk categories and the possible corresponding MDR risk classes accor ding to Rule 11 of the MDR. It must be noted \nthat this table does not take into account MDSW which is Class I.   \nSub-rule 11b): \nMDSW that is intended to monitor physiological processes will, under most circumstances, provide \n\u201cinformation which is used to take decisions with diagnosis or therapeutic purposes and hence fall under sub-rule 11a. Sub-rule 11b) should therefore be considered as a specific rule for MDSW \nintended only for monitoring purposes. Sub-rule 11b) was introduced to ensure that MDSW which has \nthe same intended purpose as (hardware) devices which would fall under rule 10, third indent, are in \nthe same risk class.  \nHowever, this sub rule applies to MDSW intended to be used for monitoring any/all physiological \nprocesses and not just vital physiological processes (equivalent to rule 10, third indent).  \nVital physiological processes and parameters include, for example, respiration, heart rate, cerebral \nfunctions, blood gases, blood pressure and body temperature. \nSub-rule 11c): \nSub-rule 11c) implies that all other MDSW is classified as class I. \n4.2.2.  Rule 12 \u2013 Active devices intended to administer and/or remove \nsubstances \nAs software devices cannot physically administer and/or remove substances, please refer to the \nimplementation rule 3.3 of Annex VIII for MDSW covered by this rule.  \n4.2.3.  Rule 13 \u2013 All other active devices \nTaking into consideration all implementing and classification rules applicable to active devices, if no \nother rule applies, all other active devices are class I. 24 \n4.2.4.  Rule 15 - Devices used  for contraception \nRule 15 applies to devices used for contraception or prevention of the transmission of sexually \ntransmitted diseases. Software used for contraception will be classified as class IIb. \n                                                 \n24 Specific implementation or classification rules for active Annex XVI devices (which might also include software) are \nexpected to be provided together with the relevant Common Specifications for those devices.   \nPage 15 of 28 \n 4.2.5.  Rule 22 \u2013 Closed loop systems \nActive therapeutic devices with an integrated or incorporated diagnostic function which significantly \ndetermines the patient management by the device, such as closed loop systems or automated external \ndefibrillators, are classified as class III.  \nSee also implementing rule 3.3 fo r MDSW covered by this rule. \nFurther horizontal Guidance on the application of MD classification and implementing rules can be \nfound at https://ec.europa.eu/growth/sectors/medical-devices/new-regulations/guidance_en . This is \nexpected to provide useful orientation in relation to the application of non-software specific \nclassification rules.   \n5. Classification and implementing rules per IVDR 2017/746 \n5.1. Implementing Rules: \nAll implementing rules in Annex VIII of Regulation (EU) 2017/746 shall be considered.  \nSpecial considerations on Implementing Rule 1.4 and 1.9:  \nImplementing rule 1.4  is only applicable for software which drives or influences the use of an in vitro  \ndiagnostic medical device. This rule should also be considered at least as an orientation for finding the \nright (minimum) classification of software which is placed on the market in combination with a \n(hardware) medical device.  \nAccording to the second sentence of implementing rule 1.4 , if the software is independent of any other \ndevice, it shall be classified in its own right.  \nExamples for applying this implementing rule under the in vitro  diagnostic medical devices regulation:  \n\u0081 Software that is exclusively intended to drive or influence the use of an instrument intended by \nthe manufacturer specifically to be used for in vitro diagnostic procedures is classified in the \nsame class as the instrument. \n\u0081 A software that is intended to operate (driving) a C-reactive protein (CRP) measuring \nanalyser from a remote location is classified in the same class as the analyser i.e. if the \nanalyser is a classified as class A then the software operating the analyser falls into Class A. \n\u0081 MDSW that integrates genotype of multiple genes to predict risk a disease or medical \ncondition developing or recurring; this is an independent IVD MDSW and is classified on its \nown.  \nImplementing rule 1.9  states that if several classification rules apply to the same device based on the \ndevices\u2019 intended purpose, the rule resulting in higher classification will apply. To classify In Vitro \nDiagnostic Medical Device Software (IVD MDSW) which is independent of any other device, see the \nMDCG Guidance on Classification of IVDs when available at \nhttps://ec.europa.eu/growth/sectors/medical-devices/new-regulations/guidance_en . \n5.2. Classification Rules:  \nIn determining the proper classification of MDSW  under the IVDR, the manufacturer shall consider \nall classification and implementing rules of Annex VIII of the IVD Regulation (EU) 2017/746. \nAs spelled out by Implementing Rule 1.1 of Annex VIII of Regulation (EU) 2017/746, the application \nof the classification rules shall be governed by the intended purpose of the MDSW.   \nPage 16 of 28 \n Guidance on the application of the IVD classification and implementing rules can be found at \nhttps://ec.europa.eu/growth/sectors/medical-devices/new-regulations/guidance_en25 \nExamples for the classification of MDSW under the IVDR: \n\u0081 Software intended to be installed on a fully automated enzyme-linked immunosorbent assay \n(ELISA) analyser, and intended to determine the Human HbA1c concentration in serum from \nthe results obtained with a Human HbA1c ELISA, intended to screen for and diagnose \ndiabetes and monitor diabetic patients, should be in class C per Rule 3(k). \n\u0081 Software within a PAP stain automated cervical cytology screening system, intended to \nclassify the PAP cervical smear as either normal or suspicious, should be in class C per Rule \n3(h). \n\u0081 Software for the interpretatio n of automated readings of line immunoassay for the \nconfirmation and determination of antibodie s to HIV-1, HIV-1 group O and HIV-2 in human \nserum and plasma, should be in class D per Rule 1. \n\u0081 Software that uses maternal parameters such as age, concentration of serum markers and \ninformation obtained through foetal ultrasound ex amination for evaluating the risk of trisomy \n21, should be in class C per Rule 3(l). \nClassification examples in Annex IV are provided for guidance purposes and aim to illustrate how \na particular rule may be applied to a device. The indicated classification in the example is not a confirmation of the final classification of the device, as other rules must also be considered.  \n6. Considerations on placing on the market and conformity \nassessment of MDSW \nThe type of interconnection between the MDSW and the device (e.g. embedded systems, wires, Wi-Fi, \nBluetooth) does not affect the qualification of the software as a device under the MDR and IVDR (e.g. \nwhether the software is incorporated in a device or is at a different location). However, MDSW can be \nplaced on the market in two different ways: as a medical device or in-vitro  diagnostic medical device \nin its own right or as an integral component or part of a hardware device. \n6.1.  Option 1: as a medical d evice in its own right \nMDSW may be placed on the market or put into service in its own right. \n\u0081 MDSW intended to be installed on a fully aut omated enzyme-linked immunosorbent assay \n(ELISA) analyser, and intended to determine the Human HbA1c concentration in serum from \nthe results obtained with a Human HbA1c ELISA. \n\u0081 MDSW app that provides a 10-year risk of cardiovascular disease from data input by a lay \nuser. \n\u0081 MDSW app that calculates anticoagulant dosage fo r patients in oral anticoagulant therapy, \nfrom INR test results input by IVD instrume nts and other manually entered patient data. \n\u0081 MDSW app that analyses digital images of stained HEp-2 cell substrates from a microscope, \nfor detecting antinuclear antibody (ANA) patterns to guide confirmatory testing useful in elucidating a specific clinical diagnosis or prognosis. \nConformity assessment:  \n                                                 \n25 Please note that at the time of the adoption of this document, the referenced Guidance on the application of IVDR \nclassification and implementing rules was under finalisation.   \nPage 17 of 28 \n MDSW placed on the market as a device or put into service in its own right shall undergo an \nappropriate regulatory process that shall take into consideration the qualification, classification and intended purpose of the MDSW. \n6.2. Option 2: as an integral component/part of a device \nMDSW may be placed on the market or put into service as an integral component/part of a device.  \n\u0081 MDSW contained within a blood gas analyser that enables a user to run tests on the \ninstrument. \n\u0081 MDSW that is part of a handheld hardware device intended for near-patient testing (POCT: \npoint of care testing) for the determinat ion of the blood glucose concentration. \n\u0081 A fully automated enzyme-linked immunosorb ent assay (ELISA) analyser, composed of \nhardware and MDSW, intended to determine the Human HbA1c concentration in serum from \nthe results obtained with a Human HbA1c ELISA. \n\u0081 MDSW that is part of a pulse oximeter intended to digitally filter the noise from low perfusion \nperformance and motion artefacts, to calculate the ratio of red light/infrared light and to use a \nlookup table based on Beer-Lambert law to convert the ratio into the oxygen saturation in a person\u2019s blood (SpO2). \nConformity assessment: \nMDSW that is placed on the market or put into se rvice solely as an integral component/part of a \n(hardware) device may not have to undergo its own regulatory process.\n26 In this case, the MDSW shall \nbe assessed through the regulatory process applied to the device as a whole, as it is placed on the \nmarket. \nApplying the classification rules to these hardware devices, which is de-facto  a combination of the \nhardware device and the MDSW, requires careful consideration of the intended purpose of the \nMDSW. This must also be analysed when later changes to the MDSW are done. \nNote:  MDSW could be independent under both scenarios described in 6.1 and 6.2, despite the \npresentation in which it is placed on the market. \n7. Modules \nSome medical device software may be segregated into a number of applications where each of these \napplications is correlated with a module. Some of  these modules have a medical purpose, some not. \nSuch modules may be intended to cover many needs, e.g.: \n\u0081 Collect and maintain administrative patient data; \n\u0081 Keep on file the medical history of the patient; \n\u0081 Invoicing and other accounting functions; \n\u0081 Provide a link to the social security system for reimbursement; \n\u0081 Provide a link to drug prescription systems (with possible link to drug dispensing outlets); \n\u0081 Provide expert system assistance for medical decision making (e.g. radiotherapy dose \nplanner). \n                                                 \n26 Note: MDSW that is intended specifically to replace a part or com ponent of a device and that significantly changes the \nperformance or safety characteristics or the intended purpose of the device shall be considered to be a device and shall meet the requirements laid down in this Regulation (see Article 23.2 (2)).\n  \nPage 18 of 28 \n This raises the issue as to whether the whole product can be CE marked when not all applications have \na medical purpose.   \nComputer programmes used in healthcare can have applications which consist of both medical device \nand non-medical device modules. \n \nThe modules which are subject to the Medical Devices Regulations (figure 1 and 2) must comply with \nthe requirements of the medical device regulations and must carry the CE marking. The non-medical \ndevice modules are not subject to the requirements for medical devices. It is the obligation of the manufacturer to identify the boundaries and the interfaces of the different modules.  \n \nThe boundaries of the modules which are subject to the medical device regulations should be clearly \nidentified by the manufacturer based on the intended use. \nIf the modules which are subject to the medical device regulations are intended for use in combination \nwith other modules of the whole software stru cture, other devices or equipment, the whole \ncombination, including the connection system, must be safe and must not impair the specified \nperformances of the modules which are subject to the medical device regulations.\n27 \n8. Consideration of changes to an MDSW \nManufacturers shall evaluate the potential impact of any changes to the function, intended use, \nessential design, and manufacturing characteristics on the software\u2019s qualification as MDSW and its \nclassification (including the classification of the combination of the MDSW with another medical \ndevice). \nIt is to be noted that a change to or the addition of functionality to a software may lead it to be \nqualified as MDSW, or a revision of the classificati on of the MDSW. Similarly, a module that is added \nto a software might be qualified as a MDSW on its own. \nWhen determining the risk class of a combinati on of a modified MDSW and a medical device, the \nintended purpose and functionality of that (new) combination must be considered. \nNote:  For all MDSW, the manufacturer shall ensure safety and performance throughout the lifecycle \nof the software, through a continuous process of clinical and/or performance evaluation and risk management.  \n \n \n \n9. Annex I: Illustrative examples of qualification of software \nused in the healthcare environment \nSoftware for a medical purpose is rapidly evolving. Thus, the list of examples provided below is not \nexhaustive. The examples have been drafted in light of today\u2019s state of the art, in order to give the reader a better understanding of the application of the principles set out in the guideline. \nThe Manual on borderline and classification in the Community regulatory framework for medical \ndevices contains many examples related to qualification of software and apps, under the current \n                                                 \n27 i.e. general safety and performance requirements 14.1 of EU MDR 2017/745 and 13.1 of EU IVDR 2017/746   \nPage 19 of 28 \n Directives28.  The Manual is currently under revision for adaptation to MDRs. In light of the \ntechnological progress, further examples will be regularly published in both the Manual and in this guidance.  \n \na) Hospital Information Systems \nHospital Information Systems mean, in this context, systems that support the process of patient \nmanagement. Typically they are intended for patient admission, for scheduling patient appointments, \nfor insurance and billing purposes. \nThese Hospital Information Systems are not qualified as medical devices. However, they may be used \nwith additional modules, as described hereafter. These modules might be qualified in their own right as medical devices. \n \nb) Decision Support Software \nIn general, these are computer based tools which combine general medical information databases and \nalgorithms with patient-specific data. They are intended to provide healthcare professionals and/or \nusers with recommendations for diagnosis, prognosis, monitoring and treatment of individual patients. \n \nBased on Figure 1, they are qualified as medical devices.  \n\u0081 Radiotherapy treatment planning systems\n29 are intended to calculate the dosage of ionizing \nirradiation to be applied to a specific patient . They are considered to control, monitor or \ndirectly influence the source of ionizing radiation and are qualified as medical devices. \n \n\u0081 Drug planning systems (e.g. chemotherapy) are intended to calculate the drug dosage to be \nadministered to a specific patient and therefore are qualified as medical devices. \n \n\u0081 Computer Aided Detection systems are intended to provide information that may suggest or \nexclude medical conditions are qualified as medical devices (MDSW). For example, such \nsystems would be able to automatically analyse x-ray images or interpret ECGs. \n \nc) Information Systems \nInformation Systems that are intended only to transfer, store, convert, format, archive data are not \nqualified as medical devices in themselves. However, they may be used with additional modules which maybe qualified in their own right as medical devices (MDSW). \nc.1.) Electronic Patient Record Systems \nElectronic patient record systems are intended to store and transfer electronic patient records. They \narchive all kinds of documents and data related to a specific patient. The electronic patient records \nshould not be qualified as a medical device, i.e. an electronic patient record that simply replaces a patient\u2019s paper file does not meet the definition of a medical device. The modules used with electronic \npatient record system modules that might be qualified in their own right as medical devices (MDSW) \nare for example: \n\u0081 An image viewer with functionality for diagnosis based on digital images; \n\u0081 A medication module \n                                                 \n28 http://ec.europa.eu/DocsRoom/documents/12867/a ttachments/1/translations/en/renditions/native   \n29 See EN 62083 \u201cRequirements for the safety and radiotherapy treatment planning systems\u201d   \nPage 20 of 28 \n c.1.1.) Clinical Information Systems \u2013 CIS / Patient Data Manag ement Systems \u2013 PDMS \nA CIS/PDMS is a software-based system primarily intended to store and transfer patient information \ngenerated in association with the patient\u2019s intensive care treatment (e.g. intensive care units).  \nUsually the system contains information such as patient identification, vital intensive care parameters and other documented clinical observations.  \nThese CIS/PDMS are not qualified as medical devices. \nModules that are intended to provide additional information that contributes to diagnosis, therapy and \nfollow-up (e.g. generate alarms) are qualified as medical devices. \nc.1.2.) Pre-hospital Electrocardiograph (ECG) System \nA system for managing pre-hospital ECG is a software-based system intended for ambulance services \nto store and transfer information from patients to a doctor at remote location. Usually the system \ncontains information about patient identification, vital parameters and other documented clinical \nobservations. These Pre-hospital Electrocardiograph (ECG) Systems are not qualified as medical \ndevices.  \nModules that create and provide new patient treatment information to the paramedics or to the doctor \nat a remote location to start the patient\u2019s treatment while the patient is being transported are qualified \nas medical devices.   \n \nc.1.3.) Picture Archive Communication System (PACS) \nThe Manual on Borderline and Classification in th e Community Regulatory Framework for Medical \nDevices addresses the qualification of PACS.\n30 The transposition of this Directive Guidance to the \nRegulations is currently underway and will be published at \nhttps://ec.europa.eu/growth/sectors/medical-devices/new-regulations/guidance_en  \nd) Communication Systems \nThe healthcare sector uses communication systems (e.g. email systems, mobile telecommunication \nsystems, video communication systems, paging, etc.) to transfer electronic information. Different \ntypes of messages are sent such as prescription, referrals, images, patient records, etc. \nMost of the communication systems handle types of messages other than medical information. This communication system is intended for general purpos es, and is used for transferring both medical and \nnon-medical information. \nCommunication systems are normally based on software for general purposes, and do not fall within \nthe definition of a medical device. \nCommunication system modules might be used with other modules that might be qualified in their own right as medical devices (MDSW). \n \nA software module generating alarms based on th e monitoring and analysis of patient specific \nphysiological parameters is qualified as a medical device (MDSW). \n \nd.1) Telemedicine systems \nTelemedicine Systems are intended to allow monitoring and/or delivery of healthcare to patients at \nlocations remote from where the healthcare professional is located. \n                                                 \n30 https://ec.europa.eu/docsroom/documents/35582/attachments/1/translations/en/renditions/native   \nPage 21 of 28 \n d.1.1.) Telesurgery \nTelesurgery is intended to conduct a surgical procedure from a remote location. Virtual reality \ntechnology may be used to support a remote surgeon to control a surgical robot performing the \nsurgical procedure. Telesurgery systems should be qualified as medical devices according to Figure 2 of this document.  \nRemote control software used in combination with telesurgery robots is a software that drives or \ninfluences the use of a medical device. Communication modules themselves are not medical devices. \nOther modules that are intended to influence the su rgery procedure are qualified as medical devices \n(MDSW). \ne) Web systems for monitoring of data \nA web system for the monitoring of clinical data typically interacts with a medical device (e.g. \nimplanted devices or homecare devices), and uses a transmitter to send the information over the \ninternet, a landline telephone or a mobile network. \nThe information is collected and stored on a web server usually run by an external party who is \ngenerally the manufacturer of the system. The information can be reached by authorized health \nprofessionals or the patient through an internet connection. \n\u0081 Monitoring of performance of medical devices: \nModules that are intended to monitor the medical performance of medical devices fall under \nthe medical device regulations. \nThis includes the clinical performance and failures that could affect medical performance of the device. One example of such a product is a web system for monitoring of active implants \nsuch as pacemakers or Intra Cardiac Defibrillators (ICDs). \n \n\u0081 Monitoring of non-medical performance of medical devices \nModules that are intended to perform administrative monitoring of non-medical performance \nof medical devices do not necessarily fall under the scope of the medical devices regulations. \nSoftware for the monitoring of medical devices in hospital systems for the purpose of \nmaintenance and repair.  \nf) In vitro  diagnostic medical device software \n \nf.1.) Laboratory Information Systems (LIS) and Work Area Managers (WAM) \nLaboratory Information System (LIS) and Work Area Managers (WAM) mean, in this context, \nsystems that support the process from patient sample to patient result. Typically, they have pre-\nanalytical functions for ordering, sorting and distribution of test samples. The main task is the management and validation of incoming information obtained from in vitro  \ndiagnostic medical device analysers connected to the system, such as calibration, quality control, \nproduct expiry and feedback (e.g. retesting of samples needed) through interconnections with various \nanalytical instruments (technical and clinical validation). \nFinally the post-analytical process allows communication of laboratory results, statistics and optional reporting to external databases. \nThe software normally supports the following functions: \n\u0081 Ordering of laboratory tests, samples with labels and sorting; \n\u0081 Technical and clinical validation, connection to analytic instruments; \n\u0081 Laboratory results and reports on paper, fax or electronic records that can be directly returned \nto e.g. the ordering clinic\u2019s patient record; \n\u0081 Analytical instruments can be interfaced with Hospital Information Systems (HIS), Electronic \nPatient Record Systems, Infectious control databases, etc.  \nPage 22 of 28 \n Note : software intended to modify the representation of available in vitro  diagnostic medical device \nresults is not considered an in vitro  diagnostic medical device, e.g. basic operations of arithmetic (e.g. \nmean, conversion of units) and/or plotting of results in function of time, and/or a comparison of the \nresult to the limits of acceptance set by the user. \nThe results are available, readable and understandable without the intervention of the software. \nLaboratory Information Systems (LIS) and Work Area Managers (WAM) are not qualified as \nmedical devices in themselves.  However, they may be used with additional modules. These modules \nmight be qualified in their own right as medical devices. \nA module whose intended purpose is to assess the criticality of tests required and to perform \nautomatic reprioritisation of the order based on patient data is qualified as a MDSW.  \nf.2.) Expert system \nMDSW which is intended to provide information within the scope of the in vitro diagnostic medical \ndevices definition by capturing and analysing together one or multiple results obtained for one patient \nby means of in vitro  examination of body samples (possibly combined with information from medical \ndevices and non-medical devices). \n\u0081 MDSW that integrates genotype of multiple genes to predict risk a disease or medical \ncondition developing or recurring; \n\u0081 MDSW that uses an algorithm to characterise viral resistances to various drugs, based on a \nnucleotide sequence generated by genotyping assays. This software serves to generate new information (virus resistance profile) from avai lable information on the genotype of the virus; \n\u0081 MDSW intended to be used in microbiology for the identification of clinical isolates and/or the \ndetection of antimicrobial resistances. \nRefer to Figure 2 of this guidance if data is obtained from both in vitro  diagnostic medical devices and \nmedical devices.  \nf.3.) Interpretation of raw data \nIn the case where MDSW is necessary to render raw data, readable for the user, obtained from an in \nvitro  diagnostic medical device by means of in vitro  examination of body samples, this MDSW is to \nbe considered driving or influencing the use of the in vitro  diagnostic medical device when it is \nspecifically intended to be used together with this in vitro  diagnostic medical device to enable it to be \nused in accordance with its intended purpose. \n \nMDSW intended for the analysis and interpretatio n of enzyme-linked immunosorbent assay (ELISA) \nreader optical density results, line patterns or spot patterns of a blot. \n \nf.4.) Home care monitoring, wired or mobile \nSoftware intended for archiving patient result s or for transferring results obtained from in vitro  \ndiagnostic medical devices from the home environment to the healthcare provider is not an in vitro  \ndiagnostic medical device. The results are available, readable and understandable by the user without \nthe intervention of the software. \n \nf.5.) Image Management System (IMS) \nAn IMS is a software-based system primarily intended to be networked with digital pathology \nsystems, e.g., whole slide scanners, scanning microscopes, as well as LIS. It does not contain controls \nfor the direct operation of the digital pathology syst ems, and is intended to access, display, annotate, \nmanage, store, archive and share collections of digitised patient images. IMS may be configured to  \nPage 23 of 28 \n provide limited or extensive capabilities to further visualise or analyse patient images acquired from \nnetworked digital pathology systems. \n \nAn IMS only used for viewing, archiving and transmitting images are not considered medical devices \nin themselves. However, these IMS may be used with additional modules that might be qualified in \ntheir own right as medical devices (MDSW). \n \nIMS that incorporate functions to support post-processing of images for diagnostics purposes, e.g., \nimage processing functions which alter image data or complex quantitative functions to aid in diagnosis, are qualified as MDSW. \n   \nPage 24 of 28 \n 10. Annex II - Qualification examples of Medical Device \nSoftware (MDSW) according to Figures 1 and 2 \nFigure 1 - Example 1: \nA software module which runs on an in vitro  diagnostic medical device instrument and tracks how the \nlaboratory is performing in real-time on key operational metrics such as test volumes, turnaround \ntimes, pending tests, and quality control. Its intent is to improve a laboratory\u2019s operations by providing \nreal-time monitoring of performance metrics that can drive change management and continuous improvement initiatives within the lab. The software is configurable so that customers can choose the \nmetrics on which they would like to focus. \n \nQualification: Step 1 is concluded with a \u201cyes\u201d as the software is a product which uses a set of \ninstructions (or algorithm) to process input data and create output data.  Step 2 determines that the software is not an MDR Annex XVI device, nor is it an accessory for a medical device, nor a software \ndriving or influencing the use of a medical device. Step 3 is answered \u201cyes\u201d since the software is \ndoing more than storage, archival, communication or simple search of information. Step 4 is answered \n\u201cno\u201d as the software does not perform this action for the benefit of individual patients.  The conclusion \nis that the software does not fall under the Medical Devices Regulations.  This is appropriate since the software is intended to be a Laboratory Information Systems (LIS), which is not considered a medical \ndevice. \n \nFigure 2 - Example 2:  \nMDSW intended to generate a risk score in order to trigger care processes to help reduce ICU \ntransfers, readmissions, adverse events and length of stay. The risk score by default includes \nrespiratory rate, heart rate, blood pressure and Sp O2, but a user can configure it to include other \nparameters, including in vitro  diagnostic medical device results. \n \nQualification:  In decision Step 1, the MDSW can be understood  to meet criteria (a), (f) and (h), it is \ntherefore answered \u201cyes\u201d. Step 2 is answered with a \u201cNo\u201d as an in vitr o diagnostic medical device \nresult may be included in the in the calculation. Step 3 directs the significance of the medical device \nderived information as driving the intended purpose, re sulting in the qualification of the software as an \nMD MDSW (as the data received from the in vitro  diagnostic medical device is not deemed decisive \nfor the overall calculation result (output) achieved by the MDSW) \n \nFigure 2 - Example 3: \nA MDSW algorithm intended to provide information on the statistical predisposition for Down \nsyndrome (Trisomy 21) and Edwards syndrome (Trisomy 18) in the first and second trimesters of \npregnancy. 31 The MDSW analyses input data from various in vitro  diagnostic medical device assays32 \nas well as, ultrasound measurements of the nasal bone or neck fold.  The MDSW  provides \nclinicians/obstetricians with a risk factor score for a foetus\u2019s likelihood of having genetic mutations in \nthe first or second trimester of pregnancy.  The risk score suggests whether or not additional diagnostic testing is needed to confirm the genetic mutations of Trisomy 21, Trisomy 18.\n33 \n \nQualification: Step 1 can be answered \u201cyes\u201d as the software bears a medical purpose and fulfils the \ndefinition of MDSW. The MDSW meets criteria (c) as it provides information according to the in vitro  \n                                                 \n31 The software can also detect neural tube defects (NTD) in the second trimester as well as the risk for Patau\u2019s syndrome \n(Trisomy 13). \n32 AFP (LKAP, L2KAP), Unconjugated Estriol (LKUE3, L2KUE3), hCG (LKCG, L2KCG), free \u03b2-hCG (LKFB, L2KFB), \nPAPP A (LKPC, L2KPC) \n33 or neural tube defects and Trisomy 13   \nPage 25 of 28 \n diagnostic medical devices definition. Decision step 2 is answered \u201cno\u201d as an imaging measurement is \nincluded in the calculation. Step 3 is answered \u201cyes\u201d as the intended purpose is substantially driven by in vitro  diagnostic medical device data resulting in the qualification of the software as an IVD MDSW \n(as the data received from the in vitro  diagnostic medical devices (markers) are deemed decisive for \nthe overall calculation result (output) achieved by the MDSW). \n \nFigure 2- Example 4:  \nA bioinformatics MDSW intended to analyse digi tal Next Generation Sequencing (NGS) raw data \ncoming from sequenced patient\u2019s cancer genomes. It allows the detection and visualisation of somatic genome alterations (such as substitutions, small insertions and deletions (indels), copy number \nalterations, and genomic rearrangements) across a selected number of genes. Additionally, it is also \ncapable of determining genomic signatures* (such as microsatellite instability [MSI] and/or tumour \nmutational burden [TMB]). The types of somatic genome alterations and genomic signatures detected \ndepend on the test chosen.  The MDSW assists the user in identifying and visualising genomic alterations and is intended to identify somatic genome alterations to support diagnosis and treatment \ndecisions.   \n \nQualification: Decision step 1 is concluded with a \u201cyes\u201d as the MDSW is intended for analysing \ncongenital data to provide information on the predisposition to a medical condition or disease, thus meeting criteria (b) and (c) laid out in the decision step. As the MDSW processes data coming only \nfrom in vitro  diagnostic medical devices into the calculation, then the software is qualified as an IVD \nMDSW according to Step 2.  \n \n \n   \nPage 26 of 28 \n 11. Annex III - Usability of the IMDRF risk classification \nframework in the context of the MDR 34 \nThe table below, which is intended for illustrative purposes only, may provide operators placing \nMDSW on the EU market with some useful indicative orientation on the risk class applicable to their \nproducts as a result of the application of Rule 11 a of the MDR.  \nNote:  MDR 2017/745 Sub-rule 11(a), point i., referr ing above to MDR class III, aligns with IMDRF \nrisk category IV . Sub-rule 11(a), point ii.,, referring above to MDR class IIb, aligns with IMDRF risk \ncategory III  products mentioned in section 7.2 of the mentioned IMDRF document. The IMDRF risk \ncategory II and IMDRF risk category I products are classified as MDR class IIa as per Rule 11. \nThis table does not take into account MDSW which is Class I.   \n \n  Significance of Information provided by the \nMDSW to a healthcare situation related to \ndiagnosis/therapy  State of Healthcare  \nsituation or patient condition   High \nTreat or  \ndiagnose  \n~ IMDRF 5.1.1  Medium  \nDrives clinical \nmanagement  \n~ IMDRF 5.1.2  Low \nInforms clinical \nmanagement  \n(everything else)  \nCritical situation \nor patient \ncondition  \n~ IMDRF 5.2.1  Class III \nCategory IV.i Class IIb \nCategory III.i Class IIa \nCategory II.i \nSerious situation \nor patient \ncondition  \n~ IMDRF 5.2.2 Class IIb \nCategory III.ii Class IIa \nCategory II.ii Class IIa \nCategory I.ii \nNon-serious \nsituation or \npatient condition  \n(everything else) Class IIa \nCategory II.iii Class IIa \nCategory I.iii Class IIa \nCategory I.i \nTable 1: Classification Guidance on Rule 11 \n \n \n \n                                                 \n34 Annex III and IV are not relevant for IVD MDSW. See sec tion 4.2 in order to classify IVD MDSW. MDCG Guidance on \nClassification of IVDs should also be considered.   \nPage 27 of 28 \n 12. Annex IV \u2013 Classification examples  \nThe examples are provided for guidance purposes only, to illustrate how a particular rule may be \napplied to a device. The indicated classification in  the example is not a confirmation of the final \nclassification of the device, as other rules might also be considered.  \nMoreover, the proposed classification reflects the specific intended purpose, or the healthcare context \nor situation, in which the device is used as described in the example itself. Any change to the intended \npurpose or the healthcare context/situation in which that same device is used might result in a different risk class. \n\u0081 MDSW intended to  perform diagnosis by means of image analysis for making treatment \ndecisions in patients with acute stroke should be classified as class III  under Rule 11(a)  \n- IMDRF Risk Category IV.i as the healthcare situation (stroke) is critical and the \nsignificance of the information is \u201ctreat or diagnose\u201d.   \n\u0081 Cognitive therapy MDSW that includes a diagnostic function which is intended to  feed back \nto the software to determine follow-up therapy , e.g. software adapts treatment of depression \nbased on diagnostic feedback, should be in class III per Rule 22 . When a specialist \ndetermines the necessary cognitive therapy base d on the outcome provided by the MDSW, the \nMDSW would be classified as class IIa per Rule 11(a).  \n- IMDRF Risk Category II.ii as the healthcare situation is serious and the significance \nof the information is to \u201cdrive clinical management\u201d. \n\u0081 Medical devices including MDSW intended to be used for continuous surveillance of vital \nphysiological processes in anaesthesia, intensive care or emergency care should be classified as class IIb per (Rule 11(b)) . \n\u0081 Medical devices, including MDSW intended to monitor physiological processes that are not \nconsidered to be vital, and devices intended to be used to obtain readings of vital physiological signals in routine check-ups incl uding monitoring at home should be classified \nas class IIa (Rule 11(b)).  \n\u0081 A mobile app intended to analyse a user\u2019s he artbeat, detect abnormalities and inform a \nphysician accordingly should be classified as class IIb per Rule 11(a) , if the information \nprovided by the software is intended to guide the physician in the diagnosis.  \n- IMDRF Risk Category III.i as the information drives clinical management. \n\u0081 Diagnostic MDSW intended for scoring depression based on inputted data on a patient\u2019s \nsymptoms (e.g. mood, anxiety) should be classified as class IIb under Rule 11(a) ,  \n- (IMDRF  Risk Category III.ii)  as the healthcare situation (depression) is serious and \nthe significance of the information is \u201cdiagnosis\u201d). \n\u0081 Ambulatory respiratory ventilation systems MD SW intended for long-term use (e.g. at home) \nthat alert the user/operator to any disconnection or deviation to the programmed respiratory \nvolume should be classified as class IIb per Rule 9 .  \n\u0081 Active devices, such as electronic thermometers and stethoscopes, which include MDSW \nintended for direct diagnosis may be classified as class IIa per Rule 10 , third indent since \nbody temperature and heart rate are considered decisive information for diagnosis \n(implementing rule 3.7), where the nature of the variations of these parameters would not \nresult in immediate danger to the patient.  \n\u0081 MDSW intended to rank therapeutic suggestions for a health care professional based on \npatient history, imaging test results, and patient characteristics, for example, MDSW that lists and ranks all available chemotherapy options for BRCA-positive individuals, should be \nclassified as class IIa per Rule 11(a)    \nPage 28 of 28 \n - IMDRF Risk Category II.i as it informs clinical management for cancer, a critical \ndisease. \n\u0081 MDSW app intended to support conception by calculating the user\u2019s fertility status based on a \nvalidated statistical algorithm. The user inputs health data including basal body temperature (BBT) and menstruation days to track and predict ovulation. The fertility status of the current \nday is reflected by one of three indicator lights: red (fertile), green (infertile) or yellow \n(learning phase/cycle fluctuation). This MDSW app should be classified as class I per Rule \n11c."}, {"title": "md_mfr_factsheet.pdf.txt", "text": "Factsheet for  \nManufacturers  \nof Medical Devices\nWhat you need to know!MEDICAL DEVICES  CHANGE OF LEGISLATION\nThis Factsheet is aimed at manufacturers of medical devices. \nFor a general overview of the impact of the In-Vitro   Medical \nDevices Regulation (IVDR) on manufacturers see the Factsheet \nfor manufacturers of in-vitro diagnostic medical devices. Refer -\nences to  Annexes and Articles in this factsheet refer to the MDR \n(2017/745/EU).\nThe new Medical Devices Regulation \n(2017/745/EU) (MDR) and the In-vitro \nDiagnostic Medical Devices Regulation \n(2017/746/EU) (IVDR) bring EU legislation \ninto line with technical advances, chang -\nes in medical  science, and progress in law \nmaking.\nThe new Regulations will create a robust, \ntransparent, and sustainable regulatory \nframework, recognised internationally, that \nimproves clinical safety and creates fair \n market access for manufacturers.\nIn contrast to Directives, Regulations do \nnot need to be transposed into national \nlaw. The MDR and the IVDR will therefore \nreduce the risks of discrepancies in inter -\npretation across the EU market.\nTransitional periods are planned to smooth \nthe application of the new Regulations. \nHowever, you should bear in mind that con -\nsultants, in-house professionals, and Notified \nBodies will all get busier as the deadline \ndraws closer. \nAct now to be ready on time!       Medical Devices Regulation  \n   (MDR) background\nThe MDR will replace the existing Medical Devices Directive (93/42/EEC) \n(MDD) and the Active Implantable Medical Devices Directive (90/385/EEC) \n(AIMDD). The MDR was published in May 2017, marking the start of a \nthree-year period of transition from the MDD and the AIMDD.\nDuring the transitional period the MDR will come into force gradually, start -\ning with the provisions related to the designation of Notified Bodies and \nthe ability of manufacturers to apply for new certificates under the MDR.\nThe transitional period will end on 26 May 2020, the \u201cDate of Application\u201d \n(DoA) of the Regulation. From that date the MDR will apply fully.\n1\nInternal market, \nIndustry,  \nEntrepreneurship  \nand SMEs\nRef. Ares(2018)3873669 - 20/07/20182To avoid market disruption and allow a smooth transition from \nthe Directives to the Regulation, several transitional provisions \nare in place (Article 120). Some devices with certificates issued \nunder the Directives (AIMDD/MDD certificates) may continue to \nbe placed on the market until 27 May 20241, and made avail -\nable until 27 May 20252 .\nDuring the transition phase, products certified under the Direc -\ntives and products certified under the Regulation will coexist on \nthe market. Both will have equal status under the law, and no \ndiscrimination in public tenders may take place.\n   What has changed?  \nIn terms of their impacts on manufacturers and products, the \nDirectives and the MDR largely share the same basic regulatory \nrequirements. No existing requirements have been removed, but \nthe MDR adds new requirements.\nCompared to the current Directives, the MDR places more em -\nphasis on a life-cycle approach to safety, backed up by clinical \ndata.\nThe MDR brings more stringent requirements for the designation \nof Notified Bodies, with increased control and monitoring by the \nnational competent authorities and the Commission.\nThe MDR reclassifies certain devices and has a wider scope. \nFor instance, the MDR explicitly covers all devices for cleaning, \nsterilising or disinfecting other medical devices (Article 2.1); re -\nprocessed single-use medical devices (Article 17)3; and certain \ndevices with no intended medical purpose (Annex XVI).\nThe MDR also covers internet sales of medical devices and med -\nical devices used for diagnostic or therapeutic services offered \nat a distance (Article 6).\nThe MDR introduces a clinical evaluation consultation procedure \nfor some Class IIb devices and for implantable Class III devices \nby an independent expert panel (Article 54).\nA new Unique Device Identification system (Article 27) will \nsignificantly enhance the traceability and the effectiveness of \npost-market safety-related activities.\nThe MDR will also provide increased transparency, with infor -\nmation on devices and studies being made public. The new Eu -\nropean Database for Medical Devices \u2013 Eudamed \u2013 will play a \ncentral role in making data available and increasing both the \nquantity and quality of data (Article 33).\n1  For definition see Article 2 paragraph 282\n2  For definition see Article 2 paragraph 27\n3  Reprocessing and further use of single-use devices may only take place where permitted by national law and only in accordance with this Article.  \n4  EEA: European Economic Area   What does this mean  \n   in practice?\nScope (Article 1)\nThe scope of the MDR has broadened, so as a manufacturer you \nmust check your product portfolios to find out whether more of \nyour devices fall within the scope of the Regulation compared \nto the Directives. Pay attention to products listed in Annex XVI, \nwhich will be covered by the Regulation once the respective Im -\nplementing Regulation setting out common specifications has \nbeen adopted. The list of products excluded from the scope can \nbe found in paragraph 6. Some products that combined a medi -\ncal device and an in-vitro diagnostic device or a medicinal prod -\nuct follow specific rules (see paragraphs 7, 8, 9).\nIt is now explicit that devices and services sold online fall under \nthe scope of this Regulation (Article 6).\nDefinitions (Article 2)\nThe definition of a medical device has been slightly modified \nand there are more definitions of terms in the Regulation than in \nthe Directives, in order to ensure a common understanding at EU \nlevel. Examples include: Unique Device Identifier (Definition 15), \nclinical data (Definition 48), clinical evidence (Definition 51), and \nserious incident (Definition 65).\nObligations of manufacturers\nThe obligations of the different actors and their relations are \nnow clearly stated in the Regulation.\nAccording to Article 10, manufacturers shall have systems \nfor risk management (paragraph 2) and quality management \n(paragraph 9); conduct clinical evaluations (paragraph 3); com -\npile technical documentation (paragraph 4); and apply a confor -\nmity assessment procedure (paragraph 6). Manufacturers are \nalso responsible for their devices once they are on the market \n(paragraphs 12, 13, 14). They must have systems in place to \ncover their financial responsibility for harm caused by defective \ndevices (paragraph 16).\nEvery manufacturer shall have a named person responsible for \nregulatory compliance (Article 15).\nManufacturers of some implantable devices will have to provide \nan implant card for the patient (Article 18).\nOnce they have completed all these obligations, manufacturers \nshall draw up a declaration of conformity (Article 19) and apply \nCE marking to their devices (Article 20).\nManufacturers outside the EU/EEA shall have a contract with an \nauthorised representative inside the EU/EEA4 (Article 11).3The obligations of authorised representatives (Article 11), \n importers (Article 13) and distributors (Article 14) are also \n clearly described.\nRisk classes of devices\nAs a manufacturer you must check your portfolio of products \nto determine whether some of your devices will be reclassified \nor will need to be scrutinised by a Notified Body. Determining \nthe risk class of a medical device is essential in specifying the \nsteps required for CE marking (Article 51), especially in terms \nof the choice of conformity assessment procedure and clinical \nrequirements.\nThe MDR sets out 22 rules for determining risk classes (Annex \nVIII), compared to 18 rules under the Directive. You should pay \nspecial attention to rules regarding: invasive devices, surgically \ninvasive devices and implantable devices (Section 5: Rules 5 to \n8); active devices (Section 6: Rules 9 to 13, for example, soft -\nware now falls under Rule 11); devices utilising tissues and cells \n(Rule 18); devices incorporating nanomaterials (Rule 19); and \ndevices composed of substances (Rule 21).\nNotified Bodies (Chapter IV)\nNotified Bodies have to be designated under the new Regula -\ntion. They will be required to meet more stringent criteria, par -\nticularly in terms of clinical competence. Notified Bodies can \napply to be designated from 26 November 2017. The process \nof designation, which might take 12 months or more, involves \nassessors from different national and European authorities. This \nmeans that the first Notified Bodies designated under the new \nRegulation might be available by the end of 2018.\nThe database of Notified Bodies (NANDO) can be found here.\nhttp://ec.europa.eu/growth/tools-databases/nando/\nAs a manufacturer you must verify whether your Notified Body \nwill be designated under the new Regulation and whether the \nscope of its designation will cover all your products. You must \nalso start working with your Notified Body to plan the timing \nof certification for your product portfolio, taking into account \nthe availability of your Notified Body, the need for additional \ndata on devices and the transitional provisions in the new \nRegulation.\nDevice identification\nA system of unique device identifiers (UDIs) will enhance the \nidentification  (Article 27)  and traceability (Article 25) of MDs. \nThis is a completely new feature of the Regulation.\nEach MD \u2013 and as applicable, each package \u2013 will have a UDI \ncomposed of two parts: a device identifier (UDI-DI) specific to a \ndevice, and a production identifier (UDI-PI) to identify the unit \nproducing the device.Manufacturers are responsible for entering the necessary data \non the European database (Eudamed), which includes the UDI \ndatabase, and for keeping it up to date.\nConformity assessment (Chapter V Section 2)\nThe assessment of the conformity of a device for CE marking \nvaries according to the risk class and specific features of certain \ndevices (Article 52). The intervention of a Notified Body is need -\ned for all Class IIa, IIb and III devices, as well as some specific \nClass I devices (see paragraphs 7a5, b6, and c7). The different \nroutes of assessment according to the class of the device are \ndescribed in Article 52 and the Annexes IX, X, XI. In some cases \nmanufacturers have some choice regarding the conformity as -\nsessment route.\nFor certain Class III and Class IIb devices there is a new clinical \nevaluation consultation procedure to be carried out by an inde -\npendent expert panel, based on the clinical evaluation assess -\nment report of the Notified Body (Article 54).\nAnnex I specifies the general safety and performance require -\nments, while Annexes II and III specify the makeup of the tech -\nnical documentation.\nThe scope of the Quality Management System (Article 10 para -\ngraph 9) now includes clinical evaluation and post-marketing \nclinical follow-up (PMCF). A clinical evaluation plan must pre -\ncede the clinical evaluation itself (Annex XIV, Part A).\nCommon specifications defining additional requirements may be \nput in place for certain devices (Article 9).\nClinical requirements (Chapter VI)\nThe new Regulation reinforces the requirements for clinical \nevaluation (Article 61), introducing some of the biggest changes \ncompared to the previous regime.\nAs under the Directives, it includes the collection of clinical data \nalready available in the literature as well as the setting up of \nany necessary clinical investigations. The concept of equiva -\nlence with other devices for which clinical data already exists \ncan still be used, but only in a limited number of situations, and \nthe new rules are tighter (Article 61 paragraphs 4, 5, 6).\nArticle 62 and Annex XV set out the new and more precise re -\nquirements for clinical investigations. With only certain excep -\ntions, implantable and Class III medical devices must now go \nthrough clinical investigations.\nFor all Class III devices, and for Class IIb devices intended to \nadminister a medicinal product (or remove it from the body), \nthe manufacturer has the option to consult a group of European \nexperts to obtain an upstream review of its intended clinical de -\nvelopment strategy (Article 61 paragraph 2).\n5 \u201cDevices placed on the market in sterile condition, to the aspects relating to establishing, securing and maintaining sterile conditions\u201d.\n6 \u201cDevices with a measuring function, to the aspects relating to the conformity of the devices with the metrological requirements\u201d.\n7 \u201cReusable surgical instruments, to the aspects relating to the reuse of the device, in particular cleaning, disinfection, sterilization,  \n maintenance and functional testing and the related instructions for use\u201d.4Summary of safety and clinical performance  \n(Article 32)\nFor Class III and implantable devices, manufacturers shall draw \nup a summary of their safety and clinical performance in a form \nthat intended users (and patients, if relevant) can understand. \nThis summary will form part of the technical documentation \nsent to the Notified Body\n   Timing your transition  \n                  to the new Regulation\nAs a manufacturer, the timing of your transition to the MDR is \nup to you.\nFrom 26 May 2020, all new certificates will have to be delivered \naccording to the Regulation. The certificates delivered under the \nDirectives can be valid until their date of validity for a maximum \nof four years (27 May 20248 at the latest). However, in the latter \ncase, the requirements of the new Regulation relating to post-mar -\nket surveillance, market surveillance, vigilance, and the registration \nof economic operators and devices shall apply from the Date of \nApplication (Article 120 paragraph 3).\nClass I devices (other than those that have a valid certificate \nunder the Directive) will have to conform to the new Regulation \nfrom 26 May 2020.\nClass I (except sterile devices, devices with a measuring func -\ntion and reusable surgical instruments) and Class IIa might be \neasiest to start with. Classes IIb and III will be more challenging \nbecause of the more stringent requirements for clinical data.\nAs a manufacturer, you can start now by making sure that:\n1. all your products are classified appropriately;\n2. all product documentation and evidence of compliance will \nbe available in a timely fashion and conforms with the \nMDR; and\n3. you have the necessary systems in place to handle clinical \nevaluation, quality management, post-market surveillance, \nand liability for defective devices.\nMore information\nFor more information on any of the above topics, please refer to \nthe Medical Devices section  on the DG GROW website.\nhttps://ec.europa.eu/growth/sectors/medical-devices_en         Frequently asked  \n   questions\nBelow you can find an extract from the FAQs of the Competent \nAuthorities for Medical Devices. For a complete list, see: \nhttp://www.camd-europe.eu/sites/default/files/media/docu -\nments/FAQ_MDR_180117_V1.0.pdf .\nWhen does the Medical Devices Regulation (MDR) \napply?\nThe MDR (EU) 2017/745 will apply from 26 May 2020 \u2013 the \n\u201cDate of Application\u201d (DoA).\nSome provisions of the MDR will come into force earlier (e.g. \nregarding Notified Bodies and the Medical Device Coordination \nGroup). Some will apply later (e.g. regarding UDI labelling).\nWhen do the existing Directive cease to apply?\nIn general, Directives 90/385/EEC and 93/42/EEC will be  \nrepealed on 26 May 2020 (the DoA). However, there are some \nexceptions, such as:\n\u2022 for the continued marketing of devices that comply with the \nDirectives (see below); and\n\u2022 to serve as a backup in case Eudamed is not fully functional \nby the DoA.\nWhat is the applicable legislation up to 26 May 2020?\nUntil the Date of Application, the laws and regulations adopted \nby Member States in accordance with the Directives will contin -\nue to apply. However, there are some exceptions.\nIs it possible to place devices on the market that \nare compliant with the MDR prior to the DoA?\nYes, you may certainly place MDR-compliant devices on the \nmarket before the end of the transitional period. This applies \nto devices in all risk classes, and includes, for example, cus -\ntom-made devices, systems and procedure packs.\nHowever, devices subject to the \u201cclinical evaluation consultation \nprocedure\u201d, which covers certain devices in Classes IIb and III, \nmay not be placed on the market before the Medical Device \nCoordination Group (MDCG) and the expert panels have been \nestablished.\nDepending on the risk class of the device, conformity assess -\nment may involve an appropriate Notified Body. This require -\nment may create further delays before such devices can be \nmarketed due to the delays in the availability of appropriate \nNotified Bodies for all technologies.\n8 There are some exceptions described in Article 120 paragraph 25As a manufacturer, which obligations of the Regulation \ndo I need to fulfil in order to place compliant devices \non the market before the DoA?\nYou should meet as many obligations as possible, bearing in \nmind that the complete MDR infrastructure, including Eudamed, \nis unlikely to be complete before the Date of Application.\nBoth the device and the manufacturer must comply with the \nMDR. You should assess the conformity of your device \u2013 a pro -\ncess that may require the involvement of a Notified Body. Other \nimportant points include:\n\u2022 Clinical evaluation\n\u2022 Risk management\n\u2022 Quality Management System (QMS)\n\u2022 Post-market surveillance\n\u2022 Technical documentation and other reports\n\u2022 Liability for defective devices.\nUntil Eudamed is fully operational, some parts of the Directives \nwill have to substitute for the corresponding requirements of \nthe Regulation. These include the registration of devices and \neconomic operators.\nA person responsible for regulatory compliance needs to be \navailable but not necessarily registered until Eudamed is \n operational.\nDo certificates issued by Notified Bodies  \nunder the existing Directives remain valid  \nafter the DoA?\nYes, AIMDD/MDD certificates will generally remain valid un -\ntil their indicated expiry dates. This applies to all the certifi -\ncates commonly issued by Notified Bodies, including the EC \nDesign- Examination Certificates, Certificates of Conformity, EC \nType  Examination Certificates, the EC Certificate Full Quality \n Assurance System, and the EC Certificate Production Quality \n Assurance.However, all certificates issued after 25 May 2017 will be void \nat the latest by 27 May 2024. After this date there will be no \nmore valid AIMDD/MDD certificates.\nIs it possible to have valid MDR and AIMDD/MDD \ncertificates in parallel until 27 May 2024?\nYes.\nCan manufacturers still place on the market/put \ninto service Directive-compliant devices after the \nend of the transition period?\nYes, under certain conditions there will be an option to con -\ntinue placing on the market/putting into service devices that \ncomply with the Directives until their existing certificates ex -\npire. This may avoid the immediate need for a new certificate \nunder the MDR.\nTo use this option, all the existing certificates will have to be val -\nid (including, for example, the QMS), the purpose and nature of \nthe device must not change, and you must follow the new MDR \nrules for registration, surveillance and vigilance.\nWhat is the \u201csell-off\u201d provision about? \nThe \u201csell-off\u201d provision is intended to limit the time during which \ndevices that are compliant with the Directives and have already \nbeen placed on the market may be made available. \nAny devices that are still within the supply chain and that have \nnot reached their final user as being ready for use, for example \na hospital, on 27 May 2025 are no longer marketable and must \nbe withdrawn. \nOnce a Directive-compliant device has been made available to \nthe final user by the deadline, the further making available of \nthis device is not subject to/covered by the Regulation.\n\u00a9 European Union, [2018]  Reuse is authorised provided the source is acknowledged.\nThe reuse policy of European Commission documents is regulated by Decision 2011/833/EU (OJ L 330, 14.12.2011, p. 39).\nISBN: 978-92-79-89634-7    DOI: 10.2873/614436\nET-03-18-102-EN-N"}, {"title": "cnd_general_principles_en.pdf.txt", "text": "Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 1 of 13 \n The CND Nomenclature  \n\u2018Classificazione Nazionale Dispositivi medici\u2019  \n \n \nTable of Contents  \n1. Background and General Principles  ................................ ................................ ................................ ...... 2 \n2. The CND structure  ................................ ................................ ................................ ................................ .. 4 \nAnatomic Categories \u2013 by anatomical area of use:  ................................ ................................ ...................  6 \nFunctional Categories \u2013 by intended use or clinical method:  ................................ ................................ .... 6 \nSpecial Categories \u2013 by other criteria:  ................................ ................................ ................................ .......  6 \nGroups: the second hierarchical level  ................................ ................................ ................................ ........  7 \nType: the third hierarchical level (expands into several levels of detail (1\u00b0, 2\u00b0, 3\u00b0, 4\u00b0 and 5\u00b0))  ...........  7 \n3. External links  ................................ ................................ ................................ ................................ ...........  8 \n \n \nThe purpose of this document is to provide information regarding the basic principles and the \nstructure of the Italian  \u201cClassificazione Nazionale Dispositivi medici\u201d (CND) . In March 2019, an d \naccording to the criteri a set out by the Medical Device  Coordination Group1 (MDCG) , the CND \nwas selected as the basis for the future European M edical Device Nomenclature  (EMDN ). The \nEMDN  will support the functi oning of EUDAMED  as stated by the MDCG and in accordance with \nArticles 23 of Regulation (EU) 2017/745 \u2013 MDR and Regulation (EU) 2017/746.  \n \n \n  \n                                                           \n1 (MDCG 2018 -2) \u2013 Future EU medical device nomenclature: Description of requirements  Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 2 of 13 \n 1. Background and General Principles2 \nIn 2005, the Italian Ministry of Health set out that the  CND would be the  official Italian medical \ndevice  classification and  nomenclature. Since then, t he CND has been  implemented not only in  Italy, \nbut also  in Portugal and Greece.  \nAbout 15.000 manufacturers3 from various countries have used the CND for the registration of \nmedical devices and in vitro  diagnostic medical devices in the Italian database. The distribution of \nmanufacturers of medical devices and in vitro  diagnostic  medical  devices per countr y is reported \nbelow in Figure 1. \n \n \n   Fig. 1 Distribution of manufacturers of medical devices per countr y \n \nThe CND nomenclature  is one of the tools used in the  governance of the medical device sector  and \nis characteri sed by its refined and hierarchical structure . It aims to support the improvement of \npatient safety and the quality of health systems by enabling information to be communicated in a \nstandard ised manner . \n \nUpdates and maintenance of CND:  \n                                                           \n2 The principles and rules presented thereafter are the ones historically established/followed when building the CND nomenclature u p \nto the last update in 2018. This is without prejudice to the new rules that will govern the EMDN  which will be  established by th e \nMDCG.  \n3 Source NSIS: data updated on 10 August 2019  31,6%  \n15,2%  \n10,2%  9,8%  \n3,9%  3,6%  2,7%  2,5%  2,0%  18,5%  \n0,0%5,0%10,0%15,0%20,0%25,0%30,0%35,0%Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 3 of 13 \n The construction of the CND , its subsequent updates and maintenance have been  based  on three  \nfundamental principles.  \nA) Participative approach:  \nFor the update and maintenance of a qualitative nomenclature, highly differentiated and \nqualified expertise is required. As the  medical device sector is acknowledged  for its \nheterogeneity and complex ity, a broad participation of all stakeholders (economic operators and \nhealthcare professional from NHS - at all levels of its organisation ) is essential.   \n \nB) Qualified validation of proposals :  \nNomenclature and Classification proposals are technically validated based on  assessment s of \nactual need . Factors taken into  consideration are: \n\uf0b7 other existing nomenclature and classification systems available at international level  \n\uf0b7 consumption and expense information  \n\uf0b7 assessment with sector experts from the different disciplines  \n \nC)  Formal adoption and free public availability:  \nThe CND system , which represents the basis of the whole information system on medical \ndevices is formally approved and thus constitutes an offici al reference, freely available to all \nstakeholders.  \n \nMore information on previous  updates of the CND up to 2018 can be found in Annex I of this \ndocument.  \n \nThe following pr oducts are currently not included in the CND : \n\uf0b7 Medicinal products  \n\uf0b7 Cosmetics products  \n\uf0b7 Human blood and its derivatives;  \n\uf0b7 Organs, tissues and cells of human origin, products including human tissues and cells and \nproducts derived therefrom.  \n\uf0b7 Organs, tissues and cells of animal origin except medical devices manufactured using \nanimal devitalized tissues o r devitalized products derived from animal tissue.  \n\uf0b7 Individual Protection Devices  Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 4 of 13 \n 2. he CND structure   \nThe CND is characterised by its alphanumeric  structure that  is established  in a multi -level \nhierarchical tree . It clusters medical devices in  three main levels:  \n\uf0b7 Category:  the first hierarchical level  \n\uf0b7 Group:  the second hierarchical level  \n\uf0b7 Type:  the third hierarchical level  (which  if necessary, expands into several levels of detail \n(1\u00b0, 2\u00b0, 3\u00b0, 4\u00b0 e 5\u00b0))  \n \n \n \nEach medical device is classified by an alphanumeric code consisting of a letter referring to the \n\u201cCategory\u201d, a couple of numbers referring to the \u201cGroup\u201d and a series of other couples of numbers \nreferring to the \u201cType\u201d (whose amount depends on the level o f detail) up to a maximum of 7 levels . \n \n \nEach level isidentified by:\n\u2022an alphanumeric code (max 13 digits )\nA ## ## ## ## ## ##\nLevel 1: \nC ategoriesLevel 2: \nGroupsLevel from 3 to 7:\nTypesMedical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 5 of 13 \n Categories:  the first hierarchical level  \nThe first hierarchical level of the CND is defined  as a \u201cCategory\u201d.  There are 22 categories, each \nidentif ied by a letter of the alphabet:  \n \nEach \u201cCategory \u201d includes devices regulated under Directive 93/42/EEC, 90/385/EEC or 98/79/EC \nor following a dedicated prescription from reimbursement rules in Italy. These \u201ccategories\u201d are used \nfor the same specific apparatus, anatomical district or organ or as a replace ment of them \n(anatomical categories), or devices characterised by similar use, intended use or clinical m ethod \n(functional categories).  \nConsidering these criteria and the ramified tree structure with different detail level, the following \nAnatomic (8), Fun ctional (9) and Special (5) Categories have been defined:  \n \nMedical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 6 of 13 \n Anatomic Categories \u2013 by anatomic al area of use:  \n\u2022 B \u2013 HEMATOLOGY AND HEMOTRANSFUSION DEVICES  \n\u2022 C \u2013 CARDIOCIRCULATORY DEVICES  \n\u2022 F \u2013 DYALISIS DEVICES  \n\u2022 G \u2013 GASTROINTESTINAL DEVICES  \n\u2022 N \u2013 DEVICES FOR NERVOUS AND MEDULLAR SYSTEMS  \n\u2022 Q \u2013 DENTAL, OPHTALMOLOGIC AND ENT DEVICES  \n\u2022 R \u2013 RESPIRATORY SISTEM AND ANAESTHESIA DEVICES  \n\u2022 U \u2013UROGENITAL APPARATUS  DEVICES  \n \nFunctional Categories \u2013 by intended use or clinical method:   \n\u2022 A \u2013  DEVICES FOR ADMINISTRATION, COLLECTING AND PICKING  \n\u2022 D \u2013 DISINFECTANTS, ANTISEPTICS AND P ROTEOLYTICS FOR MEDICAL \nDEVICES  (regulated by Italian Legislative Decree No. 46/97  and European Directive \n93/42/EEC ) \n\u2022 H \u2013 SUTURE DEVICES  \n\u2022 K \u2013 ENDOTHERAPY AND ELECTROSURGICAL DEVICES  \n\u2022 L \u2013 REUSABLE SURGICAL INSTRUMENT S \n\u2022 M \u2013 DEVICES FOR GENERIC AND SPECIALISTIC MEDICATION  \n\u2022 S \u2013 STERILIZATION DEVICES  \n\u2022 T \u2013 PROTECTION DEVICES AND INCONTINENCE AIDS ( regulated by Italian \nLegislative Decree No. 46/97  and European Directive 93/42/EEC ) \n\u2022 V \u2013 MEDICAL DEVICES - VARIOUS  \n \nSpecial Categories \u2013 by other criteria : \n\u2022 J \u2013 ACTIVE -IMPLANTABLE DEVICES : MDs  regulated by Directive 385/90 EEC   \n\u2022 P \u2013 IMPLANTABLE PROSTHETIC DEVICES AND OSTEOSYNTHESIS DEVICES : \nnon-active implantable MDs  \n\u2022 Y \u2013 SUPPORTS OR TECHNICAL AIDS FOR DISABLED PERSONS  \n\u2022 W \u2013 IN VITRO DIAGNOSTIC DEVICES MDs regulated by Directive 98/79  EEC  \n\u2022 Z \u2013 MEDICAL EQUIPMENT AND RELATED ACCESSORIES AND MATERIALS  \n Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 7 of 13 \n Groups : the second hierarchical level  \nThe second  hierarchical level s are  called \u201cGroup s\u201d. There are 146 anatomical/functional Medical \nDevices Gr oups  4, which  represent the various differentiations that distinguish devices contained in \nthe Categories. They are identified by two -digit nu mbers from 01 to 99 for each Category.  \nNumber \u201c90\u201d identifies the gr oups of devices having various characteristics that are not related to \nexisting gro ups. Number \u201c99\u201d  \u201cAltri \u2013 Others\u201d is reserved to medical d evices that are not included \nin already existing Groups and will be categori sed in later updates.  \nType: the third hierarchical level (expands into several levels of detail (1\u00b0, 2\u00b0, 3\u00b0, \n4\u00b0 and 5\u00b0)) \nThe \u201cType\u201d represents the third hierarchical level . If necessary, it expands into several level s of \ndetail (1\u00b0, 2\u00b0, 3\u00b0, 4\u00b0 and 5\u00b0). The group of every type includes medical devices characteri sed by a \nhigh affinity of use, intended use or s imilar clinical method. In case of doubt, the peculiar \ncharacteristics of the medical device under examination should be considered for a proper \ncollocation or search proces s (i.e. the anatomic -functional characteristics and/or the intended use \ndeclared by the manufacture r). \nAs explained, the term \u201cot hers\u201d marked with the code \u201c99 \u201don the first detail level is suitable for \ndevices not included i n existing types. The \u201c99\u201d  types will be submitted for later updates. Th e code \nreserved to the generic term \u201cothers\u201d must be used by users only if it is not possible to classify the \nmedical device in existing typologies .  This type is subject  to continuous checks and monitoring.  \nRegarding accessories, e very accessory follows the CND classification code of the medical device \nthat it is associated with , according to the intended use  given by the manufacturer . If an accessory \ncan be used with multiple medical devices belonging to several group s, it must be placed  in the \nprevalent type.  \n \n  \n                                                           \n4 Updated as of the Italian Ministerial Decree of 13 March 2018.  Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 8 of 13 \n 3. External links  \n \nFor more information, please  consult the Italian Ministry website at: \nhttp://www.salute.gov.it/portale/temi/p2_6.jsp?lingua=italiano&id=328&area=dispositivi -\nmedici&menu=classificazione  \n      \nThe fo llowing documents  may also be of use : \n\uf0b7 National Classification of Medical Devices (CND) - as modified by Ministerial Decree \n13.03.2018 ( PDF format)  \n\uf0b7 National Classification of Medical Devices (CND) - as modified by Ministerial Decree \n13.03.2018 (XLSX format)  \n\uf0b7 English translation of National Classification of Medical Devices Codes (as modified by \nMinister ial Decree 13.03.2018 -pdf, format).  \n\uf0b7 English translation of National Classification of Medical Devices Codes (as modified by \nMinisterial Decree 13.03.2018 -XLSX format).  \n\uf0b7 Search code and description of the CND  \n\uf0b7 Search in alphabetical order  \n \n  Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 9 of 13 \n Annex I \u2013 CND updates up to 2018  \nThe periodical updating process of the CND was schematically subdivided into four main phases:  \n \n\uf0b7 Phase 1:  \nCollection of proposals  This phase is open to all stakeholders who submit proposals for \nthe definition of new classifications or for the revision of existing \nones.  \n\uf0b7 Phase 2:  \nPreliminary technical \nevaluation and elaboration \nof the proposal.  The MoH MD Technical Team (MDTT) analyses th e collected \nproposals, the existing systems and the contents of the medical \ndevices database to identify elements useful for classification.  \n\uf0b7 Phase 3:  \n \u201cWidespread validation\u201d \nof the proposal.  The proposal is formally evaluated in three steps:  \nA) the regional levels of the NHS involving clinical professionals \nin technical sessions  \nB) Technical Health Committee - medical devices section of the \nMinistry of Health  \nC) State - Regions Conference   \n\uf0b7 Phase 4:  \nFormal adoption of the \nproposal  Finally, the proposal is approved by formal MoH act and \npublished on the Italian Official journal as well as the website of \nthe Italian MoH  \n \n \nMost of the inputs adopted for updating purposes are listed below:  \n\uf0b7 The analysis of the terminal typologies \"90\" and \"99\":  \nImplemented and consolidated, it originates from the analysis of information within the Italian \ndatabank and consider s data from  all the medical device s registered and classified in the CND \nterminal types with code \" 90\" ( - various) and \"99\" ( - other) of specific categories or groups \nidentified. In fact, the classification system had already foreseen ab origine that medical devices \nthat are not placed in a specific \u201ctypology\u201d are classified in the generic typologies in dicated \nwith the codes 90 and 99.  \n\uf0b7 Manufacturer requests:  \nWhen a manufacturer is unable to classify a medical device in an appropriate way inside the \nCND terminal level, a specific request for the introduction of a new CND class is required, with \na communic ation to the MoH of a rationale and the technical characteristics and / or intended \nuse that differentiate the device from the specific terminal classes already represented in the \nCND.  \n\uf0b7 The analysis of CND coming from vigilance system:  Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 10 of 13 \n Market surveillance and the vigilance system are part of the institutional activities of the MOH. \nThe lack of classificatory level can emerge in order to identify products that need particular \nattention for public health.   Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 11 of 13 \n \uf0b7 The analysis of consumption by the NHS:  \nThe revision of the CND made through the processing of the consumption data of the \nMonitoring Database is based on identification of medical devices with great economic \nrelevance or price variability.  \n\uf0b7 The analysis coming from HTA Report s: \nHealth Technology Assessment documents are periodically published by the Ministry of Health. \nThese reports are considered when evaluating  the revision of the CND.  \nThe following principles were considered in the revision of the CND:  \n\uf0b7 the number of levels in the CND structure can be inc reased up to a maximum of seven, by \ncoherently applying the homogeneity of the classification rules and of the coding system \ndefined for the first CND structure.  \n\uf0b7 for the definition of a new CND branch the number of manufacturers manufacturing the medical \ndevices that will be placed in the new typology of the CND should be more than 1;  \n\uf0b7 significant characteristics of medical devices detected by NHS professionals should be \nevaluated  \n\uf0b7 the proposal of relocation of medical devices placed in class 90 or 99 should  be consistent.  \n\uf0b7 for the definition of a new CND branch significant differences of price between similar medical \ndevices could be considered if necessary:  \n\uf0b7 for the definition of a new CND branch an assessments related to the use of medical devices is \nconside red (quantity and number of users in NHS);  \n \nFor each update proposal of the CND, the information associated to the devices registered in the \nItalian database were analysed and, if necessary, the information detect ed by the \u201cConsumption \nMonitoring Database\u201d were processed.  \n \n \n \n \n  Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 12 of 13 \n Annex II \u2013 CND VERSIONS  \nArt. No. 57 of the Italian Law n\u00b0 289 of the 27 December 2002 stated the  requirement of the  \nestablishment of a Commission on Medical Devices (CUD) as a technical advisory board to the \nMinistry of H ealth. The CUD has the task of defining and updating the repertoire of medical \ndevices and classifying all medical devices in specific classes and sub -classes.  \nThe CUD d efined the first version of the Classificazione Nazionale dei Dispositivi Medici (CND) \non July 2005 (Italian Ministerial Decree of 22 Sept .2005). In Vitro  Diagnostic Medical Devices \n(regulated by European Directive No. 98/79 EEC and Italian Legislative De cree No. 332/2000) \nwere not  included in the first version of the Classification , although they belong to a class of \nMedical Devices.  \nThe Italian Financial Law of 2006 (Law No. 266 of the year 2005, art. 1, par. 409) established that \nthe CND has to be appr oved by a decree of the Minister of Health in agreement with the State -\nRegions Conference.  \nThe CUD considered it appropriate to review and update the CND with the inclusion of in vitro  \ndiagnostic medical devices before proceeding with the State -Regions Con ference . Therefore,  on 20 \nFebruary 2007 , and after a revision of the classification, the Health Minister decreed  the approval of \nthe Classificazione Nazionale dei Dispositivi Medici (CND) drawn up by the CUD. The \nclassification refers to the medical device s regulated by Italian legislative decrees N\u00b0. 507/92, N\u00b0. \n46/97, N\u00b0. 332/2000 and subsequent amendments.  \nIn 28 March2013, the Italian D.P.R. n.44, replaced the Commission on Medical Devices (CUD) \nwith the Technical Committee section F on medical devices.  \nThe Classification represented the first step towards the establishment of the Italian Repertoire of \nthe Medical Devices.  \nAccording to the art. N\u00b0 2 of The Italian Financial Law No. 266, the Technical Committee section F  \n(previously CUD) , review the CND a nd make  the necessary changes and updates. Every update is \napproved by a Ministerial Decree:  \n \n1. Decree of the Italian Ministry of Health (13 Mar 2008) regarding Modification and update of \nClassificazione Nazionale dei Dispositivi Medici (CND) published in th e Official Gazette - GU \nNo. 125 of 29/05/2008. Links:  \nhttp://www.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_2_file.pdf   Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 13 of 13 \n www.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_3_file.xls   \n2. Decree of the Italian Ministry of Health (12 Feb 2010) regarding Modification and update  of \nClassificazione Nazionale dei Dispositivi Medici (CND) published in the Official Gazette - GU \nNo.119 of 24/05/2010. Links:  \nhttp://www.salute.gov.it/imgs/C_1 7_pagineAree_328_listaFile_itemName_5_file.pdf   \nwww.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_7_file.xls   \n3. Decree of the Italian Ministry of Heal th (7 Oct 2011) regarding Modification and update of \nClassificazione Nazionale dei Dispositivi Medici (CND) published in the Official Gazette - GU \nNo.259 of 7/11/2011.Links:  \nhttp://www.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_9_file.pdf   \nwww.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_10 _file.xls   \n4. Decree of the Italian Ministry of Health (29 July 2013) regarding Modification and update of \nClassificazione Nazionale dei Dispositivi Medici (CND) published in the Official Gazette - GU \nNo. 258 of 04/11/2013). Links:  \nhttp://www.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_16_file.pdf   \nwww.sa lute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_17_file.xlsx   \n5.  Decree of the Italian Ministry of Health (8 J une 2016 ) regarding Modification and update of the \nClassificazione Nazionale dei Dispositivi Medici (CND )  published in the Official Gazette G.U. \nSerie Generale, n. 242 del 15/10/2016).  \n6. Decree of the Italian Ministry of Health (13 march 2018) regarding Mod ification and update of \nthe Classificazione Nazionale dei Dispositivi Medici (CND ) published in the Official Gazette \nG.U. Serie Generale, No. 116 del 21/05/2018). Links:  \nhttp://www.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_15_file.pdf   \nwww.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_18_file.xlsx"}, {"title": "emdn_eudamed_nomenclature_en.pdf.txt", "text": "Medical Devices                January 2020  \nDG Health and Food Safety   \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \n \n \nPage 1 of 1 \n The European Medical Device  Nomenclature (EMDN)  \nThe European Medical Device Nomenclature (EMDN) will be the nomenclature of use by \nmanufacturers when registering their medical devices in the EUDAMED  database.  \nFounded on  pre-established criteria and requirements1 and based on orientations provided by \nthe Medical Device Coordination Group  (MDCG) , the European Commission decided in \nfavour of the use of the \u2018Classificazione Nazionale Dispositivi medici  (CND)\u20192 as the basis \nfor the EMDN . \nCurrently, a n extrao rdinary revision of the CND is ongoing so that  to release the first version \nof the EMDN, which will be i ntegrated in EUDAMED  for use by operators. The EMDN will \nbe fully available and accessible to any operators and will be copyright free.  \nTo the extent possible, t he Commission will map the EMDN to the G lobal Medical Device \nNomenclature (GMDN) . This task has been undertaken with th e hopes of  possibly facilitating \nEMDN code search by operators current ly using  GMDN . The correspondence between the \nnomenclatures is intended to be visible to operators and incorporated in the future database in \nthe form of a searching tool. Therefore, and  in cooperation with GMDN, t he mapping \nexercise is currently ongoing . The level of quality and reliability of this mapping is dependent \non the commitment of all relevant parties to work together in ma pping and validating the \nresult s.     \nA sub -group of the  MDCG on nomenclature which includes experts from National \nCompetent Authorities and stakeholders has been established to oversee  regulatory activities \nlinked to nomenclature . The sub -group will aim to define the rules and processes related to \nthe creation, update , maintenance and  use of  the European Medical Device  Nomenclature.  \nAdditionally, t he Commission is currently collaborating  with the World Health Organisation \n(WHO ) in the context of their work  and activities on a future international medic al device \nnomenclature.  \n                                                 \n1 (MDCG 2018 -2) \u2013 Future EU medical device nomenclature: Description of requirements  \n2 CND is currently used in Italy, Portugal and Greece."}, {"title": "FAQ_MDR_180117_V1.0-1.pdf.txt", "text": "Page 1 of 13 \n \nCAMD Transition Sub Group  \nFAQ \u2013 MDR Transitional provisions  \nDisclaimer : \nThe information presented in this document is for the purpose of general information only and is not intended to represent legal advice to any individual \nor entity. It reflects  the outcome of discussions within the Transition Sub Group (TSG) of the CAMD (established in May 2017) to establish \nrecommendations on the interpretation of transition -related provisions. It is not intended to be a guidance document . We recommend that you should \nobtain  your own legal advice before taking any action based on information given here. The content of this FAQ table will be updated cont inuously. While \nwe strive to provide the following information in as timely and accurate a manner as possible , this document does not make any claims or guarantees \nabout the accuracy, completeness or sufficiency of its contents. Participants of the Transit ion Sub Group, authors and reviewers of this document \nexpressly disclaim liability for any errors and omissions in the contents.  \n  \nPage 2 of 13 \n Glossary:  \n\u2022 AIMDD/MDD compliant device = device that is compliant with Directive 90/385/EEC/ Directive 93/42/EEC  \n\u2022 AIMDD/MDD certificates = certificates in accordance with Directive 90/385/EEC/ Directive 93/42/EEC  \n\u2022 DoA = date of application  of the MDR  \n\u2022 MDR = Medical Device Regulation (EU) 2017/745  \n\u2022 MDR compliant de vice = device that is compliant with the MDR  \n\u2022 MDCG = Medical Device Coordination Group  \n\u2022 MFR = manufacturer  \n\u2022 PRRC = person responsible for regulatory compliance  \n\u2022 NB = notified body  \n\u2022 \u201cold\u201d NB = NB that has issued an AIMDD/MDD certificate  \n\u2022 The Directives = Directives 90/385/EEC, 93/42/EEC  \nDocument History  \nVersion  Publication  Note  \nV1.0 17/01/18  Original publication  \n   \n   \n   \nConten ts: \nI - Issue: Transition in general  ................................ ................................ ................................ ................................ ................................ ..............................  3 \nII - Issue: Placing on the market of MDR compliant devices until 26 May 2020 (Art. 120 para 5 -7 MDR)  ................................ ................................ .............  4 \nIII - Issue: Placing on the market of devices in conformity with the Directives after 26 May 2020 (Art. 120 para 2 -3 MDR)  ................................ .................  7 \nIV - Issue: The so called \u201csell off\u201d provision of Art. 120 para 4 MDR  ................................ ................................ ................................ ................................ .. 11 \nV \u2013 Issue: EUDAMED and its relevance for the application of certain provisions of the MDR (Art. 123 para 3 d and e, Art. 120 para  8, Art. 122 MDR)  .... 12 \n \n   \nPage 3 of 13 \n  \nI - Issue: Transition in general  \n1 Question:  When does the Medical Devices Regulation (EU) 2017/745 (= MDR) apply?  \n Answer:  The MDR shall apply from 26 May 2020 (= date of application (DOA)) , see Art. 123 para 2  MDR .  \nThere are however exceptions to  that general rule. Some provisions apply earlier (e.g. regarding notified bodies or the \nMedical Device Coordination Group), some later (e.g. regarding UDI labelling). For the exceptions,  see Art. 123 para 3  \nMDR (earlier application: a -c, i; p ostponed application: d \u2013h). \n \n   \n2 Question:  When do the Directives 90/385/EEC , and 93/42/EEC [= the Directives] cease to apply ? \n Answer:  In general  the Directives 90/385/EEC and 93/42/EEC are repealed  with effect from 26 May 2020 (= DoA), see Art. 122  \nMDR . However there are some exceptions , e.g.  \n\u2022 in order to deal with devices that are compliant with the Directives or  \n\u2022 to serve as a \u201cback up\u201d in case EUDAMED is not fully functional at DoA  \n(see Art. 122 MDR).  \n   \n3 Question:  What is  the applicable legislation until  26 May 2020 (= DoA )? \n Answer:  Laws and regulations adopted by Member States in accordance with the Directives (= Directives regime). There are \nhowever exceptions (see for example Art. 123 para 3 a \u2013 c, i MDR and Art. 120 para 5 and 6  MDR ). \n   \n   \nPage 4 of 13 \n II - Issue: Placing on the market of MDR compliant  devices until 26 May 2020 (Art. 120 \npara 5 -7 MDR)  \n4 Question:  Is it possible to place a device, which is compliant with the MDR (= MDR compliant  \ndevice ), on the market prior to 26 May 2020  (= DoA) ? \n Answer:  Yes, see Art. 120 para 5 MDR.  \nManufacturer s (= MFR ) are \u2013 until 26 May 2020  (= DoA)  normally required to place devices on the market that comply with \nthe Directives  (= AIMDD/MDD compliant devices) , however Art. 120 para 5 MDR offers the option  to place MDR compliant \ndevices on the market before  DoA.  \n \n   \n5 Question:  Is it possible for all types  of devices  (for all different risk classes I \u2013 III) compliant with the MDR (= MDR compliant device) \nto be placed on the market prior to 26 May 2020  (according to Art. 120 para 5 MDR )? \n \n Answer:  Yes, all types  of devices  - regardless of their risk class \u2013 may be placed on the market according to Art. 120 para 5 MDR. \nThis includes for example custom made devices  (Art. 2 para 3  MDR ) and system s and procedure packs  (Art. 2 para 10  and \npara 11  MDR).  \nHowever , devices being subject to the \u201cclinical evaluation consultation procedure\u201d according to Art. 54 MDR (= certain \nclass III and class IIb devices) may not be placed on the market in ac cordance with Article 120 para 5 MDR  before  the \nMedical Device Coordination Group ( MDCG ) and the expert panels have been  established  (see Art. 120 para 7 MDR) . \nDepending on the risk class of the device, conformity assessment may requir e the involvement of a NB designated and \nnotified in accordance with the MDR  (see Art. 120 para 6 MDR). In this c ase, such devices cannot complete a  \nconformity assessment, and therefore may not be placed on the market, before  NBs have been designated and notified \nunder the MDR.  \n    \nPage 5 of 13 \n 6 Question:  As a MFR , which obligations of the MDR  do I need to fulfil in order to place  a MDR compliant  device on the market  \nbefore  the DoA according to Art. 120 para 5 MDR?  \n Answer:  As many obligations as are possible , while taking into account that   \n\u2022 EUDAMED is not fully functional and  \n\u2022 the MDR is not fully applicable  \nat that point in time .  \n \nGenerally speaking, that is to say that:  \n\u2022 first, the device  as such needs to be MDR compliant (see Annex I) and  \n\u2022 second, the  MFR  has to comply with the MDR.  \nIn particular, the MFR shall undertake an assessment of the conformity of that device in accordance with the \napplicable conformity assessment procedures set out in Art. 52 MDR . This may, depending on the risk class of the \ndevic e, necessitate the involvement of a notified body designated and notified in accordance with the MDR  (see Art. 120 \npara 6 MDR).  \n \nThe following requirements of the MDR  need to be fulfilled by t he MFR (non -exhaustive list) : \n\u2022 clinical evaluation  \n\u2022 risk management  \n\u2022 QMS  \n\u2022 Post-market surveillance  \n\u2022 Technical documentation and other reports  \n\u2022 Liability for defective devices  \n  \nPage 6 of 13 \n However, exceptions /adaptations  are possible /necessary , particularly due to the fact that EUDAMED may not  be fully \nfunctional before  the DoA . For example : \n \n\u2022 in the absence of a fully functional EUDAMED some requirements of the Directives  shall \u2013 where necessary - \napply in place of the relevant provisions of the Regulation (e.g. registration of d evices and economic operators).  \n \n\u2022 A person responsi ble for regulatory compliance  (PRRC, Art. 15 MDR) needs to be available  but not \nnecessarily registered until EUDAMED is available . . \n \n\u2022 The assignment of an UDI (Art. 27 para 3 MDR)   \nis not possible as long as there are  \n- no issuing entities  designated by the Commission according to Art. 27 para 2 MDR  or  \n- as long as the legal fiction according to Art. 120 para 12 does not apply (it shall apply from 26 May 2019 , see Art. \n123 para 3 i MDR ).  \nIt is of no significant use as long as there is no UDI database .  \n \n\u2022 An implant card and the information according to Art. 18 MDR  need to be provided, however without the UDI \nrelated content  (as the requirement to place the UDI carrier on the devices will be stepwise  introduced after the \nDoA).  \n   \n7 Question:  Are MDR compliant devices  placed on the market according to Art . 120 para 5 MDR subject to the so called \u201csell off\u201d \nprovision  in Art. 120 para 4 MDR (see below)?  \n Answer  No, the possibility of their being made available/put into service is not time-limited.  \n   \n  \nPage 7 of 13 \n III - Issue: Placing on the market of devices in conformity with the Directives  after 26 \nMay 2020 (Art. 120 para 2 -3 MDR)  \n8 Question:  Do certificates  issued by notified bodies in accordance with the Directives  (= AIMDD/MDD certificates ) prior to 25 May \n2020 remain valid after the DoA?  \n Answer:  Yes, as specified in Art. 120 para 2 MDR.  \nIn general , they remain valid until the end of the period indicated on the certificate. Certain AIMDD/MDD certificates (Annex \n4/IV, refer to Art. 120 para 2 first sentence MDR) become void at the latest on 27 May 2022, others (refer to Art. 120 para 2  \nsecond sentence  MDR) on 27 May 2024 at the latest. In other words, after 27 May 2024 there will be no more valid \nAIMDD/MDD certificates.   \n   \n9 Question:  What  kind of certificates remain valid  according to Art. 120 para 2 MDR?  \n Answer:  All certificates which are commonly issued by Notified Bodies  with reference to the Council Directives MDD and AIMDD.  \nThat is [see for example NBOG BPG 2010 -3, similar NB-MED/2.5. 1Rec 4]:  \n\uf02d EC Design -Examination Certificate  \n(Annex II section 4 MDD, Annex 2, section 4 AIMD)   \n\uf02d Certificate of Conformity  \n(Annex IV MDD, Annex 4 AIMD)  \n\uf02d EC Type Examination Certificate   \n(Annex III MDD; Annex 3 AIMD)  \n\uf02d EC Certificate Full Quality Assurance System  \n(Annex II excluding section 4  MDD; Annex 2 section 2 AIMD)  \n\uf02d EC Certificate Production Qualit y Assurance  \n(Annex V MDD, Annex 5 AIMD)   \nPage 8 of 13 \n \uf02d EC Certificate Product Quality Assurance System  \n(Annex VI MDD)  \n   \n10 Question:  May a \u201c declaration of conformity \u201d be considered as a \u201ccertificate\u201d  according  Art.120 para 2 MDR?  \n Answer:  No, since it is not a certificate issued by a NB.  \n   \n11 Question:  Is it possible for a MFR to have valid MDR and valid AIMDD/MDD certificates in parallel  until the 27 May 2024 expiry \ndate? \n Answer:  Yes.  \n   \n12 Question:  May devices, that are compliant with the Directives  (= MDD/AIMDD compliant devices ), be placed on the market/put into \nservice after 26 May 2020  (= DoA) ? \n Answer:  Yes, under certain conditions  (see answer on question 1 7) as specified in Art. 120 para 3 MDR.  \n \nIn general , after 26 M ay 2020 , devices need to comply with the MDR  in order to be placed on the market/put into service  \n(see Art. 5 MDR) . However , for a limited time (depending on the validity of the MDD/AIMDD  certificates) there is the option  \nto continue to place devices on the market  that are compliant with the Directives. Making use of this option  may postpone \nthe immediate need for a new certificate under the MDR.  \n   \n13 Question:  May MFR s of class I devices , that are compliant with the Directives , make use of the derogation in  Art. 120 para 3 \nMDR (= be placed on the market after the DoA)?  \n Answer:  No, they must comply with the MDR , unless the device  concerned is a class I device with measurement function or in \nsterile condition  covered by a valid  MDD certificate .  \n    \nPage 9 of 13 \n 14 Question:  May devices that are excluded  from the scope of the MDR (e.g. via Art. 1 para 6 lit h) nonetheless benefit from Art. 120 \npara 3 MDR ? \n Answer:  No, these devices do not fall under the MDR, thus Art. 120 para 3 MDR is not applicable.  \n   \n15 Question:  May MDD/AIMDD compliant devices , which  under the MDR will be subject to an \u201cupgrade\u201d in risk class  (\u201cup-\nclassification\u201d) , e.g. formerly class IIa -> then class III , benefit from Art. 120 para 3  MDR ? \n Answer:  Yes, under the conditions specified in Art. 120 para 3 MDR (e.g. valid AIMDD/MDD certificate ). Devices which are in a \ndifferent respectively higher risk class in MDR than under the Directives are not as such excluded from the scope of Art. \n120 para 3  MDR . \n   \n16 Question:  If, according to Art. 120 para 3 MDR, a MFR intend s to place  a MDD/ AIMDD compliant device  on the market after the \nDoA, that , under the MDR , will be subject to an \u201cupgrade\u201d in risk class  (\u201cup-classification\u201d) , what is the relevant risk \nclass  with regard to the applicable MDR requirements  listed in Article 120 para 3  MDR (e.g. PSUR)?  \n Answer:  The risk class under MDD/AIMDD . \n   \n17 Question:  What are the requirements  for the placing on the market/putting into service of MDD/AIMDD compliant devices  \naccording to Art. 120 para 3 MDR  after DoA? \n Answer:  See Art. 120 para 3 MDR.  \nIn short:  \n1. A valid AIMDD/MDD  certificate according to Art. 120 para 2 MDR  \n[All certificates necessary for the placing on the market of the device in question need to be valid , e.g. a class III \ndevice needs to have a valid QMS as well as product specific certificate .] \n2. Continuous compliance of the device  with the Directives    \nPage 10 of 13 \n 3. No signif icant changes  in the design and intended purpose  \n[If there is a significant change in either the design or the intended purpose , Art. 120 para 3  MDR cannot be \nclaimed .  Qualification  of a change as \u201csignificant \u201d according to Art. 120 para 3 MDR shall be determined on a \ncase by case basis. However,  \n- limitations of the intended purpose  \n- design changes related to corrective actions  assessed and accepted by the Competent Authority  \nare not considered \u201c significant \u201d in the sense of Art. 120 para 3 MDR. . \n4. Appl ication of MDR requirements  in place of the corresponding requirements of the Directives with regard to:  \na. Registration of economic operators and of devices   \n(see Art. 31 MDR and Art. 29 MDR)  \nb. Post market surveillance  (PMS)  \n(see Art. 83 -86, 92 MDR including Annex III but without the PMS having to be an integral part of the QMS)  \nc. Market surveillance   \n(see Art. 93 \u2013 100 MDR, but device s tandards to be met = Directives ) \nd. Vigilance   \n(see Art - 87-92 MDR)  \nHowever exceptions are possible in the case that EUDAMED is no t fully functional in time (then see Art. 123 \npara 3 d and e MDR).  \n \nMoreover, the \u201cold\u201d NB which issued the AIMDD/MDD certificate shall continue to be responsible for the appropriate \nsurveillance of all the applicable requirements relating to the devices it has certified. This should be agreed on between the \n\u201cold\u201d NB and the MFR on a contractual basis . \n   \n \n   \nPage 11 of 13 \n IV - Issue: The so called \u201csell off\u201d  provision  of Art. 120 para 4 MDR  \n18 Question:  What is the so called \u201csell off\u201d provision (Art. 120 para 4 MDR) about?  \n Answer:  It is intended to  limit the time  during which AIMDD/MDD compliant devices, that have already been placed on the \nmarket (either before the DoA or by virtue of Art. 120 para 3 after the DoA) , may be made available  e.g. by a \ndistributor . \nAfter May 27, 2025 these devices may not be made available/put into service (= deadline) . If such devices are still within \nthe supply chain by this date - i.e. have not reached the final user as being ready for use (e.g. the hospital) - they are not \n\u201cmarketable\u201d any more.  \n \nThis provision is thus primarily dealing with the \u201cmaking available\u201d  of AIMD/MDD compliant  devices once they have \nbeen placed on the market , e.g. within the supply chain . It does not apply to  the \u201cplacing on the market\u201d  of these \ndevices by the MFR . \n \nPlease  also note, that this provision is not intended to apply to second hand sales  (see recital 3).  This means , once a \ndevice has been made available to the final use r (e.g. the hospital) as being ready for use, the further making available  \nof this device is not subject to/covered by the MDR.  \n   \n19 Question:  Does Art. 120 para 4 MDR enable MFRs to place MDD/AIMDD compliant devices  on the market until May 27, 2025? \n Answer:  No. Art. 120 para 4 MDR is not applicable to  the \u201cplacing on the marke t\u201d of MDD/AIMDD compliant devices (see question \n18). The only way to place MDD/AIMDD compliant devices on the market after DoA is Art. 120 para 3  MDR (see \nquestion s 12-17). Given th at MDD/AIMDD certificate s will no longer be  valid after May 27 2024 , this option ceases to \nexist from that date onwards .  \n   \n   \nPage 12 of 13 \n V \u2013 Issue: EUDAMED  and its relevance for the application of certain provisions of the MDR \n(Art. 123 para 3 d and e, Art. 120 para 8, Art. 122 MDR)  \n20 Question:  Do all devices  have to be registered according to Art. 29 para 4 MDR  by the DoA? \n Answer:  No. Even if EUDAMED is  fully functional at the DoA there will be a n 18-month \u201cinterim  phase \u201d (= EUDAMED fully \nfunctional but Art. 29 para 4 MDR not yet applicable) during which the different devices to be placed on the market may \nbe registered \u201cstep by step\u201d  in EUDAMED  accordin g to Art. 29 para 4 MDR instead of nationally according to the \nDirectives (see Art. 123 para 3 e  and Art. 120 para 8 MDR) . However , at the end  of this \u201cinterim  phase \u201d it must be \nensured that  all devices of a MFR\u2019s portfolio have been registered in EUDAMED.  \n \nIf EUDAMED is not fully functional  until a date after the DoA,  the 18 -month \u201cinterim phase\u201d will be postponed accordingly \n(beginning at the later of the dates referred to in point d) of Art. 123 para 3 MDR).  \n   \n21 Question:  Must  NBs have entered all the certificate related information of all devices  according to Art. 56 para 5 MDR into \nEUDAMED by the DoA ? \n Answer:  No. Even if EUDAMED is fully functional at the DoA there will be an 18-month \u201cinterim phase\u201d  (= EUDAMED fully \nfunctional but Art. 56 para 5 MDR not yet applicable) during which the relevant information according to Art. 56 para 5 \nMDR may be registered in EUDAMED \u201cstep by step = certificate by certificate\u201d instead of nationally acco rding to the \nDirectives (see Art. 123 para 3 e and Art. 120 para 8 MDR). However , at the end of this \u201cinterim phase\u201d it must be \nensured that all the relevant data regarding all certificates  have been  registered in EUDAMED.  \n \nIf EUDAMED is not fully functio nal until a date after the DoA, the 18 -month \u201cinterim phase\u201d will be postponed accordingly \n(beginning at the later of the dates referred to in point d) of Art. 123 para 3 MDR).  \n    \nPage 13 of 13 \n 22 Question:  What happens if EUDAMED  is not fully functional  at the DoA?  How does this affect the application of obligations and \nrequirements of the MDR that relate to EUDAMED ? \n Answer:  The relevant provisions to refer to  are mainly Art. 123 para 3 d and e . \n \nArt. 123 para 3 d MDR:  \nThe different Articles  listed in Art. 123 para 3 d  (= dealing with e.g. the registration of devices and economic operators, \nclinical investigations, notified bodies, vigilance, post -market surveillance, market surveillance) are not fully  postponed \nwith regard to their applicati on but generally  remain applicable  from the DoA. However , their application is postponed as \nfar as  the obligations and requirements within these Articles relate to EUDAMED (which is not fully functional yet). To \nthat extent  they shall apply  from the date c orresponding to 6 months after the date of notice of full functionality . \nMeanwhile ( until EUDAMED is fully functional ) the corresponding provisions of the Directives regarding exchange of \ninformation  continue to apply .  \nThe principle is that the derogation applies to the electronic exchange of information/upload to EUDAMED. If the \nderogation is applicable this does not necessarily mean that the information itself does not need to be \nprepared/exchanged. This exchange of in formation e.g. reports will have to be done by other means in lieu  of exchange \nvia EUDAMED (Directives regime ). The underlying idea behind this paragraph was to ensure  compliance with the new \nobligations and requirements via the \u201cold\u201d systems  as far as pos sible.  \n \nThe actual practical implication of this concept with regard to the different Articles listed in Art. 123 para 3 d MDR needs a \ncloser look and further guidance , which is in progress.  \n \nArt. 123 para 3 e MDR : \nFor the application of Art. 29 para 4 MDR and Art. 56 para 5 MDR  in the case that EUDAMED is not fully functional in \ntime, see question  20 and 2 1."}, {"title": "ivd_mfr_stepbystep.pdf.txt", "text": "MEDICAL DEVICES  CHANGE OF LEGISLATION\nInternal market, \nIndustry,  \nEntrepreneurship  \nand SMEs1STEP  INTENTION / ACTION\nPre-assessmentBrief management to ensure a clear understanding of the importance and  \nbusiness implications of the IVDR\nConsider organisational challenges: management awareness, staffing capability \nand availability, budget implications\nGAP analysis and actions  \nresulting from thisAssess impact on products, internal resources, organisation and budget\nCheck new classification rules (IVDR Classes A\u2013D) and confirm conformity assess -\nment routes for existing and future products. Check the requirement for involving the \nNotified Bodies\nReview the changes needed to existing technical documentation (Technical Files)\nReview and upgrade quality management system (QMS) (point 3 below)\nCheck the adequacy of available clinical evidence and risk management and \nidentify any gaps (Article 56)\nReview product labelling (Annex I Chapter III)\nEnsure post-market surveillance (PMS) arrangements are adequate (Chapter VII \nSection 1)\nPrepare a post-market performance follow-up plan (PMPF, Annex XIII Part B) \nGet ready for the new vigilance requirements (Chapter VII Section 2)\nEnsure the respect of traceability obligations (Chapter III)\nQuality Management  \nSystem (QMS)Review adequacy of QMS to meet standards and processes for IVDs under the \nnew Regulation\nBuild new regulatory requirements into the QMS\nIdentify/hire the person responsible for regulatory compliance within your  \norganisation (Article 15) and be sure it is adequately qualified and trained1\n2\n3What you need to know!Implementation Model for\nIn-Vitro Diagnostic Medical \nDevices Regulation  \nStep by Step Guide\nRef. Ares(2018)3873813 - 20/07/20182Legal entitiesClarify how the company is affected: legal entities, obligation of economic  \noperators, organisational structures and resources\nConsider organisational challenges: management awareness, staffing capability \nand availability, budget implications\nEnsure product liability insurance is adequate\nPortfolioDo a cost/benefit analysis for your product portfolio; bear in mind costs related \nto the new risk classification system and the need of involving a Notified Body \nand costs for post-market surveillance and gaps in the technical documentation, \nand plan your transition to the IVDR accordingly\nReview supply chain provisions, and clarify roles and responsibilities of business \npartners (authorised representatives, importers, distributors)\nMaster implementation \nplanBuild a roadmap for implementation, including definition of sub-projects, re -\nsource requirements and a steering group, and ensure overall responsibility for \nIVDR implementation has been established\nGive special consideration to certificate expiry dates, bearing in mind the transi -\ntional period, transitional provisions and availability of your Notified Bodies\nNotified BodiesContact the selected Notified Bodies and determine their capacity and  \navailability to service the implementation plan \nRegulatory trainingEmpower and train staff through IVDR implementation and transition workshops\nExecute master  \nimplementation planImplement the various sub-projects (performance evaluation, technical  \ndocumentation, relations with other economic operators, Unique Device Identifica -\ntion, labelling, post-market surveillance, vigilance, and reporting IT systems)\nEnsure a cross-functional project management team is in place to cover all \naspects of implementation\nEnsure overall and individual responsibilities for IVDR implementation have been \nestablished\nReview efficiency and  \neffectivenessImplement regular meetings on project status and progress, discrepancy and \ngap analyses, risks, next steps and requirements\nHold regular progress reviews against the IVDR implementation plan and include \nthese in the management review process\nNotified Body submissionDiscuss submission dates to avoid delays in the approval process\nOngoing monitoringActively monitor the still-developing European regulatory environment and \nguidelines expected in the coming months (check DG GROW web pages on  \nmedical devices and subscribe to the newsletter)\nEstablish a procedure for dealing with unannounced inspections from Notified Bodies \nRegularly review the IVDR implementation plan, identifying and addressing key \nareas of risk4\n5\n6\n7\n8\n9\n10\n11\n12\n\u00a9 European Union, [2018]  Reuse is authorised provided the source is acknowledged.\nThe reuse policy of European Commission documents is regulated by Decision 2011/833/EU (OJ L 330, 14.12.2011, p. 39).\nISBN: 978-92-79-89124-3    DOI: 10.2873/41862\nET-04-18-659-EN-N"}, {"title": "scheer_o_015.pdf.txt", "text": "Final Version  \n \nGuidelines on the benefit -risk assessment of the presence of phthalates in certain \nmedical devices  \n  \n \n \n \n \n \nScientific Committee on Health, Environmental and Emerging Risks  \nSCHEER  \n \nGUIDELINES   \non the benefit -risk assessment of the presence of  \nphthalates in certain medical devices  \ncovering phthalates which are carcinogenic, mutagenic, toxic to \nreproduction (CMR) or have endocrine -disrupting (ED) \nproperties  \n \n \n \n \n \nThe SCHEER adopted this document at plenary meeting on 18 June 2019  \n  \nGuidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n2 \n ABSTRACT  \nThe SCHEER was requested to provide Guidelines on the benefit -risk assessment (BRA)  \nof the presence, in the medical devices specified in the regulation , of phthalates , which \nhave one or more of the following properties: carcinogenic, mutagenic, toxic to \nreproduction (CMR) or endocrine -disrupt ing (ED), according to the criteria outlined in the \nlegal obligation section from the mandate.  \n  \nPhthalates are widely used in industry as plastici sers of polymers, in a variety of \napplications such as coated fabrics and roofing membranes, as well as in me dical \ndevices, adhesives, paints, inks and enteric -coated tablets. Di -(2-(ethylhexyl) phthalate \n(DEHP) is the most widely used phthalate in medical devices. Dimethyl phthalate (DMP) \nand diethyl phthalate  (DEP) are not used as plasticis ers but e.g. as addit ives in \ncosmetics, medical devices, and household products.  \nThe interaction of phthalates with the polymers they are embedded in is weak, so they \nmay be released from the plastic product into the environment and into the human body \nif the product is in con tact with it.  \n \nThe Medical Device Regula tion, Regulation (EU) 2017/745 allows the use of CMR 1A/1B \nand/or ED substances in medical devices above a concentration of 0.1% w/w. when a \nproper justification can be provided (Annex I, Chapter II Section  10.4). Fo r such a \njustification several steps need to be considered including  the availability  of alternative \nsubstances, materials, designs, and medical treatments. In addition, the risk associated \nwith such alternatives should be weighed against the risk of the u se of CMR 1A/1B and/or \nED identified phthalates covered under MDR Annex I Chapter II Section  10.4.1 . However, \nthe risk by itself is not the only parameter to consider:  also the impact of the possible \nalternatives on the functionality, performance and the overall benefit -risk ratio of the \nmedical device shall be evaluated.  \n \nThese Guidelines describe the methodology on how to perform a BRA for the justification of \nthe presence of CMR 1A or 1B and/or ED phthalates (CMR/ED phthalates) in medical devices \nand/or or parts or materials used therein  at percentages above 0.1% by weight (w/w).  \nThey also describe  the evaluation of possible alternatives for these phthalates used in \nmedical devices , including  alternative materials, designs or medical treatments .  \nThey are intended to be used by the relevant stakeholders e.g. manufacturers, notified \nbodies and regulatory bodies.  \nThe approach of these Guidelines may also be used for a BRA of other CMR/ED \nsubstances present in medical devices.  \n \nDuring the preparation of these Guidelines for BRA of the use of CMR/ED phthalates in \nmedical devices, SCHEER noticed that a number of BRA methodologies are theoretically \navailable. However , there is a considerable lack of data  needed for the BRA  for potential \nrelevant  alternatives to be used in medical devices. Therefore, SCHEER encourages \nmanufacturers to generate data of high quality on  such alternatives  for CMR/ED \nphthalates in medical devices.  \nPending on new scientific evidence, it is recommended to evaluate the use and \nusefulness of these Guidelines after an application  period of three years.  \n \nKeywords: Guidelines, benefit -risk assessment , CMR/ED phthalates, medical devices, \nSCHEER . \nGuidelines  to be cited as:  SCHEER (Scientific Committee on Health, Environmental and \nEmerging Risks), Guidelines on the benefit -risk assessment of the presence of phthalates \nin certain medical devices  covering phthalates which are ca rcinogenic, mutagenic, toxic \nto reproduction (CMR)  or have endocrine -disrupting (ED) properties, final version \nadopted at  SCHEER plenary on 18 June 2019.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n3 \n  \nACKNOWLEDGMENTS  \n \n \nMembers of the Working Group are acknowledged for their valuable contribution to this \nopinion. The members of the Working Group are:  \n \nSCHEER members:  \nTeresa Borges  \nRodica Mariana Ion  \nWim H. de Jong    (Chair and Rapporteur)  \nDemosthenes Panagiotakos   \nEmanuela Testai  \nTheo Vermeire  \n \n \nSCCS members:  \nUlrike Bernauer  \nChristophe Rousselle  \n \n \nExternal experts:  \nSt\u00e9phane B\u00e9gu\u00e9  (Etablissement Fran\u00e7ais du Sang, EFS, Paris, France)  \nHilde B. M. Kopperud  (Nordic Institute of Dental Materials, Oslo, Norway)  \nMaria Rosaria Milana   (Istituto Superiore di Sanit\u00e0, Dip. Ambiente e Salute, Roma, Italy)  \nTanja Schmidt   (Ansbach University of Applied Science,  Ansbach,  Germany)  \n \n \nExperts from EU Agencies : \nFrancesco Pignatti   (European Medicines  Agency ) \nEvgenia Stoyanova   (European Chemicals Agency ) \nKatarina Volk    (European Food & Safety Authority ) \n  \n \n \n \n \nAll Declarations of Working Group members are available at  the following webpage:  \nhttp://ec.europa.eu/health/scientific_committees/experts/declarations/scheer_wg_en   \n \n \n \n \n \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n__________________________________________________________________________________\n4About the Scientific Committees (2016 -2021)  \nTwo independent non -food Scientific Committees provide the Commission with the \nscientific advice it needs when preparing policy and proposals relating to consumer \nsafety, public health and the environment. The Committees also draw the Commissio n's \nattention to the new or emerging problems which may pose an actual or potential threat . \nThey are: the Scientific Committee on Consumer Safety (SCCS) and the Scientific \nCommittee on Health, Environmental and Emerging Risks (SCHEER). The Scientific \nComm ittees review and evaluate relevant scientific data and assess potential risks. Each \nCommittee has top independent scientists from all over the world who are committed to \nwork in the public interest. \nIn addition, the Commission relies upon the work of other Union bodies, such as the \nEuropean Food Safety Authority (EFSA), the European Medicines Agency (EMA), the \nEuropean Centre for Disease prevention and Control (ECDC) and the European Chemicals \nAgency (ECHA).  \nSCHEER  \nThis Committee, on request of Commission services, provides Opinions on questions \nconcerning health, environmental and emerging risks. The Committees addresses \nquestions on: \n-health and environmental risks related to pollutants in the environmental media  and\nother biological and physical factors in relation to air quality, water, waste and soils.\n-complex or multidisciplinary issues requiring a comprehensive assessment of risks to\nconsumer safety or public health, for example antimicrobial resistance, n anotechnologies,\nmedical devices and physical hazards such as noise and electromagnetic fields.\nSCHEER members  \nRoberto Bertollini, Teresa Borges, Wim de Jong, Pim de Voogt, Raquel Duarte -Davidson, \nPeter Hoet, Rodica Mariana Ion, Renate Kraetke, Demosthen es Panagiotakos, Ana \nProykova, Theo Samaras, Marian Scott , Remy Slama, Emanuela Testai, Theo Vermeire, \nMarco Vighi, Sergey Zacharov  \nContact  \nEuropean Commission  \nDG Health and Food Safety  \nDirectorate C: Public Health, Country Knowledge, Crisis management  \nUnit C2 \u2013 Country Knowledge and Scientific Committees \nOffice: HTC 03/073   L -2920 Luxembourg\nSANTE- C2-SCHEER@ec.europa.eu   \nISBN 978-92-76-15387-0\u00a9 European Union, 2020 \nISSN 2467-4559\ndoi: 10.2875/784367 EW-CA-20-001-EN-N\nThe Opinions of the Scientific Committees present the views of the independent scientists \nwho are members of the committees. They do not necessarily reflect the views of the \nEuropean Commission. The Opinions are published by the European Commission in their \noriginal language only. \nhttp://ec.europa.eu/health/scientific_committees/policy/index_en.htm  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n5 \n  \nTABLE OF CONTENTS  \n \nACKNOWLEDGMENTS  ................................ ................................ ................................ ...........  3 \nA. GUIDELINES on benefit -risk assessment for CMR and/or endocrine -disrupting phthalates \nused in medical devices  ................................ ................................ ..............................  6 \n1. Introduction  ................................ ................................ ................................ ..............  7 \n2. Framework for Benefit -Risk Assessment  ................................ ................................ ..... 10 \n3. Assessment of the presence of phthalates in a medical device  ................................ ....... 15 \n4. Assessment of possible alternative substances, materials, designs or medical treatments  . 18 \n5. Assessment of potential relevant alternative substances, materials, designs or medical \ntreatments versus CMR/ED phthalates  ................................ ................................ ........  23 \n6. Justification for the use of CMR/ED phthalate  ................................ ..............................  25 \n7. Benefit assessment  ................................ ................................ ................................ .. 27 \n7.1 Material benefit  ................................ ................................ ................................ ....... 28 \n7.2 Clinical benefits  ................................ ................................ ................................ ....... 28 \n8. Methodologies for Benefit \u2013Risk Assessment  ................................ ...............................  29 \n9. Uncertainty analysis  ................................ ................................ ................................ . 30 \n10. Conclusions  ................................ ................................ ................................ .............  34 \n11. Consideration of the responses received during the public consultation process  ...............  35 \nB. REFERENCES  ................................ ................................ ................................ ...........  36 \nC. ANNEXES  ................................ ................................ ................................ ................  40 \nAnnex  1: SCHEER mandate on benefit -risk assessment on the use of CMR/ED phthalates  ...........  40 \nAnnex 2: Medical Device Regulation (Regulation 2017/745) on CMR and/or ED substances  .........  44 \nAnnex 3: Definitions/descriptions \u2013 References - Glossary  ................................ .......................  45 \nAnnex 4: CMR and/or ED substances  ................................ ................................ ....................  51 \nAnnex 5: Legislation on CMR and/or ED phthalates  ................................ ................................ . 53 \nAnnex 6: Use of phthalates in medical devices  ................................ ................................ ....... 57 \nAnnex 7: Approaches for Benefit -Risk Assessment  ................................ ................................ .. 60 \n \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n6 \n  \nA. GUIDELINES  on benefit -risk assessment  for CMR and/or endocrine -\ndisrupting phthalates used in medical devices  \n \nScope  \nThe Regulation  (EU) 2017/745 on m edical devices (MDR), Annex I \u201cGeneral Safety and \nPerformance Requirements\u201d, Chapter II \u201cRequirements regarding design and \nmanufacture\u201d, Section  10.4 deals with the presence of substances that may be released \nfrom a medical device. Annex I Chapter II Section  10.4.1 state s that substances that are \ncarcinogenic, mutagenic, or reprotoxic (CMR) of category 1A and 1B, or substances \nhaving endocrine -disrupting (ED) properties for which there is scientific evidence of \nprobable serious effects on humans, shall only be present in device s, or parts thereof or \nthose materials used therein , above 0.1% weight by weight (w/w) when justified \naccording to a set of criteria listed under Section  10.4.2.  \nThese Guidelines1 describe the methodology on how to perform a BRA for the justification \nof the presence of CMR 1A or 1B and/or ED phthalates (CMR/ED phthalates) in medical \ndevices at percentages above 0.1% by weight (w/w). They also describe the evaluation \nof possible alt ernatives for these phthalates used in medical devices , including  alternative \nmaterials, designs or medical treatments . They are intended to be used by the relevant \nstakeholders e.g. manufacturers, notified bodies and regulatory bodies.  \nThese Guidelines apply to those medical devices and components thereof indicated in \nAnnex I section 10.4.1.of the MDR . They do not provide information for the BRA of the \nuse of a medical device itself . However, the BRA as described can be integrated within \nthe risk management system for individual medical devices. For the BRA of medical \ndevices in general, stakeholders are referred to  section A7.2. of MEDDEV 2.7/1, revision \n4. Additional information may be found elsewhere, for example in the following \ndocuments  FDA 2 016, 2018, EN ISO 14971,  ISO/TR 24971. It should be noted that the \nacceptability of any risk is evaluated in relation to the benefit of the use of the medical \ndevice.  \nWhen the word \u201cpatient\u201d is used in these Guidelines, this also covers  professional users  \nand other persons (e.g. donors in case of blood donation) exposed to the medical device \nas well.  \nAnnex 1 to these Guidelines describes the mandate, Annex 2 describes Annex I Chapter \nII Section  10.4. of the MDR regarding the use of substances  that could be  released from \nthe medical device and pose a risk to patients,  and Annex 3 describes the definitions \nused in these Guidelines.  \n \n \n \n                                                           \n1 It should be noted that, in accordance with Regulation (EC) 2017/745, Annex I, Chapter II Section 10.4.3. \nand 10.4.4., updates of these Guidelines might be available in the future.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n7 \n  \n1. Introduction  \n \nPlacing medical devices  on the market,  making them available on the market and putting \nthem into service are all activities governed by Regulation (EU) 2017/745 that replaces \nDirective s 90/385/EEC and  93/42/EEC . Medical devices are defined in the MDR as \npresented in the text box below:  \nFor the purposes of this Regulation, the following definitions apply  \n(1) \u2018medical device\u2019 means any instrument, apparatus, appliance, software, implant, \nreagent, material or other article intended by the manufacturer to be used, alone \nor in combination, for human beings for one or more of the following specific \nmedical purposes :  \n\u2014 diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of \ndisease,  \n\u2014 diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or \ndisability,  \n\u2014 investigation, replacement or modification of the anat omy or of a physiological or \npathological process or state,  \n\u2014 providing information by means of in vitro examination of specimens derived from \nthe human body, including organ, blood and tissue donations, and which does not \nachieve its principal intended a ction by pharmacological, immunological or metabolic \nmeans, in or on the human body, but which may be assisted in its function by such \nmeans.  \nThe following products shall also be deemed to be medical devices:  \n\u2014 devices for the control or support of conce ption;  \n\u2014 products specifically intended for the cleaning, disinfection or sterilisation of \ndevices as referred to in Article 1(4) and of those referred to in the first paragraph of \nthis point.  \nAs a general requirement , the medical device shall perform acc ording to its intended \npurpose and be safe for professional  users and patients , or where applicable other \npersons (e.g. donor s) on which the device is used. The conformity of medical devices \nshall be evaluated against the requirements of the Regulation (EU) 2017/745. They shall \nbe presumed to be in conformity with this Regulation if they are in conformity with EU -\nharmonised standa rds or the relevant parts of those standards, the references of which \nhave been published in the Official Journal  of the European Union. Although not \nmandatory, these standards provide a route to comply with the MDR.  \nFor medical devices the horizontal standards EN ISO 14971 and EN ISO 10993 -1 are \nespecially relevant. EN ISO 14971 describes the application of a risk management \nprocess for medical devices, whereas EN ISO 10993 -1 deals with the biological evaluation \nand t esting of medical devices within a risk management process. According to EN ISO \n10993 -1, evaluation of the biological safety of a medical device should be a strategy Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n8 \n planned on a case -by-case basis to identify the hazards and estimate the risks of known \nhazards. In Annex A of EN ISO 10993 -1, a series of endpoints is indicated from which a \nselection can be made for the biological evaluation of a medical device. The selection is \nbased on the nature of the device's contact with the body (device category: surfa ce \ndevice, external communicating device, or implant device; type of contact: skin, mucosal \nmembrane, compromised surface, blood, tissues, organs; duration of the contact: limited \n\u226424 h, prolonged >24 h to 30 days, permanent >30 days). A systematic literat ure \nreview is part of the biological evaluation of a medical device in order to avoid \nunnecessary testing  (EN ISO 10993 -1). This systemic literature review should also be \nperformed for a CMR/ED phthalate or potential relevant alternatives identified for a given  \nin a medical device.  \nIn addition to EN ISO 10993 -1, a series of EN ISO 10993 standards has been published \ndescribing various assays and approaches for the evaluation of the endpoints identified in \nEN ISO 10993 -1 for the biological evaluation of medic al devices. Assays described in the \nvarious standards include cytotoxicity, sensitisation, irritation, systemic toxicity, \nimplantation, haemocompatibility, genotoxicity, and carcinogenicity endpoints.  \nAdditionally immunotoxicity and organ -specific toxiciti es need to be considered, if \nappropriate.  In addition, reproductive and developmental toxicity should be addressed for \nnovel materials, materials containing substances with a known reproductive or \ndevelopmental toxicity, medical devices with relevant targe t populations (e.g. pregnant \nwomen), and/or medical devices where there is the potential for local presence of device \nmaterials in the reproductive organs (EN ISO 10993 -1:2018). For the risk assessment EN \nISO 10993 -17 describes determination of allowable l imits for leachable substances, \nwhereas EN ISO 10993 -18 describes methods for chemical characterization of materials \nused in medical devices. In addition to the horizontal standards, vertical i.e. device \nspecific standards and standards for clinical investigation are available ( e.g. EN ISO \n14155).  \nFurthermore, the EU also provides guidance in MEDDEV documents (e.g. MEDDEV 2.7/1 \nrev.4 for clinical evaluation of medical devices).  \nThe MDR states that substances that are classified as carcinogenic, muta genic, or toxic to \nreproduction (CMR) of category 1A or 1B, or substances identified at EU level as having \nendocrine -disrupting (ED) properties for which there is scientific evidence of probable \nserious effects on humans  (CMR/ED substances, in this text) , shall only be present in a \ndevice s or parts thereof or those materials used therein  above 0.1% weight  by weight \n(w/w) when justified. Annex 4 provides further information on the classification of CMR \nand on identification of ED substances. The justificatio n for the use of CMR/ED \nsubstances in a medical device above 0.1% w/w, shall be based on an analysis of \npotential patient and user exposure, availability of possible alternatives, an \nargumentation why possible alternatives are appropriate or inappropriate,  and on the \nmost recent Guidelines of this Scientific Committee.  \nPhthalates are a group of substances widely used in medical devices. When  used as  \nplastici sers they may comprise a substantial part of the medical device. A typical \nconcentration of Bis(2 -ethylhexyl) phthalate (DEHP; CAS 117 -81-7) in plastici sed \npolyvinyl chloride (PVC) can be 30% based on weight (ECB 2008, SCENIHR 201 5). For \nmany years the reproductive toxicity and the possible endocrine disrupting activity of \ncertain phthalates has been a source for debate.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n9 \n Phthalates currently classified as reproductive toxicants category 1B under the \nClassification, Labelling and Pa ckaging (CLP) regulation (EC 1272/2008) and identified as \nsubstances of very high concern (SVHC)  under Article 57 (c) of REACH Regulation (EC) \n1907/2006 are listed in Annex 5  of this document . This list may be updated, so it is \nrecommended to consult the An nex VI of the CLP Regulation.  \nIn addition, the Commission Implementing Decision (EU) 2017/1210 and Commission \nImplementing Decision (EU) 2018/636 identified some phthalates as substances of very \nhigh concern (SVHC) according to Article 57(f) of REACH Regu lation (EC) 1907/2006,  \ndue to their endocrine disrupting properties with probabl e serious effects to humans, \nnamely Bis(2 -ethylhexyl) phthalate (DEHP), Benzyl butyl phthalate (BBP), Dibutyl \nphthalate (DBP) , Diisobutyl phthalate (DIBP) , and Dicyclohexylphthalate  (DCHP) . Bis(2-\nethylhexyl) phthalate (DEHP), was also identified in 2014 as a substance of very high \nconcern in  accordance with Article 57(f) of Regulation (EC) 1907/2006 (REACH) because \nit is a substance with endocrine disrupting prop erties for which there is scientific evidence \nof probable serious effects to the environment which give rise to an equivalent level of \nconcern to those of other substances listed in points (a) to (e) of Article 57 REACH. \nhttps://echa.europa.eu/documents/10162/21837b30 -0318-8b45-92db-9e8c39f89dee  \nSCENIHR adopted an Opinion on the safety of medical devices containing DEHP -\nplasticised PVC in 2008, and a revision of this  Opinion in 201 5 (SCENIHR 2008, 201 5). \nThe main source for DEHP exposure of the general population was determined to be food. \nIn addition, the use of medical devices can increase the exposure considerably in the \ncourse of specific medical treatments, for e xample during massive blood transfusions, \nhaemodialysis, and in neonatal intensive care units (NICU) for prematurely born \nneonates (SCENIHR 201 5). Although quite a number of alternative substances were \navailable for DEHP, for some of them serious data gaps were observed regarding hazard \nidentification and exposure estimation (Bui et al., 2016, SCENIHR 201 5). The Danish EPA \nassessed different alternatives and concluded that to various degrees some substances \ncan be considered to be relevant alternatives to DEHP in terms of human health hazards, \nespecially regarding the endpoints reproductive and developmental toxicity (Nielsen et al. \n2014). However, for a number of possible alternatives the data set was limited. Some \nalternatives showed a low  migration rate and some of them are already used as \nsubstitutes in medical devices for traditional DEHP -applications. For example, four \nadditional plasticisers for PVC (BTHC, DEHT, DINCH, and TOTM) used in medical devices \nhave recently been included in th e updated chapters of the European Pharmacopoeia \n(Council of Europe, EDQM 2018).  \nPhthalates classified as CMR of category 1A or 1B according to the procedure described in \nAnnex 4 are listed in Annex VI of the CLP regulation (CLP -Regulation (EC) No 1272/200 8, \nOJ L353). According to  article 57 (f) of REACH (Regulation (EC) 1907/2006) or the \nBiocides Regulation ( Regulation (EC)  528/2012) phthalates can be identified as having \nED-properties when  there is scientific evidence of probable serious effects to human \nhealth .  \nThese Guidelines provide a framework of how to perform a BRA for the presence of such \nCMR and/or ED phthalates in medical devices or parts or materials used therein at \npercentages above 0.1% weight by weight (w/w) , and shall be used by all relevant \nstakeholders, e.g. manufacturers and notified bodies, and regulatory bodies for the \njustification of the presence of CMR/ED phthalates . The evaluation according to the Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n10 \n Guidelines should be performed by a multidisciplinary team including amongst others  e.g. \na material scientist, medical device specialist, toxicologist and clinician.  \nA justification for the use of a CMR/ED phthalate can also be based on an already \navailabl e justification relating to a medical device for which equivalence with the device \nin question can be demonstrated according to the MDR Annex XIV Section 3. The existing \njustification can be used as a reference, and the data used for this justification sho uld be \navailable . \nThe approach of these Guidelines can also be u sed for a BRA of other CMR/ED substances \npresent in medical devices.  \nOther descriptions for BRA may be \u201cbenefit -risk analysis\u201d or \u201cbenefit -risk determination\u201d \nas defined in the MDR. As Annex I Section 10.4.3 indicates a benefit -risk assessment this \nterminology is used in these Guidelines.  \n \n \n2. Framework for Benefit -Risk A ssessment   \n \nThe MDR allows the use of CMR 1A/1B and/or ED substances in medical devices above a \nconcentration of 0.1% w/w when a proper justification can be provided ( MDR Annex I, \nChapter II  Section  10.4). For such a justification several steps need to be considered \nincluding the availability  of alternative substances, materials, designs, and medical \ntreatments. In addition, the r isk associated with such alternatives shall be weighed \nagainst the risk of the use of CMR 1A/1B and/or ED identified phthalates covered  under \nMDR Annex I Chapter II Section  10.4.1. However, the risk is not the only parameter to \nconsider . The impact of the possible alternatives on the functionality, performance and \nthe overall benefit -risk ratio of the medical device should also be evaluated.   \nThe justification for the presence of CMR 1A or 1B and/or ED phthalates for which there \nis scientific evidence of probable  serious effects on humans should be based on a number \nof considerations as described below and in Figure 1 .  \nIn order to perform the BRA as indicated above , it is important to describe the \nterminology to compare the risk s of the presence of the phthalates  to be evaluated (see \ntext box below). Annex 3  provides  a selection of definitions as present in the MDR and/or \nthe OECD Substitution and Alternatives Assessment Toolbox. (http://www.oecdsaatoolbox.org/ ) \nFor the purpose of these Guidelines the following definition for \"alternatives\" is used:  \n\u201calternatives  are defined as substances, materials, designs  and medical treatments  that \ncan be used to replace the use of CMR and/or ED  substances in medical devices\u201d  \nThe alternative therefore is not limited to a possible substitute substance or material but \ncould also be another device design (e.g. coating/production process/ techniques /lower \nconcentration  of substances)  or medical treatment (e.g. procedure, device) or a \ncombination of technical and substance alternatives that can substitute or eliminate the \nuse of the CMR/ED phthalate (modified from the ECHA REACH guidance on the \npreparation of an application for authori sation).  \nThe functionality and performance of the alternative should  be comparable to the extent \nthat there would be no clinical ly relevant  difference foreseen in the performance of the Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n11 \n device or in the outcome of the alternative medical procedure. Conside rations of \nfunctionality and performance shall be based on proper scientific justification. In order to \njustify the use of a CMR 1A or 1B and/or ED phthalate, the manufacturer shall clearly \ndemonstrate that the identified alternative(s) are not appropriate  to maintain the \nfunctionality, performance and benefit -risk ratios of the medical device.  \nA number of aspects need to be considered for the justification of the presence of a \nphthalate classified as CMR category 1A or 1B and/or identified as ED above  content > \n0.1% w/w in a medical device , or parts thereof or those materials used therein, as \nintended to be used.   \nIn summary, these aspects can be considered by a stepwise approach given below and \npresented in Figure 1. Further details and examples on the steps used in the Guidelines \nare given in the following chapters.  \nAssessment of the CMR/ED phthalate  (CMR/ED scenario)  \nStep 1:  \nDescription and characterisation of the composition of the medical device  (or parts \nor materials thereof) . Identif ication  of the  presence and concentration of CMR/ED \nphthalate (s) in weight by weight percentage (% w/w) . \n \nStep 2:  \nDescription of the use and function of the CMR/ED phthalate used in medical \ndevice.  \n2a. Description of functionality/performance provided by the presence of the \nCMR/ED phthalate.  \n2b. Description of the benefit (material and/or clinical) of the presence  of CMR/ED \nphthalate in the medical device.  \n \nStep 3:  \nAssessment of the risks of the CMR/ED phthalate.  \n3a. Determin ation of  the patient exposure based on realistic worst -case2 use \nscenario  in the intended use . \n3b. Identif ication of  biocompatibility, general toxicological and specific CMR/ED \nhazards associated with the phthalate.  \n3c. Determin ation of  the maxim um tolerable/ acceptable exposure for the patient,  \nbased on pre -clinical and clinical information (if available).  \n3d. Determination of the risks for various intended  use scenarios and patient \ngroups.  \n \nAssessment of possible alternative (s) (non CMR/ED  phthalate scenario)  \nStep 4:  \nInventory of possible alternative (s).  \n4a. Substances.  \n4b. Materials.  \n                                                           \n2 Realistic worst case is the situation where the exposure is estimated us ing a range of factors (i.e. duration, \namount, exposure controls), where applicable, the ones that would be expected to lead to maximum amount of \nexposure (e.g. exposure might be assessed under realistic simulated -use scenarios by EN ISO 10993 -12 and \nEN IS O 10993 -18 or a non-volatile  residue test (USP <661>)). The realistic worst case does not include \ndeliberate misuse. (EU Biocides Regulation 528/2012).  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n12 \n 4c. Designs and/or medical treatments3. \n \nStep 5:  \nIdentification of the potential relevant candidates for assessment as alternatives \nto CMR/ED  phthalates and justification for the selection and exclusion of possible \nalternatives.  This also includes assessment of the availability of the potential \nalternative (s). \n \nStep 6:  \nDescription of identified potential relevant alternative(s).  \n6a. Description of functionality and performance  of the potential alternative(s).  \n6b. Description of the benefit (material and/or clinical) of the use o f the potential \nalternative(s).  \n \nStep 7:  \nAssessment of the risk of identified potential relevant alternative (s). \n7a. Determination of patient exposure o f the alternative based on a realistic \nworst -case use scenario in the intended use.  \n7b. Identification, where available, of biocompatibility, toxicological and CMR/ED \nhazards associated with the alternative.  \n7c. Determination of maximum tolerable/acceptabl e exposure of the alternative \nfor patient (if available).  \n7d. Determination of risk of potential alternatives for various use scenarios and \npatient groups.  \n \nAssessment of potential relevant alternative (s) versus CMR/ED phthalate  \nStep 8:  \nComparison of functionality and performance of CMR/ED phthalate as used in the \nmedical device with functionality and performance of identified potential relevant \nalternative (s). \n \nStep 9:  \nComparison of hazard (s) of original CMR/ED phthalate as used in the medical \ndevice with hazard (s) of identified potential relevant alternative (s). \n \nStep 10:  \nComparison of benefit and risk of CMR/ED phthalate used in the medical device \nwith identified potential relevant alternatives.  \n \nIn addition to patients, the same  approach shall be used for the justification of the \npresence of CMR/ED phthalate in medical devices to evaluate the risk for professional \nusers and for other persons (e.g. donors) exposed to the CMR/ED phthalates. When \nalternative designs or medical treat ments were identified as potential alternatives in step \n5, adequately adopted endpoints for risks and benefits shall be chosen.  \nIt should be noted that scientific developments may be available after the initial \nassessment regarding the use of alternatives for CMR/ED phthalates . Therefore, a \n                                                           \n3 It should be noted that for alternative designs and/or medical treatments, appropriate endpoints for r isks and \nbenefits shall be selected.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n13 \n revision of the BRA of the presence of the CMR and/or ED phthalate may be necessary. \nRevisions of the above indicated BRA shall occur as indicated in the relevant sections of \nMDR for the general risk assessment of the me dical device.   \nFigure 1 illustrates the BRA and is based on Eliason and Morose (2011), EMA (2014), FDA \n(2016) and a critical selection from the OECD Substitution and Alternatives Assessment \nToolbox ( http://www.oecdsaatoolbox.org ). It presents the stepwise approach described \nabove including a general description of factors to consider when performing a BRA.  \nFigure 1 presents a use scenario in which the CMR/ED is used in a medical device versus \na non -use scenario in which a proper potential alternative is evaluated.  \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n14 \n Figure 1 . BRA for evaluation of presence  of CMR/ED phthalates and their  \npotential alternatives in medical devices  (relevant sections between brackets) . \nStep 3 (3)\nUse scenario\nAssessment of the risks of phthalate\n3a. Exposure assessment patient\n3b. Biocompatibility, hazard assessment\n3c. Maximum tolerable /acceptable dose\n3d. Risk characterisation Step 4 (4)\nInventory of possible alternatives\n4a. Substitute substances\n4b. Substitute materials\n4c. Alternative designs/treatmentsDefine aim and \nscope\nStep 1 (3)\nDescription and characterisation of \ncomposition of medical device, \nIdentifIcation of presence and \namount of CMR/ED phthalate\nStep 2\nDescription of phthalate \n2a. Use, functionality and performance of \nphthalate (3)\n2b. Benefit (7)Step 5 (4) \nIdentification of  potential candidates for \nalternatives and justification for the \nselection and exclusion\nStep 6\nDescription of identified potential \nrelevant alternatives\n6a. Functionality, performance (4)\n6b. Material and clinical benefit of the \nuse (7)\nStep 7 (4)\nAssessment of the risks of Identified \npotential relevant alternative(s)\n7a. Exposure assessment patient or user\n7b. Biocompatibility, hazard assessment\n7c. Maximum tolerable /acceptable dose\n7d. Risk characterisation\nStep 8 (5)\nComparIson of  functionality,  \nperformance of use and non- \nuse scenario\nOverall summary report\nJustification for continued use of \nCMR/ED phthalate (6)Step 9 (5)\nComparison of hazard(s) of use \nand non-use scenario\nStep 10 (5,7, 8)\nComparison of benefit and risk \nof  use and non-use scenario\nUncertainty analysis (9)Non-CMR/ED \nphthalate \nscenarioCMR/ED \nphthalate \nscenario\n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n15 \n  \n3. Assessment of the presence of phthalates in a medical device4 \n \nIt is already necessary to provide most of the information as indicated for the use of \nCMR/ED phthalates in order to prove compliance with the general safety and \nperformance requirements for the phthalate containing medical device.  \n \nWhen more than one CMR/ED phthalate is used simultaneously in the medical device, a \njustification shall be provided for each of the phthalates and their combination.  Some risk \nassessment data regarding the combinat ion of phthalates are available, as EFSA has \nrecently proposed a Group TDI for some of them, having a similar Mode of Action (MOA) \nin vivo  (EFSA 2019, see Annex 5). Information on assessment of combined exposures to \nphthalates can be found for example at the report by the National Research Council \nCommittee on the Health Risk of Phthalates (2008) and the ECHA website on the  \nrestriction of f our phthalates ( https://echa.europa.eu/registry -of-restriction -intentions/ -\n/dislist/details/0b0236e180d73895 ) and EFSA guidance on cumulative expos ure (EFSA, \n2019 https://doi.org/10.2903/j.efsa.2019.5634 )  \n \nStep 1: Description and characterisation of the composition of the medical device.  \nProvide a description of the medical device and its composition including identification \nand the concentration of each CMR/ED phthalate in the device , and the type of chemical \n/physical binding of the phthalate in the formulation/device, when there is an impact on \nleakage.  Use available chemical information  for identifying target phthalates (e.g. CAS \nN\u00ba; EINECS N\u00ba; IUPAC name).  The chemical composition of a medical device can be \nevaluated by using e.g. EN ISO 10993 -18 (FDIS published in 2019) . \n \nStep 2: Use and function of CMR/ED phthalates in the medical dev ice.  \nCharacterise the function and use of the CMR/ED phthalates in the medical device and \nthe properties it imparts to the device. Provide a description of the intended use, \nfunctionality and performance of the medical device containing the CMR/ED phthala te \nand how the use of the phthalate is critical for its functionality and performance . For \nexample, for PVC consider, with regard to the performance of the medical device, \nmaintenance, flexibility, durability and for the phthalate viscosity and PVC compatibility. \nProvide a description of the patients targeted (e.g. with respect to sex, age, probable \nvulnerable groups5). Provide a description of use types of the medical device for which it \nis intended (e.g. single  vs repeated exposure ). Other aspects that can be relevant include \nthe critical properties (e.g., flexibility), the conditions of use, critical quality criteria, \nprocess/treatment and performance constraints (e.g., sterilization, device/drug \ninteractions), regulatory or clinical or other requi rements that the CMR/ED phthalates \nand the phthalate -containing device need to deliver. Key criteria for the function,  \n                                                           \n4 The analysis presented in section 3 (steps 1 -3) describes the current use scenario of the CMR/ED phthalate, \ni.e., the scenario that would continue in the future if no additional action (other than, e.g., a planned regulatory \naction entering into force) is taken to limit, substitute or eliminate the presence of the CMR/ED phthalate in the \nmedical device. The current scenario can also be referred to as baseline, business as usual or continued use \nscenario.  \n5 Vulnerabl e Groups (in these Guidelines): vulnerable groups of the population such as children and individuals \nwith increased susceptibility due to pre -existing disease, medication, compromised immunity, pregnancy or \nbreastfeeding, women and men in reproductive age.  These vulnerable groups also include infants, elderly \npeople or people with poor health conditions.  \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n16 \n performance and overall use should be outlined and applied as the basis for an \nidentification and screening of possible alternatives and a more detailed assessment of \npotential alternatives. Justification for the selection of these criteria should be provided.  \n \nBenefits of the device with CMR/ED phthalates should also be considered  e.g. treatment \nof specific patients groups due to tuning of  flexibility of the medical device . Present an \ninventory of the benefits of the CMR/ED phthalates in the medical device for the patients \n(separately for vulnerable groups). More detailed information on the benefit assessment \nis presented in section 7.  \n \nStep 3: Assessment of the risks of the CMR/ED phthalate.  \nPerform a risk assessment of the CMR/ED phthalate present in the medical device. The \nrisk assessment should contain a description of the potential phthalate exposure of \nvarious patient groups for which  the medical device is intended (e.g. single  vs repeated \nexposure ). This should separately include vulnerable groups. EN ISO 10993 -1 provides \ninformation on use type in terms of exposure potential (e.g.  limited ( \u226424h), prolonged \n(>24h to 30d) and permanen t (>30d))  that slightly differs from the duration of use as \ndefined in the MDR (Annex VIII, 1, transient <60 minutes, short term 60 minutes to 30 \ndays, long term >30 days).  \n \nExposure estimation  \n \nProvide information , preferably based on data from direct measurement or, when not \navailable, an estimation based on worst -case scenario or from scientific literature , on the \nrelease of the CMR/ED phthalate from the medical device when used in various clinical \nmodalities. For  data generation , analytical contact conditions for the evaluation of \nleaching of substances from medical device s, should consider fo r example temperature, \ncontact duration and frequency, polarity of contact liquids, flow rates, contact surface, \nand volume  of contact liquids (EN ISO 10993 -1, EN ISO 10993 -12, EN ISO 10993 -18,  USP \n661). The contact conditions should be set to represent realistic worst -case conditions \ntaking into account the intended use of the medical device.  \n \nEstimate exposure to the phtha late(s) considering data on the release of the substance \nfrom the device. Consider repeated use scenarios (e.g. dialysis, apheresis donation, \nchronic treatment)  and different population groups. The combined exposure to different  \nCMR/ED  phthalates also needs to be considered  when present in a medical device. More \ndetails on the use of phthalates in medical devices  are presented in Annex 6.  Risk \nmanagement measures in place and their effectiveness should be described and taken \ninto account in the assessme nt (EN ISO 14971, EN ISO 10993 -1). In addition, data from \nbiomonitoring programs may become available that could also provide information on \nexposure levels of phthalates in the general population and more specifically during \nmedical treatment.   \n \nHazard id entification  \n \nDescribe hazards associated with the CMR/ED phthalate by considering all relevant \ntoxicological endpoints for acute as well as for repeated dose toxicity. EN ISO 10993 -1 \nprovides information on hazard endpoints to be considered depending on the exposure \nand use category of a medical device, whereas allowable limits can be determined \naccording to EN ISO 10993 -17.  Possible hazardous effects of combined exposure  should Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n17 \n also be assessed.  Identify  an adequate point of departure (PoD) for risk ass essment. In \ncase of a threshold Mode of Action, such a PoD could be the most sensitive no-observed -\nadverse -effect -level (NOAEL ) or lowest -observ ed-adverse -effect -levels (LOAEL ), or a \ndose that causes a predefined response (Benchmark dose \u2013 BMD) obtained by  \nBenchmark dose modelling. In case of non -threshold effects (e.g. in the case of \ngenotoxic carcinogens or for certain substances acting via an ED -mediated MoA), such a \ndose descriptor could be a T256 value or the benchmark dose associated with a 10% \nresponse (BMD10) (ECHA, 2012).  \n \nWhere a reference DNEL and /or a reference DMEL have already been derived in the \ncontext of other EU legislations, the analysis could refer to these derived figures without \nreferring to detailed assessment how these data have been derived (e.g. under REACH \nlegislation, Food Contact Material legislation). However, as some of these data may have \nbeen derived in the past, relevant up -to-date scientific evidence (based upon a \nsystematic li terature review) and up -to-date risk assessment methodology for all \nrelevant toxicological endpoints needs to be considered . If such DNEL/DMELs are not \nused in the assessment, a justification should be presented (e.g. new \ninformation /studies). Some of thes e other legislations  are defined under Annex 4. In \naddition, information can also be obtained in the SCENIHR 201 5 Opinion on DEHP.  \n \nThe ED property of the phthalate can be described according to the recently published \nEFSA/ECHA guidance document . \nhttps://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2018.5311   \nThis includes impacts on fertility, birth defects (e.g., cryptorchidism, hypospadias), \ndevelopmental effects, and other effects associated with the CMR/ED phthalates.   \n \nDescribe risk (risk characterisation)  \n \nThe risk can be described by comparing exposure levels that are considered safe with the \nexpected exposure (worst -case scenario) to obtain a risk characterisation ratio (RCR). \nStarting points (points of departure, PoD) for exposure levels that are considered safe \ncould be the most sensitive no -observed -adverse -effect -level (NOAEL) or lowest -\nobserved -adverse -effect -levels (LOAEL), or a dose that causes a predefined response \n(Benchmark dose \u2013 BMD) for threshold substances. For non -threshold substances, a T25 \nvalue or the benchmark dose associated with a 10% response (BMD10) could be used. \nFrom these PoDs, acceptable expo sure values can be derived such as \u201cDer ived No -Effect \nLevel \u201d (DNEL), \u201cDerived Minimum Effect Level\u201d (DMEL) or intakes over lifetime without \npresenting an appreciable risk to health (ADI or TDI/TWI or TE).  As such data are often \nobtained in rat studies, th e use of the TDI seems more appropriate in view of the critical \neffect window for androgenic reproductive toxicity in rats has been reported to be a few \ndays (Welsh et al. , 2008). In addition, patients may be exposed to medical devices only \nfor a limited p eriod of time.  EN ISO 10993 -17:2002 7 calculates for medical devices a \nTolerable Exposure (TE), which is based on a product of the tolerable intake, the body \nmass and the utilization factor.  When necessary, acceptable exposure levels  can be \nderived by dividing the point of departure for risk assessment by appropriate assessment \nor uncertainty factors . Specifically for ED effects additional assessment factors might be \nconsidered as proposed recently (Hass et al.,  2019).  \n                                                           \n6 Animal dose -descriptor; chronic dose rate that will give 25% of the animal's tumours at a specific tissue site \nafter correction for spontaneous incidenc e (Dybing et al.,  1997)  \n7 EN ISO 10993 -17:2002 is currently under revision. It is discussed to replace in the updated version TE by TI.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n18 \n  \nThe risks can also be described by calculation of the Margin of Safety (MoS), which is the \nratio between the lowest PoD and the expected exposure (worst case scenario) and \ncomparison with a reference MoS (see SCCS Notes of Guidance \u2013 SCCS/1602/18).  \nPerform this evaluation for e very group (patients/donors) for which the device is \nintended to be used.  \n \nDetermine and describe in which situation the risk can be acceptable for the use of the \nCMR/ED phthalate in the medical device. The benefit -risk assessment for the use of the \nCMR/ED  phthalate can be performed using for example MEDDEV 2.7/1rev4 and EN ISO \n14971 (see also Section 8).  The MDR considers a risk acceptable when outweighed by \nthe benefit of using the device in patients (Chapter I of MDR , Chapter VI Article 62 ). \n \nIn addition to potential CMR/ED effects, discuss any other potential hazards associated \nwith the composition of the device (e.g. by using the EN ISO 10993 series of standards).  \nEvaluate if such effects are associated with the use of the CMR/ED phthalates i n the \ndevice.  \n \nNote: It should be noted that for some genotoxic carcinogens a no effect level is \nassumed not to exist.  Similarly, a scientific debate is ongoing about whether this also \napplies to ED activity.  \n \nThe assessment of the risk should be accompan ied by an estimation of the impact of \nuncertainties in the described outcomes  (see section  9). \n \n \n4. Assessment of possible alternative substances, materials, designs or \nmedical treatments8 \n \nIn general a similar risk assessment as presented in step 3 above has to be performed \nfor the alternative (substance s, material s, designs or medical treatment ). An inventory \nshould be prepared  in order to be able to evaluate possible alternative s. An alternative \ncould be another substance/material or device design modifi cation or it could be a clinical \nprocedure (e.g. a process, technique, treatment or modification) or a combination of \ntechnical and substance alternatives.  \n \nStep 4: Inventory of possible alternatives  \nPrepare a list of possible alternatives ( such as  substances, materials, designs or medical \ntreatments)9.  \nA description of the alternative scenario (CMR/ED phthalate \"non -use scenario\u201d) needs to \nbe presented including identification of alternative substances , materials, designs or \nmedical treatment , e.g.  by includ ing consideration of all available information, such as \nalternative medical devices available on the market, information about independent \nresearch, published peer-reviewed studies, systematic literature reviews, risk assessment \nreports or scient ific opinions from relevant scientific committees and the results of in -\n                                                           \n8 The analysis presented in section 4 constitutes the non -use scenario or the scenario that would transpire if the \nCMR/ED phthalates would no longer be used in the medical device.  \n9 Information source for alternatives might be the European Pharmacopoeia.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n19 \n house research and development.  The identif ication of  possible  alternatives should be \nproperly documented.  \nStep 5: Identification of the candidates for assessment as potential relevant  alternatives \nfor phthalates  \nThe MDR indicates that an analysis of all possible alternatives shall be performed. \nHowever, when many alternatives are available it would not be feasible to do an \nextensive evaluation of all alternatives. It is therefo re recommended to select a number \nof potential relevant  alternatives  based on screening against key criteria for function, \nperformance, toxicity, and overall use in the medical device in question  (see below). In \naddition, analysis of availability and technical feasibility might affect choices for \nalternatives as well.   \nA preliminary analysis of possible alternative substances, materials or designs or medical \ntreatments should be performed . This preliminary analysis  should include a description of \ntheir possible use as alternative substance , material , designs or medical treatment s. \nJustification on how and why alternatives are rejected for further assessment by defining \ninclusion and exclusion criteria should be provided.  \nInformation/data on functionalit y (e.g. level of flexibility in tubes) as well as performance \nand/or chemical safety assessment (e.g. hazard profile) may be used for rejection of the \nless likely alternatives (see below ) and no further risk assessment for the alternative is \nrequired. The rejection of the less likely alternatives requires justification and \ndocumentation.  The chemical safety assessment should be done after assessment of the \nfunctionality and performance.  \nIn addition to the comparison in terms of functionality, technical per formance and risks \nto patients and users, which are critical elements for the benefit -risk assessment, Annex \nI Section 10.4.2 of the MDR states that the justification for the presence of CMR/ED \nsubstances should also be based on an analysis of the availabi lity of possible alternatives. \nAvailability has several aspects, including for example the availability of necessary \nquantity (volumes) of the alternative on the market within a required timeframe and the \nability to gain access to alternatives that may be proprietary (e.g., via licensing).   \nIf potential alternatives can be identified, a shortlist of the potential alternatives can be \nestablished  for further detailed assessment with regard to technical feasibility, health \nbenefits, comparison of risks, exist ing legal requirements, availability (e.g. sufficient \navailability or accessible to the manufacturer), and technical performance.  In the event \nthat no alternative  is identified, i nformation should be presented on the actions \nundertaken  to identify alternat ives. \n \nA compilation of resources and elements in support of chemical substitution and an \nassessment of alternatives can be found on the OECD webpage : \nhttp://www.oecdsaatoolbox.org/  \nStep 6: Description of identified potential relevant  alternative(s)  and conclusion on their \ntechnical feasibility  \nCMR/ED phthalates are present in medical devices for a specific purpose depending on \nthe intended use of the medical device. For example, phthalates offer the possibility for \nfine tuning the flexibility  (e.g. optimal flexibility without kinking)  of a PVC -based medical Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n20 \n device. In addition, DEHP has a stabilising effect on red blood cells in blood bags \n(SCENIHR 201 5). Technical feasibility of an alternative is based on the alternative \nfulfilling the function of the CMR/ED phthalate. Therefore, the assessment of the \nfunctional properties in relation to the intended use of the medical device is essential. \nBesides functionality, performance under intended use conditi ons should also be \nconsidered.  \n \nArgumentation shall be provided for justifying why possible substances and/or material \nsubstitutes, if available, or design or medical treatment changes, if feasible, are \ninappropriate in relation to main taining the functionality and/or performance of the \nmedical device. For example, it might be the case that replacement is possible for one \nspecific functional use whereas for another functionality the use of the CMR/ED phthalate \nremains necessary . Also oth er aspects related to performance of the alternatives need to \nbe considered like material processing conditions (Crespo et al.,  2007), material quality \nafter sterilisation (Burgos and Jim\u00e9nez 2009), and possible interaction with drugs in \ntherapeutic infusi on systems (Treleano et al. , 2009, Salloum et al. , 2015, Tortolano et \nal., 2018).  \n \nThe benefit(s) should also be considered. An inventory of the benefit(s) of the potential \nalternative substances, materials, designs or medical treatments for patient populations \n(separately for vulnerable patient groups) should be presented (see section 7 ).  \n \nThe evaluation of the identified potential relevant alternatives can be done in a tiered \nway to avoid full assessments for each candidate alternative. For example, based on the \noutcome of the functionality evaluation, the choice of the potential relev ant candidates \nmight be reconsidered and some might be discarded before performing the risk \nassessment (see Step 7).  \n \nThe ECHA guidance on the preparation of an application for authorisation  and ECHA \nformats for Analysis of Alternatives  provide more detailed information on how to conduct \nan initial screening of possible alternatives and to assess the technical feasibility of \npotential alternatives. Submitted applications for authorisations contain a number of  \nexamples (https://echa.europa.eu/applying -for-authorisation/preparing -applications -for-\nauthorisation ) of technical feasibility assessment for uses of substances of very high \nconcern. \nStep 7:  Assessment of the risk of identified potential relevant  alternatives  \nThe risk assessment of alternatives is comparative in nature. Its aim is to assist in the \nconclusion in section 5 whether the transition to the alternatives would lead to lower \nbenefit and/or risk to human health for patients when compared to the current u se of the \nCMR/ED phthalates in the medical device. Th e methodology of the assessment in this  \nstep is similar to that in step 3 as performed for the phthalate to be evaluated with \nreference to the alternative.  \n \nIf potential relevant alternative s were identified under Steps 1 -6, a risk  assessment of \nthese potential relevant  alternative substance/material or designs or medical treatments \nshould be performed. The risk assessment should contain a description of the potential \nsubstance/material (alternative  medical procedure) exposure of various person groups \n(e.g. including patients, donors, professional users)  for which the medical device is \nintended to be used (considering single or repeated use). This should include separately Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n21 \n vulnerable groups . For each  subgroup a different level of risk may be accepted based on \nthe potential benefit of the medical device for that particular group . Risk management \nmeasures (EN ISO 14971, EN ISO 10993 -1) and their effectiveness to reduce exposure \nshould be described and t aken into account in the assessment.  \n \nExposure estimation  \n \nEstimate the potential release of the alternative substance(s) when used in various \ntreatment modalities. Consider also the rate of leaching to estimate the potential \nexposure to the alternative substance. Multiple use scenarios (including various types of \npossible contact) should be considered for the exposure estimation of the alternative \nsubstance (e.g. frequent use of dialyzer) and different population groups.  \n \nHazard identification  \n \nIdentify hazards based on literature, supplier documentation and other information (such \nas risk assessments performed by regulatory bodies). Describe hazards associated with \nthe alternative substance/material by considering all relevant toxicological endpoints for  \nacute as well as for repeated dose toxicity including human data. Identify an adequate \npoint of departure (PoD) for risk assessment. In case of a threshold Mode of Action, such \na PoD could be the most sensitive no -observed -adverse -effect -level (NOAEL) or lowest -\nobserved -adverse -effect -levels (LOAEL), or a dose that causes a predefined response \n(Benchmark dose \u2013 BMD) obtained by Benchmark dose modelling. In case of non -\nthreshold effects (e.g. in the case of genotoxic carcinogens or for substances acting via  \nan ED -mediated MoA), such a dose descriptor could be a T25 value or the benchmark \ndose associated with a 10% response (BMD10) (ECHA, 2012).  Hazards should preferably \nbe evaluated by a relevant exposure route for the intended use of the assessed medical \ndevice. \n \nFor the hazard identification  special attention should be on the determination of any \npotential CMR and/or ED property of the alternative substance used . For further \ninformation purposes, a procedure is described in ECHA Guidance on the application of \nthe CLP criteria  \nhttps://echa.europa.eu/documents/10162/23036412/clp_en.pdf/58b5dc6d -ac2a-4910-\n9702-e9e1f5051cc5   \nor by searching Annex VI of  CLP regulation. ED propert ies of the alternative \nsubstance/material can be described according to the recently published EFSA/ECHA \nguidance document . \nhttps://echa.europa.eu/documents/10162/23036412/bpr_guidance_identif_ed_en.pdf/1a\n4d2811 -3faa-fe61-1de2-3cbce8fd4d95   \nThese effects include impacts on fertility, birth defects (e.g., cryptorchidism, \nhypospadias), developmental eff ects, and other potential toxic effects associated with \nphthalates with ED properties and reprotoxic effects category 1A/B.  It needs also to be \nconsidered that the potential alternative (substances, materials, designs or medical \ntreatments) could also have  other hazards than those of the CMR/ED activity. These \nother hazards and their possible associated risks should be discussed for example by \nusing the EN ISO 14971 and the EN ISO 10993 series. See also Table 1.  \n \nDescri ption of  risk (risk characteri sation)  \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n22 \n The risk can be described by comparing exposure levels that are considered safe with the \nexpected exposure (realistic worst case use scenario). Exposure levels that are \nconsidered safe could be \u201cDerived  No Effect-Levels\u201d (DNEL s) for threshold substances, \n\u201cDerived Minim um Effect Levels\u201d (DMEL s) for non -threshold substances or intakes over \nlifetime without presenting an appreciable risk to health (ADI or TDI/TWI or TE ). As such \ndata are often obtained in rat studies, the use of the TDI seems more appropriate in view \nof the critical effect window for androgenic reproductive toxicity in rats has been reported \nto be a few days (Welsh et al. , 2008). In addition, patients may be exposed to medical \ndevices only for a limited period of time. EN ISO 10993 -17:2002 calculates for medical \ndevices a Tolerable Exposure (TE), which is based on a product of the tolerable intake, \nthe body mass and the utilization factor. When necessary, a cceptable exposure levels   \ncan be derived by dividing the point of departure for risk assessment by appropriate \nassessment or uncertainty factors.  For medical devices allowable limits of their chemical \nconstituents can be determined by EN ISO 10993 -17. \n \nThe risks can also be described by calculation of the Margin of Exposure (MoE) or the \nMargin of Safety (MoS)  due to the substances present in a medical device , which  is the \nratio between the lowest PoD and the expected exposure (e.g. realistic worst case  use \nscenario) and comparison with a reference MoS (see SCCS Notes of Guidance \u2013 \nSCCS/1602/18 ). \nPerform this evaluation for every patient group for which the device is intended to be \nused.  \n \nWhere a reference DNEL and /or a reference DMEL have already been derived in the \ncontext of other EU legislations, the assessment  could refer to these derived figures \nwithout referring to a detailed assessment of how these data have been derived (e.g. \nunder REACH legislation, Food Contact Material legislation). Data on the relevant \nexposure route of the medical device application (e.g. intravenously) are preferred (see \nalso Table 1A, EN ISO 10993 -1). The risk can be described by the so -called risk \ncharacterisation ratio (RCR), being a ratio between the exposure and the DNEL /DMEL . If \nsuch DNEL/DMELs are not used in the assessment, a justification should be stated (e.g. \nnew information /studies).  \n \nDetermine and describe acceptability of the risk for the use of the potential alternative s. \nRisks may be acceptable when they are outweighed by the benefits for the patient.   \n \nConsider any known adverse events associated with the operation of the device using the \nphthalate, and whether the potential alternatives might affect these adverse event s. \nThese considerations can be based upon a systematic literature review  (see MEDDEV \n2.7/1rev4) . \n \nThis exercise has to be performed for each potential relevant  alternative substance  \nand/or materials .  \nA large number of phthalates exist and some may be potential relevant alternatives  for \nthe CMR/ED phthalate used in the medical device. However, a number of these  \nphthalates are also classified as CMR and/or designated ED (see above  and Table 1 \nAnnex 5 ). Such phthalates might be identified as alternatives when the CMR/ED risk is \nreduced compared to the phthalate intended to be  used.  In addition, different \nsubstances , have also been proposed as alternative plastici sers. In 201 5 SCENIHR \npublished an updated Opinion of potential alternative plastici sers for DEHP (SCENIHR Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n23 \n 2015). Although many alternatives were potentially available, it was also observed that \nfor many of them the information on potential risks and the necessary risk assessment \nwas rather limited precluding their use as alternative s. For DEHP an extensive amount of \nliterature is available, allowing a very careful evaluation of the risk associated to its use .  \n \nIn the event that the risk assessment of a potential relevant alternative cannot be \nperformed due to lack of information, document ation should be presented on the actions \nundertaken to obtain information to characterise the risk, including the outcome (for \nexample, QSAR /read across could be performed).  \n \nNote shall be taken that alternative designs or medical treatments might lead to  \nadaptation of  endpoints for the benefit -risk assessme nt when compared to the \ntoxicological endpoints of CMR/ED phthalates.  \n \nThe assessment of the risk should be accompanied by an estimation of the uncertainties \nin the described outcomes which might be qua ntitative (e.g. confidence interval, \nstandard deviation) or qualitative (see section 9).  \nConclude the analysis of the potential  relevant alternative(s) with a summary describing \nthe possible  scenario(s) ( see Fig ure 1).  \n \n \n5. Assessment of potential relevant  alternative substances, materials, \ndesigns or medical treatments versus CMR/ED phthalates  \n \nBased on the information obtained above a decision can be made on the appropriateness \nof potential relevant alternative s (substance, material , design or medical treatment ). In \nthis evaluation several factors need to be included such as weighing of technical \nfeasibility, benefits and risks . And, if possible, quantification of benefits and risks. These \nsteps entail a comparison of the CMR/ED phthalate  \u201cuse-scenario\u201d  (summarised in step \n3) with the \u201cNon-use scenario \u201d (summarised in step 4)  as shown in Figure 1.  \n \nStep 8: Comparison of functionality and performance of CMR/ED phthalate as used in the \nmedical device with functionality and performance of identified potential relevant \nalternative (s). \n \nCompare the functionality and performance of CMR/ED phthalate in the medical device \nand the potential relevant alternative substance/material (or designs or medical \ntreatments by choosing adequate endpoints).  \nPerform step 8 for each candidate identified as the potential relevant alternative in \nsection 4.  \nIf several potential relevant alternatives have a similar functionality and hazard profile, \nexposure conditions and possibilities for Risk Management Measures (RMM) res ulting in \nrisk reduction should be considered (see below).  Risk management is described in EN \nISO 14971.  \nIn this comparison also additional issues not directly related to the functionality and \nperformance of the alternative itself, like technical possibili ties, sterilisation effects and Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n24 \n interactions with infusion liquids, are important for the application of the alternative and \nthe comparison with the CMR/ED phthalates, and thus should be considered.  \nStep 9:  Comparison of risk(s) of CMR/ED phthalate as used in the medical device with \nrisk(s) of identified potential relevant alternatives.  \n \nCompare the risk of both CMR/ED phthalate and alternative substance/material (or \ndesigns or medical treatments by choosing adequate endpoints).  \nPerform step 9 for each potential relevant alternative.  \n \nThere may be difficulties in comparing the risks of a substance e.g. a phthalate, and the \nrisks of a technical alternative such as medical design or medical treatment. For example, \nthere may be risks as sociated with alternative technologies but these may not be of the \nsame nature of the risk of the phthalate. However, the potential relevant alternative \nmust represent a reduction in the overall risks to human health  (Step 10) . Therefore, a \ncomparison of risks must be conducted and the applicant will need to consider how these \ndifferent risks might be compared in terms of risks to human health. Note that an \nalternative medical design or medical treatment may also result in expo sure to other \nrisks previously not present  in the treatment modality. Possible risks of these substances \nwill also need to be considered in the assessment. The comparison with technological \nalternatives such as a medical design or medical treatment can nor mally not be fully \nquantitative (i.e. with directly comparable numeric values), as the hazards and \nassociated risks will not be expressed in similar terms, but will in most cases be \nqualitative or semi -quantitative.  Nevertheless, a clear and transparent de scription can \ngive a good basis to conclude whether overall risks are reduced  or not  (Step 10) .  \nStep 10: Comparison of benefit and risk of CMR/ED phthalate used in the medical device \nwith identified potential relevant alternatives.  \n \nPresent summary/overvi ew of comparison of benefit and risk of CMR/ED phthalate used \nin the medical device with the potential relevant alternatives, including uncertainties  \nabout the estimates or reliability of the data, assumptions, etc. for the parameters \npresented. The summary should contain various aspects of functionality, performance, \nrisk and benefit of the use of the original CMR/ED phthalate used in the medical devic e \nand the potential relevant  alternative (s). In section  6 below the justification of the use of \na CMR/ED phthalate is described based on the summary table comparing an alternative \nwith the CMR/ED phthalate.  \nPerform step 10 for every potential relevant alternative.  \n \nEach of the assessments performed in steps 1 to 1 0 is associated with uncertainties. \nCertain uncertainties can be described by the use of measures  like the standard deviation \nor confidence interval. For other uncertainties , a description may be necessary to explain \nthe extent of the uncertainty  and its impact on the final outcome . \n \nBenefit and risks should be described and weighted against each other in the use of the \npotential alternative substance /material  in the medical device (or designs or medical \ntreatments  by choosing adequate endpoints)  similar to the procedure for the CMR/ED \nphthalate (see step 2).  \n \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n25 \n  \n6. Justification for the u se of CMR/ED phthalate  \n \nBased on the comparison of functionality, performance, availability, risk and benefit, an \nargumentation can be built as to why a possible substance and/or material alternative, if \navailable, or changes in designs or medical treatment, if feasible, are inap propriate in \nrelation to maintaining the functionality, performance and the benefit -risk ratio or profile \n(quantitative/semi -quantitative or qualitative) of the medical device containing a CMR/ED \nphthalate.  \n \nExplain the importance of any difference in ter ms of benefits and risks between the \nCMR/ED phthalate to be used in the medical device and potential relevant alternatives \nusing value judg ements and explain how  the use of the CMR/ED phthalate can be \njustified over the alternatives by describing the accep tability of trade -offs in the \nachievement of some criteria against others.  Any advantage in benefits needs to be \nweighed against possible disadvantages in terms of functionality and risks. Both \ndifferences in benefits and risks need to be considered jointly.  \n  \nIn building the argumentation for the use of a CMR/ED phthalate, note can be taken of \nthe Memorandum on weight of evidence and uncertainties of SCHEER (SCHEER 2018). \nThis Memorandum describes a  methodology  that classifies the strength of evidenc e in the \nhuman health risk assessment  based on integration of different lines of evidence  into \nstrong, moderate, weak, uncertain and inconclusive (no suitable evidence available).  Any \nweight of evidence evaluation needs to show the overall confidence in t he assessment.   \n \nThe argumentation should specifically take into account the intended use of such devices. \nThis should include consideration and discussion of possible high risk groups such as \nchildren or pregnant or breastfeeding women, and other patient groups considered \nparticularly vulnerable to such substances and/or materials. In addition, where applicable \nand available, any future update of these Guidelines shall be considered. A Table with the \nmost relevant information and values should be used to p resent an overview of the \nperformed assessment comparing the CMR/ED phthalate with potential alternative(s). A \nnon-exhaustive example of such Table is presented below. The Table should  be extended \ndepending on the number of criteria evaluated and the numbe r of potential alternatives \nidentified.  \n \nTable 1:  Example for a comparison of CMR/ED phthalate with potential relevant \nalternative(s).  \n  \nAssessment criteria  Description \n(examples)  Reference \nphthalate  Alternative I  Alternative \nII etc.  \nIdentification of \nsubstances/material etc  \nName and CAS number  Chemical \ninformation  CAS \n117-81-7  \n   \nFunctionality/performance  Used as \nplasticiser  e.g. DEHP    \nClinical \nbenefit/performance  Treatment \npossibility  e.g. Flexibility \nof tubing / \nred blood   Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n26 \n cells storage  \nMaterial benefit      \nConcentration (% w/w)      \nLeaching  from medical \ndevice for relevant \nconditions e.g. media, \ntemperature, etc  \n(mg per hour/day)      \nExposure estimation \n(realistic worst case use \nscenario ) for relevant \nroute of exposure      \nHazard identification  Local and \nsystemic \nacute and \nrepeat -dose \ntoxicity, ED -\nproperties, \norgan \ntoxicity, CMR \nproperties, \nbiocompatibili\nty, and \nothers     \nIdentification of a point of \ndeparture for risk \nassessment ( LOAEL, \nNOAEL, BMD, T25, \nBMD10)  \n     \nIdentification of dose \nlevels associated with \nminimal or negligible risk  \n(e.g. DNEL, DMEL, TDI , \nTE, TI)     \nRisk characterisation \n(MoE, MoS, RCR)      \nConfidence  estimation \n(see Table 2)      \nTechnical feasibility       \nOther      \n \nThis Table shall be completed for every component of the medical device that contains \nCMR/ED phthalate(s ) above the 0.1% w/w level. For some medical devices used as a \nsystem (e.g. blood bag system) the whole system might be evaluated.  Note that in case \nof alternative designs or medical treatments adequate endpoints for the comparison shall \nbe chosen. These endpoints may represent risks that may be of a different nature than \nthat of the risk of the phthalate.  \nWhen the outcome of the comp arison shows that the alternative fulfils a comparable or \nbetter intended functionality as well as performance and shows a reduced risk, the use of \na CMR/ED phthalate is not possible. The risk assessment should also indicate whether \nthere would be a reduce d hazard concerning CMR and/or ED properties, and/or reduced \nexposure overall resulting in reduced risk. In this evaluation, other toxicities (e.g. for any Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n27 \n other organ  or system ) of the potential relevant alternatives shall also be considered. So, \nthe full  toxicological profile of the potential relevant alternatives shall be taken into \naccount.  \nA balanced weighing of the benefit  versus the risk has to be performed . For example it is \npossible to use a combination of a CMR/ED phthalate and PVC/material with h igh intrinsic \ntoxicological hazards, thus accepting a risk from a toxicological perspective, in case the \nclinical benefit is very high . In contrast, a minor loss in medical  functionality might be \nacceptable if there is a large reduction  or even absence of risk. Each comparison of a \npotential alternative for the use of a phthalate should be based on the combination of \nfunctionality , risk and benefits for patients.  \nIn this final evaluation , the assessment  of uncertainties associated with the alternatives \n(e.g. on the nature of the risks; assumptions made) should also be considered (see Table \n2 below section 9). Therefore, where possible, quantitative results should be collected \nand compared (e.g. NOAEL, estimated exposure in mg/kg) and their uncertainties should \nbe reported. Also a qualitative description of the uncertainties may be useful (see Table 2 \nbelow sec tion 9). Their impact on the conclusions should also be discussed.  \nAlthough not the main subject of these Guidelines, it should be realised that availability \nand accessibility on the market  might be a limitation for the introduction of an alternative \nsubst ance/material. Some chemicals proposed as alternatives are widely available (e.g. \nBTHC, DEHT, DINCH, and TOTM) however, this may not be the case for other alternatives \nidentified . The lack of the availability of a potential alternative for a medical device might \nresult in the conclusion that replacement is not feasible and that the use of a phthalate \nwith CMR and/or ED property continues in order to keep the device available for pat ients. \nSo, besides technical feasibility in terms of functionality and risk reduction (risk \nassessment of the phthalate versus the alternative), also availability and accessibility on \nthe market needs to be considered.  \nThe BRA of the CMR/ED phthalate shoul d be updated when new scientific information \nbecomes available on alternatives for the use of phthalates, when new Guidelines are \nreleased, or as the \"overall\" benefit -risk determination of the medical device is updated.  \nA plan to perform an update of the relevant part of the technical file of the device needs \nto be submitted during the certification process (post -market surveillance plan referred \nto in Article 84, the requirements are set out in  Section 1.1 of Annex III MDR) and this \nshould also cover upd ates needed on the justification for the presence of CMR/ED \nphthalates .  \n \n7. Benefit assessment  \n \nThese Guidelines do not provide information for the benefit -risk assessment of the use of \na medical device itself but are limited to the methodology on how to perform a BRA for \nthe justification of the  presence  of CMR 1A or 1B and/or ED phthalates in a medical \ndevice  above 0.1% (w/w).  \nThe evaluation of the overall benefit -risk assessment of a medical device is  presented in \nother documents (e.g. MEDDEV 2.7/1 rev4, EN ISO 14971).   \nThe benefits of the CMR/ED phthalate use in a medical device need to be compared to \nthe benefits of the potential relevant alternatives, with the focus of the analysis being on Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n28 \n the net or incremental benefits of use of the CMR/ED phthalate in comparison to the \nalternatives. These benefits may include material or clinical benefits. Uncertainties about \nthe estimates or reliability of the data, assumptions, etc. for the parameters need to b e \npresented.  \n \n7.1 Material benefit  \n \nA medical device does not achieve its principal intended action by pharmacological, \nimmunological or metabolic means, in or on the human body, but may be assisted in its \nfunction by such means.  For the use of phthalates in medical devices, additional \nfunctionalit ies need to be considered. One of the functionalit ies is the fine -tuning of the \nflexibility of PVC when  used as plasticiser s e.g. in intubation devices. For blood bag \nmaterials other requirements are , for example,  resistance to heat and chemicals, \nespecially during sterili sation, and permeability of gases to assure that pH and oxygen \nlevels remain stable .  In addition, DEHP has an additional property namely the stabilising \neffect on red blood cells (RBCs) (SCENIHR 2015). A number of alternatives were \nevaluated as alternative for DEHP in blood bags (Simmchen et al., 2012, SCHENIR \n2015).  \nPlatelets are extremely sensitive to changes in the pH of the medium in which they are \nsuspended, so sufficient gas permeability to O2 and CO 2 has to be assured in the \ncontainers devoted to their storage (Simmchen et al. , 2012). For this reason, DEHP has \nbeen almost fully replaced with  BTHC, DINCH, and/or Trioctyltrimellitate (TOTM or  Tri( 2 -\nethyl hexyl)trimellitate (TEHTM) ) (Simmchen et al.  2012, Prowse et al.  2014).  A better \ngas exchange has been found in bags plasticised with these chemicals . Also other \nmaterials, like polyolefins, are currently used for platelet storage bags (Prowse et al.  \n2014).  This potentially will allow  the stor age of platelet concentrates for up to 7 days, if \nmeasures to prevent bacterial contamination can be safely implemented.  \nIt should be noted that the benefit of phthalates in terms of material  functionality and \nperformance may differ from device to device. An alternative may be available  for one \napplication while this may not be available  for another in view of added or specific \ndemands on the functionality  of the p hthalate .  \n \n \n7.2 Clinical benefits  \n \nClinical benefit of medical devices is defined in the MDR as follows:  \n\u2018clinical benefit\u2019 means the positive impact of a device on the health of an individual, \nexpressed in terms of a meaningful, measurable, patient -relevant clinical outcome(s), \nincluding outcome(s) related to diagnos is, or a positive impact on patient management or \npublic health; (Regulation (EU)2017/745: Article 2 Definitions: (53)):  \nThis \u201cclinical benefit\u201d has to  be substantiated by the manufacturers in the \u201cclinical \nevaluation\u201d of the medical device, which includes a number of considerations. These  \ninclude a discussion and overall conclusions covering safety and performance results, \nassessment  of risks and clinic al benefits, discussion of clinical relevance in accordance Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n29 \n with clinical state of the art, any specific precautions for specific patient populations, \nimplications for the investigational device  and limitations of the investigation.  \nA \u201dclinical benefit \u201d could include any meaningful, measurable, patient -relevant outcome \nas presented below. SCHEER identified the following examples  that may be relevant for \nthe use of phthalates (list not exclusive):  \n\uf0b7 Improved survival rates  \n\uf0b7 Improved length of hospital stay  \n\uf0b7 Improved time of intervention  \n\uf0b7 Improved time of placing ( among others  in tubes and catheters)  \n\uf0b7 Improved product quality/ clinical performance ( among others in tubes and \ncatheters) in terms of:  \no Improved leakage rates  \no Improved breakage rates  \no Improved knotting rates  \no Improved blockage rates  \no Improved bending performance rates  \no Improved release rates of toxic substances  \no Improved release rates of (nano -)particles  \n\uf0b7 Improved displacement  rates \n\uf0b7 Improved possibilities for sterili sation \n\uf0b7 Reduction of diameters in relation to performance  \n\uf0b7 Possibility to produce \u201cmultiple -purpose\u201d devices, (e.g. inclusion of additional \nsensors), and therefore reduction of over -all patient -stress and patient -impact  \n\uf0b7 Improved observability (safety) in terms of translucence, printability, radiopaque \nlines included, identifiab ility, traceability, etc. ( among others  in tubes and \ncatheters)  \n\uf0b7 Fewer  adverse events , e.g. r educed mucosal or endothelial irritation or injury \nrates ( among others  in tubes and catheters)  \n\uf0b7 Fewer serious adve rse events  and serious incidents  \nThe benefit of the use of the CMR/ED phthalate should always be judged with respect to \nthe \u201cintended use\u201d of the medical device and the exposed patient -group to the medical \ndevice and weighed in its clinical impact (\u201cclinically relevant difference\u201d). These aspects \nshould be judged by clinical experts.  \nQuantitative information on the benefits should be provided where possible or at a \nminimum qualitative description of their magnitude. Information on the probability of  the \nbenefit to occur and/or the duration of the benefit should also be included.  \n \n \n8. Methodologies for Benefit \u2013Risk A ssessment  \n \nIn general, a Benefit - Risk A ssessment  (BRA) aims to evaluate the desired effects of \ntherapeutic mean s, medicine s or device s, against their undesired effects, i.e., risks for \nhuman health. An appropriate BRA can contribute to a more objective analysis and help  \nconformity verification bodies and  authorities towards a more objective and transparent \ndecision -making process. Weighi ng the benefits and risks can be a complex task. It may \ninvolve the evaluation of a large amount of data that should be as accurate  as possible , Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n30 \n without methodological weaknesses  and biases. There is always some uncertainty around \nthe actual benefits and r isks, because they can only be determined by looking at the \ninformation that is available at a given point in time  which may contain various sources \nof uncertainty.  \nFor the BRA of medical devices in general, guidance is available in section A7.2. of  \nMEDDEV 2.7/1, revision 4   \u201cClinical evaluation: A guide for manufacturers and notified \nbodies under directives 93/42/EEC and 90/385/EEC\u201d . EN ISO 14971  (FDIS published in \n2019)  and the accompanying  ISO/TR 24971 provide information on the risk benefit \nanalys is to be performed within a risk management process. Additional information may \nbe found elsewhere, for example in the documents  of the FDA 2016,  2018,. It should be \nnoted that the acceptability of any risk is weighted against the benefit of the use of the \nmedical device.   \nSeveral methodologies for BRA have been proposed (Guo et al, 2010 , Mt-Isa et al.  \n2014), of which most methodologies  are so far , mainly used for pharmaceutical products. \nHowever, it should be underlined that f or medical devices the quantitative determination \nof a benefit -risk ratio may be rather difficult to be made  and expressed in a figure. In \nsuch cases a qualitative approach of weighing the benefit based on expert judgement \nmight be used.  One methodology, namely the multi criteria decision analysis (MCDA), \ncan be generally applied to various areas of BRA. Therefore, this methodology might also \nbe suitable for performing the BRA of medical devices (see Annex 7).  The MCDA \nmethodology has its origins in decisi on theory aiming to evaluate multiple conflicting \ncriteria in decision making. These criteria can include the benefits and risks of the use of \na medical device on human health.   \nThe final BRA of both the used CMR/ED  phthalate and potential relevant alterna tives \nshould contain all aspects as indicated in the framework above. A quantitative or semi -\nquantitative description of the risks (e.g. MoS, RCR) and of the benefits of a medical \ndevice containing a CMR/ED phthalate or alternative should  be the basis for a BRA. \nHowever, a lthough quantitative approaches for a BRA are preferable, a qualitative \ndescription of the value judgements about the balance of benefits and risks might also be \nan acceptable approach when justified (see step 10).  \n \n \n9. Uncertainty analysis  \n \nUncertainty plays an important role in medical decision making. It is widely accepted \nthat, despite the methodological and technological improvements that were achieved in \nthe past decades, there is never absolute certainty regarding the safety, effective ness, or \nperformance  of a medical treatment or use of a device. Therefore, the degree of certainty \nand thus uncertainty of the benefits and risks of a medical device is a factor that should \nalways be considered when making BRA.  \nThere are various sources of uncertainty in bio -medical studies; a major source of \nuncertainty is the biological differences among individuals. Another source of uncertainty \nis the intra - and inter - variability of the laboratories, with respect to equipmen t, \nreagents, and methods used. It is also accepted that diagnostic tools which evaluate \nbenefit and risk share several limitations , giving false negative and false positive results \nin a variety of cases. Observer variation occurs quite often  and should alw ays be taken Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n31 \n into account. Other factors that may influence the degree of uncertainty include: the type \nof clinical information available (e.g., clinical investigation  data, observational studies, \nevidence derived from registries or use experience), the re presentativeness of the \ninformation (e.g., sample size, relevance  of the sample to the referent population \nexposed to the device), as well as the statistical inferences derived from the information.  \nA number of techniques for uncertainty analysis are descr ibed in t he Guidance for Socio -\nEconomic Analysis of ECHA (ECHA 2011). The aim is to determine whether uncertainties \nin the estimation of impacts could affect the overall conclusions. More accurately , the \ntechniques shown can be used to either reduce the va riability of estimates, or to help \ntest whether uncertainties affect the conclusions drawn. The only way to actually reduce \nuncertainty is through better data, better understanding and knowledge of the \nuncertainties and through further analysis. However, i n most cases residual uncertainties \nwill remain.  \nRecently EFSA published a guidance on uncertainty analysis (EFSA 2018 a) and a \ndescription of the principles and methods behind the guidance for uncertainty analysis \n(EFSA 2018 b). The EFSA Guidance recogni ses that the form and extent of uncertainty \nanalysis, and how the conclusions should be reported, vary widely depending on the \nnature and context of each analysis and the degree of uncertainty that is present. \nTherefore it is important to identify appropriat e options for each BRA. The EFSA \ndocuments provide a flexible framework for uncertainty analysis within which different  \nmethods may be selected, according to the needs of each BRA. It seems likely that also \nfor medical devices a similar flexibility is need ed in view of the broad range of medical \ndevices used.  \nEFSA describes a number of main elements of uncertainty that need to be considered in \nthe uncertainty analysis:  \nEFSA: Main elements of uncertainty analysis  \n\uf0b7 Identifying uncertainties affecting the assessment. This is necessary in every \nassessment and should be done in a structured way to minimise the chance of \noverlooking relevant uncertainties. In assessments that follow standardised \nprocedures, it is only necessary to identify nonstandard uncertai nties.  \n\uf0b7 Prioritising uncertainties within the assessment plays an important role in planning \nthe uncertainty analysis, enabling the assessor to focus detailed analysis on the \nmost important uncertainties and address others collectively when evaluating \novera ll uncertainty. Often prioritisation will be done by expert judgement during \nthe planning process, but in more complex assessments it may be done explicitly \nusing influence analysis or sensitivity analysis.  \n\uf0b7 Dividing the uncertainty analysis into parts. In some assessments, it may be \nsufficient to characterise overall uncertainty for the whole assessment directly, by \nexpert judgement. In other cases, it may be preferable to evaluate uncertainty for \nsome or all parts of the assessment separately and then comb ine them, either by \ncalculation or expert judgement.  \n\uf0b7 Ensuring the questions or quantities of interest are well -defined. Each question or \nquantity of interest must be well -defined so that the true answer or value could be \ndetermined, at least in principle.  This is necessary to make the question or \nquantity a proper subject for scientific assessment, and to make it possible to \nexpress uncertainty about the true answer or value clearly and unambiguously. Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n32 \n Some assessments follow standardised procedures, within  which the questions \nand/or quantities of interest should be predefined. In other assessments, the \nassessors will need to identify and define the questions and/or quantities of \ninterest case by case.  \n\uf0b7 Characterising uncertainty for parts of the uncertainty analysis. This is needed for \nassessments where assessors choose to divide the uncertainty analysis into parts \nbut may only be done for some of the parts, with the other parts being considered \nwhen characterising overall uncertainty.  \n\uf0b7 Combining uncertainty f rom different parts of the uncertainty analysis. This is \nneeded for assessments where the assessors quantify uncertainty separately for \ntwo or more parts of the uncertainty analysis.  \n\uf0b7 Characterising overall uncertainty. Expressing quantitatively the overall  impact of \nas many as possible of the identified uncertainties, and describing qualitatively \nany that remain unquantified. This is necessary in all assessments except those \nstandardised assessments where only standard uncertainties are identified  (e.g. \ninter-and intra -species uncertainty factors).  \n\uf0b7 Prioritising uncertainties for future investigation. This is implicit or explicit in any \nassessment where recommendations are made for future data collection or \nresearch, and may be informed by influence or sensit ivity analysis.  \n\uf0b7 Reporting uncertainty analysis. Required for all assessments, but extremely brief \nin standardised assessments where only standard  uncertainties  are identified.  \nA number of methods that can be used in the uncertainty analysis include:  \n\uf0b7 Sensitivity analysis  \n\uf0b7 Scenario analysis  \n\uf0b7 Expert judgement  \n\uf0b7 Monte Carlo Simulations  \nSome of these techniques can be used in combination (e.g. scenario analysis together \nwith expert judgement to establish ranges for key variables) but also together with less  \ncommonly used techniques such as risk -risk analysis, Delphi techniques and portfolio \nanalysis, which can be used to help reduce the variability of estimates but are not \ndiscussed in these Guidelines.  \nAfter performing the uncertainty analysis , the observed overall confidence associated \nwith a BRA can be expressed as a probability score. This score gives the risk assessor an \nindication what the uncertainty is in the BRA. \nIn situations where sufficient data are available, a quantitative categori sation of \nprobability levels is preferred. If this is not possible, the manufacturer should give a \nqualitative description. A good qualitative description is preferable to an inaccurate \nquantitative description ( EN ISO  14971).  \nEFSA (EFSA, 2018 b) and SCHEER (2018) use a rather detailed probability scale  of 9 and \n7 probab ility levels, respectively. EFSA stresses that this scale may be used as an aid to \nsupport the development of judgements and that other ranges or qualitative descriptions \ncan be used as well. EFSA (2018 b) also argues that presenting the numerical \nprobabilities alongside verbal expressions of probability, e.g. \u2018Likely (> 66% probability)\u2019, \nincreases the consistency of interpretation.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n33 \n A detailed scale does not seem to be applicable for the uncertainties that can be obtained \nduring a  BRA evaluation of medical devices. For medical devices, a probability scale as \nindicated in Table 2  may b e used  EN ISO showing a 5-level scale recommended by ISO \nfor semi -quantitative assessments ( EN ISO  14971, Table D4 ). Table 2 further show s the \nverbal terms and subjective probability ranges that are based on a simplification of the \nEFSA/SCHEER scales.  \n \nTable 2: Probability scale for (semi -)quantitative  description of the overall \nconfidence  \nISO probabil ity term  \n Subjective  probability range  Probability term  \n \nFrequent  \n \nProbable  \n \nOccasional  \n \nRemote  \n \nImprobable  \n  \n> 90% \n \n66-90% \n \n33-66% \n \n10-33% \n \n<10%  \nvery l ikely \n \nlikely \n \nas likely as not  \n \nunlikely  \n \nvery unlikely  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n34 \n  \n10.  Conclusions  \n \nThese G uidelines are intended to be used for  a BRA of the presence of phthalates in \ncertain medical devices  covering phthalates which are carcinogenic, mutagenic, toxic to \nreproduction (CMR) or have endocrine -disrupting (ED) properties . The Guidelines can be \nused for the justification of the use of CMR/ED phthalates in a medical device according \nto the Regulation (EU) 2017/745 on medical devices. They also provide a framework on \nhow to assess  and compare possible alternative substances, materials , designs  or \nmedic al treatments  to the use of CMR/ED phthalates in medical devices. Major aspects \ninclude the functionality of phthalates, the performance  of the medical device using  the \nphthalate or the potential  relevant alternative for the phthalate, as well as the risk \nassessment of the phthalate or the alternative s. In the end , the benefit (s) shall be \nweighed against the possible risk s of the use of the CMR/ED phthalate and of the \nalternative substance, materials , desig ns or medical treatments . This overall analysis  will \ndetermine whether it is justified  or not  to use  a CMR/ED phthalat e in a medical device.  \nIn view of the concern of the CMR/ED properties of phthalates, further research to \npossibilities to replace these p hthalates in medical devices is highly encouraged  by the \nSCHEER .  \nDuring the preparation of these Guidelines for BRA of the use of CMR/ED phthalates in \nmedical devices , SCHEER noticed that a number of BRA methodologies are theoretically \navailable. However , there is a considerable lack of data for the BRA for potential  relevant \nalternatives to be used in medical devices. Therefore, SCHEER encourages manufacturers \nto generate data of high quality on such alternatives for CMR/ED phthalates in medical \ndevices . As the BRA of the presence of phthalates may have an impact on the \nconclusions of the \"overall\" benefit -risk determination of the medical device, a  periodic  \nupdate of the BRA of the medical device may be needed. The BRA of the presence of the \nCMR/ ED phtha late should be updated when new scientific information becomes available \non alternatives for the use of phthalates, when new Guidelines are released, or as the \n\"overall\" benefit -risk determination of the medical device is updated . A plan to perform \nan update of the general BRA for the medical device should be included in the dossier \nbefore marketing the device, and this should also include a plan regarding the necessary \nupdates on the evaluation of alternatives for CMR/ED phthalate s.  \nPending on new scientific evidence, i t is recommended to evaluate the use and \nusefulness of these Guidelines after an application  period of three years.  \n \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n35 \n  \n11.  Consideration of the responses received during the public \nconsultation process   \n \nA public consultation on these Guidelines was opened on the website of the non -food \nscientific committees from 18 March to 29 April 2019 . Information about the public \nconsultation was broadly communicated to national authorities, international \norganisation s and other stakeholders. A to tal of 197 submissions from 19  contributors \n(providing 378 comments  and additional references ) provided input to different chapters \nand subchapters of the document.  The vast majority of comments came from industry  \nand were requesting clarifications .  Each submission was carefully considered by the \nSCHEER and the scientific opinion has been revised to take account of relevant \ncomments. The literature has been accordingly updated with relevant publications. The \nSCHEE R expresses their thanks to all contributors for their comments and for the \nliterature references provided during the public consultation. The text of the comments \nreceived and the response provided by the SCHEER is available at:   \nhttps://ec.europa.eu/health/scientific_committees/consultations/public_consultations/sch\neer_consultation_08_en   \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n36 \n  \nB. REFERENCES  \n \n\uf0b7 Bui TT, Giovanoulis G, Cousins AP, Magn\u00e9r J, Cousins IT, de Wit CA. Human \nexposure, hazard and risk of alternative plasticizers to phthalate esters.  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The effects of phthalates in the \ncardiovascular and reproductive systems: A review.  Environ Int. 2016;94:758 -\n776. doi: 10.1016 /j.envint.2016.07.004.  \n \n\uf0b7 Mt-Isa S, Hallgreen C.E., Wang N., Callr\u00e9us T.,  Genov G., Hirsch I., Hobbiger S., \nHockley .S., Luciani D., Phillips L.D., Quartey G., Sarac S.B., Stoeckert I., Tzoulaki \nI., Micaleff A., Ashby D. , IMI-PROTECT benefit -risk participants.  Balancing benefit \nand risk of medicines a systematic review and clas sification of available \nmethodologies, Pharmacoepidemiol Drug Saf. 23(7):667 -78, 2014. doi: \n10.1002/pds.3636.  \n \n\uf0b7 Nielsen BS, Andersen BN, Giovalle E, Bjergstrom M, Larsen PB. Alternatives to \nclassified phthalates in medical devices. The Danish Environmental Protection \nAgency 2014, Copenhagen, Denmark  \n \n\uf0b7 Prowse CV, de Korte D, Hess JR, van der Meer PF; Biomedical Excellence for Safer \nTransfusion (BEST) Collaborative.Commercially available blood storage containers.  \nVox Sang. 106(1):1 -13, 2014. doi: 10.1111/vox.12 084.  \n \n\uf0b7 Salloum HA, Saunier J, Aymes -Chodur C, Barakat H, Yagoubi N. Impact of the \nnature and concentration of plasticizers on the ability of PVC to sorb drug. \nInternational Journal of Pharmaceutics 496, 664 \u2013675, 2015.  \n \n\uf0b7 SCHEER 2018 Memorandum on weight of evidence and  uncertainties. Revision \n2018. \nhttps://ec.europa.eu/health/sites/health/files/scientific_committees/scheer/docs/s\ncheer_o_014.pdf  \n \n\uf0b7 SCENIHR Opinion on The safety of medical devices containing DEHP  plasticized   \nPVC or other plasticizers on neonates and other groups possibly at risk (2015 \nupdate).  2015 \nhttps://ec.europa.eu/health/scientific_committees/emerging/docs/scenihr_o_047.\npdf \n \n\uf0b7 Simmchen J , Ventura R , Segura J . Progress in the removal of di -[2-ethylhexyl] -\nphthalate as plasticizer in blood bags. Transfus Med Rev. 2012; 26(1):27 -37. doi: \n10.1016/j.tmrv.2011.06.001. Epub 2011 Aug 5.  \n \n\uf0b7 Tortolano L, Matmati H, Bourhis M,Manerlax K, Lemare F, Saunier J,Yagoubi N. \nDinCH and ESBO actual migration from PVC infusion tubings used in an \noncopediatric unit. J. Appl. Polym.  Sci. 135, 46649, 2018.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n39 \n  \n\uf0b7 Treleano A,Wolz  G,Brandsch  R, Welle  F. Investigation into the sorption of \nnitroglycerin and diazepam intoPVC tubes and alternative tube materials during \napplication . Intl JPharmac 369, 30 \u201337, 2009.  \n \n\uf0b7 Welsh M, Saunders PT, Fisken M, Scott HM, Hutchison GR, Smith LB, Sharpe RM.  \nIdentification in rats of a programming window for reproductive tract \nmasculinization, disruption of which leads to hypospadias and cryptorchidism. J \nClin Invest. 2008 ; 118(4):1479 -90. doi: 10.1172/JCI34241.  \n \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n40 \n  \nC. ANNEXES  \n \nAnnex   1: SCHEER mandate on benefit -risk assessment on the use of CMR/ED phthalates  \n \n1. Background  \n \nWhat are phthalates?  \nPhthalates are the esters of 1,2 -benzenedicarboxylic acid (o -phthalic acid) and their \nchemical structure consists of one benzene  ring and two ester functional groups linked \nwith two consecutive carbons on the ring10. The hydrocarbon chains of the ester groups \nare either straight or branching; they give each substance its name and they are \nresponsible for the different properties amo ng phthalates. Phthalate esters (PEs) may be \ncategori sed into three distinct groups according to the length of their carbon chain. High \nmolecular weight (HMW) phthalates include those with 7 \u201313 carbon atoms in their carbon \nchain and low molecular weight (L MW) those with 3 \u20136 carbon atoms in their backbone. \nDEHP is classified as a LMW phthalate. A third group includes dimethyl phthalate (DMP) \nand diethyl phthalate (DEP)11. \n \nWhat are they used for?  \nPhthalates are widely used in industry as plastici sers of polym ers such as polyvinyl \nchloride (PVC). HMW phthalates are used in a variety of applications such as coated \nfabrics and roofing membranes.  LMW phthalates are used in medical devices, adhesives, \npaints, inks and enteric -coated tablets. DEHP is the most widel y used phthalate in \nmedical devices. DMP and DEP are not used as plastici sers but e.g. as  additives in \ncosmetics, medical devices, and household products.  \n \nPotential CMR  or endocrine -disrupting properties  \nThe interaction of phthalates with the polymers the y are embedded in is weak, so they \nmay migrate from the plastic product into the environment and into the human body if \nthe product is in contact with it.  \nCorrelation between exposure to a range of phthalates and adverse health effects has \nbeen documented in animals and humans (see for example tables in Mariana et al. 2016 \nand Katsikantami et al.  2016). A number of phthalates are suspected of and/or have \nbeen classified or identified as having CMR or endocrine -disrupting properties.  \n                                                           \n10 A global assessment of phthalates burden and related links to health effects. Katsikantami et al., Environ Int. \n2016 Dec;97:212 -236. https://www.ncbi.nlm.nih.gov/pubmed/?term=katsikantami   \n11 Footnote added by SCHEER. It should be noted that there are hundreds of phthalates of which only a limited \nnumber is used as plasticiser in polymers. Phthalates can be categorised according to the length of the carbon \nchain and one of these categorisations is mentioned in the mandate of DG GROW.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n41 \n  \nPrevious work of Commission Scientific Committees on phthalates  \nPrevious opinions on the most commonly used phthalate DEHP [di -(2-(ethylhexyl) \nphthalate] in medical devices were issued by EU Scientific Committees in 2002 \n(SCMPMD), 2008 and 2015 (SCENIHR). The 2008 Opinion concluded that \"So far, there is \nno conclusive scientific evidence that DEHP exposure via medical treatments has harmful \neffects in humans\",  but noted that \"newborn and pre -term born male infants are of \nspecial concern\" . In the 2015 Opinion, SCENIHR additi onally identified that \"patients \nsubject to haemodialysis procedure may be at risk of DEHP induced effects\" . The \nCommittee noted that \"Food is the primary source of exposure to DEHP for the general \npopulation.\"  \nIn both opinions, the Committee emphasised th at \"the benefit of the medical devices \nmust also be considered\"  and in the 2008 Opinion the Committee states that \"each \nalternative to DEHP, however, must also be evaluated with regard to their functionality in \nrespect to medical devices. The risk and bene fits of using alternative plasti cizers should \nbe evaluated case by case.\"  In the 2015 opinion, the Committee states that \u201cThe \npotential for replacement of DEHP in these products should be considered against their \nefficiency in the treatment, as well as the  toxicological profile and leaching properties of \nthe alternative materials.\u201d  \n \nThe legal obligation  \nArticle 5 paragraph 2 of the Regulation 2017/745 on medical devices stipulates: \"A \ndevice shall meet the general safety and performance requirements set out  in Annex I \nwhich apply to it, taking into account its intended purpose.\"   \nAccordingly, Section 10.4 of Annex I, which deals with substances in medical devices, \nstates that \"Devices shall be designed and manufactured in such a way as to reduce as \nfar as possible the risks posed by substances or particles, including wear debris, \ndegradation products and  processing residues, that may be released from the device.\"  \nParticular substances of concern are those which (a) are carcinogenic, mutagenic or toxic \nto reproduction (CMR),  of category 1A or 1B,12 or (b) have endocrine -disrupting \nproperties (ED)13. The Regulation states that:  \n \n\"Devices, or those parts thereof or those materials used therein that:  \n\uf02d are invasive and come into direct contact with the human body,   \n\uf02d (re)administer medicines, body liquids or other substances, including gases, \nto/from the body, or  \n\uf02d transport or store such medicines, body fluids or substances, including gases, to \nbe (re)administered to the body\"  \n \n                                                           \n12 in accordance with Part 3 of Annex VI to Regulation (EC) No 1272/2008  \n13 identified as such in accordance with the relevant provisions of Regulation (EC) No 1907/2006 or respectively \nof Regulation (EU) No 528/2012  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n42 \n shall only contain any such substance ab ove the concentration of 0.1% weight by weight \nwhere justified pursuant to Section 10.4.2. The justification shall be based on several \nelements, including the latest relevant scientific committee guidelines on benefit -risk \nassessment of the presence of suc h substance in devices.  \nAccording to Section 10.4.3, the Commission shall provide a mandate to the relevant \nscientific committee to prepare such guidelines for phthalates which are subject to these \nprovisions. These guidelines are explicitly requested by t he Regulation to be available at \nthe latest on the date of application of the Regulation, and are to be updated whenever \nappropriate on the basis of the latest scientific evidence, or at least every five years.  \n \n2. Terms of reference  \n \nThe Scientific Committee  is requested to provide guidelines on the benefit -risk \nassessment of the presence, in the medical devices specified below, of phthalates which \nhave one or more of the following properties: carcinogenic, mutagenic, toxic to \nreproduction or endocrine -disrup ting, according to the criteria outlined in the previous \nsection.  \nThe devices covered, or those parts thereof of those materials used therein, are those \nwhich:  \n\uf0b7 are invasive and come into direct contact with the human body,  \n\uf0b7 (re)administer medicines, body l iquids or other substances, including gases, \nto/from the body, or  \n\uf0b7 transport or store such medicines, body fluids or substances, including gases, to \nbe (re)administered  to the body.  \n \nThe guidelines shall include guidance on how, for an individual device, to: \n\uf0b7 analyse and estimate potential patient or user exposure to the substance,  \n\uf0b7 analyse possible alternative substances, materials, designs, or medical \ntreatments,  \n\uf0b7 to justify why possible substance and/or material substitutes, if available, or \ndesign change s, if feasible, are inappropriate in relation to maintaining the \nfunctionality, performance and the benefit -risk ratios of the product, including \ntaking into account if the intended use of such devices includes treatment of \nchildren or treatment of pregnan t or breastfeeding women or treatment of other \npatient groups considered particularly vulnerable to such substances and/or \nmaterials.  \n \nIn addition, the Scientific Committee is requested to : \n\uf0b7 identify any relevant knowledge gap , and \n\uf0b7 to give consideration to what extent of new evidence would be deemed \nappropriate to justify an update of these guidelines before the maximum period of \nfive years.  \n \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n43 \n  \nIn order to ensure the appropriateness of this guidance the Scientific Committee should \ninter alia : \n\uf0b7 involve at the appropriate level the notified bodies active in the field of medical \ndevices, or other relevant stakeholders such as Competent Authorities, \nprofessional and patient associations, industry associations, while maintaining \nscientific independence , \n\uf0b7 involve to the necessary extent the relevant EU Agencies  and Scientific \nCommittees.  \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n44 \n  \nAnnex  2: Medical Device Regulation (Regulation 2017/745) on CMR and/or ED \nsubstances  \n \nThe requirement for justification of the presence  of CMR 1A or 1B and/or ED hazardous \nsubstances is described in Annex I 10.4.2 as presented in the text box below.  \n \n \n \n10.4. Substances  \n \n10.4.1. Design and manufacture of devices  \n \nDevices shall be designed and manufactured in such a way as to reduce as fa r as possible the \nrisks posed by substances or particles, including wear debris, degradation products and \nprocessing residues that  may be released from the device.  \nDevices, or those parts thereof or those materials used therein that:  \n \n\u2014 are invasive and come into direct contact with the human body,  \n \n\u2014 (re)administer medicines, body liquids or other substances, including gases, to/from the \nbody, or  \n \n\u2014 transport or store such medicines, body fluids or substances, including gases, to be \n(re)administered to the body,  \n  \nshall only contain the following substances in a concentration that is above 0,1 % weight by \nweight (w/w) where justified pursuant to Section 10.4.2:  \n  \n(a) substances which are carcinogenic, mutagenic or toxic to reproduction (\u2018CMR\u2019), of category \n1A or 1B, in accordance with Part 3 of Annex VI to Regulation (EC) No 1272/2008 of the \nEuropean Parliament and of the Council (1), or  \n  \n(b) substances having endocrine -disrupting properties for which there is scientific ev idence of \nprobable serious effects to human health and which are identified either in accordance with the \nprocedure set out in Article 59 of Regulation (EC) No 1907/2006 of the European Parliament \nand of the Council (2) or, once a delegated act has been ad opted by the Commission pursuant \nto the first subparagraph of Article 5(3) of Regulation (EU) No 528/2012 of the European \nParliament and the Council (3), in accordance with the criteria that are relevant to human \nhealth amongst the criteria established the rein.  \n \n10.4.2. Justification regarding the presence of CMR and/or endocrine -disrupting substances  \n \nThe justification for the presence of such substances shall be based upon:  \n(a) an analysis and estimation of potential patient or user exposure to the subs tance;  \n(b) an analysis of possible alternative substances, materials or designs, including, where \navailable, information about independent research, peer -reviewed studies, scientific opinions \nfrom relevant scientific committees and an analysis of the avail ability of such alternatives;  \n(c) argumentation as to why possible substance and/ or material substitutes, if available, or \ndesign changes, if feasible, are inappropriate in relation to maintaining the functionality, \nperformance and the benefit -risk ratio s of the product; including taking into account if the \nintended use of such devices includes treatment of children or treatment of pregnant or \nbreastfeeding women or treatment of other patient groups considered particularly vulnerable to \nsuch substances an d/or materials; and  \n(d) where applicable and available, the latest relevant scientific committee guidelines in \naccordance with Sections 10.4.3 and 10.4.4.  \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n45 \n  \nAnnex 3:  Definitions/descriptions \u2013 References - Glossary  \n \nDefinitions ( Regulation  (EU) 2017/745 ) \n \nBenefit -risk determination:  means the analysis of all assessments of benefit and risk \nof possible relevance for the use of the device for the intended purpose, when used in \naccordance with the intended purpose given by the manufacturer.  \n \nPerformance:  means the ability of a device to achieve its intended purpose as stated by \nthe manufacturer.  \n \nClinical performance:  means the ability of a device, resulting from any direct or \nindirect medical effects which stem from its technical or functional characteri stics, \nincluding diagnostic characteristics, to achieve its intended purpose as claimed by the \nmanufacturer, thereby leading to a clinical benefit for patients, when used as intended by \nthe manufacturer.  \n \nClinical benefit:  means the positive impact of a de vice on the health of an individual, \nexpressed in terms of a meaningful, measurable, patient -relevant clinical outcome(s), \nincluding outcome(s) related to diagnosis, or a positive impact on patient management or \npublic health.  \n \nRisk: means the combination of the probability of occurrence of harm and the severity of \nthat harm.  \n \nAdverse event:  means any untoward medical occurrence, unintended disease or injury \nor any untoward clinical signs, including an abnormal laboratory finding, in subjects, \nusers or othe r persons, in the context of a clinical investigation, whether or not related to \nthe investigational device.  \n  \nSerious adverse event:  means any adverse event that led to any of the following: (a) \ndeath, (b) serious deterioration in the health of the subjec t, that resulted in any of the \nfollowing: (i) life -threatening illness or injury, (ii) permanent impairment of a body \nstructure or a body function, (iii) hospitali sation or prolongation of patient hospitali sation, \n(iv) medical or surgical intervention to p revent life -threatening illness or injury or \npermanent impairment to a body structure or a body function, (v) chronic disease, (c) \nfetal distress, fetal death or a congenital physical or mental impairment or birth defect.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n46 \n   \nIncident:  means any malfunction or deterioration in the characteristics or performance \nof a device made available on the market, including use -error due to ergonomic features, \nas well as any inadequacy in the information supplied by the manufacturer and any \nundesir able side -effect.  \n \nSerious incident:  means any incident that directly or indirectly led, might have led or \nmight lead to any of the following: (a) the death of a patient, user or other person, (b) \nthe temporary or permanent serious deterioration of a pati ent's, user's or other person's \nstate of health, (c) a serious public health threat.  \n \nSerious public health threat : means an event which could result in imminent risk of \ndeath, serious deterioration in a person's state of health, or serious illness, that may \nrequire prompt remedial action, and that may cause significant morbidity or mortality in \nhumans, or that is unusual or unexpected for the given place and time.  \n \nDevice deficiency:  means any inadequacy in the identity, quality, durability, reliability,  \nsafety or performance of an investigational device, including malfunction, use errors or \ninadequacy in information supplied by the manufacturer.  \n \nRegulation (EU) 2017/745 Annex XIV Clinical evaluation and post -market \nclinical follow -up. Part A \u201cClinical evaluation\u201d Section 3 describes the \ncharacteristics that shall be considered for demonstration of equivalence .  \n\u201cA clinical evaluation may be based on clinical data relating to a device for which \nequivalence to the device in question can be demonstrated. T he following technical, \nbiological and clinical characteristics shall be taken into consideration for the \ndemonstration of equivalence:  \n \nTechnical : the device is of similar design; is used under similar conditions of use; has \nsimilar specifications and pr operties including physicochemical properties such as \nintensity of energy, tensile strength, viscosity, surface characteristics, wavelength and \nsoftware algorithms; uses similar deployment methods, where relevant; has similar \nprinciples of operation and cr itical performance requirements;  \n  \nBiological : the device uses the same materials or substances in contact with the same \nhuman tissues or body fluids for a similar kind and duration of contact and similar release \ncharacteristics of substances, including de gradation products and leachables;  \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n47 \n  \nClinical : the device is used for the same clinical condition or purpose, including similar \nseverity and stage of disease, at the same site in the body, in a similar population, \nincluding as regards age, anatomy and physiology; has the same kind of user; has \nsimila r relevant critical performance in view of the expected clinical effect for a specific \nintended purpose.  \nThe characteristics shall be similar to the extent that there would be no clinically \nsignificant  difference in the safety and clinical performance of the device. Considerations \nof equivalence shall be based on proper scientific justification. It shall be clearly \ndemonstrated that manufacturers have sufficient levels of access to the data relating  to \ndevices with which they are claiming equivalence in or der to justify their claims of \nequivalence. \u201d \n \nDefinitions on assessment of alternatives (OECD Toolbox Glossary)  \nNote: The term \"chemical\" is used synonymously with \"substance\"  \n \nAlternativ es assessment : A process for identifying and comparing potential chem ical \nand non -chemical alternatives that can be used as substitutes to replace chemicals or \ntechnologies of high concern1 \n \nChemical substitution : The process of replacing a chemical of concern with a safer \nchemical, material or product, or technology/process that eliminates the need to use that \nchemical  \n \nCost/benefits and availability : The negative (cost) and positive (benefit) implications, \ndirect and indirect, resulting from some actio n. This includes both financial and non -\nfinancial information. Availability refers to the production of an alternative and its market \naccessibility3 \n \nFunctional use approach : This approach starts with identifying the function that is \ndesired. The concept is applied in two ways: \ufb01rst and foremost, to characteri se the \npurpose a chemical or mixture serves, or the properties it imparts in a product or process \n(functional use), and second, to eva luate the function of the product and how its use may \nin\ufb02uence the assessment of alternatives4, 5 \n \nMaterial substitution : The process of replacing a material containing a chemical of \nconcern with a safer chemical, material, product or technology/process that eliminates \nthe need to use that chemical  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n48 \n  \nMixture : A composition of at least two chemicals in which they do not react6 \n \nTechnical feasibility : The determination as to whether the performance or functional \nrequirements of a chemical, material or product could be fulfilled or replaced by \neliminating or using an alternative chemical, material, product, process or technology, \nwhile considering any need for process adaptations and changes3 \n \nProcess modification : Changes in manufacturing processes to eliminate, reduce or \nsubstitute chemicals of concern. Such changes may include synthesis pathways, waste \nreduction, and manufacturing procedures where chemicals are used.  \n \nProduct performance : The ability of a product to meet identified performance \nrequirements. The boundaries of performance characteristics are defined by the user3 \n \nProduct substitution : The process of replacing a product containing a chemical of \nconcern with a chemical, material or product or technology/process that eliminates, \nreduces or substitutes the need to use that chemical.  \n \n1 Adapted from Alternatives Assessment Guide, version 1.0 . 2013. Interstate Chemicals \nClearinghouse.  \n2 REACH. Title I, Chapter 2, Article 3.  \n3 Current Landscape of Alternatives Assessment Practice: A Meta -Review. Organisation \nfor Economic Cooperation and Development. 2013.  \n4 U.S. EPA. 2006. National Pollution Prevention and Toxics Advisory Committee (NPPTAC) \nRecommendation to the EPA Administrat or and Deputy Administrator on Incorporating \nthe Functional Use Approach into OPPT Activities.  \n5 Lavoie, E. T., et al.  2010. \"Chemical Alternatives Assessment: Enabling Substitution to \nSafer Chemicals.\" Environmental Science & Technology 44(24): 9244 -9249.  \n6 Adapted from U.N. Global Harmonized System of Classification and Labelling  of \nChemicals . 2003.  \n7 ECHA, 2008. Guidance on Socio -Economic Analysis - Restrictions.  \n8 Adverse event means pre -clinical and clinical occurrences of an effect whereas incident \nindicates a clinical effect occurring during post -market surveillance.  \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n49 \n  \nReference s \n\uf0b7 ECHA (2011) Guidance on the preparation of socio -economic analysis as part of \nan application for authorisation, European Chemicals Agency 2011 . \n\uf0b7 EFSA (2019)  Draft update of the risk assessment of di -butylphthalate 1 (DBP), \nbutyl-benzyl -phthalate (BBP), bis(2 -2 ethylhexyl)phthalate (DEHP), di -\nisononylphthalate (DINP) 3 and di -isodecylphthalate (DIDP) for use in food \ncontact 4 materials  http://www.efsa.europa.eu/en/consultations/call/190221 .  \n\uf0b7 Guo JJ, Pandey S, Doyle J, Bian B, Lis Y, Raisch DW. A review of quantitative risk -\nbenefit methodologies for assessing drug safety and efficacy -report o f the ISPOR \nrisk-benefit management working group. Value Health. 2010;13(5):657 -66. \n \nGlossary  \nBBP   Benzylbutylphthalate  \nBMD  Bench Mark Dose  \nBRA  Benefit -Risk Analysis  \nBTHC   Butyryl -tri-n-hexylcitrate  \nCAS  Chemical Abstracts Service  \nCEN  European Committee for Standardization  \nCLP  Classification Labelling and Packaging regulation (EC No 1272/2008)  \nCMR  Carcinogenic, Mutagenic, toxic to Reproduction (Reprotoxic)  \nDBP   DiButylphthalate,  \nDCHP   Dicyclohexylphthalate  \nDEHP   Diethylhexylphthalate  \nDIBP   Diisobutylphthalate  \nDIDP   Di isodecyl phthalate)  \nDINCH  1,2- cyclohexan edicarboxylic acid, di isononyl ester)  \nDINP   Di isononyl phthalate)  \nDIPP  Diisopentylphthalate  \nDMEP   Bis(2-methoxyethyl)phthalate  \nDNHP   Dihexylphthalate  \nDHNUP  1,2-Benzenedicarboxylic acid, di -C7-11-branched and linear alkyl esters  \nDPP   Dipentyl phthalate  \nDMEL   Derived Minimum Effect Level  \nDNEL   Derived No Effect Level  \nEC  European Commission  \nECB  European Chemicals Bureau (now ECHA)  \nECHA   European Chemicals Ag ency (formerly ECB)  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n50 \n ED  Endocrine Disruptor  \nEEC  European Economic Community  \nEMA  European Medicines Agency  \nEFSA  European Food Safety Authority  \nEN-ISO CEN and ISO combined published document  \nFDA  Food and Drug Administration (USA)  \nFDIS  Final Draft International Standard  \nISO  International Organization  for Standardization  \nLOAEL   Lowest Observed Adverse Effect Level  \nMCDA   Multi Criteria Decision Analysis  \nMDD  Medical Device Directive (Council Directive 93/42/EEC)  \nMDR  Medical Device Regulation (EU 20 17/745)  \nMoA  Mode of Action \nMoE  Margin of Exposure  \nMoS  Margin of Safety  \nNICU  Neonatal Intensive Care Unit  \nNOAEL   No Observed Adverse Effect Level  \nOECD   Organization for Economic Cooperation and Development  \nPoD  Point of departure  \nPVC  Polyvinyl chloride  \nRBC  Red Blood Cell  \nRCR  Risk Characterisation Ratio  \nREACH   Registration, Evaluation, Authorisation and restriction of CHemicals.  \nSCHEER  Scientific Committee on Health, Environmental and Emerging Risks  \nSCENIHR  Scientific Committee on Emerging and Newly Identified Health Risks  \nT25   25 % increase of the tumour rate over controls  \nTDI  Tolerable Daily Intake  \nTE  Tolerable Exposure (EN ISO 10993 -17:2002 in mg/day)  \nTEHTM   Tri( 2 -ethyl hexyl)trimellitate also TOTM Trioctyltrimellitate  \nTI  Tolerable Intake  \nTOTM   Trioctyltrimellitate also TEHTM Tri( 2 -ethyl hexyl)trimellitate  \nTWI    Tolerable Weekly Intake   Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n51 \n  \nAnnex 4:  CMR and/or ED substances  \n \nCMR substances are substances identified and classified as carcinogenic, mutagenic or \ntoxic for reproduction of different categories based on the intrinsic toxic properties of a \nsubstance for which categories 1A and 1B apply to these Guidelines. In Europe, \nclassification for  these endpoints is harmonised through harmonised classification and \nlabelling (CLH). Details  can be found at  \nhttps://echa.europa.eu/regulations/clp/understanding -clp. For a specific substance to be \nclassified as CMR 1A, 1B or 2 a dossier needs to be prepared and if the Commission finds \nthat the proposed classification is appropriate, it submits a draft decision concerning the \ninclusion of that substance in Part 3 of Annex VI to the CL P Regulation (Regulation (EC) \n1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures).  \n\uf0b7 Category 1A means that the substance is a known human carcinogen, mutagen or \nreproductive toxicant based on human evidence.  \n\uf0b7 Category 1B means that the substance is a presumed human carcinogen, \nmutagen or reproductive toxicant based on animal studies.  \n\uf0b7 Category 2 means that a substance is considered as suspected carcinogen, \nmutagen or reproductive toxicant based on limited evidence from ani mal studies \nor humans  (not part of these Guidelines) .  \nDocuments on the classification are publicly available , and  a tutorial to search entries is \ngiven here:  \nhttp://www.chemsafetypro.com/Topics/EU/Annex_VI_to_CLP:_List_of_Harmonised_Class\nification_and_Labelling_for_Certain_Hazardous_Substances.html  \nGuidance for the identification of endocrine disrupto rs (ED) in the context of Regulations \n(EU) No 528/2012 and (EC) No 1107/2009 has been published on 7th June 2018 by \nECHA and EFSA (doi: 10.2903/j.efsa.2018.5311; EFSA Journal 2018;16(6):5311) which \ncan be accessed via:   \nhttps://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2018.5311  \nThis EFSA/ECHA Guidance describes when a substance shall be considered as having \nendocrine disrupting  properties.  \n\u201cA  substance shall be considered as having endocrine disrupting properties  if it meets all \nof the following criteria:  \na) it shows an adverse effect in [an intact organism or its progeny]/[non -target \norganisms], which is a change in the morphology, physiology , growth, \ndevelopment, reproduction or life span of an organism, system or \n(sub)population6 that results in an impairment of functional capacity, an \nimpairment of the capacity to compensate for additional stress or an increase in \nsusceptibility to other in fluences;  \nb) it has an endocrine mode of action, i.e. it alters the function(s) of the endocrine \nsystem;  \nc) the adverse effect is a consequence of the endocrine mode of action.  \nIt should be highlighted that the \u2018endocrine mode of action \u2019 as stated in point  (b) \nshould be interpreted  as \u2018endocrine activity \u2019 while the term \u2018endocrine mode of Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n52 \n action\u2019 in point (c) covers the link between the adverse effect and the endocrine activity \nidentified in points a) and b), respectively.  \nKeeping this in mind point (b) abo ve should be understood as (differences from above in \nitalics ): \nit shows endocrine  activity, i.e. it has the potential to alter the function(s) of the \nendocrine system;  \nConsequently point (c) above should be understood as (differences from above in italics ): \nthe substance has an endocrine disrupting mode of action, i.e. there is a \nbiologically plausible link between the adverse effect and the endocrine activity. \u201d \nEDs identified with the procedure set out in Article 59 of Regulation (EC) No 1907/2006 \nconcern ing the Registration, Evaluation, Authorisation and Restriction of Chemicals \n(REACH),   will finally enter the REACH candidate list of substances of very high concern \nfor potential inclusion in REACH Annex XIV.  The information can be found in the \nrespecti ve decision document accessible via : https://echa.europa.eu/candidate -list-table. \nFor substances having endocrine -disrupting properties as indicated above, there is \ncurrently no information concer ning whether it is foreseen to publish them in central lists \nor annexed to a Regulation.  \nEDs identified by the delegated act pursuant to the first subparagraph of Article 5(3) of \nRegulation (EU) No 528/2012 concerning the making available on the market and  use of \nbiocidal products, can be accessed through the Biocidal Products Committee opinions on \nactive substance approval which can be accessed via ECHA\u2019s website \n(https://echa.europa.eu/regulations/biocidal -products -regulation/approval -of-active -\nsubstances/bpc -opinions -on-active -substance -approval ).  \nSubstances undergoing an ED assessment under the REACH or Biocidal Products \nregulations that have been brought for discussion to ECHA\u2019s ED Expert Group are \nincluded in ECHA\u2019s endocrine disruptor (ED) assessment list: https://echa.europa.eu/ed -\nassessment . For each substance, the table shows the assessing or evaluating Member \nState (submitter), the outcome and the suggested follow -up for the assessment, and the \ndate of the latest update to the list entry.  \nRecently the Commission Implementing Decision (EU) 2017/1210 was published that \nidentified some phthalates (Bis(2 -ethylhexyl) phthalate (DEHP), Benzyl butyl phthalate \n(BBP), Dibutyl phthalate (DBP) and Diisobutyl phthalate (DIBP)) as substances of very \nhigh concern due to their endocrine disrupting properties with probable serious effects to \nhumans (European Commission 2017).  \nhttps://publications.europa.eu/en/publication -detail/ -/publication/357b3d45 -620f-11e7-\n9dbe-01aa75ed71a1/language -en/format -PDF \nFor completeness, even if not relevant for the purpose of this guidelines, Bis(2 -\nethylhexyl) phthalate (DEHP) was also  identified in 2014 as a substance of very high \nconcern due to its endocrine disrupting properties with probable serious effects to the \nenvironment.  \nIn addition, Commission Implementing Decision (EU) 2018/636 identified \nDicyclohexylphthalate (DCHP) as subs tance of very high concern (SVHC) according to \nArticle 57(f) of REACH Regulation (EC) 1907/2006, due to its endocrine disrupting Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n53 \n properties with probable serious effects to humans.  https://eur -lex.europa.eu/legal -\ncontent/EN/TXT/PDF/?uri=CELEX:32018D0636&fr om=EN     Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n54 \n  \nAnnex 5:  Legislation on CMR and/or ED phthalates  \n \nDue to their reprotoxic properties and additionally since 2014 for DEHP due to their \nendocrine disrupting properties for the environment and since 2017 for DEHP, BBP, DBP, \nand DIBP  due to their endocrine disrupting properties  for human health , a considerable \nnumber of phthalates have been identified as substances of very high concern (SVHC) \nand therefore included in the candidate list for the inclusion in Annex XIV of the REACH \nregulation (Annex XIV of REACH EC 1907/2006 , see \nhttps://echa.europa.eu/de/candidate -list-table for the most recent update of the \ncandidate list).  \nEight phthalates are also listed on the Authorisation list (Annex XIV of REACH), namely \nDEHP, BBP, DIBP, DBP, DIPP (diisopentylphthalate), Bis(2 -methoxyethyl) phthalate, \ndipentyl phthalate, and N -pentyl -isopentylphthalate. Since February 2015 DEHP, BBP, \nDIBP, and DBP cannot be used within the European Union withou t authorisation. The \nsame provision would apply to the remaining four phthalates on Annex XIV from July \n2020. To date, applications for authorisation have been submitted for DEHP and DBP \nonly. However, imported articles do not come under the authorisation requirement. For \nthe purpose of evaluating applications for authorisation, the ECHA Committee for Risk \nAssessment (RAC) has developed reference DNELs for several substances, including \nDEHP, BBP, DBP, and DIPP. (See Evaluating Applications table/Ref erence D NELs on \nECHA\u2019s website:  \nhttps://echa.europa.eu/applying -for-authorisation/evaluating -applications .) \nRisks to human health arising from the use of an Annex XIV substan ce in medical devices \nregulated by Directives 90/385/EEC, 93/42/EEC or 98/79/EC are exempted from \nauthorisation requirements under Title VII of the REACH Regulation14. ECHA is currently \npreparing a recommendation on the inclusion of the ED properties for environment for \nDEHP in Annex XIV to REACH .15 If DEHP is included on Annex XIV for environmental \nhazards , applications for authorisations may need to be prepared for uses of the \nsubstance in medical devices in the future.  \nREACH Annex XVII (entry 51) also restricts the placing on the market of articles \ncontaining DEHP, BBP, DBP, and DIBP in concentration greater than 0.1% weight by \nweight of the plasticised material, individually or in combination in a range of articles. \nThese articles include toys16 and childcare articles, as well as other primarily consumer \nand professional use articles whic h lead to dermal or inhalation exposure. (For risk \nassessment conclusions, including derivation of a DNEL for DIBP, see Compiled RAC & \nSEAC opinion and background document on ECHA\u2019s website:  \nhttps://echa.europa.eu/previous -consultations -on-restriction -proposals/ -/substance -\nrev/13919/term .)   \n                                                           \n14 These Regulations will be replaced by:  \n\uf0b7 Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical \ndevices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No \n1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC  \n\u2022Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro  \ndiagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU  \n15 https://echa.europa.eu/draft -recommendation -for-amendment -of-authorisation -list-entries -previous -\nconsultation   \n16 The Toy Safety Directive (2009/48/EC) stipulates that chemicals that are susceptible to cause cancer, change \ngenetic information, harm fertility or harm an unborn child (CMR substances) are no longer allowed in \naccessible parts of toys beyond the concentration limits set in the CLP Regulation ((EC) No 1272/2008).  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n55 \n REACH Annex XVII (entry 52) restricts the placing on the market and the use of DINP, \nDIDP, and DNOP, as a  substance or in mixture, in concentrations greater than 0.1% \nweight by weight of the plasticised material in toys and childcare articles which can be \nplaced in the mouth of children. In 2010, the European Commission requested ECHA to \nreview the scientific  evidence on the risks posed by articles containing these phthalates \nwith the view to conclude on the need or not for further actions under REACH. The report \nand RAC risk assessment conclusions (including information on the derivation of DNELs) \ncan be foun d on ECHA\u2019s website: https://echa.europa.eu/consultations -draft-review -\nreport -previous -consultations/ -/substance -rev/1108/term .  \nEFSA recently launched a consultation on its updated 2005 risk assessments of DBP, \nBBP, DEHP, DINP and DIDP which are authorised for use in plastic FCM, by using the \nsame database as ECHA for its 2017 assessment of certain phthalates. The draft update \nof the ri sk assessment can be found here:  \nhttp://www.efsa.europa.eu/en/consultations/call/190221  \nIn addition to the REACH legislation, there is also product -specific legislation which \nregulates certain phthalates, i.e. the Cosmetic Products\u2019 Regulation (EC/1223/2009) and \nthe Regulation on materials and articles intended to come into contact with food ( Food \nContact Materials,  Regulation EC 1935/2004 , as general framework regulation and \nRegulation EU 10/2011 specific for plastic materials and articles destined to be in contact \nwith foodstuffs , recently amended by Regulation 2018/831 ). Both in the MDD \n(93/42/EEC) and the more recent MDR (2017/745), phthalates are specifically mentioned \nfor their use in medical devices.  \nFor a number of phthalates there is legislation available that might contain information \nrelevant for the use of phthalates in medical devices. Of specific relevance for medical \ndevices may be the Regulation EU 10/ 2011, which also incl udes provisions for the use of \nphthalates in food contact materials and articles with respect to migration limits. This \nmay be a parallel with migration (and thus potential internal exposure) of phthalates as \npresent in polymers used for medical device man ufacturing. In Annex I of the Regulation \nEU 10/2011 all substances are listed, which are authorised for the use as starting \nmaterial or additive for plastic layers in plastic materials and articles. Each substance \nmust not exceed its specific migration lim it (SML). The following phthalates and other \nplastici sers17 are authorised for use as additives:  \n \nDBP (SML) = 0.3 mg/kg food  \nonly to be used as:  \n(a) plasticiser in repeated use materials and articles in contact with  non -fatty foods;   \n(b) technical supp ort agent in polyolefins in concentrations up to 0.05% in the final  \nproduct  \n \nBBP, SML = 30 mg/kg food  \nOnly to be used as:  \n(a) plasticiser in repeated use materials and articles;  \n                                                           \n17 Not exhausti ve examples for other than phthalates  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n56 \n (b) plasticiser in single -use materials and articles in contact with  non -fatty foods, not for \ncontact with infant formulae and follow -on formulae (Directive 2006/141/EC) and \nprocessed cereal -based foods and baby foods for infants and young children (Direc tive \n2006/125/EC);  \n(c) technical support agent in concentrations up to 0.1% in the final product.  \n \nDEHP, SML = 1.5 mg/kg food   \nOnly to be used as:  \n(a) plasticiser in repeated use materials and articles in contact with non -fatty foods;  \n(b) technical su pport agent in concentrations up to 0.1% in the final product.  \n \nDINP SML = 9 mg/kg food (cumulative with DIDP)  \nonly to be used as  \n(a) plasticiser in repeated use materials and articles;  \n(b) plasticiser in single -use materials and articles in contact with  non -fatty foods , not \nfor contact with  infant formulae and follow -on formulae ( Directive 2006/141/EC) and \nprocessed cereal -based foods and baby foods for infants and young children (Di rective \n2006/125/EC)  \n(c) technical support agent in concentrations up to 0.1% in the final product.   \n \nDIDP, SML = 9 mg/kg food ( cumulative with DINP)  \nOnly to be used as  \n(a) plasticiser in repeated use materials and articles;  \n(b) plasticiser in single -use materials and articles in contact with  non -fatty foods , not \nfor contact with infant formulae and follow -on formulae ( Directive 2006/141/EC) and \nprocessed cereal -based foods and baby foods for infants and young children (Directive \n2006/125/EC)  \n(c) te chnical support agent in concentrations up to 0.1% in the final product.   \n \nFurthermore, for certain plasticizers listed in Regulation (EU) 10/2011, including a \nnumber of phthalates, applies a group restriction  (Group restriction number 32),  that is, \nthe sum of these substances must not exceed an SML of 60 mg/kg foodstuff.  \nDEHP, BBP, DBP and DIBP must not be contained in homogenous materials above the \nconcentration of 0.1% w/w from July 2019 on according to the Restriction of Hazardous \nSubstances Directive  in electrical and electronic equipment RoHS2 (2011/65/EC). For \nmedical devices and  in vitro  diagnostic products this restriction takes effect in July 2021.  \n \n \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n57 \n  \nTable 1  CMR Classification*) and ED designation**) of phthalates (status Jan 2019)  \nPhthalate  Abbreviation  CAS \nnumber  CMR \nClassification*  ED \nidentification**  \nbis(2-\nmethoxyethyl)phthalate  DMEP  117-82-\n8 Repr 1B  - \nbis  \n(2-ethylhexyl)phthalate  DEHP  117-81-\n7 Repr 1B  ED \ndibutyl phthalate  DBP 84-74-2 Repr 1B  ED \n1,2-\nbenzenedicarboxylic \nacid, dipentylester, \nbranched and linear   84777 -\n06-0 Repr 1B  - \nn-pentyl -\nisopentylphthalate  PIPP No CAS  \n776297 -\n69-9? Repr 1B  - \ndi-n-pentyl phthalate  DnPP 131-18-\n0 Repr 1B  - \ndiisopentylphthalate  DiPeP  605-50-\n5 Repr 1B  - \nbenzyl butyl phthalate  BBP 85-68-7 Repr 1B - ED \ndiisobutylphthalate  DIBP 85-69-5 Repr 1B  ED \ndihexylphthalate  DHP 84-75-3 Repr 1B   \ndicyclohexylphthalate  DCHP  84-61-7 Repr 1B  ED \n*) as indicated in Annex VI to CLP_ATP10 (in force from 1 December 2018).  \n**) according to the ECHA Candidate List of substances of very high concern for Authorisation  published in \naccordance with Article 59(10) of the REACH Regulation  https://echa.europa.eu/candidate -list-table  \n \nAs substances of concern, knowledge on the exposure to phthalates is important and \nbiomonitoring of populations provides important information.  For some of the phthalates \nalready human biomonitoring assessment values, namely Biomonitoring equi valents (BE) \nor human biomonitoring (HBM) values, have been derived \u2013 these are concentrations of \nbiomarkers (metabolites) in urine, which reflect an acceptable chronic exposure, since \nthe basic assumption is an equilibrium between external exposure and in ternal burden \n(Angerer et al.  2011, Apel et al.  2017). In the course of the work done within the \nHBM4EU project, Human Biomonitoring Guidance Values (HBM -GVs) could be derived for \nDEHP and DINCH (see HBM4EU Deliverable D5.2, https://www.hbm4eu.eu ). In addition, \nHBM-GVs for the following SVHC phthal ates are finalised in September 2019 (Deliverable \nD5.6) and will also be published on the website: BBzP, DiBP, and DnBP.   Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n58 \n  \nAnnex 6:  Use of phthal ates in medical devices  \n \nPhthalates are abundantly used in polyvinyl chloride (PVC) medical devices such as blood \nbags, intravenous bags, nutrition pockets, tubing, catheters, respiratory masks or \ndisposable gloves. More than 40% of all plastic -based disposable medical devices are  \nmade from PVC. Di -2-ethylhexyl phthalate (DEHP) has been for many years the most \ncommonly used phthalate ester plasticiser in medical devices. A survey among the \nDanish Medical Device Industry found that 95% of the products contained DEHP [Huntley \nP, edit or The classified phthalates should be phased out of medical devices. Alternatives \nto Classified Phthalates in PVC Medical Devices Conference; 2014 Mar 27; Copenhagen, \nDenmark].  \n \nSafety concerns have been expressed for several high -risk patients groups, s uch as \nneonates, infants, pregnant and breast -feeding women exposed to DEHP. The SCENIHR \nin its Opinion of 201 5 indicated that \u201ca lack of evidence of causation between DEHP -PVC \nand any disease or adverse effect does not mean that there are no risks\u201d. This lack of \nevidence applies to all phthalates classified as CMR and/or identified as ED. Therefore the \nrequirement of patient subgroup analysis for the target patient groups as defined in the \n\u201cIntended Use\u201d of a medical device is now included in the Regulatio n (EU) 2017/745.  \n \nFor the use of DEHP, high risk groups were identified including patients undergoing \nhaemodialysis, extracorporeal membrane oxygenation (ECMO), and prematurely born \ninfants in Neonatal Intensive Care Units (NICU), (SCENIHR 201 5). The actua l exposure of \nsuch patient groups relative to the toxicity including CMR/ED property needs to be \ndetermined. However, even if the remaining risk is high, the benefit of the treatment \nshould be considered as well. It might be useful to evaluate the patient subgroups \nseparately:  \n \n\uf0b7 Paediatric Population (see subgroups)  \n\uf0b7 Peripubertal males  \n\uf0b7 Pregnant women  \n\uf0b7 Breast -feeding women  \n\uf0b7 any other patient group considered particularly vulnerable or exposed to high \nlevels of phthalates.  \n \nFor purposes of this Guideline, the following ranges of paediatric subpopulations are \nproposed to be used as a guide for manufacturers in medical devices (ref. SCCS Notes of \nGuidance \u2013 SCCS/1602/18, section 3 -6.9.1, page 7818) \n \n \n \n \n \n \n \n \n                                                           \n18 https://ec.europa.eu/health/sites/health/files/scientific_committees/consumer_safety/docs/sccs _o_224.pdf   Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n59 \n  \nDefinition of Paediatric Population Subgroups  \n \nPaediatri c Subgroup  Approximate Age Range  \nFull-term neonate  <1 week  \nNewborn  1 week\u20132 months  \nEarly infant  2\u20136 months   \nCrawlers/toddler  6 months \u20132 years  \nPreadolescent  2\u201312 years   \nAdolescent  12\u201318 years   \n \nIn view of ED activity, a dditional (paediatric ) subpopulations may need to be considered \ninclud ing:  \n \n\uf0b7 very low birth weight describes newborns less than 1.5 Kg  \n\uf0b7 low birth weight describes newborns less than 2.5 Kg  \n\uf0b7 preadolescent age group typically ranges from 11 to 13 years.  \n\uf0b7 peripubertal males  or females  \n \nIt should be realised that the benefit of medical devices including the use of phthalates \nmust also be considered: The survival of prematurely born infants often depends on the \navailability of the same medical devices that result in a relative ly high phthalate content \nexposure due to treatment. Whenever possible, material with low release potential \nshould be used (see SCENIHR opinion 201 5). \n \nBesides the direct patient benefits of the treatment with a medical device containing \nphthalates, other functionalities may also need to be considered.  For example, DEHP has \na stabilising effect on red blood cells (RBCs). RBCs have increased survival rates when \nstored in DEHP containing blood bags. DEHP is incorporated into the cell walls of RBCs \nand stabil ises the membrane integrity of the RBCs. This results in a prolonged shelf life \nand thus patient availability of blood stored in DEHP containing blood bags (SCENIHR \n2015). A maximum limit of extractable DEHP of 15 mg/100 mL for flexible PVC \ncontaining DEHP  is indicated in EN ISO 3826 -1 on containers for the collection of human \nblood and blood components.   \n \nThe plasticiser industry has been investing and developing alternatives to DEHP in \nmedical devices. Today, other plasticisers such as Di -isononyl cyclohe xanoate (DINCH, \nCAS 166412 -78-8), Tri -2-ethylhexyl trimellitate (TEHTM, CAS 3319 -31-1), butyryl tri -n-\nhexyl citrate (BTHC, CAS 102818 -95-1) and Dioctyl Terephthalate (DOTP, CAS \u200e6422-86-\n2) are being proposed in medical applications such as medical tubing and blood bags.  \nhttps://www.plasticisers.org/applications/medical -applications/   \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n60 \n In conclusion, for any BRA on the use of phthalates and the development of alternatives \nin me dical devices, careful consideration should be used to appropriate patient subgroup \nanalysis regarding medical device use and the resulting potential exposure.  \n \nReference  \nHuntley P, Editor . The classified phthalates  should be phased out of medical devices. \nProgram Meeting on Alternatives to Classified Phthalates in PVC Medical Devices \nConference; 2014 Mar 27; Copenhagen, Denmark.  \nhttps://pvc.dk/wp -content/uploads/2016/02/pvc -alternativer -til-klassificerede -ftalater -\nprogram.pdf  \n \n \n   Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n61 \n  \nAnnex 7:  Approaches for Benefit -Risk Assessment  \n \nSeveral approaches for BRA have been proposed especially in the context of medicinal \nproducts. The Innovative Medicines Initiative PROTECT Project (www.imiprotect.eu), \npresented a detailed review of approaches used for BRA (Mt -Isa et al.  2014). In this \nreview, a large number of approaches were identified and classified as descriptive \n(qualitative or semi -qualitative) or quantitative frameworks (relying on quantitative \nmethods of trading risks and benefits following mathematical principles), metrics \n(measure s for benefits and risks that are usually endpoint specific), estimation \ntechniques (i.e., simulation techniques and meta -analysis) , and utility survey techniques \n(to elicit stakeholders\u2019 preferences).  \nConcerning quantitative frameworks, according to the European Medicines Agency (EMA) \nProject Report (EMA/227124/2011), there is no agreement on any one approach to be \nused in regulatory submission on the benefits and risks of medicines. However, EMA has \nencouraged the use of quantitative frameworks in regulatory submissions of applications \nfor marketing authorisation of medicinal products.  \nAlthough there is little experience with quantitative frameworks in the area of medical \ndevices, some of the BRA appro aches used for pharmaceuticals may also be relevant for \nmedical devices and particularly regarding the use of CMR/ED phthalates. In particular, \napproaches based on multicriteria decision analysis ( MCDA) have attracted much \nattention during the past years in the field of medical decisions. For an introduction to \nMCDA see Dodgson et al. (2009).  \nIn brief, MCDA is based on decision theory and belongs to the general class of multi -\ncriteria analysis mode ls that accommodate decision making with multiple objectives. The \nmain purpose of MCDA is to bring together evaluations of options on different criteria into \none overall evaluation.  The starting point for MCDA approaches include s identification of \nthe alte rnatives and the criteria against which the alternatives are appraised.  MCDA \nincludes weighting, which ensures that the units of value on all the criteria are \ncomparable so that benefits and risks can be compared by using a common unit of value. \nIn this wa y, the added value of benefits can be compared to the loss of value from the \nrisks. A number of different weighting methods can be used, ranging from precise \nelicitation of weights, to weights based on qualitative judgements or including \nuncertainty.  \nA generic framework for conducting an MCDA can be based on the steps of the PROACT -\nURL framework (Hammond et al. , 1999), as presented below. A detailed description of \nthe different implementations of MCDA techniques is beyond the scope of this guideline. \nThe c hosen techniques and analyses should be presented and justified among others on \nthe basis of internal consistency, logical soundness and transparency.  \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n62 \n  \nSTEP Description and relation to framework for Benefit -Risk \nAssessment described in section A of the  Guidelines  \nProblem  Describe the medical device, its intended use, and the \ntherapeutic context; frame the decision problem in terms \nof potential alternatives to CMR/ED phthalate. See Step 1: \nDescription and characterisation of the composition of the \nmedic al device; and Step 2: Use and function of the \nphthalates in the medical device.  \nObjectives  Identify the full set of criteria to evaluate different \nalternatives. See Step 2: Use and function of the \nphthalates in the medical device; and Step 3: Assessment  \nof the risks of the CMR/ED phthalate. See 7 Benefit \nassessment . \nAlternatives  Identify alternatives that are being evaluated against each \nother. See Step 4: Inventory of possible alternatives; and \nStep 5: Identification of the candidates for assessment as  \npotential relevant alternatives for phthalates . \nConsequences  Describe how the alternatives perform for each of the \ncriteria, i.e., the magnitudes of all effects in terms of the \ndifferent benefits and risks. See Step 2: Use and function \nof the phthalates in the medical device; Step 3: \nAssessment of the risks of the C MR/ED phthalate; Step 6: \nDescription of identified relevant potential alternative(s); \nStep 7: Assessment of the risk of identified potential \nrelevant alternatives. For a summary table see Table 1. \nExample for a comparison of CMR/ED phthalate with \npotential  alternative(s).  \nTrade -offs Assess the balance between benefits and risks using \njudgements of weights associated with the criteria and the \nvalue associated with the benefits and risks of every \nalternative. MCDA techniques commonly achieve this \nthrough num erical analysis. A number of different \nweighting methods can be used. Conduct sensitivity \nanalyses to explore uncertainties using different scenarios, \nand assess how different weights affect the overall \nordering of the alternatives.  \nSee also Step 8: Compar ison of functionality and \nperformance of CMR/ED phthalate as used in the medical \ndevice with functionality and performance of identified \npotential relevant alternatives; Step 9: Comparison of \nrisk(s) of original CMR/ED phthalate as used in the medical \ndevice with risk(s) of identified potential relevant \nalternatives; and Step 10: Comparison of benefit and risk \nof CMR/ED phthalate used in the medical device with \nidentified potential relevant alternatives.  \nUncertainty  Report the uncertainty associated with the benefits and  \nRisks. Consider how the balance between benefits and \nrisks is affected by uncertainty. A quantitative model will Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n63 \n explore in sensitivity analyses and scenario analyses (or by \nexplicitly incorporating probability distributions in the \nmodel) the effects on the overall benefit -risk balance of all \nsources of uncertainty. See 1.9 Uncertainty analysis.  \nRisk tolerance  Describe any considerations that could or should affect the \ndecision maker\u2019s attitude toward risks (e.g., special \npopulation, unmet  medical need).  \nLinked -decisions  Discuss how the value judgements and data are consistent \nwith similar decisions on medical devices.  \n  \n \nReferences  \n\uf0b7 Dodgson J, Spackman M, Pearman A, Phillips LD. Multi -criteria analysis: A \nmanual. London: Department for Communities and Local Government, First \npublished in 2000 by the Department for Environment, Transport and the \nRegions; 2009.  \n \n\uf0b7 ECHA 2011 Guidance on the preparation of socio -economic analysis as part of an \napplication for authorisation, European Chemicals Agency 2011 . \n \n\uf0b7 Hammond JS, Keeney RL, Raiffa H, Smart Choices: A Practical Guide to making \nBetter Decisions, Boston, MA: Harvard Business School Press; 1999.  \n \n\uf0b7 Mt-Isa S, Hallgreen C.E., Wang N., Callr\u00e9us T., Genov G., Hirsch I., Hobbiger S., \nHockley .S., Luciani D., Phillips L.D., Quartey G., Sarac S.B., Stoeckert I., Tzoulaki \nI., Micaleff A., Ashby D. - Balancing benefit and risk of medicines a systematic \nreview and classification of available methodologies, Pharmacoepidemiology and \nDrug Safety, May 2014 ."}, {"title": "md_transitional-provisions-art-3-and-4_en.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document                          MDCG 2020 -2 rev.1  \n \n \n \n \n     MDCG  2020 -2 rev. 1  \n       Class I Transitional provisions under  Article      \n      120 (3 and 4) \u2013 (MDR)             \n \n             March 2020  \n         July 2020 rev.1  \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group  (MDCG) established by \nArticle 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member \nStates and it is chaired by a representative of the European Commission.  \nThe document is not a European Commission document and it cannot be regarded as reflecting the \nofficial position of the European Commission. Any views expressed in this document are not legally \nbinding and only the Court of Justice of the European Union can give binding interpretations of Union \nlaw. \n \n \n \n  Medical Device       \nMedical Device Coordination Group Document                          MDCG 2020 -2 rev.1  \n \nMDCG 2020 -2 revision 1 changes  \nMDR postponement dates  : from 2020 to 2021  \nHow can a ffected manufacturers of some class I devices1 make efficient \nuse of the transitional provisions in A rticle 120 (3 ) and (4) of Regulation \n(EU) 2017/745 \u2013 Medical Devices Regulation ( MDR )? \nBackground:  \nThe corrected MDR2 Article 120 (3) allows  under certain condition s, some class I devices pursuant to \nDirective 93/42/EEC  \u2013 Medical Devices Directive (MDD) , for which the Declaration of C onformity \nwas drawn up prior to 26 May 2021 and for which the conformity assessment procedure pursuant to \nthe MDR would require the involvement of a notified body,  to be placed on the market3 until 2 6 May \n20244.  \nIn order  to make use of this article , the following conditions must be met:  \n1. The device continues to comply with Directive 93/42/EEC,  \n2. A notified body will need to be involved under the MDR (e.g. re -usable surgical instruments \nor up -classified devices)  \n3. A valid Declaration of C onformity , according to Annex VII  of the MDD , must be drawn up \nbefor e 26 May 2021,  \n4. No significant changes to the design or intended purpose of the device  after 26 May 202 15, \n5. The requirements of the MDR relating to post -market surveillance, market surveillance, \nvigilance, registration of economic operators and of devices shall apply in place of the \ncorresponding  requirements in Directive 93/42/EEC .6 This shall be in place on the 26 May \n2021. \n \nScope  \nThe scope of this document is to provide guidance related to the information to be provided in the \nform of a  Declaration of Conformity by manufacturers of Class I devices  (devices which are non -\n                                                           \n1 Class I devices for which the conformity assessment procedure pursuant to the MDR would require the involvement of a \nnotified body.  \n2 Corrigendum to Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical \ndevices, amending Directive 2001/83/EC, Regulation (EC) No\u202f178/2002 and Regulation (EC) No\u202f1223/2009 and repealing \nCouncil Directives 90/385/E EC and 93/42/EEC (OJ L 117, 5.5.2017), of 27.12.2019.  \n3 Devices which are not placed on the market but put into service may also make use of the transitional provisions .  \n4 Article 120(4) \u2018and may continue to be made available on the market \u2026until 26  May 2025\u2019 . \n5 Guidance on significant changes under Article 120 of the MDR with regard to devices covered by certificates according to \nMDD or AIMDD . \n6 Upcoming guidance on harmonised practices and technical solutions  to facilitate exchange of information in absence of \nEUDAMED .  Medical Device       \nMedical Device Coordination Group Document                          MDCG 2020 -2 rev.1  \n \nsterile or do not have a measuring function) that are required to have certificates after 26 May 2024 \naccording to the MDR.  \nContent of a val id Declaration of Conformity  \nThe manufacturer or his authorised representative established in the European Union is  obliged to \nissue a  Declaration of Conformity  that the  product has undergone  a conformity assessment  procedure \nrequired by the MDD  before being placed on the market.   \n \nWith the Declaration of Conformity, the manufacturer declares that the products concerned meet the \nrelevant provisions of the MDD.  \nMDD Annex II, Annex V, Annex VI set out that a Declaration of Conformity must cover one or more \nmedical devices manufactured  7 clearly identified by means of product name, product code or other \nunambiguous reference for class IIa, IIb and III devices, and also class Im and class Is devices. This is \nhowever not necessary for  other  Class I devices, as it is not required by the MD D (Annex VII) and as \nthere is no certificate from a notified body to which the issued Declaration of Conformity is related.  \nGuidance on  the content of the Declaration of C onformity can be found, inter alia, in the \u201cThe \u2018Blue \nGuide\u2019 on the implementa tion of EU products rules 2016 (2016/C272/01) \u201d8 and the  standard EN \nISO/IEC 17050 -1.9 According to this standard , the declaration may take the form of a document or any \nother suitable medium , and should contain sufficient information to enable all products  covered to be \ntraced back to it.  The model declaration in Annex III of Decision No 768/2008/EC  and the \u2018Blue \nGuide\u2019  on the implementation of EU products rules 2016 (2016/C272/0 1) describe the content of the \nDeclaration of C onformity to be as follows:   \n1.  A number identifying the product. This number does not need to be unique to each product. It \ncould refer to a product, batch, type or a serial number .10 This is left to the discretion of the \nmanufacturer .11   \n2.  The name and address of the manufacturer or  the authorised representative issuing the \ndeclaration.  \n3.  A statement that the declaration is issued under the sole responsibility of the manufacturer.  \n                                                           \n7 MDD Annex II, paragraph 2  \u2018This declaration must cover one or more medical devices manufactured, clearly identified by \nmeans of product name, product code or other unambiguous reference and must be kept by the manufacturer.\u2019  \n8 https://eur -lex.europa.eu/legal -content/GA/TXT/?uri=CELEX:52016XC0726(02) . \n9 EN ISO/IEC 17050 -1 : 2004 Conf ormity assessment \u2013 Supplier\u2019s D eclaration of Conformity \u2013 Part 1: General requirements \n/EN ISO/IEC 17050 -2 : 200 4 Conformity assessment \u2013 Supplier\u2019s Declaration of C onformity \u2013 Part 2: Supporting \ndocumentation . \n10 The \u2018number\u2019 may be an alpha -numerical code  or could also refer to a software version .  \n11 In addition, whether this is expressly envisaged or not by the Union harmonisation legislation,  manufacturers are free to \nadd a number identifying the Declaration of Conformity itself in line with EN ISO/IEC 17050 -2. Medical Device       \nMedical Device Coordination Group Document                          MDCG 2020 -2 rev.1  \n \n4.  The identification of the product allowing traceability. This is any relevant information \nsuppleme ntary to point 1 describing the product and allowing for its traceability . Where relevant \nfor the identification of the product , it may  contain an image, but unless specified as a \nrequirement in the Union harmonisation legislation this is left to the discr etion of the \nmanufacturer.  \n5.  All relevant Union harmonisation legislation complied with; the referenced standards or other \ntechnical specifications (such as national technical standards and specifications) in a precise,  \ncomplete and clearly defined way;  this implies that the version and/or date of the relevant \nstandard is specified.12  \n6.  If applicable, t he name and identification number of the notified body ,13 when it has been \ninvolved in the conformity assessment procedure ,14 15 and the reference to the relevant \ncertificate.  \n7.  If applicable, a ll supplementary information that may be required (for example category) . \n8.  The date of issue of the declaration; signature and title or an equivalent marking of the \nauthorised person16 17 \n\uf0fc This could be any date after the complet ion of the conformity assessment , but must be before \n26 May 202 1 if the manufacturer wants to make use of the transitional period in Article \n120(3) and (4)  of the MDR . \nEvery Declaration of C onformity must be based on proper technical documentation according to \nAnnex VII para graph  3 of the MDD.  The technical documentation and the D eclaration of Conformity \nshould be subject to appropriate  measures of document and record control. The Declaration  of \nConformity is to be kept by the manufacturer and shall be at the  disposal of the competent  authorities \nfor a period ending at least five years after the last product  has been manufactured.  \nNecessary amendm ents/updates to the t echnical documentation should be done in a transparent \nmanner. Both t he changes and the dates of when the changes were  made should be recorded. On the \nbasis of the Declaration of Conformity and the corresponding technical documentation, the \nmanufacturer should be able to demonstrate that the Declaration of Conformity was lawfully18 issued \nbefore 26 May 202 1 and that, subsequently, there are no significant changes  in the design or intended \n                                                           \n12 According to the MDD , referencing st andards or technical specifications complied with is voluntary .  \n13 For class I devices in scope of this guidance document, the involvement of a notified body is not required.  \n14 Not all Union harmonisation legislation requires the intervention of a notified  body (e.g. the Low Voltage Directive and the \nToys D irective . \n15 The name and address of the person who keeps the technical documentation may also be required by some pieces of Union \nharmonisation legislation since according to those, not only the manufactu rer shall keep the technical documentation.  \n16 This could be the m anaging director of the company or another representative of the company to whom this responsibility \nhas been delegated.  \n17 It is not necessary for the signatory to be domiciled in the Europea n Union. A manufacturer established outside the Union \nis entitled to carry out all the conformity assessment procedures at his premises and, to sign the Declaration of Conformity . \n18 Lawfully according to the Directive and to any relevant national provisions which apply.  Medical Device       \nMedical Device Coordination Group Document                          MDCG 2020 -2 rev.1  \n \npurpose19 in the meaning of Article 120(3) MDR. Taking into account Article 123(3) and 123 (3)(d), \nand a s EUDAMED will not be fully functional in May 202 1, it is required that the manufacturer keep \nthe Declaration of Conformity together with the  technical documentation available to the Competent \nAuthorities . This would also include details o f all device registrations and economic operator \nregistrations completed pursuant to national provisions implementing the requirements of Articles 14 \n(1) and (2) of Directive 93/42/EEC.  \n \n \n                                                           \n19 Guidance on significant changes under Article 120 of the MDR with regard to devices covered by certificates according to \nMDD or AIMDD ."}, {"title": "09 MDCG 2020-9 Regulatory Requirements for Ventilators and Reated Accessories.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document   MDCG  2020-9  \n \n  \n  \n \n \n \nMDCG 2020-9 \n  \n         REGULATORY REQUIREMENTS    \n      FOR VENTILATORS AND \n      RELATED ACCESSORIES    \n           \n \n April 2020 \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.The document is not a European \nCommission document and it cannot be regarded as reflecting the official \nposition of the European Commission. Any views expressed in this document are \nnot legally binding and only the Court of Justice of the European Union can give \nbinding interpretations of Union law. \n \n   \n2 REGULATORY REQUIREMENTS FOR VENTILATORS AND \nRELATED ACCESSORIES  \nOptions for supporting production and/or placing on the market of \nventilators in the context of COVID-19 pandemic \n1. INTRODUCTION AND SCOPE  \nThe World Health Organization (WHO) declared the COVID-19 outbreak a pandemic on \nMarch the 12th 2020. Patients infected by SARS-CoV-2 virus and developing the \nCOVID-19 disease with acute and severe respiratory symptoms have to be treated with \nmechanical ventilators to assure possibilities of survival.  \nThis guidance document focuses on ventilators and related accessories that are currently \nregulated under the Council Directive 93/42/EEC (MDD)1. According to the MDD, \ndevices may be placed on the market and/or put into service only if they comply with the \nrequirements laid down in this Directive when duly supplied and properly installed, \nmaintained and used in accordance with their intended purpose2. \nThe devices must meet the essential requirements set out in Annex I of the MDD, which \napply to them, taking account of the intended purpose of the devices concerned. In \naddition, devices may be placed and circulate on the European single market if they have \nbeen subject to a conformity assessment in accordance with the provisions of Article 11 \nof the MDD.  \nUnder the current COVID-19 context, the demand for ventilators and related accessories \nhas rapidly increased. Therefore, this document intends to outline the different regulatory \noptions for placing these devices on the EU market indicating their feasibility to allow \nshort-term supply. \n2. TYPES OF MEDICAL DEVICES AND THEIR PARTS /COMPONENTS  \n2.1. Ventilators \nVentilators are breathing support devices and can fall into different types according to \ntheir intended use and characteristics3: \n                                                \n1 However, placing on the market of devices which comply with MDD is limited to 27 May 2024. After \nthis date every device placed on the market has to comply with the requirements of Regulation (EU) \n2017/745 (MDR). According to the Article 120 section 5 and 6 of the MDR devices which comply \nwith MDR may be placed on the market before its application and notified bodies which are \ndesignated and notified in accordance with MDR may carry out the conformity assessment procedures \nlaid down in MDR and issue certificates in accordance with MDR. \n2 According to Article 1(g) of the MDD, intended purpose is the use for which the device is intended \naccording to the data supplied by the manufacturer on the labelling, in the instructions and/or in \npromotional materials. \n3 This list of ventilators includes some standards applicable to the specific ventilator. However, it should be \nnoted that this is not an exhaustive list and other standards also apply to these devices and should be \ntaken into account (e.g. EN 60601-1-2, EN 60601-1-6, EN 60601-1-8, EN 60601-1-11, EN 62304, EN \n62366). In addition, the current state of the art should be considered. This applies also to accessories.   \n3 - Ventilator for critical care:   automatic equipment that is intended to augment or \nprovide ventilation of the lungs of the patient when connected to the airway of the \npatient: \no intended for use in an environment that provides specialized care for \npatients whose conditions can be life threatening and who can require \ncomprehensive care and constant monitoring in a professional healthcare \nfacility; \no intended to be operated by a healthcare professional operator; and \no intended for those patients who need differing levels of support from \nartificial ventilation including for ventilator-dependent patients. \n(See e.g. EN ISO/IEC 80601-2-12:2011 + Cor.:2011).   \n- Home healthcare environment ventilators for ventilator-dependent patients: \nintended for use in the home healthcare environment; intended for use by a lay \noperator; intended for use with patients who are dependent on mechanical \nventilation for their life support. Depending on the intended purpose can be also \nused in the clinical setting (See e.g. EN ISO 80601-2-72:2015). \n- Ventilators for emergency and transport : these ventilators are used in \nEmergency Medical Service environment, e.g. in ambulances, transport of \npatients to the hospital, patient transport from hospital to hospital or transport \nwithin the hospital. The alarm and safety concept of emergency and transport \nventilators in general is designed for a permanent presence of the user. This \nfacilitates fast recognition and response in the event of an alarm or in the event of \nany malfunction (See e.g. EN 794-3:1998+A2:2009).  \n- Anaesthetic ventilator:  are designed for use during anaesthesia with an \nanaesthetic breathing system (See e.g. EN ISO 80601-2-13:2012). \nVentilators for critical care are usually invasive, which enables the ventilator machine to \nprovide lung support for inspiration and expiration through tracheal intubation. However, \nmost critical care ventilators allow non-invasive ventilation modes for critical care \npatients as well. Ventilators for non-critical care are usually non-invasive and therefore \nprovide air pressure support to natural breathing through e.g. a facemask. \nVentilators may offer different types of additional complementary functions that include: \n\uf0b7 High flow oxygen supply (nasal high flow therapy); \n\uf0b7 Monitoring systems; \n\uf0b7 Nebulisation systems. \n \n2.2. Accessories \nVentilators need to be \u201cconnected\u201d to the patients through dedicated accessories4 to the \nventilator that allow the machine to support the patient\u2019s breathing; therefore, it is \nimportant to proof compatibility with the ventilator(s). These accessories can be placed \non the market individually and usually fall into one of the following categories: \n                                                \n4 See MEDDEV 2.1/1  Definitions of 'medical devices', 'accessory' and 'manufacturer' \n(https://ec.europa.eu/docsroom/documents/10278/attachments/1/translations ).  \n4 \uf0b7 Breathing systems and circuits, such as: \no Circuits; \no Connections/Adapters; \no Tubes; \no Nasal cannulas for O 2; \no Masks or helmets for non-invasive ventilation; \no Air compressors; \n\uf0b7 Nebulizers; \n\uf0b7 Humidifiers and filters; \n\uf0b7 Monitoring accessories, including alarms, in-built safety features. \nAccessories are provided either disposable or reusable and are treated as medical devices \nin their own right5. \n2.3. Parts or components \nParts or components of medical devices that do not qualify as accessories are generally \nnot considered medical devices and thus not requiring themselves to be CE marked \naccording to the MDD (e.g. expiratory valves or flow sensors).  \n3. CLASSIFICATION  \n3.1. Ventilators \nThere are different types of ventilators depending on the degree of invasiveness and the \nsetting in which they are used in (e.g. Intensive Care Unit - ICU). Ventilators fall under \ntwo different classes in accordance with rule 11 (or rule 9) of Annex IX6,7 to the MDD: \n- Class IIa: only applicable to non-invasive devices, e.g. continuous positive airway \npressure \u2013 CPAP non-intended for critical care, or devices that only support \nspontaneous breathing. \n- Class IIb: applicable to most ventilators.  \nThe classification depends on the intended purpose of the ventilator and has important \nimplications in the selection of appropriate conformity assessment procedure(s) for the \ndevice including timing and complexity (see section 4 for details).  \n3.2. Accessories \nAccessories are classified in their own right usually in accordance with rule 2 or 5 of \nAnnex IX to the MDD, under Class I, IIa or IIb.  \n                                                \n5 Art. 1(1) of the MDD \n6 See MEDDEV 2.4/1 rev.9 Classification of Medical Devices -  \n(https://ec.europa.eu/docsroom/documents/10337/attachments/1/translations).  \n7 Please note that if a conformity assessment under the MDR is followed, the rules of classification \nspecified in Annex VIII to the MDR apply. Breathing support devices may be classified to class IIa or \nIIb (rule 12) or class III (rule 22) if they integrate or incorporate diagnostic functions which \nsignificantly determine the patient management by the device, such as closed loop systems.  \n5 3.3. Impact of classification on conformity assessment \nGiven that ventilators are classified as Class IIa or Class IIb, and accessories (except for \nClass I non-sterile and without measuring function), will in principle need the \ninvolvement of a notified body prior to their placing on the market.  Other options for the \nplacing on the market are provided in section 4 for both ventilators and accessories. \n4. REGULATORY OPTIONS FOR PLACING VENTILATORS ON THE MARKET  \nIn the context of the COVID-19 outbreak, several industries have expressed their \nwillingness to support and scale up the production of ventilators8. There are different \nregulatory options9 available for supporting production or placing on the market of \nventilators. These options are presented below, ordered by feasibility, to allow a swift \nsupply in the current context. \n4.1. Supplying parts, components or the finished devices to medical devices \nmanufacturers currently placing on the market ventilators  \nWhen the legal manufacturer10 has already undergone a conformity assessment for the \nventilator, has obtained a certificate and is lawfully placing ventilators on the market \nunder its own name, other producers (e.g. not currently working in the medical devices \nfield) can support its production. Such producers can provide parts or components, or the \nfinished device, therefore becoming suppliers or subcontractors of this manufacturer. \nGiven that the medical devices sector is highly regulated and complex, leveraging the \nknowledge and responsibilities of an already established manufacturer of ventilators \ncould be the least burdensome and fastest option to scale up the production of \nventilators.   \n4.1.1. Producers supplying parts or components to medical devices manufacturers \ncurrently placing on the market ventilators \nManufacturers of medical devices can have many suppliers, which in case of quality \nsystem certification are qualified, approved and controlled by the manufacturer. These \nsuppliers may need to be assessed by a notified body as part of the conformity \nassessment procedure on the basis of their criticality and the manufacturer\u2019s process in \nplace to control suppliers and the verification of purchased products11. When the \nmanufacturer wishes to use an additional supplier, this might need to be communicated in \nadvance to the notified body.  \n                                                \n8 Scaling up of production might also be needed for accessories. These medical devices can follow the \nsame options explained in section 4 but small differences can be applicable in case they have a \ndifferent classification (e.g. class Is).   \n9 This document mainly focuses on regulatory options provided by the MDD. If a conformity assessment \nunder the MDR is followed, similar procedures will apply under Annex IX, X or XI of the MDR \ndepending on the classification of the product.  \n10 Legal manufacturer refers to the definition of manufacturer established in Art. 1(f) of the MDD.  \n11 See Guidance for Notified Bodies auditing suppliers to medical device manufacturers \u2013 \n(http://www.doks.nbog.eu/Doks/NBOG_BPG_2010_1.pdf)   \n6 4.1.2. Producers manufacturing the ventilator itself for the medical device \nmanufacturer currently placing on the market ventilators \nManufacturers of medical devices producing ventilators may provide the specifications \nof a ventilator (e.g. current or older/simpler design) including parts of the technical \ndocumentation to a producer that becomes its subcontractor. The producer will \nmanufacture the ventilator but the medical device manufacturer will keep its role of legal \nmanufacturer according to the MDD.  \nThe legal manufacturer of the ventilator, which holds a quality system certification, \nqualifies, approves and controls the subcontractor that will need to be assessed by a \nnotified body as part of the conformity assessment procedure. When the manufacturer \nwishes to use an additional subcontractor, this will need to be communicated in advance \nto the notified body (i.e. as the subcontractor is considered critical11) that will assess the \navailable information and will decide the actions to be put in place e.g. whether or not it \nis necessary to carry out an (on-site12) audit. \nAlternatively, the manufacturer of medical devices could also follow other conformity \nassessment routes such as the EC type-examination, as established in Annex III to the \nMDD, and/or EC verification, as established in Annex IV to the MDD (these routes are \nelaborated in 4.3.2).     \n4.2. Derogation procedure \u2013 placing on the market authorised by the \nrelevant authorities of one Member State in the interest of public health \nThe relevant authority of one Member State may decide to authorise the placing on the \nmarket of devices in the interest of protection of health, even if the applicable conformity \nassessment procedures have not been finalised or initiated ('national derogation'). \nIn view of the epidemiological context as well as the exponential growth in demand for \nmedical devices, the Commission has published a Guidance on medical devices, active \nimplantable medical devices and in vitro diagnostic medical devices in the Covid-19 \ncontext.  \nQuestion 5 of this guidance provides information on the derogation procedures for \nmedical devices which is established in Article 11(13) of the MDD. In particular, the \nguidance specifies that the Covid-19 context warrants the application of such \nderogations.  \nBy amendment of 23 April 202013, Article 59(1) of Medical Devices Regulation (EU) \n2017/745 (MDR) empowers Member States to adopt national derogations under both the \nMDD and the MDR from the date of entry into force of that amendment. \nThe relevant competent authority of the Member State in this case authorises the placing \non the market within its territory and can also organise the purchase.  \n                                                \n12 See MDCG 2020-4 Guidance on temporary extraordinary measures related to medical device Notified \nBody audits during COVID-19 quarantine orders and travel restrictions \n(https://ec.europa.eu/docsroom/documents/40705).   \n13 Regulation 2020/561  amending Regulation (EU) 2017/745 on medical devices as regards the dates of \napplication of certain of its provisions.  \n7 In practice, this implies that each competent authority would need to assess whether the \nproducts produced by the manufacture provides an adequate level of safety in respect to \nthe applicable legal requirements. The assessment procedures can vary among Member \nStates and in some cases will involve the support of third parties (e.g. testing \nlaboratories).   \nIn the exceptional COVID-19 context, the assessment procedures will ensure a short-\nterm supply while guaranteeing patient safety14. The Member State will evaluate the \navailable technical documentation to find evidence that essential performance and safety \nrequirements are guaranteed in the context of use. In particular, the role of healthcare \nteams and health facilities is essential to allow a rational use and a continuous assessment \nof these crisis solutions. \nOnce this assessment is performed, the authority has to take a decision, whether or not \nthe respective device produced by the manufacturer may enter the national territory of the \nMember State. Competent authorities should inform the Commission and their \ncounterparts in other Member States of any temporary agreement they have granted to \nspecific devices.  \nIn addition, Article 59(3) of the MDR empowers the Commission to extend, in \nexceptional cases relating to public health or patient safety or health, by means of \nimplementing acts, for a limited period of time the validity of a national derogation, \ngranted by a Member State under the MDD or the MDR, to the territory of the Union and \nset the conditions under which a device may be placed on the market or put into service. \nThis allows the Commission and the Member States to address potential shortages Union \nwide of vitally important medical devices in an effective manner. \nTiming to obtain a national derogation by a competent authority will greatly depend on \nthe quality and adequacy of the evidence provided by the manufacturer.  When technical \ndocumentation and evidence of safety of performance is adequate, this can be a feasible \noption to ensure short-term supply.  \n \n4.3. Manufacturing of the finished device by a producer that was not \npreviously placing on the market ventilators  \nIf the ventilator is entirely manufactured by a producer that decides to place it on the \nmarket under its name, such producer will become the legal manufacturer in its own \nright. This means that the manufacturer will need to fulfil all requirements of the MDD \n(e.g. including the need to draw up the technical documentation and clinical evaluation \nrelated to the ventilator, and to establish and keep up to date a systematic procedure to \nreview experience gained from devices in the post-production phase).  \nThe manufacturer who places the finished CE marked ventilator on the market under its \nown name needs to ensure that the device complies with the essential requirements \n(established in Annex I of the MDD) and provide relevant evidence. A notified body will \nbe involved in the conformity assessment in all cases.  \n                                                \n14 Some Member States have published guidance on their respective websites to support this assessment \ne.g. in case of implementation of innovative manufacturing processes such as 3D printing.   \n8 Given that the medical devices sector is highly regulated and complex, the scenarios \npresented below will be the most burdensome and therefore only applicable to increase \nsupply in the medium-long term.  \n4.3.1. Medical devices manufacturers\u2019 not currently producing ventilators request \nan extension of their product range. \nThis option is available for medical devices manufacturers currently certified. It includes, \nfor instance, medical devices manufacturers already holding a full quality management \nsystem certificate under Annex II to the MDD for other devices and wishing to add \nventilators to their certification. They could seek the support from (non-medical devices) \nproducers to act as subcontractors and extend the scope of their certificate.   \nFrom a procedural point of view, the medical devices manufacturer may produce the \nventilator itself or may utilise a subcontractor (i.e. producer linked or not to the medical \ndevices field). In the latter case, the manufacturer will qualify, approve and control the \nsubcontractor that will be assessed by the notified body as part of the conformity \nassessment procedure. When the manufacturer wishes to use an additional subcontractor, \nthis will need to be communicated in advance to the notified body (i.e. as the \nsubcontractor is considered critical11) that will assess the available information and will \ndecide the actions to be put in place e.g. whether or not it is necessary to carry out an (on-\nsite12) audit. \nMost importantly, the manufacturer will need to request an extension of the product \nrange from its notified body. The notified body will assess the available information in \nrelation to the new product (that include an assessment of the technical documentation \nand clinical evaluation) and update the certificate. \nThe manufacturer of medical devices could also use other conformity assessment routes \nsuch as the EC Type-Examination and EC Verification and testing of every product \nunder Annex III and IV respectively (these routes are elaborated in section 4.3.2).   \n \n4.3.2. Ventilator manufactured entirely by a producer that is not currently a legal \nmanufacturer under the MDD \nProducers that do not currently qualify as legal manufacturers under the MDD and decide \nto place ventilators on the market under their own name need to be aware of all the legal \nrequirements for manufactures under the MDD. It is important to mention that in the field \nof medical devices some Member States could have additional requirements, for instance, \nthe need to authorise the facility of the medical device manufacturer prior to starting \nproduction.  \nIn addition to this, the involvement of a notified body will depend on the classification. \nIn particular: \n1. Class IIa ventilators can follow the following routes established in the relevant \nAnnexes of the MDD: \na. Annex II (excluding point 4) \u2013 which involves the assessment of the full \nmanufacturer\u2019s quality management system. This will require an on-site \naudit (which may be performed remotely in the current context) and  \n9 regular surveillance audits at least annually. In addition, the notified body \nwill assess the technical documentation and the clinical evaluation of the \nproduct to be certified prior to certification on a sampling basis15.   \nb. Declaration of conformity (Annex VII) combined with either an \nassessment of the quality assurance of the production or of the product \n(Annex V or VI) or a EC verification (set out in Annex IV): \n\uf0a7 The assessment of the quality system performed by the notified \nbody will be similar to the one outlined in section 1.a above. \n\uf0a7 The verification by testing of products by the notified body will be \nperformed by examination and testing of every product.   \n \n2. Class IIb ventilators can follow the following routes: \na. Annex II (excluding point 4) \u2013 which involves the assessment of the full \nmanufacturer\u2019s quality management system. This will require an on-site \naudit (which may be performed remotely in the current context) and \nregular surveillance audits at least annually. In addition, the notified body \nwill assess the technical documentation and the clinical evaluation of the \nproducts to be certified prior to certification on a sampling basis15.   \nb. EC type-examination (Annex III) combined with either an assessment of \nthe quality assurance either of the production or of the product (Annex V \nor VI) or EC verification by testing of products (set out in Annex IV). EC \nType-examination consists in the assessment of the technical \ndocumentation and testing of a number of features of the device type to \nensure it conforms to the requirements. The additional procedures (Annex \nIV, V or VI) are the same as the ones described in 1.b above. \nThe assessment of the quality management system of the manufacturer (Annex II, V and \nVI) can be partly fulfilled by compliance with a harmonised standard (EN ISO 13485) \nbut this route will unlikely be fast enough to ensure short-term supply. This is due to the \ntimelines and experience required to get a certificate under these annexes of the MDD \nand taking into account the current circumstances where auditing capacity is restricted by \nthe Covid19 situation. \nA faster route but also time-consuming route will probably be the performance of tests on \nthe products that might be combined with the assessment of the technical documentation, \nnamely:  \n- declaration of conformity (Annex VII) + verification of products (Annex IV) for \nClass IIa; or \n- EC type-examination (Annex III) + verification of products (Annex IV) for \nClass IIb. \nThrough this route, the device type or device samples are tested and there is no obligation \nto have a certified quality management system in place and subject to regular \nsurveillance audits. However, quality management processes are important and critical to \nthe production of safe and functional medical devices. The conformity assessment will be \n                                                \n15 See Annex II, section 3.3 to the MDD  \n10 based on the manufacturers testing strategy that must ensure compliance with the safety \nand performance requirements.  \nIt should be noted that this option is burdensome and will take several months, especially \nto draw up an adequate technical documentation. In addition, there is only a limited \nnumber of notified bodies designated to perform EC type-examination and/or EC \nverification in ventilators (according to NANDO16 18 notified bodies out of 56 are \nauthorised to perform these tests at the moment).  \n                                                \n16 This information can be found in NANDO, by searching notified bodies under the MDD that are \ndesignated under Annex III and IV for code MD 1102 - Respiratory devices, devices including \nhyperbaric chambers for oxygen therapy, inhalation anaesthesia -   \nhttps://ec.europa.eu/growth/tools-databases/nando/index.cfm?fuseaction=directive.notifiedbody&dir_id=13"}, {"title": "Mdr.Html.txt", "text": "L_2017117EN.01000101.xml\n\n\n\n\n\n\n\n\n\n\n\n5.5.2017\u00a0\u00a0\u00a0\n\n\nEN\n\n\nOfficial Journal of the European Union\n\n\nL 117/1\n\n\n\n\n\n\n\n\n            REGULATION (EU) 2017/745 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL\n         \nof 5 April 2017\n         \non medical devices, amending Directive\u00a02001/83/EC, Regulation\u00a0(EC)\u00a0No\u00a0178/2002 and Regulation\u00a0(EC)\u00a0No\u00a01223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC\n(Text with EEA relevance)\n\n\nTHE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION,\n\nHaving regard to the Treaty on the Functioning of the European Union, and in particular Article\u00a0114 and Article\u00a0168(4)(c) thereof,\n\n\nHaving regard to the proposal from the European Commission,\n\n\nAfter transmission of the draft legislative act to the national parliaments,\n\n\nHaving regard to the opinion of the European Economic and Social Committee\u00a0(1),\n\n\nAfter consulting the Committee of the Regions,\n\n\nActing in accordance with the ordinary legislative procedure\u00a0(2),\n\nWhereas:\n\n\n\n\n\n\n\n(1)\n\n\nCouncil Directive\u00a090/385/EEC\u00a0(3) and Council Directive\u00a093/42/EEC\u00a0(4) constitute the Union regulatory framework for medical devices, other than in vitro diagnostic medical devices. However, a fundamental revision of those Directives is needed to establish a robust, transparent, predictable and sustainable regulatory framework for medical devices which ensures a high level of safety and health whilst supporting innovation.\n\n\n\n\n\n\n\n\n\n\n\n\n(2)\n\n\nThis Regulation aims to ensure the smooth functioning of the internal market as regards medical devices, taking as a base a high level of protection of health for patients and users, and taking into account the small- and medium-sized enterprises that are active in this sector. At the same time, this Regulation sets high standards of quality and safety for medical devices in order to meet common safety concerns as regards such products. Both objectives are being pursued simultaneously and are inseparably linked whilst one not being secondary to the other. As regards Article\u00a0114 of the Treaty on the Functioning of the European Union (TFEU), this Regulation harmonises the rules for the placing on the market and putting into service of medical devices and their accessories on the Union market thus allowing them to benefit from the principle of free movement of goods. As regards Article\u00a0168(4)(c)\u00a0TFEU, this Regulation sets high standards of quality and safety for medical devices by ensuring, among other things, that data generated in clinical investigations are reliable and robust and that the safety of the subjects participating in a clinical investigation is protected.\n\n\n\n\n\n\n\n\n\n\n\n\n(3)\n\n\nThis Regulation does not seek to harmonise rules relating to the further making available on the market of medical devices after they have already been put into service such as in the context of second-hand sales.\n\n\n\n\n\n\n\n\n\n\n\n\n(4)\n\n\nKey elements of the existing regulatory approach, such as the supervision of notified bodies, conformity assessment procedures, clinical investigations and clinical evaluation, vigilance and market surveillance should be significantly reinforced, whilst provisions ensuring transparency and traceability regarding medical devices should be introduced, to improve health and safety.\n\n\n\n\n\n\n\n\n\n\n\n\n(5)\n\n\nTo the extent possible, guidance developed for medical devices at international level, in particular in the context of the Global Harmonization Task Force (GHTF) and its follow-up initiative, the International Medical Devices Regulators Forum (IMDRF), should be taken into account to promote the global convergence of regulations which contributes to a high level of safety protection worldwide, and to facilitate trade, in particular in the provisions on Unique Device Identification, general safety and performance requirements, technical documentation, classification rules, conformity assessment procedures and clinical investigations.\n\n\n\n\n\n\n\n\n\n\n\n\n(6)\n\n\nFor historical reasons, active implantable medical devices, covered by Directive\u00a090/385/EEC, and other medical devices, covered by Directive\u00a093/42/EEC, were regulated in two separate legal instruments. In the interest of simplification, both directives, which have been amended several times, should be replaced by a single legislative act applicable to all medical devices other than in vitro diagnostic medical devices.\n\n\n\n\n\n\n\n\n\n\n\n\n(7)\n\n\nThe scope of application of this Regulation should be clearly delimited from other Union harmonisation legislation concerning products, such as in vitro diagnostic medical devices, medicinal products, cosmetics and food. Therefore, Regulation\u00a0(EC)\u00a0No\u00a0178/2002 of the European Parliament and of the Council\u00a0(5) should be amended to exclude medical devices from its scope.\n\n\n\n\n\n\n\n\n\n\n\n\n(8)\n\n\nIt should be the responsibility of the Member\u00a0States to decide on a case-by-case basis whether or not a product falls within the scope of this Regulation. In order to ensure consistent qualification decisions in that regard across all Member\u00a0States, particularly with regard to borderline cases, the Commission should be allowed to, on its own initiative or at the duly substantiated request of a Member\u00a0State, having consulted the Medical Device Coordination Group (\u2018MDCG\u2019), decide on a case-by-case basis whether or not a specific product, category or group of products falls within the scope of this Regulation. When deliberating on the regulatory status of products in borderline cases involving medicinal products, human tissues and cells, biocidal products or food products, the Commission should ensure an appropriate level of consultation of the European Medicines Agency\u00a0(EMA), the European Chemicals Agency and the European Food Safety Authority, as relevant.\n\n\n\n\n\n\n\n\n\n\n\n\n(9)\n\n\nSince in some cases it is difficult to distinguish between medical devices and cosmetic products, the possibility of taking a Union-wide decision regarding the regulatory status of a product should also be introduced in Regulation\u00a0(EC)\u00a0No\u00a01223/2009 of the European Parliament and of the Council\u00a0(6).\n\n\n\n\n\n\n\n\n\n\n\n\n(10)\n\n\nProducts which combine a medicinal product or substance and a medical device are regulated either under this Regulation or under Directive\u00a02001/83/EC of the European Parliament and of the Council.\u00a0(7) The two legislative acts should ensure appropriate interaction in terms of consultations during pre-market assessment, and of exchange of information in the context of vigilance activities involving such combination products. For medicinal products that integrate a medical device part, compliance with the general safety and performance requirements laid down in this Regulation for the device part should be adequately assessed in the context of the marketing authorisation for such medicinal products. Directive\u00a02001/83/EC should therefore be amended.\n\n\n\n\n\n\n\n\n\n\n\n\n(11)\n\n\nUnion legislation, in particular Regulation\u00a0(EC)\u00a0No\u00a01394/2007 of the European Parliament and of the Council\u00a0(8) and Directive\u00a02004/23/EC of the European Parliament and of the Council\u00a0(9), is incomplete in respect of certain products manufactured utilising derivatives of tissues or cells of human origin that are non-viable or are rendered non-viable. Such products should come under the scope of this Regulation, provided they comply with the definition of a medical device or are covered by this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(12)\n\n\nCertain groups of products for which a manufacturer claims only an aesthetic or another non-medical purpose but which are similar to medical devices in terms of functioning and risks profile should be covered by this Regulation. In order for manufacturers to be able to demonstrate the conformity of such products, the Commission should adopt common specifications at least with regard to application of risk management and, where necessary, clinical evaluation regarding safety. Such common specifications should be developed specifically for a group of products without an intended medical purpose and should not be used for conformity assessment of the analogous devices with a medical purpose. Devices with both a medical and a non-medical intended purpose should fulfil both the requirements applicable to devices with, and to devices without, an intended medical purpose.\n\n\n\n\n\n\n\n\n\n\n\n\n(13)\n\n\nAs is the case for products that contain viable tissues or cells of human or animal origin, that are explicitly excluded from Directives\u00a090/385/EEC and 93/42/EEC and hence from this Regulation, it should be clarified that products that contain or consist of viable biological materials or viable organisms of another origin in order to achieve or support the intended purpose of those products are not covered by this Regulation either.\n\n\n\n\n\n\n\n\n\n\n\n\n(14)\n\n\nThe requirements laid down in Directive\u00a02002/98/EC of the European Parliament and of the Council\u00a0(10) should continue to apply.\n\n\n\n\n\n\n\n\n\n\n\n\n(15)\n\n\nThere is scientific uncertainty about the risks and benefits of nanomaterials used for devices. In order to ensure a high level of health protection, free movement of goods and legal certainty for manufacturers, it is necessary to introduce a uniform definition for nanomaterials based on Commission Recommendation\u00a02011/696/EU\u00a0(11), with the necessary flexibility to adapt that definition to scientific and technical progress and subsequent regulatory development at Union and international level. In the design and manufacture of devices, manufacturers should take special care when using nanoparticles for which there is a high or medium potential for internal exposure. Such devices should be subject to the most stringent conformity assessment procedures. In preparation of implementing acts regulating the practical and uniform application of the corresponding requirements laid down in this Regulation, the relevant scientific opinions of the relevant scientific committees should be taken into account.\n\n\n\n\n\n\n\n\n\n\n\n\n(16)\n\n\nSafety aspects addressed by Directive\u00a02014/30/EU of the European Parliament and of the Council\u00a0(12) are an integral part of the general safety and performance requirements laid down in this Regulation for devices. Consequently, this Regulation should be considered a lex\u00a0specialis in relation to that Directive.\n\n\n\n\n\n\n\n\n\n\n\n\n(17)\n\n\nThis Regulation should include requirements regarding the design and manufacture of devices emitting ionizing radiation without affecting the application of Council Directive\u00a02013/59/Euratom\u00a0(13) which pursues other objectives.\n\n\n\n\n\n\n\n\n\n\n\n\n(18)\n\n\nThis Regulation should include requirements for devices' design, safety and performance characteristics which are developed in such a way as to prevent occupational injuries, including protection from radiation.\n\n\n\n\n\n\n\n\n\n\n\n\n(19)\n\n\nIt is necessary to clarify that software in its own right, when specifically intended by the manufacturer to be used for one or more of the medical purposes set out in the definition of a medical device, qualifies as a medical device, while software for general purposes, even when used in a healthcare setting, or software intended for life-style and well-being purposes is not a medical device. The qualification of software, either as a device or an accessory, is independent of the software's location or the type of interconnection between the software and a device.\n\n\n\n\n\n\n\n\n\n\n\n\n(20)\n\n\nThe definitions in this Regulation, regarding devices themselves, the making available of devices, economic operators, users and specific processes, the conformity assessment, clinical investigations and clinical evaluations, post-market surveillance, vigilance and market surveillance, standards and other technical specifications, should be aligned with well-established practice in the field at Union and international level in order to enhance legal certainty.\n\n\n\n\n\n\n\n\n\n\n\n\n(21)\n\n\nIt should be made clear that it is essential that devices offered to persons in the Union by means of information society services within the meaning of Directive\u00a0(EU)\u00a02015/1535 of the European Parliament and of the Council\u00a0(14) and devices used in the context of a commercial activity to provide a diagnostic or therapeutic service to persons within the Union comply with the requirements of this Regulation, where the product in question is placed on the market or the service is provided in the Union.\n\n\n\n\n\n\n\n\n\n\n\n\n(22)\n\n\nTo recognise the important role of standardisation in the field of medical devices, compliance with harmonised standards as defined in Regulation (EU)\u00a0No\u00a01025/2012 of the European Parliament and of the Council\u00a0(15) should be a means for manufacturers to demonstrate conformity with the general safety and performance requirements and other legal requirements, such as those relating to quality and risk management, laid down in this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(23)\n\n\nDirective\u00a098/79/EC of the European Parliament and of the Council\u00a0(16) allows the Commission to adopt common technical specifications for specific categories of in vitro diagnostic medical devices. In areas where no harmonised standards exist or where they are insufficient, the Commission should be empowered to lay down common specifications which provide a means of complying with the general safety and performance requirements, and the requirements for clinical investigations and clinical evaluation and/or post-market clinical follow-up, laid down in this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(24)\n\n\nCommon specifications (\u2018CS\u2019) should be developed after consulting the relevant stakeholders and taking account of European and international standards.\n\n\n\n\n\n\n\n\n\n\n\n\n(25)\n\n\nThe rules applicable to devices should be aligned, where appropriate, with the New Legislative Framework for the Marketing of Products, which consists of Regulation\u00a0(EC)\u00a0No\u00a0765/2008 of the European Parliament and of the Council\u00a0(17) and Decision\u00a0No\u00a0768/2008/EC of the European Parliament and of the Council\u00a0(18).\n\n\n\n\n\n\n\n\n\n\n\n\n(26)\n\n\nThe rules on Union market surveillance and control of products entering the Union market laid down in Regulation\u00a0(EC)\u00a0No\u00a0765/2008 apply to devices covered by this Regulation which does not prevent Member\u00a0States from choosing the competent authorities to carry out those tasks.\n\n\n\n\n\n\n\n\n\n\n\n\n(27)\n\n\nIt is appropriate to set out clearly the general obligations of the different economic operators, including importers and distributors, building on the New Legislative Framework for the Marketing of Products, without prejudice to the specific obligations laid down in the various parts of this Regulation, to enhance understanding of the requirements laid down in this Regulation and thus to improve regulatory compliance by the relevant operators.\n\n\n\n\n\n\n\n\n\n\n\n\n(28)\n\n\nFor the purpose of this Regulation, the activities of distributors should be deemed to include acquisition, holding and supplying of devices.\n\n\n\n\n\n\n\n\n\n\n\n\n(29)\n\n\nSeveral of the obligations on manufacturers, such as clinical evaluation or vigilance reporting, that were set out only in the Annexes\u00a0to Directives\u00a090/385/EEC and\u00a093/42/EEC, should be incorporated into the enacting provisions of this Regulation to facilitate its application.\n\n\n\n\n\n\n\n\n\n\n\n\n(30)\n\n\nHealth institutions should have the possibility of manufacturing, modifying and using devices in-house and thereby address, on a non-industrial scale, the specific needs of target patient groups which cannot be met at the appropriate level of performance by an equivalent device available on the market. In that context, it is appropriate to provide that certain rules of this Regulation, as regards medical devices manufactured and used only within health institutions, including hospitals as well as institutions, such as laboratories and public health institutes that support the healthcare system and/or address patient needs, but which do not treat or care for patients directly, should not apply, since the aims of this Regulation would still be met in a proportionate manner. It should be noted that the concept of \u2018health institution\u2019 does not cover establishments primarily claiming to pursue health interests or healthy lifestyles, such as gyms, spas, wellness and fitness centres. As a result, the exemption applicable to health institutions does not apply to such establishments.\n\n\n\n\n\n\n\n\n\n\n\n\n(31)\n\n\nIn view of the fact that natural or legal persons can claim compensation for damage caused by a defective device in accordance with applicable Union and national law, it is appropriate to require manufacturers to have measures in place to provide sufficient financial coverage in respect of their potential liability under Council Directive\u00a085/374/EEC\u00a0(19). Such measures should be proportionate to the risk class, type of device and the size of the enterprise. In this context, it is also appropriate to lay down rules concerning the facilitation, by a competent authority, of the provision of information to persons who may have been injured by a defective device.\n\n\n\n\n\n\n\n\n\n\n\n\n(32)\n\n\nTo ensure that devices manufactured in series production continue to be in conformity with the requirements of this Regulation and that experience from the use of the devices they manufacture is taken into account for the production process, all manufacturers should have a quality management system and a post-market surveillance system in place which should be proportionate to the risk class and the type of the device in question. In addition, in order to minimize risks or prevent incidents related to devices, manufacturers should establish a system for risk management and a system for reporting of incidents and field safety corrective actions.\n\n\n\n\n\n\n\n\n\n\n\n\n(33)\n\n\nThe risk management system should be carefully aligned with and reflected in the clinical evaluation for the device, including the clinical risks to be addressed as part of clinical investigations, clinical evaluation and post-market clinical follow up. The risk management and clinical evaluation processes should be inter-dependent and should be regularly updated.\n\n\n\n\n\n\n\n\n\n\n\n\n(34)\n\n\nIt should be ensured that supervision and control of the manufacture of devices, and the post-market surveillance and vigilance activities concerning them, are carried out within the manufacturer's organisation by a person responsible for regulatory compliance who fulfils minimum conditions of qualification.\n\n\n\n\n\n\n\n\n\n\n\n\n(35)\n\n\nFor manufacturers who are not established in the Union, the authorised representative plays a pivotal role in ensuring the compliance of the devices produced by those manufacturers and in serving as their contact person established in the Union. Given that pivotal role, for the purposes of enforcement it is appropriate to make the authorised representative legally liable for defective devices in the event that a manufacturer established outside the Union has not complied with its general obligations. The liability of the authorised representative provided for in this Regulation is without prejudice to the provisions of Directive\u00a085/374/EEC, and accordingly the authorised representative should be jointly and severally liable with the importer and the manufacturer. The tasks of an authorised representative should be defined in a written mandate. Considering the role of authorised representatives, the minimum requirements they should meet should be clearly defined, including the requirement of having available a person who fulfils minimum conditions of qualification which should be similar to those for a manufacturer's person responsible for regulatory compliance.\n\n\n\n\n\n\n\n\n\n\n\n\n(36)\n\n\nTo ensure legal certainty in respect of the obligations incumbent on economic operators, it is necessary to clarify when a distributor, importer or other person is to be considered the manufacturer of a device.\n\n\n\n\n\n\n\n\n\n\n\n\n(37)\n\n\nParallel trade in products already placed on the market is a lawful form of trade within the internal market on the basis of Article\u00a034 TFEU subject to the limitations arising from the need for protection of health and safety and from the need for protection of intellectual property rights provided for under Article\u00a036 TFEU. Application of the principle of parallel trade is, however, subject to different interpretations in the Member\u00a0States. The conditions, in particular the requirements for relabelling and repackaging, should therefore be specified in this Regulation, taking into account the case-law of the Court of Justice\u00a0(20) in other relevant sectors and existing good practice in the field of medical devices.\n\n\n\n\n\n\n\n\n\n\n\n\n(38)\n\n\nThe reprocessing and further use of single-use devices should only take place where permitted by national law and while complying with the requirements laid down in this Regulation. The reprocessor of a single-use device should be considered to be the manufacturer of the reprocessed device and should assume the obligations incumbent on manufacturers under this Regulation. Nevertheless, Member\u00a0States should have the possibility of deciding that the obligations relating to reprocessing and re-use of single-use devices within a health institution or by an external reprocessor acting on its behalf may differ from the obligations on a manufacturer described in this Regulation. In principle, such divergence should only be permitted where reprocessing and reuse of single-use devices within a health institution or by an external reprocessor are compliant with CS that have been adopted, or, in the absence of such CS, with relevant harmonised standards and national provisions. The reprocessing of such devices should ensure an equivalent level of safety and performance to that of the corresponding initial single-use device.\n\n\n\n\n\n\n\n\n\n\n\n\n(39)\n\n\nPatients who are implanted with a device should be given clear and easily accessible essential information allowing the implanted device to be identified and other relevant information about the device, including any necessary health risk warnings or precautions to be taken, for example indications as to whether or not it is compatible with certain diagnostic devices or with scanners used for security controls.\n\n\n\n\n\n\n\n\n\n\n\n\n(40)\n\n\nDevices should, as a general rule, bear the CE marking to indicate their conformity with this Regulation so that they can move freely within the Union and be put into service in accordance with their intended purpose. Member\u00a0States should not create obstacles to the placing on the market or putting into service of devices that comply with the requirements laid down in this Regulation. However, Member\u00a0States should be allowed to decide whether to restrict the use of any specific type of device in relation to aspects that are not covered by this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(41)\n\n\nThe traceability of devices by means of a Unique Device Identification system\u00a0(UDI\u00a0system) based on international guidance should significantly enhance the effectiveness of the post-market safety-related activities for devices, which is owing to improved incident reporting, targeted field safety corrective actions and better monitoring by competent authorities. It should also help to reduce medical errors and to fight against falsified devices. Use of the UDI system should also improve purchasing and waste disposal policies and stock-management by health institutions and other economic operators and, where possible, be compatible with other authentication systems already in place in those settings.\n\n\n\n\n\n\n\n\n\n\n\n\n(42)\n\n\nThe UDI system should apply to all devices placed on the market except custom-made devices, and be based on internationally recognised principles including definitions that are compatible with those used by major trade partners. In order for the UDI system to become functional in time for the application of this Regulation, detailed rules should be laid down in this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(43)\n\n\nTransparency and adequate access to information, appropriately presented for the intended user, are essential in the public interest, to protect public health, to empower patients and healthcare professionals and to enable them to make informed decisions, to provide a sound basis for regulatory decision-making and to build confidence in the regulatory system.\n\n\n\n\n\n\n\n\n\n\n\n\n(44)\n\n\nOne key aspect in fulfilling the objectives of this Regulation is the creation of a European database on medical devices (Eudamed) that should integrate different electronic systems to collate and process information regarding devices on the market and the relevant economic operators, certain aspects of conformity assessment, notified bodies, certificates, clinical investigations, vigilance and market surveillance. The objectives of the database are to enhance overall transparency, including through better access to information for the public and healthcare professionals, to avoid multiple reporting requirements, to enhance coordination between Member\u00a0States and to streamline and facilitate the flow of information between economic operators, notified bodies or sponsors and Member\u00a0States as well as between Member\u00a0States among themselves and with the Commission. Within the internal market, this can be ensured effectively only at Union level and the Commission should therefore further\u00a0develop and manage the European databank on medical devices set up by Commission Decision\u00a02010/227/EU\u00a0(21).\n\n\n\n\n\n\n\n\n\n\n\n\n(45)\n\n\nTo facilitate the functioning of Eudamed, an internationally recognised medical device nomenclature should be available free of charge to manufacturers and other natural or legal persons required by this Regulation to use that nomenclature. Furthermore, that nomenclature should be available, where reasonably practicable, free of charge also to other stakeholders.\n\n\n\n\n\n\n\n\n\n\n\n\n(46)\n\n\nEudamed's electronic systems regarding devices on the market, the relevant economic operators and certificates should enable the public to be adequately informed about devices on the Union market. The electronic system on clinical investigations should serve as a tool for the cooperation between Member\u00a0States and for enabling sponsors to submit, on a voluntary basis, a single application for several Member\u00a0States and to report serious adverse events, device deficiencies and related updates. The electronic system on vigilance should enable manufacturers to report serious incidents and other reportable events and to support the coordination of the evaluation of such incidents and events by competent authorities. The electronic system regarding market surveillance should be a tool for the exchange of information between competent authorities.\n\n\n\n\n\n\n\n\n\n\n\n\n(47)\n\n\nIn respect of data collated and processed through the electronic systems of Eudamed, Directive\u00a095/46/EC of the European Parliament and of the Council\u00a0(22) applies to the processing of personal data carried out in the Member\u00a0States, under the supervision of the Member\u00a0States' competent authorities, in particular the public independent authorities designated by the Member\u00a0States. Regulation\u00a0(EC)\u00a0No\u00a045/2001 of the European Parliament and of the Council\u00a0(23) applies to the processing of personal data carried out by the Commission within the framework of this Regulation, under the supervision of the European Data Protection Supervisor. In accordance with Regulation\u00a0(EC)\u00a0No\u00a045/2001, the Commission should be designated as the controller of Eudamed and its electronic systems.\n\n\n\n\n\n\n\n\n\n\n\n\n(48)\n\n\nFor implantable devices and for class III devices, manufacturers should summarise the main safety and performance aspects of the device and the outcome of the clinical evaluation in a document that should be publicly available.\n\n\n\n\n\n\n\n\n\n\n\n\n(49)\n\n\nThe summary of safety and clinical performance for a device should include in particular the place of the device in the context of diagnostic or therapeutic options taking into account the clinical evaluation of that device when compared to the diagnostic or therapeutic alternatives and the specific conditions under which that device and its alternatives can be considered.\n\n\n\n\n\n\n\n\n\n\n\n\n(50)\n\n\nThe proper functioning of notified bodies is crucial for ensuring a high level of health and safety protection and citizens' confidence in the system. Designation and monitoring of notified bodies by the Member\u00a0States, in accordance with detailed and strict criteria, should therefore be subject to controls at Union level.\n\n\n\n\n\n\n\n\n\n\n\n\n(51)\n\n\nNotified bodies' assessments of manufacturers' technical documentation, in particular documentation on clinical evaluation, should be critically evaluated by the authority responsible for notified bodies. That evaluation should be part of the risk-based approach to the oversight and monitoring activities of notified bodies and should be based on sampling of the relevant documentation.\n\n\n\n\n\n\n\n\n\n\n\n\n(52)\n\n\nThe position of notified bodies vis-\u00e0-vis manufacturers should be strengthened, including with regard to their right and duty to carry out unannounced on-site audits and to conduct physical or laboratory tests on devices to ensure continuous compliance by manufacturers after receipt of the original certification.\n\n\n\n\n\n\n\n\n\n\n\n\n(53)\n\n\nTo increase transparency with regard to the oversight of notified bodies by national authorities, the authorities responsible for notified bodies should publish information on the national measures governing the assessment, designation and monitoring of notified bodies. In accordance with good administrative practice, this information should be kept up to date by those authorities in particular to reflect relevant, significant or substantive changes to the procedures in question.\n\n\n\n\n\n\n\n\n\n\n\n\n(54)\n\n\nThe Member\u00a0State in which a notified body is established should be responsible for enforcing the requirements of this Regulation with regard to that notified body.\n\n\n\n\n\n\n\n\n\n\n\n\n(55)\n\n\nIn view, in particular, of the responsibility of Member\u00a0States for the organisation and delivery of health services and medical care, they should be allowed to lay down additional requirements on notified bodies designated for the conformity assessment of devices and established on their territory as far as issues that are not regulated in this Regulation are concerned. Any such additional requirements laid down should not affect more specific horizontal Union legislation on notified bodies and equal treatment of notified bodies.\n\n\n\n\n\n\n\n\n\n\n\n\n(56)\n\n\nFor class III implantable devices and class IIb active devices intended to administer and/or remove a medicinal product, notified bodies should, except in certain cases, be obliged to request expert panels to scrutinise their clinical evaluation assessment report. Competent authorities should be informed about devices that have been granted a certificate following a conformity assessment procedure involving an expert panel. The consultation of expert panels in relation to the clinical evaluation should lead to a harmonised evaluation of high-risk medical devices by sharing expertise on clinical aspects and developing CS on categories of devices that have undergone that consultation process.\n\n\n\n\n\n\n\n\n\n\n\n\n(57)\n\n\nFor class\u00a0III devices and for certain class\u00a0IIb devices, a manufacturer should be able to consult voluntarily an expert panel, prior to that manufacturer's clinical evaluation and/or investigation, on its clinical development strategy and on proposals for clinical investigations.\n\n\n\n\n\n\n\n\n\n\n\n\n(58)\n\n\nIt is necessary, in particular for the purpose of the conformity assessment procedures, to maintain the division of devices into four product classes in line with international practice. The classification rules, which are based on the vulnerability of the human body, should take into account the potential risks associated with the technical design and manufacture of the devices. To maintain the same level of safety as provided by Directive\u00a090/385/EEC, active implantable devices should be in the highest risk class.\n\n\n\n\n\n\n\n\n\n\n\n\n(59)\n\n\nRules under the old regime applied to invasive devices do not sufficiently take account of the level of invasiveness and potential toxicity of certain devices which are introduced into the human body. In order to obtain a suitable risk-based classification of devices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body, it is necessary to introduce specific classification rules for such devices. The classification rules should take into account the place where the device performs its action in or on the human body, where it is introduced or applied, and whether a systemic absorption of the substances of which the device is composed, or of the products of metabolism in the human body of those substances occurs.\n\n\n\n\n\n\n\n\n\n\n\n\n(60)\n\n\nThe conformity assessment procedure for class I devices should be carried out, as a general rule, under the sole responsibility of manufacturers in view of the low level of vulnerability associated with such devices. For class\u00a0IIa, class\u00a0IIb and class\u00a0III devices, an appropriate level of involvement of a notified body should be compulsory.\n\n\n\n\n\n\n\n\n\n\n\n\n(61)\n\n\nThe conformity assessment procedures for devices should be further strengthened and streamlined whilst the requirements for notified bodies as regards the performance of their assessments should be clearly specified to ensure a level playing field.\n\n\n\n\n\n\n\n\n\n\n\n\n(62)\n\n\nIt is appropriate that certificates of free sale contain information that makes it possible to use Eudamed in order to obtain information on the device, in particular with regard to whether it is on the market, withdrawn from the market or recalled, and on any certificate on its conformity.\n\n\n\n\n\n\n\n\n\n\n\n\n(63)\n\n\nTo ensure a high level of safety and performance, demonstration of compliance with the general safety and performance requirements laid down in this Regulation should be based on clinical data that, for class\u00a0III\u00a0devices and implantable devices should, as a general rule, be sourced from clinical investigations that have been carried out under the responsibility of a sponsor. It should be possible both for the manufacturer and for another natural or legal person to be the sponsor taking responsibility for the clinical investigation.\n\n\n\n\n\n\n\n\n\n\n\n\n(64)\n\n\nThe rules on clinical investigations should be in line with well-established international guidance in this field, such as the international standard ISO\u00a014155:2011 on good clinical practice for clinical investigations of medical devices for human subjects, so as to make it easier for the results of clinical investigations conducted in the Union to be accepted as documentation outside the Union and to make it easier for the results of clinical investigations conducted outside the Union in accordance with international guidelines to be accepted within the Union. In addition, the rules should be in line with the most recent version of the World Medical Association Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects.\n\n\n\n\n\n\n\n\n\n\n\n\n(65)\n\n\nIt should be left to the Member\u00a0State where a clinical investigation is to be conducted to determine the appropriate authority to be involved in the assessment of the application to conduct a clinical investigation and to organise the involvement of ethics committees within the timelines for the authorisation of that clinical investigation as set out in this Regulation. Such decisions are a matter of internal organisation for each Member\u00a0State. In that context, Member\u00a0States should ensure the involvement of laypersons, in particular patients or patients' organisations. They should also ensure that the necessary expertise is available.\n\n\n\n\n\n\n\n\n\n\n\n\n(66)\n\n\nWhere, in the course of a clinical investigation, harm caused to a subject leads to the civil or criminal liability of the investigator or the sponsor being invoked, the conditions for liability in such cases, including issues of causality and the level of damages and sanctions, should remain governed by national law.\n\n\n\n\n\n\n\n\n\n\n\n\n(67)\n\n\nAn electronic system should be set up at Union level to ensure that every clinical investigation is recorded and reported in a publicly accessible database. To protect the right to the protection of personal data, recognised by Article\u00a08 of the Charter of Fundamental Rights of the European Union (\u2018the Charter\u2019), no personal data of subjects participating in a clinical investigation should be recorded in the electronic system. To ensure synergies with the area of clinical trials on medicinal products, the electronic system on clinical investigations should be interoperable with the EU database to be set up for clinical trials on medicinal products for human use.\n\n\n\n\n\n\n\n\n\n\n\n\n(68)\n\n\nWhere a clinical investigation is to be conducted in more than one Member\u00a0State, the sponsor should have the possibility of submitting a single application in order to reduce administrative burden. In order to allow for resource-sharing and to ensure consistency regarding the assessment of the health and safety-related aspects of the investigational device and of the scientific design of that clinical investigation, the procedure for the assessment of such single application should be coordinated between the Member\u00a0States under the direction of a coordinating Member\u00a0State. Such coordinated assessment should not include the assessment of intrinsically national, local and ethical aspects of a clinical investigation, including informed consent. For an initial period of seven years from the date of application of this Regulation, Member\u00a0States should be able to participate on a voluntary basis in the coordinated assessment. After that period, all Member\u00a0States should be obliged to participate in the coordinated assessment. The Commission, based on the experience gained from the voluntary coordination between Member\u00a0States, should draw up a report on the application of the relevant provisions regarding the coordinated assessment procedure. In the event that the findings of the report are negative, the Commission should submit a proposal to extend the period of participation on a voluntary basis in the coordinated assessment procedure.\n\n\n\n\n\n\n\n\n\n\n\n\n(69)\n\n\nSponsors should report certain adverse events and device deficiencies that occur during clinical investigations to the Member\u00a0States in which those clinical investigations are being conducted. Member\u00a0States should have the possibility of terminating or suspending the investigations or revoking the authorisation for those investigations, if considered necessary to ensure a high level of protection of the subjects participating in a clinical investigation. Such information should be communicated to the other Member\u00a0States.\n\n\n\n\n\n\n\n\n\n\n\n\n(70)\n\n\nThe sponsor of a clinical investigation should submit a summary of results of the clinical investigation that is easily understandable for the intended user together with the clinical investigation report, where applicable, within the timelines laid down in this Regulation. Where it is not possible to submit the summary of the results within the defined timelines for scientific reasons, the sponsor should justify this and specify when the results will be submitted.\n\n\n\n\n\n\n\n\n\n\n\n\n(71)\n\n\nThis Regulation should cover clinical investigations intended to gather clinical evidence for the purpose of demonstrating conformity of devices and should also lay down basic requirements regarding ethical and scientific assessments for other types of clinical investigations of medical devices.\n\n\n\n\n\n\n\n\n\n\n\n\n(72)\n\n\nIncapacitated subjects, minors, pregnant women and breastfeeding women require specific protection measures. However, it should be left to Member\u00a0States to determine the legally designated representatives of incapacitated subjects and minors.\n\n\n\n\n\n\n\n\n\n\n\n\n(73)\n\n\nThe principles of replacement, reduction and refinement in the area of animal experimentation laid down in the Directive\u00a02010/63/EU of the European Parliament and of the Council\u00a0(24) should be observed. In particular, the unnecessary duplication of tests and studies should be avoided.\n\n\n\n\n\n\n\n\n\n\n\n\n(74)\n\n\nManufacturers should play an active role during the post-market phase by systematically and actively gathering information from post-market experience with their devices in order to update their technical documentation and cooperate with the national competent authorities in charge of vigilance and market surveillance activities. To this end, manufacturers should establish a comprehensive post-market surveillance system, set up under their quality management system and based on a post-market surveillance plan. Relevant data and information gathered through post-market surveillance, as well as lessons learned from any implemented preventive and/or corrective actions, should be used to update any relevant part of technical documentation, such as those relating to risk assessment and clinical evaluation, and should also serve the purpose of transparency.\n\n\n\n\n\n\n\n\n\n\n\n\n(75)\n\n\nIn order to better protect health and safety regarding devices on the market, the electronic system on vigilance for devices should be made more effective by creating a central portal at Union level for reporting serious incidents and field safety corrective actions.\n\n\n\n\n\n\n\n\n\n\n\n\n(76)\n\n\nMember\u00a0States should take appropriate measures to raise awareness among healthcare professionals, users and patients about the importance of reporting incidents. Healthcare professionals, users and patients should be encouraged and enabled to report suspected serious incidents at national level using harmonised formats. The national competent authorities should inform manufacturers of any suspected serious incidents and, where a manufacturer confirms that such an incident has occurred, the authorities concerned should ensure that appropriate follow-up action is taken in order to minimise recurrence of such incidents.\n\n\n\n\n\n\n\n\n\n\n\n\n(77)\n\n\nThe evaluation of reported serious incidents and field safety corrective actions should be conducted at national level but coordination should be ensured where similar incidents have occurred or field safety corrective actions have to be carried out in more than one Member\u00a0State, with the objective of sharing resources and ensuring consistency regarding the corrective action.\n\n\n\n\n\n\n\n\n\n\n\n\n(78)\n\n\nIn the context of the investigation of incidents, the competent authorities should take into account, where appropriate, the information provided by and views of relevant stakeholders, including patient and healthcare professionals' organisations and manufacturers' associations.\n\n\n\n\n\n\n\n\n\n\n\n\n(79)\n\n\nThe reporting of serious adverse events or device deficiencies during clinical investigations and the reporting of serious incidents occurring after a device has been placed on the market should be clearly distinguished to avoid double reporting.\n\n\n\n\n\n\n\n\n\n\n\n\n(80)\n\n\nRules on market surveillance should be included in this Regulation to reinforce the rights and obligations of the national competent authorities, to ensure effective coordination of their market surveillance activities and to clarify the applicable procedures.\n\n\n\n\n\n\n\n\n\n\n\n\n(81)\n\n\nAny statistically significant increase in the number or severity of incidents that are not serious or in expected side-effects that could have a significant impact on the benefit-risk analysis and which could lead to unacceptable risks should be reported to the competent authorities in order to permit their assessment and the adoption of appropriate measures.\n\n\n\n\n\n\n\n\n\n\n\n\n(82)\n\n\nAn expert committee, the Medical Device Coordination Group (MDCG), composed of persons designated by the Member\u00a0States based on their role and expertise in the field of medical devices including in vitro diagnostic medical devices, should be established to fulfil the tasks conferred on it by this Regulation and by Regulation\u00a0(EU)\u00a02017/746 of the European Parliament and of the Council\u00a0(25), to provide advice to the Commission and to assist the Commission and the Member\u00a0States in ensuring a harmonised implementation of this Regulation. The MDCG should be able to establish subgroups in order to have access to necessary in-depth technical expertise in the field of medical devices including in vitro diagnostic medical devices. When establishing subgroups, appropriate consideration should be given to the possibility of involving existing groups at Union level in the field of medical devices.\n\n\n\n\n\n\n\n\n\n\n\n\n(83)\n\n\nExpert panels and expert laboratories should be designated by the Commission on the basis of their up-to-date clinical, scientific or technical expertise, with the aim of providing scientific, technical and clinical assistance to the Commission, the MDCG, manufacturers and notified bodies in relation to the implementation of this Regulation. Moreover, expert panels should fulfil the tasks of providing an opinion on clinical evaluation assessment reports of notified bodies in the case of certain high-risk devices.\n\n\n\n\n\n\n\n\n\n\n\n\n(84)\n\n\nCloser coordination between national competent authorities through information exchange and coordinated assessments under the direction of a coordinating authority is essential for ensuring a consistently high level of health and safety protection within the internal market, in particular in the areas of clinical investigations and vigilance. The principle of coordinated exchange and assessment should also apply across other authority activities described in this Regulation, such as the designation of notified bodies and should be encouraged in the area of market surveillance of devices. Joint working, coordination and communication of activities should also lead to more efficient use of resources and expertise at national level.\n\n\n\n\n\n\n\n\n\n\n\n\n(85)\n\n\nThe Commission should provide scientific, technical and corresponding logistical support to coordinating national authorities and ensure that the regulatory system for devices is effectively and uniformly implemented at Union level based on sound scientific evidence.\n\n\n\n\n\n\n\n\n\n\n\n\n(86)\n\n\nThe Union and, where appropriate, the Member\u00a0States should actively participate in international regulatory cooperation in the field of medical devices to facilitate the exchange of safety-related information regarding medical devices and to foster the further development of international regulatory guidelines that promote the adoption in other jurisdictions of regulations that lead to a level of health and safety protection equivalent to that set by this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(87)\n\n\nMember\u00a0States should take all necessary measures to ensure that the provisions of this Regulation are implemented, including by laying down effective, proportionate and dissuasive penalties for their infringement.\n\n\n\n\n\n\n\n\n\n\n\n\n(88)\n\n\nWhilst this Regulation should not affect the right of Member\u00a0States to levy fees for activities at national level, Member\u00a0States should, in order to ensure transparency, inform the Commission and the other Member\u00a0States before they decide on the level and structure of such fees. In order to further ensure transparency, the structure and level of the fees should be publicly available on request.\n\n\n\n\n\n\n\n\n\n\n\n\n(89)\n\n\nThis Regulation respects the fundamental rights and observes the principles recognised in particular by the Charter and in particular human dignity, the integrity of the person, the protection of personal data, the freedom of art and science, the freedom to conduct business and the right to property. This Regulation should be applied by the Member\u00a0States in accordance with those rights and principles.\n\n\n\n\n\n\n\n\n\n\n\n\n(90)\n\n\nThe power to adopt delegated acts in accordance with Article\u00a0290 TFEU should be delegated to the Commission in order to amend certain non-essential provisions of this Regulation. It is of particular importance that the Commission carry out appropriate consultations during its preparatory work, including at expert level, and that those consultations be conducted in accordance with the principles laid down in the Interinstitutional Agreement of 13\u00a0April\u00a02016 on Better Law-Making\u00a0(26). In particular, to ensure equal participation in the preparation of delegated acts, the European Parliament and the Council receive all documents at the same time as Member\u00a0States' experts, and their experts systematically have access to meetings of Commission expert groups dealing with preparation of delegated acts.\n\n\n\n\n\n\n\n\n\n\n\n\n(91)\n\n\nIn order to ensure uniform conditions for the implementation of this Regulation, implementing powers should\u00a0be conferred on the Commission. Those powers should be exercised in accordance with Regulation\u00a0(EU)\u00a0No\u00a0182/2011 of the European Parliament and of the Council\u00a0(27).\n\n\n\n\n\n\n\n\n\n\n\n\n(92)\n\n\nThe advisory procedure should be used for implementing acts that set out the form and presentation of the data elements of manufacturers' summaries of safety and clinical performance, and that establish the model for certificates of free sale, given that such implementing acts are of a procedural nature and do not directly have an impact on health and safety at Union level.\n\n\n\n\n\n\n\n\n\n\n\n\n(93)\n\n\nThe Commission should adopt immediately applicable implementing acts where, in duly justified cases relating to the extension to the territory of the Union of a national derogation from the applicable conformity assessment procedures, imperative grounds of urgency so require.\n\n\n\n\n\n\n\n\n\n\n\n\n(94)\n\n\nIn order to enable it to designate issuing entities, expert panels and expert laboratories, implementing powers should be conferred on the Commission.\n\n\n\n\n\n\n\n\n\n\n\n\n(95)\n\n\nTo allow economic operators, especially SMEs, notified bodies, Member\u00a0States and the Commission to adapt to the changes introduced by this Regulation and to ensure its proper application, it is appropriate to provide for a sufficient transitional period for that adaptation and for the organisational arrangements that are to be made. However, certain parts of the Regulation that directly affect Member\u00a0States and the Commission should be implemented as soon as possible. It is also particularly important that, by the date of application of this Regulation, a sufficient number of notified bodies be designated in accordance with the new requirements so as to avoid any shortage of medical devices on the market. Nonetheless, it is necessary that any designation of a notified body in accordance with the requirements of this Regulation prior to the date of its application be without prejudice to the validity of the designation of those notified bodies under Directives\u00a090/385/EEC and 93/42/EEC and to their capacity to continue issuing valid certificates under those two Directives until the date of application of this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(96)\n\n\nIn order to ensure a smooth transition to the new rules for registration of devices and of certificates, the obligation to submit the relevant information to the electronic systems set up at Union level pursuant to this Regulation should, in the event that the corresponding IT\u00a0systems are developed according to plan, only become fully effective from 18\u00a0months after the date of application of this Regulation. During this transitional period, certain provisions of Directives\u00a090/385/EEC and 93/42/EEC should remain in force. However, in order to avoid multiple registrations, economic operators and notified bodies who register in the relevant electronic systems set up at Union level pursuant to this Regulation should be considered to be in compliance with the registration requirements adopted by the Member\u00a0States pursuant to those provisions.\n\n\n\n\n\n\n\n\n\n\n\n\n(97)\n\n\nIn order to provide for a smooth introduction of the UDI system, the moment of application of the obligation to place the UDI carrier on the label of the device should vary from one to five years after the date of application of this Regulation depending upon the class of the device concerned.\n\n\n\n\n\n\n\n\n\n\n\n\n(98)\n\n\nDirectives\u00a090/385/EEC and 93/42/EEC should be repealed to ensure that only one set of rules applies to the placing of medical devices on the market and the related aspects covered by this Regulation. Manufacturers' obligations as regards the making available of documentation regarding devices they placed on the market and manufacturers' and Member\u00a0States' obligations as regards vigilance activities for devices placed on the market pursuant to those Directives should however continue to apply. While it should be left to Member\u00a0States to decide how to organise vigilance activities, it is desirable for them to have the possibility of reporting incidents related to devices placed on the market pursuant to the Directives using the same tools as those for reporting on devices placed on the market pursuant to this Regulation. It is furthermore appropriate, in order to ensure a smooth transition from the old regime to the new regime, to provide that Commission Regulation\u00a0(EU)\u00a0No\u00a0207/2012\u00a0(28) and Commission Regulation\u00a0(EU)\u00a0No\u00a0722/2012\u00a0(29) should remain in force and continue to apply unless and until repealed by implementing acts adopted by the Commission pursuant to this Regulation.\nDecision\u00a02010/227/EU adopted in implementation of those Directives and Directive\u00a098/79/EC should also remain in force and continue to apply until the date when Eudamed becomes fully functional. Conversely, no such maintenance in force is required for Commission Directives\u00a02003/12/EC\u00a0(30) and 2005/50/EC\u00a0(31) and Commission Implementing Regulation (EU)\u00a0No\u00a0920/2013\u00a0(32).\n\n\n\n\n\n\n\n\n\n\n\n\n(99)\n\n\nThe requirements of this Regulation should be applicable to all devices placed on the market or put into service from the date of application of this Regulation. However, in order to provide for a smooth transition it should be possible, for a limited period of time from that date, for devices to be placed on the market or put into service by virtue of a valid certificate issued pursuant to Directive\u00a090/385/EEC or pursuant to Directive\u00a093/42/EEC.\n\n\n\n\n\n\n\n\n\n\n\n\n(100)\n\n\nThe European Data Protection Supervisor has given an opinion\u00a0(33) pursuant to Article\u00a028(2) of\u00a0Regulation\u00a0(EC)\u00a0No\u00a045/2001.\n\n\n\n\n\n\n\n\n\n\n\n\n(101)\n\n\nSince the objectives of this Regulation, namely to ensure the smooth functioning of the internal market as regards medical devices and to ensure high standards of quality and safety for medical devices, thus ensuring a high level of protection of health and safety of patients, users and other persons, cannot be sufficiently achieved by the Member\u00a0States but can rather, by reason of its scale and effects, be better achieved at Union level, the Union may adopt measures, in accordance with the principle of subsidiarity as set out in Article\u00a05 of the Treaty on European Union. In accordance with the principle of proportionality, as set out in that Article, this Regulation does not go beyond what is necessary in order to achieve those objectives,\n\n\n\n\n\nHAVE ADOPTED THIS REGULATION:\n\n\n\nCHAPTER I\n\n\nSCOPE AND DEFINITIONS\n\n\n\nArticle\u00a01\n\nSubject matter and scope\n\n\n1.\u00a0\u00a0\u00a0This Regulation lays down rules concerning the placing on the market, making available on the market or putting into service of medical devices for human use and accessories for such devices in the Union. This Regulation also applies to clinical investigations concerning such medical devices and accessories conducted in the Union.\n\n\n2.\u00a0\u00a0\u00a0This Regulation shall also apply, as from the date of application of common specifications adopted pursuant to Article\u00a09, to the groups of products without an intended medical purpose that are listed in Annex\u00a0XVI, taking into account the state of the art, and in particular existing harmonised standards for analogous devices with a medical purpose, based on similar technology. The common specifications for each of the groups of products listed in Annex\u00a0XVI shall address, at least, application of risk management as set out in Annex\u00a0I for the group of products in question and, where necessary, clinical evaluation regarding safety.\nThe necessary common specifications shall be adopted by 26 May 2020. They shall apply as from six months after the date of their entry into force or from 26 May 2020, whichever is the latest.\nNotwithstanding Article\u00a0122, Member\u00a0States' measures regarding the qualification of the products covered by Annex\u00a0XVI as medical devices pursuant to Directive\u00a093/42/EEC shall remain valid until the date of application, as referred to in the first subparagraph, of the relevant common specifications for that group of products.\nThis Regulation also applies to clinical investigations conducted in the Union concerning the products referred to in the first subparagraph.\n\n\n3.\u00a0\u00a0\u00a0Devices with both a medical and a non-medical intended purpose shall fulfil cumulatively the requirements applicable to devices with an intended medical purpose and those applicable to devices without an intended medical purpose.\n\n\n4.\u00a0\u00a0\u00a0For the purposes of this Regulation, medical devices, accessories for medical devices, and products listed in Annex\u00a0XVI to which this Regulation applies pursuant to paragraph\u00a02 shall hereinafter be referred to as \u2018devices\u2019.\n\n\n5.\u00a0\u00a0\u00a0Where justified on account of the similarity between a device with an intended medical purpose placed on the market and a product without an intended medical purpose in respect of their characteristics and risks, the Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 to amend the list in Annex\u00a0XVI, by adding new groups of products, in order to protect the health and safety of users or other persons or other aspects of public health.\n\n\n6.\u00a0\u00a0\u00a0This Regulation does not apply to:\n\n\n\n\n\n\n(a)\n\n\n\nin vitro diagnostic medical devices covered by Regulation\u00a0(EU)\u00a02017/746;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nmedicinal products as defined in point\u00a02 of Article\u00a01 of Directive\u00a02001/83/EC. In deciding whether a product falls under Directive\u00a02001/83/EC or under this Regulation, particular account shall be taken of the principal mode of action of the product;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nadvanced therapy medicinal products covered by Regulation\u00a0(EC)\u00a0No\u00a01394/2007;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nhuman blood, blood products, plasma or blood cells of human origin or devices which incorporate, when placed on the market or put into service, such blood products, plasma or cells, except for devices referred to in paragraph\u00a08 of this Article;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\ncosmetic products covered by Regulation\u00a0(EC)\u00a0No\u00a01223/2009;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\ntransplants, tissues or cells of animal origin, or their derivatives, or products containing or consisting of them; however this Regulation does apply to devices manufactured utilising tissues or cells of animal origin, or their derivatives, which are non-viable or are rendered non-viable;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\ntransplants, tissues or cells of human origin, or their derivatives, covered by Directive\u00a02004/23/EC, or products containing or consisting of them; however this Regulation does apply to devices manufactured utilising derivatives of tissues or cells of human origin which are non-viable or are rendered non-viable;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nproducts, other than those referred to in points (d), (f) and (g), that contain or consist of viable biological material or viable organisms, including living micro-organisms, bacteria, fungi or viruses in order to achieve or support the intended purpose of the product;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nfood covered by Regulation (EC)\u00a0No\u00a0178/2002.\n\n\n\n\n\n\n7.\u00a0\u00a0\u00a0Any device which, when placed on the market or put into service, incorporates as an integral part an in vitro diagnostic medical device as defined in point\u00a02 of Article\u00a02 of Regulation\u00a0(EU)\u00a02017/746, shall be governed by this Regulation. The requirements of Regulation\u00a0(EU)\u00a02017/746 shall apply to the in vitro diagnostic medical device part of the device.\n\n\n8.\u00a0\u00a0\u00a0Any device which, when placed on the market or put into service, incorporates, as an integral part, a substance which, if used separately, would be considered to be a medicinal product as defined in point\u00a02 of Article\u00a01 of Directive\u00a02001/83/EC, including a medicinal product derived from human blood or human plasma as defined in point\u00a010 of Article\u00a01 of that Directive, and that has an action ancillary to that of the device, shall be assessed and authorised in accordance with this Regulation.\nHowever, if the action of that substance is principal and not ancillary to that of the device, the integral product shall be governed by Directive\u00a02001/83/EC or Regulation\u00a0(EC)\u00a0No\u00a0726/2004 of the European Parliament and of the Council\u00a0(34), as applicable. In that case, the relevant general safety and performance requirements set out in Annex\u00a0I to this Regulation shall apply as far as the safety and performance of the device part are concerned.\n\n\n9.\u00a0\u00a0\u00a0Any device which is intended to administer a medicinal product as defined in point\u00a02 of Article\u00a01 of Directive\u00a02001/83/EC shall be governed by this Regulation, without prejudice to the provisions of that Directive\u00a0and of Regulation\u00a0(EC)\u00a0No\u00a0726/2004 with regard to the medicinal product.\nHowever, if the device intended to administer a medicinal product and the medicinal product are placed on the market in such a way that they form a single integral product which is intended exclusively for use in the given combination and which is not reusable, that single integral product shall be governed by Directive\u00a02001/83/EC or Regulation\u00a0(EC)\u00a0No\u00a0726/2004, as applicable. In that case, the relevant general safety and performance requirements set out in Annex\u00a0I to this Regulation shall apply as far as the safety and performance of the device part of the single integral product are concerned.\n\n\n10.\u00a0\u00a0\u00a0Any device which, when placed on the market or put into service, incorporates, as an integral part, non-viable tissues or cells of human origin or their derivatives that have an action ancillary to that of the device shall be assessed and authorised in accordance with this Regulation. In that case, the provisions for donation, procurement and testing laid down in Directive\u00a02004/23/EC shall apply.\nHowever, if the action of those tissues or cells or their derivatives is principal and not ancillary to that of the device and the product is not governed by Regulation\u00a0(EC)\u00a0No\u00a01394/2007, the product shall be governed by Directive\u00a02004/23/EC. In that case, the relevant general safety and performance requirements set out in Annex\u00a0I to this Regulation shall apply as far as the safety and performance of the device part are concerned.\n\n\n11.\u00a0\u00a0\u00a0This Regulation is specific Union legislation within the meaning of Article\u00a02(3) of Directive\u00a02014/30/EU.\n\n\n12.\u00a0\u00a0\u00a0Devices that are also machinery within the meaning of point\u00a0(a) of the second paragraph\u00a0of Article\u00a02 of Directive\u00a02006/42/EC of the European Parliament and of the Council\u00a0(35) shall, where a hazard relevant under that Directive\u00a0exists, also meet the essential health and safety requirements set out in Annex\u00a0I to that Directive\u00a0to the extent to which those requirements are more specific than the general safety and performance requirements set out in Chapter\u00a0II of Annex\u00a0I to this Regulation.\n\n\n13.\u00a0\u00a0\u00a0This Regulation shall not affect the application of Directive\u00a02013/59/Euratom.\n\n\n14.\u00a0\u00a0\u00a0This Regulation shall not affect the right of a Member\u00a0State to restrict the use of any specific type of device in relation to aspects not covered by this Regulation.\n\n\n15.\u00a0\u00a0\u00a0This Regulation shall not affect national law concerning the organisation, delivery or financing of health services and medical care, such as the requirement that certain devices may only be supplied on a medical prescription, the requirement that only certain health professionals or healthcare institutions may dispense or use certain devices or that their use be accompanied by specific professional counselling.\n\n\n16.\u00a0\u00a0\u00a0Nothing in this Regulation shall restrict the freedom of the press or the freedom of expression in the media in so far as those freedoms are guaranteed in the Union and in the Member\u00a0States, in particular under Article\u00a011 of the Charter of Fundamental Rights of the European Union.\n\n\n\nArticle\u00a02\n\nDefinitions\n\nFor the purposes of this Regulation, the following definitions apply:\n\n\n\n\n\n\n(1)\n\n\n\u2018medical device\u2019 means any instrument, apparatus, appliance, software, implant, reagent, material or other article intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the following specific medical purposes:\n\n\n\n\n\n\n\u2014\n\n\ndiagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndiagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninvestigation, replacement or modification of the anatomy or of a physiological or pathological process or state,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nproviding information by means of in vitro examination of specimens derived from the human body, including organ, blood and tissue donations,\n\n\n\n\nand which does not achieve its principal intended action by pharmacological, immunological or metabolic means, in or on the human body, but which may be assisted in its function by such means.\nThe following products shall also be deemed to be medical devices:\n\n\n\n\n\n\n\u2014\n\n\ndevices for the control or support of conception;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nproducts specifically intended for the cleaning, disinfection or sterilisation of devices as referred to in Article\u00a01(4) and of those referred to in the first paragraph\u00a0of this point.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(2)\n\n\n\u2018accessory for a medical device\u2019 means an article which, whilst not being itself a medical device, is intended by its manufacturer to be used together with one or several particular medical device(s) to specifically enable the medical device(s) to be used in accordance with its/their intended purpose(s) or to specifically and directly assist the medical functionality of the medical device(s) in terms of its/their intended purpose(s);\n\n\n\n\n\n\n\n\n\n\n(3)\n\n\n\u2018custom-made device\u2019 means any device specifically made in accordance with a written prescription of any person authorised by national law by virtue of that person's professional qualifications which gives, under that person's responsibility, specific design characteristics, and is intended for the sole use of a particular patient exclusively to meet their individual conditions and needs.\nHowever, mass-produced devices which need to be adapted to meet the specific requirements of any professional user and devices which are mass-produced by means of industrial manufacturing processes in accordance with the written prescriptions of any authorised person shall not be considered to be custom-made devices;\n\n\n\n\n\n\n\n\n\n\n(4)\n\n\n\u2018active device\u2019 means any device, the operation of which depends on a source of energy other than that generated by the human body for that purpose, or by gravity, and which acts by changing the density of or converting that energy. Devices intended to transmit energy, substances or other elements between an active device and the patient, without any significant change, shall not be deemed to be active devices.\nSoftware shall also be deemed to be an active device;\n\n\n\n\n\n\n\n\n\n\n(5)\n\n\n\u2018implantable device\u2019 means any device, including those that are partially or wholly absorbed, which is intended:\n\n\n\n\n\n\n\u2014\n\n\nto be totally introduced into the human body, or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nto replace an epithelial surface or the surface of the eye,\n\n\n\n\nby clinical intervention and which is intended to remain in place after the procedure.\nAny device intended to be partially introduced into the human body by clinical intervention and intended to remain in place after the procedure for at least 30\u00a0days shall also be deemed to be an implantable device;\n\n\n\n\n\n\n\n\n\n\n(6)\n\n\n\u2018invasive device\u2019 means any device which, in whole or in part, penetrates inside the body, either through a body orifice or through the surface of the body;\n\n\n\n\n\n\n\n\n\n\n(7)\n\n\n\u2018generic device group\u2019 means a set of devices having the same or similar intended purposes or a commonality of technology allowing them to be classified in a generic manner not reflecting specific characteristics;\n\n\n\n\n\n\n\n\n\n\n(8)\n\n\n\u2018single-use device\u2019 means a device that is intended to be used on one individual during a single procedure;\n\n\n\n\n\n\n\n\n\n\n(9)\n\n\n\u2018falsified device\u2019 means any device with a false presentation of its identity and/or of its source and/or its CE\u00a0marking certificates or documents relating to CE\u00a0marking procedures. This definition does not include unintentional non-compliance and is without prejudice to infringements of intellectual property rights;\n\n\n\n\n\n\n\n\n\n\n(10)\n\n\n\u2018procedure pack\u2019 means a combination of products packaged together and placed on the market with the purpose of being used for a specific medical purpose;\n\n\n\n\n\n\n\n\n\n\n(11)\n\n\n\u2018system\u2019 means a combination of products, either packaged together or not, which are intended to be inter-connected or combined to achieve a specific medical purpose;\n\n\n\n\n\n\n\n\n\n\n(12)\n\n\n\u2018intended purpose\u2019 means the use for which a device is intended according to the data supplied by the manufacturer on the label, in the instructions for use or in promotional or sales materials or statements and as specified by the manufacturer in the clinical evaluation;\n\n\n\n\n\n\n\n\n\n\n(13)\n\n\n\u2018label\u2019 means the written, printed or graphic information appearing either on the device itself, or on the packaging of each unit or on the packaging of multiple devices;\n\n\n\n\n\n\n\n\n\n\n(14)\n\n\n\u2018instructions for use\u2019 means the information provided by the manufacturer to inform the user of a device's intended purpose and proper use and of any precautions to be taken;\n\n\n\n\n\n\n\n\n\n\n(15)\n\n\n\u2018Unique Device Identifier\u2019 (\u2018UDI\u2019) means a series of numeric or alphanumeric characters that is created through internationally accepted device identification and coding standards and that allows unambiguous identification of specific devices on the market;\n\n\n\n\n\n\n\n\n\n\n(16)\n\n\n\u2018non-viable\u2019 means having no potential for metabolism or multiplication;\n\n\n\n\n\n\n\n\n\n\n(17)\n\n\n\u2018derivative\u2019 means a \u2018non-cellular substance\u2019 extracted from human or animal tissue or cells through a manufacturing process. The final substance used for manufacturing of the device in this case does not contain any cells or tissues;\n\n\n\n\n\n\n\n\n\n\n(18)\n\n\n\u2018nanomaterial\u2019 means a natural, incidental or manufactured material containing particles in an unbound state or as an aggregate or as an agglomerate and where, for\u00a050 % or more of the particles in the number size distribution, one or more external dimensions is in the size range 1-100\u00a0nm;\nFullerenes, graphene flakes and single-wall carbon nanotubes with one or more external dimensions below 1\u00a0nm shall also be deemed to be nanomaterials;\n\n\n\n\n\n\n\n\n\n\n(19)\n\n\n\u2018particle\u2019, for the purposes of the definition of nanomaterial in point\u00a0(18), means a minute piece of matter with defined physical boundaries;\n\n\n\n\n\n\n\n\n\n\n(20)\n\n\n\u2018agglomerate\u2019, for the purposes of the definition of nanomaterial in point\u00a0(18), means a collection of weakly bound particles or aggregates where the resulting external surface area is similar to the sum of the surface areas of the individual components;\n\n\n\n\n\n\n\n\n\n\n(21)\n\n\n\u2018aggregate\u2019, for the purposes of the definition of nanomaterial in point\u00a0(18), means a particle comprising of strongly bound or fused particles;\n\n\n\n\n\n\n\n\n\n\n(22)\n\n\n\u2018performance\u2019 means the ability of a device to achieve its intended purpose as stated by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(23)\n\n\n\u2018risk\u2019 means the combination of the probability of occurrence of harm and the severity of that harm;\n\n\n\n\n\n\n\n\n\n\n(24)\n\n\n\u2018benefit-risk determination\u2019 means the analysis of all assessments of benefit and risk of possible relevance for the use of the device for the intended purpose, when used in accordance with the intended purpose given by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(25)\n\n\n\u2018compatibility\u2019 is the ability of a device, including software, when used together with one or more other devices in accordance with its intended purpose, to:\n\n\n\n\n\n\n(a)\n\n\nperform without losing or compromising the ability to perform as intended, and/or\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nintegrate and/or operate without the need for modification or adaption of any part of the combined devices, and/or\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nbe used together without conflict/interference or adverse reaction.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(26)\n\n\n\u2018interoperability\u2019 is the ability of two or more devices, including software, from the same manufacturer or from different manufacturers, to:\n\n\n\n\n\n\n(a)\n\n\nexchange information and use the information that has been exchanged for the correct execution of a specified function without changing the content of the data, and/or\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ncommunicate with each other, and/or\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nwork together as intended.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(27)\n\n\n\u2018making available on the market\u2019 means any supply of a device, other than an investigational device, for distribution, consumption or use on the Union market in the course of a commercial activity, whether in return for payment or free of charge;\n\n\n\n\n\n\n\n\n\n\n(28)\n\n\n\u2018placing on the market\u2019 means the first making available of a device, other than an investigational device, on the Union market;\n\n\n\n\n\n\n\n\n\n\n(29)\n\n\n\u2018putting into service\u2019 means the stage at which a device, other than an investigational device, has been made available to the final user as being ready for use on the Union market for the first time for its intended purpose;\n\n\n\n\n\n\n\n\n\n\n(30)\n\n\n\u2018manufacturer\u2019 means a natural or legal person who manufactures or fully refurbishes a device or has a device designed, manufactured or fully refurbished, and markets that device under its name or trademark;\n\n\n\n\n\n\n\n\n\n\n(31)\n\n\n\u2018fully refurbishing\u2019, for the purposes of the definition of manufacturer, means the complete rebuilding of a device already placed on the market or put into service, or the making of a new device from used devices, to bring it into conformity with this Regulation, combined with the assignment of a new lifetime to the refurbished device;\n\n\n\n\n\n\n\n\n\n\n(32)\n\n\n\u2018authorised representative\u2019 means any natural or legal person established within the Union who has received and accepted a written mandate from a manufacturer, located outside the Union, to act on the manufacturer's behalf in relation to specified tasks with regard to the latter's obligations under this Regulation;\n\n\n\n\n\n\n\n\n\n\n(33)\n\n\n\u2018importer\u2019 means any natural or legal person established within the Union that places a device from a third country on the Union market;\n\n\n\n\n\n\n\n\n\n\n(34)\n\n\n\u2018distributor\u2019 means any natural or legal person in the supply chain, other than the manufacturer or the importer, that makes a device available on the market, up until the point of putting into service;\n\n\n\n\n\n\n\n\n\n\n(35)\n\n\n\u2018economic operator\u2019 means a manufacturer, an authorised representative, an importer, a distributor or the person referred to in Article\u00a022(1) and 22(3);\n\n\n\n\n\n\n\n\n\n\n(36)\n\n\n\u2018health institution\u2019 means an organisation the primary purpose of which is the care or treatment of patients or the promotion of public health;\n\n\n\n\n\n\n\n\n\n\n(37)\n\n\n\u2018user\u2019 means any healthcare professional or lay person who uses a device;\n\n\n\n\n\n\n\n\n\n\n(38)\n\n\n\u2018lay person\u2019 means an individual who does not have formal education in a relevant field of healthcare or medical discipline;\n\n\n\n\n\n\n\n\n\n\n(39)\n\n\n\u2018reprocessing\u2019 means a process carried out on a used device in order to allow its safe reuse including cleaning, disinfection, sterilisation and related procedures, as well as testing and restoring the technical and functional safety of the used device;\n\n\n\n\n\n\n\n\n\n\n(40)\n\n\n\u2018conformity assessment\u2019 means the process demonstrating whether the requirements of this Regulation relating to a device have been fulfilled;\n\n\n\n\n\n\n\n\n\n\n(41)\n\n\n\u2018conformity assessment body\u2019 means a body that performs third-party conformity assessment activities including calibration, testing, certification and inspection;\n\n\n\n\n\n\n\n\n\n\n(42)\n\n\n\u2018notified body\u2019 means a conformity assessment body designated in accordance with this Regulation;\n\n\n\n\n\n\n\n\n\n\n(43)\n\n\n\u2018CE marking of conformity\u2019 or \u2018CE marking\u2019 means a marking by which a manufacturer indicates that a device is in conformity with the applicable requirements set out in this Regulation and other applicable Union harmonisation legislation providing for its affixing;\n\n\n\n\n\n\n\n\n\n\n(44)\n\n\n\u2018clinical evaluation\u2019 means a systematic and planned process to continuously generate, collect, analyse and assess the clinical data pertaining to a device in order to verify the safety and performance, including clinical benefits, of the device when used as intended by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(45)\n\n\n\u2018clinical investigation\u2019 means any systematic investigation involving one or more human subjects, undertaken to assess the safety or performance of a device;\n\n\n\n\n\n\n\n\n\n\n(46)\n\n\n\u2018investigational device\u2019 means a device that is assessed in a clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(47)\n\n\n\u2018clinical investigation plan\u2019 means a document that describes the rationale, objectives, design, methodology, monitoring, statistical considerations, organisation and conduct of a clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(48)\n\n\n\u2018clinical data\u2019 means information concerning safety or performance that is generated from the use of a device and is sourced from the following:\n\n\n\n\n\n\n\u2014\n\n\nclinical investigation(s) of the device concerned,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclinical investigation(s) or other studies reported in scientific literature, of a device for which equivalence to the device in question can be demonstrated,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreports published in peer reviewed scientific literature on other clinical experience of either the device in question or a device for which equivalence to the device in question can be demonstrated,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclinically relevant information coming from post-market surveillance, in particular the post-market clinical follow-up;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(49)\n\n\n\u2018sponsor\u2019 means any individual, company, institution or organisation which takes responsibility for the initiation, for the management and setting up of the financing of the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(50)\n\n\n\u2018subject\u2019 means an individual who participates in a clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(51)\n\n\n\u2018clinical evidence\u2019 means clinical data and clinical evaluation results pertaining to a device of a sufficient amount and quality to allow a qualified assessment of whether the device is safe and achieves the intended clinical benefit(s), when used as intended by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(52)\n\n\n\u2018clinical performance\u2019 means the ability of a device, resulting from any direct or indirect medical effects which stem from its technical or functional characteristics, including diagnostic characteristics, to achieve its intended purpose as claimed by the manufacturer, thereby leading to a clinical benefit for patients, when used as intended by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(53)\n\n\n\u2018clinical benefit\u2019 means the positive impact of a device on the health of an individual, expressed in terms of a meaningful, measurable, patient-relevant clinical outcome(s), including outcome(s) related to diagnosis, or a positive impact on patient management or public health;\n\n\n\n\n\n\n\n\n\n\n(54)\n\n\n\u2018investigator\u2019 means an individual responsible for the conduct of a clinical investigation at a clinical investigation site;\n\n\n\n\n\n\n\n\n\n\n(55)\n\n\n\u2018informed consent\u2019 means a subject's free and voluntary expression of his or her willingness to participate in a particular clinical investigation, after having been informed of all aspects of the clinical investigation that are relevant to the subject's decision to participate or, in the case of minors and of incapacitated subjects, an authorisation or agreement from their legally designated representative to include them in the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(56)\n\n\n\u2018ethics committee\u2019 means an independent body established in a Member\u00a0State in accordance with the law of that Member\u00a0State and empowered to give opinions for the purposes of this Regulation, taking into account the views of laypersons, in particular patients or patients' organisations;\n\n\n\n\n\n\n\n\n\n\n(57)\n\n\n\u2018adverse event\u2019 means any untoward medical occurrence, unintended disease or injury or any untoward clinical signs, including an abnormal laboratory finding, in subjects, users or other persons, in the context of a clinical investigation, whether or not related to the investigational device;\n\n\n\n\n\n\n\n\n\n\n(58)\n\n\n\u2018serious adverse event\u2019 means any adverse event that led to any of the following:\n\n\n\n\n\n\n(a)\n\n\ndeath,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nserious deterioration in the health of the subject, that resulted in any of the following:\n\n\n\n\n\n\n(i)\n\n\nlife-threatening illness or injury,\n\n\n\n\n\n\n\n\n\n\n(ii)\n\n\npermanent impairment of a body structure or a body function,\n\n\n\n\n\n\n\n\n\n\n(iii)\n\n\nhospitalisation or prolongation of patient hospitalisation,\n\n\n\n\n\n\n\n\n\n\n(iv)\n\n\nmedical or surgical intervention to prevent life-threatening illness or injury or permanent impairment to a body structure or a body function,\n\n\n\n\n\n\n\n\n\n\n(v)\n\n\nchronic disease,\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nfoetal distress, foetal death or a congenital physical or mental impairment or birth defect;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(59)\n\n\n\u2018device deficiency\u2019 means any inadequacy in the identity, quality, durability, reliability, safety or performance of an\u00a0investigational device, including malfunction, use errors or inadequacy in information supplied by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(60)\n\n\n\u2018post-market surveillance\u2019 means all activities carried out by manufacturers in cooperation with other economic operators to institute and keep up to date a systematic procedure to proactively collect and review experience gained from devices they place on the market, make available on the market or put into service for the purpose of identifying any need to immediately apply any necessary corrective or preventive actions;\n\n\n\n\n\n\n\n\n\n\n(61)\n\n\n\u2018market surveillance\u2019 means the activities carried out and measures taken by competent authorities to check and ensure that devices comply with the requirements set out in the relevant Union harmonisation legislation and do not endanger health, safety or any other aspect of public interest protection;\n\n\n\n\n\n\n\n\n\n\n(62)\n\n\n\u2018recall\u2019 means any measure aimed at achieving the return of a device that has already been made available to the end user;\n\n\n\n\n\n\n\n\n\n\n(63)\n\n\n\u2018withdrawal\u2019 means any measure aimed at preventing a device in the supply chain from being further made available on the market;\n\n\n\n\n\n\n\n\n\n\n(64)\n\n\n\u2018incident\u2019 means any malfunction or deterioration in the characteristics or performance of a device made available on the market, including use-error due to ergonomic features, as well as any inadequacy in the information supplied by the manufacturer and any undesirable side-effect;\n\n\n\n\n\n\n\n\n\n\n(65)\n\n\n\u2018serious incident\u2019 means any incident that directly or indirectly led, might have led or might lead to any of the following:\n\n\n\n\n\n\n(a)\n\n\nthe death of a patient, user or other person,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe temporary or permanent serious deterioration of a patient's, user's or other person's state of health,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\na serious public health threat;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(66)\n\n\n\u2018serious public health threat\u2019 means an event which could result in imminent risk of death, serious deterioration in a person's state of health, or serious illness, that may require prompt remedial action, and that may cause significant morbidity or mortality in humans, or that is unusual or unexpected for the given place and time;\n\n\n\n\n\n\n\n\n\n\n(67)\n\n\n\u2018corrective action\u2019 means action taken to eliminate the cause of a potential or actual non-conformity or other undesirable situation;\n\n\n\n\n\n\n\n\n\n\n(68)\n\n\n\u2018field safety corrective action\u2019 means corrective action taken by a manufacturer for technical or medical reasons to prevent or reduce the risk of a serious incident in relation to a device made available on the market;\n\n\n\n\n\n\n\n\n\n\n(69)\n\n\n\u2018field safety notice\u2019 means a communication sent by a manufacturer to users or customers in relation to a field safety corrective action;\n\n\n\n\n\n\n\n\n\n\n(70)\n\n\n\u2018harmonised standard\u2019 means a European standard as defined in point\u00a0(1)(c) of Article\u00a02 of Regulation\u00a0(EU)\u00a0No\u00a01025/2012;\n\n\n\n\n\n\n\n\n\n\n(71)\n\n\n\u2018common specifications\u2019 (CS) means a set of technical and/or clinical requirements, other than a standard, that provides a means of complying with the legal obligations applicable to a device, process or system.\n\n\n\n\n\n\nArticle\u00a03\n\nAmendment of certain definitions\n\nThe Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 in order to amend the definition of nanomaterial set out in point\u00a0(18) and the related definitions in points\u00a0(19), (20) and (21) of Article\u00a02 in the light of technical and scientific progress and taking into account definitions agreed at Union and international level.\n\n\nArticle\u00a04\n\nRegulatory status of products\n\n\n1.\u00a0\u00a0\u00a0Without prejudice to Article\u00a02(2) of Directive\u00a02001/83/EC, upon a duly substantiated request of a Member\u00a0State, the Commission shall, after consulting the Medical Device Coordination Group established under Article\u00a0103 of this Regulation\u00a0(\u2018MDCG\u2019), by means of implementing acts, determine whether or not a specific product, or category or group of products, falls within the definitions of \u2018medical device\u2019 or \u2018accessory for a medical device\u2019. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3) of this Regulation.\n\n\n2.\u00a0\u00a0\u00a0The Commission may also, on its own initiative, after consulting the MDCG, decide, by means of implementing acts, on the issues referred to in paragraph\u00a01 of this Article. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n3.\u00a0\u00a0\u00a0The Commission shall ensure that Member\u00a0States share expertise in the fields of medical devices, in vitro diagnostic medical devices, medicinal products, human tissues and cells, cosmetics, biocides, food and, if necessary, other products, in order to determine the appropriate regulatory status of a product, or category or group of products.\n\n\n4.\u00a0\u00a0\u00a0When deliberating on the possible regulatory status as a device of products involving medicinal products, human tissues and cells, biocides or food products, the Commission shall ensure an appropriate level of consultation of the European Medicines Agency\u00a0(EMA), the European Chemicals Agency\u00a0(ECHA) and the European Food Safety Authority\u00a0(EFSA), as relevant.\n\n\n\n\nCHAPTER II\n\n\nMAKING AVAILABLE ON THE MARKET AND PUTTING INTO SERVICE OF DEVICES, OBLIGATIONS OF ECONOMIC OPERATORS, REPROCESSING, CE MARKING, FREE MOVEMENT\n\n\n\nArticle\u00a05\n\nPlacing on the market and putting into service\n\n\n1.\u00a0\u00a0\u00a0A device may be placed on the market or put into service only if it complies with this Regulation when duly supplied and properly installed, maintained and used in accordance with its intended purpose.\n\n\n2.\u00a0\u00a0\u00a0A device shall meet the general safety and performance requirements set out in Annex\u00a0I which apply to it, taking into account its intended purpose.\n\n\n3.\u00a0\u00a0\u00a0Demonstration of conformity with the general safety and performance requirements shall include a clinical evaluation in accordance with Article\u00a061.\n\n\n4.\u00a0\u00a0\u00a0Devices that are manufactured and used within health institutions shall be considered as having been put into service.\n\n\n5.\u00a0\u00a0\u00a0With the exception of the relevant general safety and performance requirements set out in Annex\u00a0I, the requirements of this Regulation shall not apply to devices, manufactured and used only within health institutions established in the Union, provided that all of the following conditions are met:\n\n\n\n\n\n\n(a)\n\n\nthe devices are not transferred to another legal entity,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nmanufacture and use of the devices occur under appropriate quality management systems,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe health institution justifies in its documentation that the target patient group's specific needs cannot be met, or cannot be met at the appropriate level of performance by an equivalent device available on the market,\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe health institution provides information upon request on the use of such devices to its competent authority, which shall include a justification of their manufacturing, modification and use;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe health institution draws up a declaration which it shall make publicly available, including:\n\n\n\n\n\n\n(i)\n\n\nthe name and address of the manufacturing health institution;\n\n\n\n\n\n\n\n\n\n\n(ii)\n\n\nthe details necessary to identify the devices;\n\n\n\n\n\n\n\n\n\n\n(iii)\n\n\na declaration that the devices meet the general safety and performance requirements set out in Annex\u00a0I to this Regulation and, where applicable, information on which requirements are not fully met with a reasoned justification therefor,\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe health institution draws up documentation that makes it possible to have an understanding of the manufacturing facility, the manufacturing process, the design and performance data of the devices, including the intended purpose, and that is sufficiently detailed to enable the competent authority to ascertain that the general safety and performance requirements set out in Annex\u00a0I to this Regulation are met;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthe health institution takes all necessary measures to ensure that all devices are manufactured in accordance with the documentation referred to in point\u00a0(f), and\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe health institution reviews experience gained from clinical use of the devices and takes all necessary corrective actions.\n\n\n\n\nMember\u00a0States may require that such health institutions submit to the competent authority any further relevant information about such devices which have been manufactured and used on their territory. Member\u00a0States shall retain the right to restrict the manufacture and the use of any specific type of such devices and shall be permitted access to inspect the activities of the health institutions.\nThis paragraph\u00a0shall not apply to devices that are manufactured on an industrial scale.\n\n\n6.\u00a0\u00a0\u00a0In order to ensure the uniform application of Annex\u00a0I, the Commission may adopt implementing acts to the extent necessary to resolve issues of divergent interpretation and of practical application. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a06\n\nDistance sales\n\n\n1.\u00a0\u00a0\u00a0A device offered by means of information society services, as defined in point\u00a0(b) of Article\u00a01(1) of Directive\u00a0(EU)\u00a02015/1535, to a natural or legal person established in the Union shall comply with this Regulation.\n\n\n2.\u00a0\u00a0\u00a0Without prejudice to national law regarding the exercise of the medical profession, a device that is not placed on the market but used in the context of a commercial activity, whether in return for payment or free of charge, for the provision of a diagnostic or therapeutic service offered by means of information society services as defined in point\u00a0(b) of Article\u00a01(1) of Directive\u00a0(EU)\u00a02015/1535 or by other means of communication, directly or through intermediaries, to a natural or legal person established in the Union shall comply with this Regulation.\n\n\n3.\u00a0\u00a0\u00a0Upon request by a competent authority, any natural or legal person offering a device in accordance with paragraph\u00a01 or providing a service in accordance with paragraph\u00a02 shall make available a copy of the EU\u00a0declaration of conformity of the device concerned.\n\n\n4.\u00a0\u00a0\u00a0A Member\u00a0State may, on grounds of protection of public health, require a provider of information society services, as defined in point\u00a0(b) of Article\u00a01(1) of Directive\u00a0(EU)\u00a02015/1535, to cease its activity.\n\n\n\nArticle\u00a07\n\nClaims\n\nIn the labelling, instructions for use, making available, putting into service and advertising of devices, it shall be prohibited to use text, names, trademarks, pictures and figurative or other signs that may mislead the user or the patient with regard to the device's intended purpose, safety and performance by:\n\n\n\n\n\n\n(a)\n\n\nascribing functions and properties to the device which the device does not have;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ncreating a false impression regarding treatment or diagnosis, functions or properties which the device does not have;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nfailing to inform the user or the patient of a likely risk associated with the use of the device in line with its intended purpose;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nsuggesting uses for the device other than those stated to form part of the intended purpose for which the conformity assessment was carried out.\n\n\n\n\n\n\nArticle\u00a08\n\nUse of harmonised standards\n\n\n1.\u00a0\u00a0\u00a0Devices that are in conformity with the relevant harmonised standards, or the relevant parts of those standards, the references of which have been published in the Official Journal of the European Union, shall be presumed to be in conformity with the requirements of this Regulation covered by those standards or parts thereof.\nThe first subparagraph\u00a0shall also apply to system or process requirements to be fulfilled in accordance with this Regulation by economic operators or sponsors, including those relating to quality management systems, risk management, post-market surveillance systems, clinical investigations, clinical evaluation or post-market clinical follow-up\u00a0(\u2018PMCF\u2019).\nReferences in this Regulation to harmonised standards shall be understood as meaning harmonised standards the references of which have been published in the Official Journal of the European Union.\n\n\n2.\u00a0\u00a0\u00a0References in this Regulation to harmonised standards shall also include the monographs of the European Pharmacopoeia adopted in accordance with the Convention on the Elaboration of a European Pharmacopoeia, in particular on surgical sutures and on interaction between medicinal products and materials used in devices containing such medicinal products, provided that references to those monographs have been published in the Official Journal of the European Union.\n\n\n\nArticle\u00a09\n\nCommon specifications\n\n\n1.\u00a0\u00a0\u00a0Without prejudice to Article\u00a01(2) and 17(5) and the deadline laid down in those provisions, where no harmonised standards exist or where relevant harmonised standards are not sufficient, or where there is a need to address public health concerns, the Commission, after having consulted the MDCG, may, by means of implementing acts, adopt common specifications (CS) in respect of the general safety and performance requirements set out in Annex\u00a0I, the technical documentation set out in Annexes\u00a0II and III, the clinical evaluation and post-market clinical follow-up set out in Annex\u00a0XIV or the requirements regarding clinical investigation set out in Annex\u00a0XV. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n2.\u00a0\u00a0\u00a0Devices that are in conformity with the CS referred to in paragraph\u00a01 shall be presumed to be in conformity with the requirements of this Regulation covered by those CS or the relevant parts of those CS.\n\n\n3.\u00a0\u00a0\u00a0Manufacturers shall comply with the CS referred to in paragraph\u00a01 unless they can duly justify that they have adopted solutions that ensure a level of safety and performance that is at least equivalent thereto.\n\n\n4.\u00a0\u00a0\u00a0Notwithstanding paragraph\u00a03, manufacturers of products listed in Annex\u00a0XVI shall comply with the relevant CS for those products.\n\n\n\nArticle\u00a010\n\nGeneral obligations of manufacturers\n\n\n1.\u00a0\u00a0\u00a0When placing their devices on the market or putting them into service, manufacturers shall ensure that they have been designed and manufactured in accordance with the requirements of this Regulation.\n\n\n2.\u00a0\u00a0\u00a0Manufacturers shall establish, document, implement and maintain a system for risk management as described in Section\u00a03 of Annex\u00a0I.\n\n\n3.\u00a0\u00a0\u00a0Manufacturers shall conduct a clinical evaluation in accordance with the requirements set out in Article\u00a061 and Annex\u00a0XIV, including a PMCF.\n\n\n4.\u00a0\u00a0\u00a0Manufacturers of devices other than custom-made devices shall draw up and keep up to date technical documentation for those devices. The technical documentation shall be such as to allow the conformity of the device with the requirements of this Regulation to be assessed. The technical documentation shall include the elements set out in Annexes\u00a0II and\u00a0III.\nThe Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 amending, in the light of technical progress, the Annexes\u00a0II and III.\n\n\n5.\u00a0\u00a0\u00a0Manufacturers of custom-made devices shall draw up, keep up to date and keep available for competent authorities documentation in accordance with Section\u00a02 of Annex\u00a0XIII.\n\n\n6.\u00a0\u00a0\u00a0Where compliance with the applicable requirements has been demonstrated following the applicable conformity assessment procedure, manufacturers of devices, other than custom-made or investigational devices, shall draw up an EU declaration of conformity in accordance with Article\u00a019, and affix the CE marking of conformity in accordance with Article\u00a020.\n\n\n7.\u00a0\u00a0\u00a0Manufacturers shall comply with the obligations relating to the UDI system referred to in Article\u00a027 and with the registration obligations referred to in Articles\u00a029 and 31.\n\n\n8.\u00a0\u00a0\u00a0Manufacturers shall keep the technical documentation, the EU declaration of conformity and, if applicable, a copy of any relevant certificate, including any amendments and supplements, issued in accordance with Article\u00a056, available for the competent authorities for a period of at least 10 years after the last device covered by the EU\u00a0declaration of conformity has been placed on the market. In the case of implantable devices, the period shall be at least 15 years after the last device has been placed on the market.\nUpon request by a competent authority, the manufacturer shall, as indicated therein, provide that technical documentation in its entirety or a summary thereof.\nA manufacturer with a registered place of business outside the Union shall, in order to allow its authorised representative to fulfil the tasks mentioned in Article\u00a011(3), ensure that the authorised representative has the necessary documentation permanently available.\n\n\n9.\u00a0\u00a0\u00a0Manufacturers shall ensure that procedures are in place to keep series production in conformity with the requirements of this Regulation. Changes in device design or characteristics and changes in the harmonised standards or CS by reference to which the conformity of a device is declared shall be adequately taken into account in a timely manner. Manufacturers of devices, other than investigational devices, shall establish, document, implement, maintain, keep up to date and continually improve a quality management system that shall ensure compliance with this Regulation in the most effective manner and in a manner that is proportionate to the risk class and the type of device.\nThe quality management system shall cover all parts and elements of a manufacturer's organisation dealing with the quality of processes, procedures and devices. It shall govern the structure, responsibilities, procedures, processes and management resources required to implement the principles and actions necessary to achieve compliance with the provisions of this Regulation.\nThe quality management system shall address at least the following aspects:\n\n\n\n\n\n\n(a)\n\n\na strategy for regulatory compliance, including compliance with conformity assessment procedures and procedures for management of modifications to the devices covered by the system;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nidentification of applicable general safety and performance requirements and exploration of options to address those requirements;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nresponsibility of the management;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nresource management, including selection and control of suppliers and sub-contractors;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nrisk management as set out in in Section\u00a03 of Annex\u00a0I;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nclinical evaluation in accordance with Article\u00a061 and Annex\u00a0XIV, including PMCF;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nproduct realisation, including planning, design, development, production and service provision;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nverification of the UDI assignments made in accordance with Article\u00a027(3) to all relevant devices and ensuring consistency and validity of information provided in accordance with Article\u00a029;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nsetting-up, implementation and maintenance of a post-market surveillance system, in accordance with Article\u00a083;\n\n\n\n\n\n\n\n\n\n\n(j)\n\n\nhandling communication with competent authorities, notified bodies, other economic operators, customers and/or other stakeholders;\n\n\n\n\n\n\n\n\n\n\n(k)\n\n\nprocesses for reporting of serious incidents and field safety corrective actions in the context of vigilance;\n\n\n\n\n\n\n\n\n\n\n(l)\n\n\nmanagement of corrective and preventive actions and verification of their effectiveness;\n\n\n\n\n\n\n\n\n\n\n(m)\n\n\nprocesses for monitoring and measurement of output, data analysis and product improvement.\n\n\n\n\n\n\n10.\u00a0\u00a0\u00a0Manufacturers of devices shall implement and keep up to date the post-market surveillance system in accordance with Article\u00a083.\n\n\n11.\u00a0\u00a0\u00a0Manufacturers shall ensure that the device is accompanied by the information set out in Section\u00a023 of Annex\u00a0I in an official Union language(s) determined by the Member\u00a0State in which the device is made available to the user or patient. The particulars on the label shall be indelible, easily legible and clearly comprehensible to the intended user or patient.\n\n\n12.\u00a0\u00a0\u00a0Manufacturers who consider or have reason to believe that a device which they have placed on the market or put into service is not in conformity with this Regulation shall immediately take the necessary corrective action to bring that device into conformity, to withdraw it or to recall it, as appropriate. They shall inform the distributors of the device in question and, where applicable, the authorised representative and importers accordingly.\nWhere the device presents a serious risk, manufacturers shall immediately inform the competent authorities of the Member\u00a0States in which they made the device available and, where applicable, the notified body that issued a certificate for the device in accordance with Article\u00a056, in particular, of the non-compliance and of any corrective action taken.\n\n\n13.\u00a0\u00a0\u00a0Manufacturers shall have a system for recording and reporting of incidents and field safety corrective actions as described in Articles\u00a087 and 88.\n\n\n14.\u00a0\u00a0\u00a0Manufacturers shall, upon request by a competent authority, provide it with all the information and documentation necessary to demonstrate the conformity of the device, in an official Union language determined by the Member\u00a0State concerned. The competent authority of the Member\u00a0State in which the manufacturer has its registered place of business may require that the manufacturer provide samples of the device free of charge or, where that is impracticable, grant access to the device. Manufacturers shall cooperate with a competent authority, at its request, on any corrective action taken to eliminate or, if that is not possible, mitigate the risks posed by devices which they have placed on the market or put into service.\nIf the manufacturer fails to cooperate or the information and documentation provided is incomplete or incorrect, the competent authority may, in order to ensure the protection of public health and patient safety, take all appropriate measures to prohibit or restrict the device's being made available on its national market, to withdraw the device from that market or to recall it until the manufacturer cooperates or provides complete and correct information.\nIf a competent authority considers or has reason to believe that a device has caused damage, it shall, upon request, facilitate the provision of the information and documentation referred to in the first subparagraph\u00a0to the potentially injured patient or user and, as appropriate, the patient's or user's successor in title, the patient's or user's health insurance company or other third parties affected by the damage caused to the patient or user, without prejudice to data protection rules and, unless there is an overriding public interest in disclosure, without prejudice to the protection of intellectual property rights.\nThe competent authority need not comply with the obligation laid down in the third subparagraph\u00a0where disclosure of the information and documentation referred to in the first subparagraph\u00a0is ordinarily dealt with in the context of legal proceedings.\n\n\n15.\u00a0\u00a0\u00a0Where manufacturers have their devices designed or manufactured by another legal or natural person the information on the identity of that person shall be part of the information to be submitted in accordance with Article\u00a030(1).\n\n\n16.\u00a0\u00a0\u00a0Natural or legal persons may claim compensation for damage caused by a defective device in accordance with applicable Union and national law.\nManufacturers shall, in a manner that is proportionate to the risk class, type of device and the size of the enterprise, have measures in place to provide sufficient financial coverage in respect of their potential liability under Directive\u00a085/374/EEC, without prejudice to more protective measures under national law.\n\n\n\nArticle\u00a011\n\nAuthorised representative\n\n\n1.\u00a0\u00a0\u00a0Where the manufacturer of a device is not established in a Member\u00a0State, the device may only be placed on the Union market if the manufacturer designates a sole authorised representative.\n\n\n2.\u00a0\u00a0\u00a0The designation shall constitute the authorised representative's mandate, it shall be valid only when accepted in writing by the authorised representative and shall be effective at least for all devices of the same generic device group.\n\n\n3.\u00a0\u00a0\u00a0The authorised representative shall perform the tasks specified in the mandate agreed between it and the manufacturer. The authorised representative shall provide a copy of the mandate to the competent authority, upon request.\nThe mandate shall require, and the manufacturer shall enable, the authorised representative to perform at least the following tasks in relation to the devices that it covers:\n\n\n\n\n\n\n(a)\n\n\nverify that the EU declaration of conformity and technical documentation have been drawn up and, where applicable, that an appropriate conformity assessment procedure has been carried out by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nkeep available a copy of the technical documentation, the EU declaration of conformity and, if applicable, a copy of the relevant certificate, including any amendments and supplements, issued in accordance with Article\u00a056, at the disposal of competent authorities for the period referred to in Article\u00a010(8);\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\ncomply with the registration obligations laid down in Article\u00a031 and verify that the manufacturer has complied with the registration obligations laid down in Articles\u00a027 and 29;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nin response to a request from a competent authority, provide that competent authority with all the information and documentation necessary to demonstrate the conformity of a device, in an official Union language determined by the Member\u00a0State concerned;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nforward to the manufacturer any request by a competent authority of the Member\u00a0State in which the authorised representative has its registered place of business for samples, or access to a device and verify that the competent authority receives the samples or is given access to the device;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\ncooperate with the competent authorities on any preventive or corrective action taken to eliminate or, if that is not possible, mitigate the risks posed by devices;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nimmediately inform the manufacturer about complaints and reports from healthcare professionals, patients and users about suspected incidents related to a device for which they have been designated;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nterminate the mandate if the manufacturer acts contrary to its obligations under this Regulation.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0The mandate referred to in paragraph\u00a03 of this Article\u00a0shall not delegate the manufacturer's obligations laid down in Article\u00a010(1), (2), (3), (4), (6), (7), (9), (10), (11) and (12).\n\n\n5.\u00a0\u00a0\u00a0Without prejudice to paragraph\u00a04 of this Article, where the manufacturer is not established in a Member\u00a0State and has not complied with the obligations laid down in Article\u00a010, the authorised representative shall be legally liable for defective devices on the same basis as, and jointly and severally with, the manufacturer.\n\n\n6.\u00a0\u00a0\u00a0An authorised representative who terminates its mandate on the ground referred to in point\u00a0(h) of paragraph\u00a03 shall immediately inform the competent authority of the Member\u00a0State in which it is established and, where applicable, the notified body that was involved in the conformity assessment for the device of the termination of the mandate and the reasons therefor.\n\n\n7.\u00a0\u00a0\u00a0Any reference in this Regulation to the competent authority of the Member\u00a0State in which the manufacturer has its registered place of business shall be understood as a reference to the competent authority of the Member\u00a0State in which the authorised representative, designated by a manufacturer referred to in paragraph\u00a01, has its registered place of business.\n\n\n\nArticle\u00a012\n\nChange of authorised representative\n\nThe detailed arrangements for a change of authorised representative shall be clearly defined in an agreement between the manufacturer, where practicable the outgoing authorised representative, and the incoming authorised representative. That agreement shall address at least the following aspects:\n\n\n\n\n\n\n(a)\n\n\nthe date of termination of the mandate of the outgoing authorised representative and date of beginning of the mandate of the incoming authorised representative;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe date until which the outgoing authorised representative may be indicated in the information supplied by the manufacturer, including any promotional material;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe transfer of documents, including confidentiality aspects and property rights;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe obligation of the outgoing authorised representative after the end of the mandate to forward to the manufacturer or incoming authorised representative any complaints or reports from healthcare professionals, patients or users about suspected incidents related to a device for which it had been designated as authorised representative.\n\n\n\n\n\n\nArticle\u00a013\n\nGeneral obligations of importers\n\n\n1.\u00a0\u00a0\u00a0Importers shall place on the Union market only devices that are in conformity with this Regulation.\n\n\n2.\u00a0\u00a0\u00a0In order to place a device on the market, importers shall verify that:\n\n\n\n\n\n\n(a)\n\n\nthe device has been CE marked and that the EU declaration of conformity of the device has been drawn up;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\na manufacturer is identified and that an authorised representative in accordance with Article\u00a011 has been designated by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe device is labelled in accordance with this Regulation and accompanied by the required instructions for use;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nwhere applicable, a UDI has been assigned by the manufacturer in accordance with Article\u00a027.\n\n\n\n\nWhere an importer considers or has reason to believe that a device is not in conformity with the requirements of this Regulation, it shall not place the device on the market until it has been brought into conformity and shall inform the manufacturer and the manufacturer's authorised representative. Where the importer considers or has reason to believe that the device presents a serious risk or is a falsified device, it shall also inform the competent authority of the Member\u00a0State in which the importer is established.\n\n\n3.\u00a0\u00a0\u00a0Importers shall indicate on the device or on its packaging or in a document accompanying the device their name, registered trade name or registered trade mark, their registered place of business and the address at which they can be contacted, so that their location can be established. They shall ensure that any additional label does not obscure any information on the label provided by the manufacturer.\n\n\n4.\u00a0\u00a0\u00a0Importers shall verify that the device is registered in the electronic system in accordance with Article\u00a029. Importers shall add their details to the registration in accordance with Article\u00a031.\n\n\n5.\u00a0\u00a0\u00a0Importers shall ensure that, while a device is under their responsibility, storage or transport conditions do not jeopardise its compliance with the general safety and performance requirements set out in Annex\u00a0I and shall comply with the conditions set by the manufacturer, where available.\n\n\n6.\u00a0\u00a0\u00a0Importers shall keep a register of complaints, of non-conforming devices and of recalls and withdrawals, and provide the manufacturer, authorised representative and distributors with any information requested by them, in order to allow them to investigate complaints.\n\n\n7.\u00a0\u00a0\u00a0Importers who consider or have reason to believe that a device which they have placed on the market is not in conformity with this Regulation shall immediately inform the manufacturer and its authorised representative. Importers shall co-operate with the manufacturer, the manufacturer's authorised representative and the competent authorities to ensure that the necessary corrective action to bring that device into conformity, to withdraw or recall it is taken. Where the device presents a serious risk, they shall also immediately inform the competent authorities of the Member\u00a0States in which they made the device available and, if applicable, the notified body that issued a certificate in accordance with Article\u00a056 for the device in question, giving details, in particular, of the non-compliance and of any corrective action taken.\n\n\n8.\u00a0\u00a0\u00a0Importers who have received complaints or reports from healthcare professionals, patients or users about suspected incidents related to a device which they have placed on the market shall immediately forward this information to the manufacturer and its authorised representative.\n\n\n9.\u00a0\u00a0\u00a0Importers shall, for the period referred to in Article\u00a010(8), keep a copy of the EU\u00a0declaration of conformity and, if applicable, a copy of any relevant certificate, including any amendments and supplements, issued in accordance with Article\u00a056.\n\n\n10.\u00a0\u00a0\u00a0Importers shall cooperate with competent authorities, at the latters' request, on any action taken to eliminate or, if that is not possible, mitigate the risks posed by devices which they have placed on the market. Importers, upon request by a competent authority of the Member\u00a0State in which the importer has its registered place of business, shall provide samples of the device free of charge or, where that is impracticable, grant access to the device.\n\n\n\nArticle\u00a014\n\nGeneral obligations of distributors\n\n\n1.\u00a0\u00a0\u00a0When making a device available on the market, distributors shall, in the context of their activities, act with due care in relation to the requirements applicable.\n\n\n2.\u00a0\u00a0\u00a0Before making a device available on the market, distributors shall verify that all of the following requirements are met:\n\n\n\n\n\n\n(a)\n\n\nthe device has been CE marked and that the EU declaration of conformity of the device has been drawn up;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe device is accompanied by the information to be supplied by the manufacturer in accordance with Article\u00a010(11);\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nfor imported devices, the importer has complied with the requirements set out in Article\u00a013(3);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthat, where applicable, a UDI has been assigned by the manufacturer.\n\n\n\n\nIn order to meet the requirements referred to in points (a), (b) and (d) of the first subparagraph\u00a0the distributor may apply a sampling method that is representative of the devices supplied by that distributor.\nWhere a distributor considers or has reason to believe that a device is not in conformity with the requirements of this Regulation, it shall not make the device available on the market until it has been brought into conformity, and shall inform the manufacturer and, where applicable, the manufacturer's authorised representative, and the importer. Where the distributor considers or has reason to believe that the device presents a serious risk or is a falsified device, it shall also inform the competent authority of the Member\u00a0State in which it is established.\n\n\n3.\u00a0\u00a0\u00a0Distributors shall ensure that, while the device is under their responsibility, storage or transport conditions comply with the conditions set by the manufacturer.\n\n\n4.\u00a0\u00a0\u00a0Distributors that consider or have reason to believe that a device which they have made available on the market is not in conformity with this Regulation shall immediately inform the manufacturer and, where applicable, the manufacturer's authorised representative and the importer. Distributors shall co-operate with the manufacturer and, where applicable, the manufacturer's authorised representative, and the importer, and with competent authorities to ensure that the necessary corrective action to bring that device into conformity, to withdraw or to recall it, as appropriate, is taken. Where the distributor considers or has reason to believe that the device presents a serious risk, it shall also immediately inform the competent authorities of the Member\u00a0States in which it made the device available, giving details, in particular, of the non-compliance and of any corrective action taken.\n\n\n5.\u00a0\u00a0\u00a0Distributors that have received complaints or reports from healthcare professionals, patients or users about suspected incidents related to a device they have made available, shall immediately forward this information to the manufacturer and, where applicable, the manufacturer's authorised representative, and the importer. They shall keep a register of complaints, of non-conforming devices and of recalls and withdrawals, and keep the manufacturer and, where available, the authorised representative and the importer informed of such monitoring and provide them with any information upon their request.\n\n\n6.\u00a0\u00a0\u00a0Distributors shall, upon request by a competent authority, provide it with all the information and documentation that is at their disposal and is necessary to demonstrate the conformity of a device.\nDistributors shall be considered to have fulfilled the obligation referred to in the first subparagraph\u00a0when the manufacturer or, where applicable, the authorised representative for the device in question provides the required information. Distributors shall cooperate with competent authorities, at their request, on any action taken to eliminate the risks posed by devices which they have made available on the market. Distributors, upon request by a competent authority, shall provide free samples of the device or, where that is impracticable, grant access to the device.\n\n\n\nArticle\u00a015\n\nPerson responsible for regulatory compliance\n\n\n1.\u00a0\u00a0\u00a0Manufacturers shall have available within their organisation at least one person responsible for regulatory compliance who possesses the requisite expertise in the field of medical devices. The requisite expertise shall be demonstrated by either of the following qualifications:\n\n\n\n\n\n\n(a)\n\n\na diploma, certificate or other evidence of formal qualification, awarded on completion of a university degree or of a course of study recognised as equivalent by the Member\u00a0State concerned, in law, medicine, pharmacy, engineering or another relevant scientific discipline, and at least one year of professional experience in regulatory affairs or in quality management systems relating to medical devices;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nfour years of professional experience in regulatory affairs or in quality management systems relating to medical devices.\n\n\n\n\nWithout prejudice to national provisions regarding professional qualifications, manufacturers of custom-made devices may demonstrate the requisite expertise referred to in the first subparagraph\u00a0by having at least two years of professional experience within a relevant field of manufacturing.\n\n\n2.\u00a0\u00a0\u00a0Micro and small enterprises within the meaning of Commission Recommendation\u00a02003/361/EC\u00a0(36) shall not be required to have the person responsible for regulatory compliance within their organisation but shall have such person permanently and continuously at their disposal.\n\n\n3.\u00a0\u00a0\u00a0The person responsible for regulatory compliance shall at least be responsible for ensuring that:\n\n\n\n\n\n\n(a)\n\n\nthe conformity of the devices is appropriately checked, in accordance with the quality management system under which the devices are manufactured, before a device is released;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe technical documentation and the EU declaration of conformity are drawn up and kept up-to-date;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe post-market surveillance obligations are complied with in accordance with Article\u00a010(10);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe reporting obligations referred to in Articles\u00a087 to 91 are fulfilled;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nin the case of investigational devices, the statement referred to in Section\u00a04.1 of Chapter II of Annex\u00a0XV is issued.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0If a number of persons are jointly responsible for regulatory compliance in accordance with paragraphs 1, 2 and 3, their respective areas of responsibility shall be stipulated in writing.\n\n\n5.\u00a0\u00a0\u00a0The person responsible for regulatory compliance shall suffer no disadvantage within the manufacturer's organisation in relation to the proper fulfilment of his or her duties, regardless of whether or not they are employees of the organisation.\n\n\n6.\u00a0\u00a0\u00a0Authorised representatives shall have permanently and continuously at their disposal at least one person responsible for regulatory compliance who possesses the requisite expertise regarding the regulatory requirements for medical devices in the Union. The requisite expertise shall be demonstrated by either of the following qualifications:\n\n\n\n\n\n\n(a)\n\n\na diploma, certificate or other evidence of formal qualification, awarded on completion of a university degree or of a course of study recognised as equivalent by the Member\u00a0State concerned, in law, medicine, pharmacy, engineering or another relevant scientific discipline, and at least one year of professional experience in regulatory affairs or in quality management systems relating to medical devices;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nfour years of professional experience in regulatory affairs or in quality management systems relating to medical devices.\n\n\n\n\n\n\n\nArticle\u00a016\n\nCases in which obligations of manufacturers apply to importers, distributors or other persons\n\n\n1.\u00a0\u00a0\u00a0A distributor, importer or other natural or legal person shall assume the obligations incumbent on manufacturers if it does any of the following:\n\n\n\n\n\n\n(a)\n\n\nmakes available on the market a device under its name, registered trade name or registered trade mark, except in cases where a distributor or importer enters into an agreement with a manufacturer whereby the manufacturer is identified as such on the label and is responsible for meeting the requirements placed on manufacturers in this Regulation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nchanges the intended purpose of a device already placed on the market or put into service;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nmodifies a device already placed on the market or put into service in such a way that compliance with the applicable requirements may be affected.\n\n\n\n\nThe first subparagraph\u00a0shall not apply to any person who, while not considered a manufacturer as defined in point\u00a0(30) of Article\u00a02, assembles or adapts for an individual patient a device already on the market without changing its intended purpose.\n\n\n2.\u00a0\u00a0\u00a0For the purposes of point\u00a0(c) of paragraph\u00a01, the following shall not be considered to be a modification of a device that could affect its compliance with the applicable requirements:\n\n\n\n\n\n\n(a)\n\n\nprovision, including translation, of the information supplied by the manufacturer, in accordance with Section\u00a023 of Annex\u00a0I, relating to a device already placed on the market and of further information which is necessary in order to market the device in the relevant Member\u00a0State;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nchanges to the outer packaging of a device already placed on the market, including a change of pack size, if the repackaging is necessary in order to market the device in the relevant Member\u00a0State and if it is carried out in such conditions that the original condition of the device cannot be affected by it. In the case of devices placed on the market in sterile condition, it shall be presumed that the original condition of the device is adversely affected if the packaging that is necessary for maintaining the sterile condition is opened, damaged or otherwise negatively affected by the repackaging.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0A distributor or importer that carries out any of the activities mentioned in points\u00a0(a) and\u00a0(b) of paragraph\u00a02 shall indicate on the device or, where that is impracticable, on its packaging or in a document accompanying the device, the activity carried out together with its name, registered trade name or registered trade mark, registered place of business and the address at which it can be contacted, so that its location can be established.\nDistributors and importers shall ensure that they have in place a quality management system that includes procedures which ensure that the translation of information is accurate and up-to-date, and that the activities mentioned in points\u00a0(a) and\u00a0(b) of paragraph\u00a02 are performed by a means and under conditions that preserve the original condition of the device and that the packaging of the repackaged device is not defective, of poor quality or untidy. The quality management system shall cover, inter\u00a0alia, procedures ensuring that the distributor or importer is informed of any corrective action taken by the manufacturer in relation to the device in question in order to respond to safety issues or to bring it into conformity with this Regulation.\n\n\n4.\u00a0\u00a0\u00a0At least 28 days prior to making the relabelled or repackaged device available on the market, distributors or importers carrying out any of the activities mentioned in points\u00a0(a) and (b) of paragraph\u00a02 shall inform the manufacturer and the competent authority of the Member\u00a0State in which they plan to make the device available of the intention to make the relabelled or repackaged device available and, upon request, shall provide the manufacturer and the competent authority with a sample or mock-up of the relabelled or repackaged device, including any translated label and instructions for use. Within the same period of 28\u00a0days, the distributor or importer shall submit to the competent authority a certificate, issued by a notified body designated for the type of devices that are subject to activities mentioned in points\u00a0(a) and\u00a0(b) of paragraph\u00a02, attesting that the quality management system of the distributer or importer complies with the requirements laid down in paragraph\u00a03.\n\n\n\nArticle\u00a017\n\nSingle-use devices and their reprocessing\n\n\n1.\u00a0\u00a0\u00a0Reprocessing and further use of single-use devices may only take place where permitted by national law and only in accordance with this Article.\n\n\n2.\u00a0\u00a0\u00a0Any natural or legal person who reprocesses a single-use device to make it suitable for further use within the Union shall be considered to be the manufacturer of the reprocessed device and shall assume the obligations incumbent on manufacturers laid down in this Regulation, which include obligations relating to the traceability of the reprocessed device in accordance with Chapter III of this Regulation. The reprocessor of the device shall be considered to be a producer for the purpose of Article\u00a03(1) of Directive\u00a085/374/EEC.\n\n\n3.\u00a0\u00a0\u00a0By way of derogation from paragraph\u00a02, as regards single-use devices that are reprocessed and used within a health institution, Member\u00a0States may decide not to apply all of the rules relating to manufacturers' obligations laid down in this Regulation provided that they ensure that:\n\n\n\n\n\n\n(a)\n\n\nthe safety and performance of the reprocessed device is equivalent to that of the original device and the requirements in points (a), (b), (d), (e), (f), (g) and (h) of Article\u00a05(5) are complied with;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe reprocessing is performed in accordance with CS detailing the requirements concerning:\n\n\n\n\n\n\n\u2014\n\n\nrisk management, including the analysis of the construction and material, related properties of the device (reverse engineering) and procedures to detect changes in the design of the original device as well as of its planned application after reprocessing,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe validation of procedures for the entire process, including cleaning steps,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe product release and performance testing,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe quality management system,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe reporting of incidents involving devices that have been reprocessed, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe traceability of reprocessed devices.\n\n\n\n\n\n\n\n\nMember\u00a0States shall encourage, and may require, health institutions to provide information to patients on the use of reprocessed devices within the health institution and, where appropriate, any other relevant information on the reprocessed devices that patients are treated with.\nMember\u00a0States shall notify the Commission and the other Member\u00a0States of the national provisions introduced pursuant to this paragraph\u00a0and the grounds for introducing them. The Commission shall keep the information publicly available.\n\n\n4.\u00a0\u00a0\u00a0Member\u00a0States may choose to apply the provisions referred to in paragraph\u00a03 also as regards single-use devices that are reprocessed by an external reprocessor at the request of a health institution, provided that the reprocessed device in its entirety is returned to that health institution and the external reprocessor complies with the requirements referred to in points (a) and (b) of paragraph\u00a03.\n\n\n5.\u00a0\u00a0\u00a0The Commission shall adopt, in accordance with Article\u00a09(1), the necessary CS referred to in point\u00a0(b) of paragraph\u00a03 by 26 May 2020. Those CS shall be consistent with the latest scientific evidence and shall address the application of the general requirements on safety and performance laid down in in this Regulation. In the event that those CS are not adopted by 26 May 2020, reprocessing shall be performed in accordance with any relevant harmonised standards and national provisions that cover the aspects outlined in point\u00a0(b) of paragraph\u00a03. Compliance with CS or, in the absence of CS, with any relevant harmonised standards and national provisions, shall be certified by a notified body.\n\n\n6.\u00a0\u00a0\u00a0Only single-use devices that have been placed on the market in accordance with this Regulation, or prior to 26\u00a0May 2020 in accordance with Directive\u00a093/42/EEC, may be reprocessed.\n\n\n7.\u00a0\u00a0\u00a0Only reprocessing of single-use devices that is considered safe according to the latest scientific evidence may be carried out.\n\n\n8.\u00a0\u00a0\u00a0The name and address of the legal or natural person referred to in paragraph\u00a02 and the other relevant information referred to in Section\u00a023 of Annex\u00a0I shall be indicated on the label and, where applicable, in the instructions for use of the reprocessed device.\nThe name and address of the manufacturer of the original single-use device shall no longer appear on the label, but shall be mentioned in the instructions for use of the reprocessed device.\n\n\n9.\u00a0\u00a0\u00a0A Member\u00a0State that permits reprocessing of single-use devices may maintain or introduce national provisions that are stricter than those laid down in this Regulation and which restrict or prohibit, within its territory, the following:\n\n\n\n\n\n\n(a)\n\n\nthe reprocessing of single-use devices and the transfer of single-use devices to another Member\u00a0State or to a third country with a view to their reprocessing;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe making available or further use of reprocessed single-use devices.\n\n\n\n\nMember\u00a0States shall notify the Commission and the other Member\u00a0States of those national provisions. The Commission shall make such information publicly available.\n\n\n10.\u00a0\u00a0\u00a0The Commission shall by 27 May 2024 draw up a report on the operation of this Article\u00a0and submit it to the European Parliament and to the Council. On the basis of that report, the Commission shall, if appropriate, make proposals for amendments to this Regulation.\n\n\n\nArticle\u00a018\n\nImplant card and information to be supplied to the patient with an implanted device\n\n\n1.\u00a0\u00a0\u00a0The manufacturer of an implantable device shall provide together with the device the following:\n\n\n\n\n\n\n(a)\n\n\ninformation allowing the identification of the device, including the device name, serial number, lot number, the UDI, the device model, as well as the name, address and the website of the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nany warnings, precautions or measures to be taken by the patient or a healthcare professional with regard to reciprocal interference with reasonably foreseeable external influences, medical examinations or environmental conditions;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nany information about the expected lifetime of the device and any necessary follow-up;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nany other information to ensure safe use of the device by the patient, including the information in point\u00a0(u) of Section\u00a023.4 of Annex\u00a0I.\n\n\n\n\nThe information referred to in the first subparagraph\u00a0shall be provided, for the purpose of making it available to the particular patient who has been implanted with the device, by any means that allow rapid access to that information and shall be stated in the language(s) determined by the concerned Member\u00a0State. The information shall be written in a way that is readily understood by a lay person and shall be updated where appropriate. Updates of the information shall be made available to the patient via the website mentioned in point\u00a0(a) of the first subparagraph.\nIn addition, the manufacturer shall provide the information referred to in point\u00a0(a) of the first subparagraph\u00a0on an implant card delivered with the device.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States shall require health institutions to make the information referred to in paragraph\u00a01 available, by any means that allow rapid access to that information, to any patients who have been implanted with the device, together with the implant card, which shall bear their identity.\n\n\n3.\u00a0\u00a0\u00a0The following implants shall be exempted from the obligations laid down in this Article: sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips and connectors. The Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 to amend this list by adding other types of implants to it or by removing implants therefrom.\n\n\n\nArticle\u00a019\n\nEU declaration of conformity\n\n\n1.\u00a0\u00a0\u00a0The EU\u00a0declaration of conformity shall state that the requirements specified in this Regulation have been fulfilled in relation to the device that is covered. The manufacturer shall continuously update the EU\u00a0declaration of conformity. The EU\u00a0declaration of conformity shall, as a minimum, contain the information set out in Annex\u00a0IV and shall be translated into an official Union language or languages required by the Member\u00a0State(s) in which the device is made available.\n\n\n2.\u00a0\u00a0\u00a0Where, concerning aspects not covered by this Regulation, devices are subject to other Union legislation which also requires an EU declaration of conformity by the manufacturer that fulfilment of the requirements of that legislation has been demonstrated, a single EU\u00a0declaration of conformity shall be drawn up in respect of all Union acts applicable to the device. The declaration shall contain all the information required for identification of the Union legislation to which the declaration relates.\n\n\n3.\u00a0\u00a0\u00a0By drawing up the EU\u00a0declaration of conformity, the manufacturer shall assume responsibility for compliance with the requirements of this Regulation and all other Union legislation applicable to the device.\n\n\n4.\u00a0\u00a0\u00a0The Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 amending the minimum content of the EU declaration of conformity set out in Annex\u00a0IV in the light of technical progress.\n\n\n\nArticle\u00a020\n\nCE marking of conformity\n\n\n1.\u00a0\u00a0\u00a0Devices, other than custom-made or investigational devices, considered to be in conformity with the requirements of this Regulation shall bear the CE marking of conformity, as presented in Annex\u00a0V.\n\n\n2.\u00a0\u00a0\u00a0The CE marking shall be subject to the general principles set out in Article\u00a030 of Regulation\u00a0(EC)\u00a0No\u00a0765/2008.\n\n\n3.\u00a0\u00a0\u00a0The CE marking shall be affixed visibly, legibly and indelibly to the device or its sterile packaging. Where such affixing is not possible or not warranted on account of the nature of the device, the CE marking shall be affixed to the packaging. The CE marking shall also appear in any instructions for use and on any sales packaging.\n\n\n4.\u00a0\u00a0\u00a0The CE marking shall be affixed before the device is placed on the market. It may be followed by a pictogram or any other mark indicating a special risk or use.\n\n\n5.\u00a0\u00a0\u00a0Where applicable, the CE marking shall be followed by the identification number of the notified body responsible for the conformity assessment procedures set out in Article\u00a052. The identification number shall also be indicated in any promotional material which mentions that a device fulfils the requirements for CE marking.\n\n\n6.\u00a0\u00a0\u00a0Where devices are subject to other Union legislation which also provides for the affixing of the CE marking, the CE marking shall indicate that the devices also fulfil the requirements of that other legislation.\n\n\n\nArticle\u00a021\n\nDevices for special purposes\n\n\n1.\u00a0\u00a0\u00a0Member\u00a0States shall not create obstacles to:\n\n\n\n\n\n\n(a)\n\n\ninvestigational devices being supplied to an investigator for the purpose of a clinical investigation if they meet the conditions laid down in Articles\u00a062 to 80 and Article\u00a082, in the implementing acts adopted pursuant to Article\u00a081 and in Annex\u00a0XV;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ncustom-made devices being made available on the market if Article\u00a052(8) and Annex\u00a0XIII have been complied with.\n\n\n\n\nThe devices referred to in the first subparagraph\u00a0shall not bear the CE marking, with the exception of the devices referred to in Article\u00a074.\n\n\n2.\u00a0\u00a0\u00a0Custom-made devices shall be accompanied by the statement referred to in Section\u00a01 of Annex\u00a0XIII, which shall be made available to the particular patient or user identified by name, an acronym or a numerical code.\nMember\u00a0States may require that the manufacturer of a custom-made device submit to the competent authority a list of such devices which have been made available in their territory.\n\n\n3.\u00a0\u00a0\u00a0At trade fairs, exhibitions, demonstrations or similar events, Member\u00a0States shall not create obstacles to the showing of devices which do not comply with this Regulation, provided a visible sign clearly indicates that such devices are intended for presentation or demonstration purposes only and cannot be made available until they have been brought into compliance with this Regulation.\n\n\n\nArticle\u00a022\n\nSystems and procedure packs\n\n\n1.\u00a0\u00a0\u00a0Natural or legal persons shall draw up a statement if they combine devices bearing a CE\u00a0marking with the following other devices or products, in a manner that is compatible with the intended purpose of the devices or other products and within the limits of use specified by their manufacturers, in order to place them on the market as a system or procedure pack:\n\n\n\n\n\n\n(a)\n\n\nother devices bearing the CE marking;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\n\nin vitro diagnostic medical devices bearing the CE marking in conformity with Regulation\u00a0(EU)\u00a02017/746;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nother products which are in conformity with legislation that applies to those products only where they are used within a medical procedure or their presence in the system or procedure pack is otherwise justified.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0In the statement made pursuant to paragraph\u00a01, the natural or legal person concerned shall declare that:\n\n\n\n\n\n\n(a)\n\n\nthey verified the mutual compatibility of the devices and, if applicable other products, in accordance with the manufacturers' instructions and have carried out their activities in accordance with those instructions;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthey packaged the system or procedure pack and supplied relevant information to users incorporating the information to be supplied by the manufacturers of the devices or other products which have been put together;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe activity of combining devices and, if applicable, other products as a system or procedure pack was subject to appropriate methods of internal monitoring, verification and validation.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0Any natural or legal person who sterilises systems or procedure packs referred to in paragraph\u00a01 for the purpose of placing them on the market shall, at their choice, apply one of the procedures set out in Annex\u00a0IX or the procedure set out in Part A of Annex\u00a0XI. The application of those procedures and the involvement of the notified body shall be limited to the aspects of the procedure relating to ensuring sterility until the sterile packaging is opened or damaged. The natural or legal person shall draw up a statement declaring that sterilisation has been carried out in accordance with the manufacturer's instructions.\n\n\n4.\u00a0\u00a0\u00a0Where the system or procedure pack incorporates devices which do not bear the CE\u00a0marking or where the chosen combination of devices is not compatible in view of their original intended purpose, or where the sterilisation has not been carried out in accordance with the manufacturer's instructions, the system or procedure pack shall be treated as a device in its own right and shall be subject to the relevant conformity assessment procedure pursuant to Article\u00a052. The natural or legal person shall assume the obligations incumbent on manufacturers.\n\n\n5.\u00a0\u00a0\u00a0The systems or procedure packs referred to in paragraph\u00a01 of this Article\u00a0shall not themselves bear an additional CE marking but they shall bear the name, registered trade name or registered trade mark of the person referred to in paragraphs 1 and 3 of this Article\u00a0as well as the address at which that person can be contacted, so that the person's location can be established. Systems or procedure packs shall be accompanied by the information referred to in Section\u00a023 of Annex\u00a0I. The statement referred to in paragraph\u00a02 of this Article\u00a0shall be kept at the disposal of the competent authorities, after the system or procedure pack has been put together, for the period that is applicable under Article\u00a010(8) to the devices that have been combined. Where those periods differ, the longest period shall apply.\n\n\n\nArticle\u00a023\n\nParts and components\n\n\n1.\u00a0\u00a0\u00a0Any natural or legal person who makes available on the market an item specifically intended to replace an identical or similar integral part or component of a device that is defective or worn in order to maintain or restore the function of the device without changing its performance or safety characteristics or its intended purpose, shall ensure that the item does not adversely affect the safety and performance of the device. Supporting evidence shall be kept available for the competent authorities of the Member\u00a0States.\n\n\n2.\u00a0\u00a0\u00a0An item that is intended specifically to replace a part or component of a device and that significantly changes the performance or safety characteristics or the intended purpose of the device shall be considered to be a device and shall meet the requirements laid down in this Regulation.\n\n\n\nArticle\u00a024\n\nFree movement\n\nExcept where otherwise provided for in this Regulation, Member\u00a0States shall not refuse, prohibit or restrict the making available on the market or putting into service within their territory of devices which comply with the requirements of this Regulation.\n\n\n\nCHAPTER III\n\n\nIDENTIFICATION AND TRACEABILITY OF DEVICES, REGISTRATION OF DEVICES AND OF ECONOMIC OPERATORS, SUMMARY OF SAFETY AND CLINICAL PERFORMANCE, EUROPEAN DATABASE ON MEDICAL DEVICES\n\n\n\nArticle\u00a025\n\nIdentification within the supply chain\n\n\n1.\u00a0\u00a0\u00a0Distributors and importers shall co-operate with manufacturers or authorised representatives to achieve an appropriate level of traceability of devices.\n\n\n2.\u00a0\u00a0\u00a0Economic operators shall be able to identify the following to the competent authority, for the period referred to in Article\u00a010(8):\n\n\n\n\n\n\n(a)\n\n\nany economic operator to whom they have directly supplied a device;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nany economic operator who has directly supplied them with a device;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nany health institution or healthcare professional to which they have directly supplied a device.\n\n\n\n\n\n\n\nArticle\u00a026\n\nMedical devices nomenclature\n\nTo facilitate the functioning of the European database on medical devices (\u2018Eudamed\u2019) as referred to in Article\u00a033, the Commission shall ensure that an internationally recognised medical devices nomenclature is available free of charge to manufacturers and other natural or legal persons required by this Regulation to use that nomenclature. The Commission shall also endeavour to ensure that that nomenclature is available to other stakeholders free of charge, where reasonably practicable.\n\n\nArticle\u00a027\n\nUnique Device Identification system\n\n\n1.\u00a0\u00a0\u00a0The Unique Device Identification system (\u2018UDI system\u2019) described in Part C of Annex\u00a0VI shall allow the identification and facilitate the traceability of devices, other than custom-made and investigational devices, and shall consist of the following:\n\n\n\n\n\n\n(a)\n\n\nproduction of a UDI that comprises the following:\n\n\n\n\n\n\n(i)\n\n\na UDI device identifier (\u2018UDI-DI\u2019) specific to a manufacturer and a device, providing access to the information laid down in Part B of Annex\u00a0VI;\n\n\n\n\n\n\n\n\n\n\n(ii)\n\n\na UDI production identifier (\u2018UDI-PI\u2019) that identifies the unit of device production and if applicable the packaged devices, as specified in Part\u00a0C of Annex\u00a0VI;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nplacing of the UDI on the label of the device or on its packaging;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nstorage of the UDI by economic operators, health institutions and healthcare professionals, in accordance with the conditions laid down in paragraphs 8 and 9 of this Article\u00a0respectively;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nestablishment of an electronic system for Unique Device Identification\u00a0(\u2018UDI database\u2019) in accordance with Article\u00a028.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The Commission shall, by means of implementing acts, designate one or several entities to operate a system for assignment of UDIs pursuant to this Regulation (\u2018issuing entity\u2019). That entity or those entities shall satisfy all of the following criteria:\n\n\n\n\n\n\n(a)\n\n\nthe entity is an organisation with legal personality;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nits system for the assignment of UDIs is adequate to identify a device throughout its distribution and use in accordance with the requirements of this Regulation;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nits system for the assignment of UDIs conforms to the relevant international standards;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe entity gives access to its system for the assignment of UDIs to all interested users in accordance with a set of predetermined and transparent terms and conditions;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe entity undertakes to do the following:\n\n\n\n\n\n\n(i)\n\n\noperate its system for the assignment of UDIs for at least 10 years after its designation;\n\n\n\n\n\n\n\n\n\n\n(ii)\n\n\nmake available to the Commission and to the Member\u00a0States, upon request, information concerning its system for the assignment of UDIs;\n\n\n\n\n\n\n\n\n\n\n(iii)\n\n\nremain in compliance with the criteria for designation and the terms of designation.\n\n\n\n\n\n\n\n\nWhen designating issuing entities, the Commission shall endeavour to ensure that UDI\u00a0carriers, as defined in Part C of Annex\u00a0VI, are universally readable regardless of the system used by the issuing entity, with a view to minimising financial and administrative burdens for economic operators and health institutions.\n\n\n3.\u00a0\u00a0\u00a0Before placing a device, other than a custom-made device, on the market, the manufacturer shall assign to the device and, if applicable, to all higher levels of packaging, a UDI created in compliance with the rules of the issuing entity designated by the Commission in accordance with paragraph\u00a02.\nBefore a device, other than a custom-made or investigational device, is placed on the market the manufacturer shall ensure that the information referred to in Part B of Annex\u00a0VI of the device in question are correctly submitted and transferred to the UDI database referred to in Article\u00a028.\n\n\n4.\u00a0\u00a0\u00a0UDI carriers shall be placed on the label of the device and on all higher levels of packaging. Higher levels of packaging shall not be understood to include shipping containers.\n\n\n5.\u00a0\u00a0\u00a0The UDI shall be used for reporting serious incidents and field safety corrective actions in accordance with Article\u00a087.\n\n\n6.\u00a0\u00a0\u00a0The Basic UDI-DI, as defined in Part C of Annex\u00a0VI, of the device shall appear on the EU\u00a0declaration of conformity referred to in Article\u00a019.\n\n\n7.\u00a0\u00a0\u00a0As part of the technical documentation referred to in Annex\u00a0II, the manufacturer shall keep up-to-date a list of all UDIs that it has assigned.\n\n\n8.\u00a0\u00a0\u00a0Economic operators shall store and keep, preferably by electronic means, the UDI of the devices which they have supplied or with which they have been supplied, if those devices belong to:\n\n\n\n\n\n\n\u2014\n\n\nclass III implantable devices;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe devices, categories or groups of devices determined by a measure referred to in point\u00a0(a) of paragraph\u00a011.\n\n\n\n\n\n\n9.\u00a0\u00a0\u00a0Health institutions shall store and keep preferably by electronic means the UDI of the devices which they have supplied or with which they have been supplied, if those devices belong to class III implantable devices.\nFor devices other than class III implantable devices, Member\u00a0States shall encourage, and may require, health institutions to store and keep, preferably by electronic means, the UDI of the devices with which they have been supplied.\nMember\u00a0States shall encourage, and may require, healthcare professionals to store and keep preferably by electronic means, the UDI of the devices with which they have been supplied with.\n\n\n10.\u00a0\u00a0\u00a0The Commission is empowered to adopt delegated acts in accordance with Article\u00a0115:\n\n\n\n\n\n\n(a)\n\n\namending the list of information set out in Part B of Annex\u00a0VI in the light of technical progress; and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\namending Annex\u00a0VI in the light of international developments and technical progress in the field of Unique Device Identification.\n\n\n\n\n\n\n11.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, specify the detailed arrangements and the procedural aspects for the UDI system with a view to ensuring its harmonised application in relation to any of the following:\n\n\n\n\n\n\n(a)\n\n\ndetermining the devices, categories or groups of devices to which the obligation laid down in paragraph\u00a08 is to apply;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nspecifying the data to be included in the UDI-PI of specific devices or device groups;\n\n\n\n\nThe implementing acts referred to in the first subparagraph\u00a0shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n12.\u00a0\u00a0\u00a0When adopting the measures referred to in paragraph\u00a011, the Commission shall take into account all of the following:\n\n\n\n\n\n\n(a)\n\n\nconfidentiality and data protection as referred to in Articles\u00a0109 and 110\u00a0respectively;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe risk-based approach;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe cost-effectiveness of the measures;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe convergence of UDI systems developed at international level;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe need to avoid duplications in the UDI system;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe needs of the healthcare systems of the Member\u00a0States, and where possible, compatibility with other medical device identification systems that are used by stakeholders.\n\n\n\n\n\n\n\nArticle\u00a028\n\nUDI database\n\n\n1.\u00a0\u00a0\u00a0The Commission, after consulting the MDCG shall set up and manage a UDI database to validate, collate, process and make available to the public the information mentioned in Part B of Annex\u00a0VI.\n\n\n2.\u00a0\u00a0\u00a0When designing the UDI database, the Commission shall take into account the general principles set out in Section\u00a05 of Part C of Annex\u00a0VI. The UDI database shall be designed in particular such that no UDI-PIs and no commercially confidential product information can be included therein.\n\n\n3.\u00a0\u00a0\u00a0The core data elements to be provided to the UDI database, referred to in Part\u00a0B of Annex\u00a0VI, shall be accessible to the public free of charge.\n\n\n4.\u00a0\u00a0\u00a0The technical design of the UDI database shall ensure maximum accessibility to information stored therein, including multi-user access and automatic uploads and downloads of that information. The Commission shall provide for technical and administrative support to manufacturers and other users of the UDI database.\n\n\n\nArticle\u00a029\n\nRegistration of devices\n\n\n1.\u00a0\u00a0\u00a0Before placing a device, other than a custom-made device, on the market, the manufacturer shall, in accordance with the rules of the issuing entity referred to in Article\u00a027(2), assign a Basic UDI-DI as defined in Part C of Annex\u00a0VI to the device and shall provide it to the UDI database together with the other core data elements referred to in Part B of Annex\u00a0VI related to that device.\n\n\n2.\u00a0\u00a0\u00a0Before placing on the market a system or procedure pack pursuant to Article\u00a022(1) and (3), that is not a custom-made device, the natural or legal person responsible shall assign to the system or procedure pack, in compliance with the rules of the issuing entity, a Basic UDI-DI and shall provide it to the UDI database together with the other core data elements referred to in Part B of Annex\u00a0VI related to that system or procedure pack.\n\n\n3.\u00a0\u00a0\u00a0For devices that are the subject of a conformity assessment as referred to in Article\u00a052(3) and in the second and third subparagraphs\u00a0of Article\u00a052(4), the assignment of a Basic UDI-DI referred to in paragraph\u00a01 of this Article\u00a0shall be done before the manufacturer applies to a notified body for that assessment.\nFor the devices referred to in the first subparagraph, the notified body shall include a reference to the Basic UDI-DI on the certificate issued in accordance with point\u00a0(a) of Section\u00a04 of Chapter I of Annex\u00a0XII and confirm in Eudamed that the information referred to in Section\u00a02.2 of Part A of Annex\u00a0VI is correct. After the issuing of the relevant certificate and before placing the device on the market, the manufacturer shall provide the Basic UDI-DI to the UDI database together with the other core data elements referred to in Part B of Annex\u00a0VI related to that device.\n\n\n4.\u00a0\u00a0\u00a0Before placing a device on the market, other than a custom-made device, the manufacturer shall enter or if, already provided, verify in Eudamed the information referred to in Section\u00a02 of Part A of Annex\u00a0VI, with the exception of Section\u00a02.2 thereof, and shall thereafter keep the information updated.\n\n\n\nArticle\u00a030\n\nElectronic system for registration of economic operators\n\n\n1.\u00a0\u00a0\u00a0The Commission, after consulting the MDCG, shall set up and manage an electronic system to create the single registration number referred to in Article\u00a031(2) and to collate and process information that is necessary and proportionate to identify the manufacturer and, where applicable, the authorised representative and the importer. The details regarding the information to be provided to that electronic system by the economic operators are laid down in Section\u00a01 of Part A of Annex\u00a0VI.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States may maintain or introduce national provisions on registration of distributors of devices which have been made available on their territory.\n\n\n3.\u00a0\u00a0\u00a0Within two weeks of placing a device, other than a custom-made device, on the market, importers shall verify that the manufacturer or authorised representative has provided to the electronic system the information referred to in paragraph\u00a01.\nWhere applicable, importers shall inform the relevant authorised representative or manufacturer if the information referred to in paragraph\u00a01 is not included or is incorrect. Importers shall add their details to the relevant entry/entries.\n\n\n\nArticle\u00a031\n\nRegistration of manufacturers, authorised representatives and importers\n\n\n1.\u00a0\u00a0\u00a0Before placing a device, other than a custom-made device, on the market, manufacturers, authorised representatives and importers shall, in order to register, submit to the electronic system referred to in Article\u00a030 the information referred to in Section\u00a01 of Part A of Annex\u00a0VI, provided that they have not already registered in accordance with this Article. In cases where the conformity assessment procedure requires the involvement of a notified body pursuant to Article\u00a052, the information referred to in Section\u00a01 of Part\u00a0A of Annex\u00a0VI shall be provided to that electronic system before applying to the notified body.\n\n\n2.\u00a0\u00a0\u00a0After having verified the data entered pursuant to paragraph\u00a01, the competent authority shall obtain a single registration number (\u2018SRN\u2019) from the electronic system referred to in Article\u00a030 and issue it to the manufacturer, the authorised representative or the importer.\n\n\n3.\u00a0\u00a0\u00a0The manufacturer shall use the SRN when applying to a notified body for conformity assessment and for accessing Eudamed in order to fulfil its obligations under Article\u00a029.\n\n\n4.\u00a0\u00a0\u00a0Within one week of any change occurring in relation to the information referred to in paragraph\u00a01 of this Article, the economic operator shall update the data in the electronic system referred to in Article\u00a030.\n\n\n5.\u00a0\u00a0\u00a0Not later than one year after submission of the information in accordance with paragraph\u00a01, and every second year thereafter, the economic operator shall confirm the accuracy of the data. In the event of a failure to do so within six months of those deadlines, any Member\u00a0State may take appropriate corrective measures within its territory until that economic operator complies with that obligation.\n\n\n6.\u00a0\u00a0\u00a0Without prejudice to the economic operator's responsibility for the data, the competent authority shall verify the confirmed data referred to in Section\u00a01 of Part A of Annex\u00a0VI.\n\n\n7.\u00a0\u00a0\u00a0The data entered pursuant to paragraph\u00a01 of this Article\u00a0in the electronic system referred to in Article\u00a030 shall be accessible to the public.\n\n\n8.\u00a0\u00a0\u00a0The competent authority may use the data to charge the manufacturer, the authorised representative or the importer a fee pursuant to Article\u00a0111.\n\n\n\nArticle\u00a032\n\nSummary of safety and clinical performance\n\n\n1.\u00a0\u00a0\u00a0For implantable devices and for class III devices, other than custom-made or investigational devices, the manufacturer shall draw up a summary of safety and clinical performance.\nThe summary of safety and clinical performance shall be written in a way that is clear to the intended user and, if relevant, to the patient and shall be made available to the public via Eudamed.\nThe draft of the summary of safety and clinical performance shall be part of the documentation to be submitted to the notified body involved in the conformity assessment pursuant to Article\u00a052 and shall be validated by that body. After its validation, the notified body shall upload the summary to Eudamed. The manufacturer shall mention on the label or instructions for use where the summary is available.\n\n\n2.\u00a0\u00a0\u00a0The summary of safety and clinical performance shall include at least the following aspects:\n\n\n\n\n\n\n(a)\n\n\nthe identification of the device and the manufacturer, including the Basic UDI-DI and, if already issued, the SRN;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe intended purpose of the device and any indications, contraindications and target populations;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\na description of the device, including a reference to previous generation(s) or variants if such exist, and a description of the differences, as well as, where relevant, a description of any accessories, other devices and products, which are intended to be used in combination with the device;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\npossible diagnostic or therapeutic alternatives;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nreference to any harmonised standards and CS applied;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe summary of clinical evaluation as referred to in Annex\u00a0XIV, and relevant information on post-market clinical follow-up;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nsuggested profile and training for users;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\ninformation on any residual risks and any undesirable effects, warnings and precautions.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, set out the form and the presentation of the data elements to be included in the summary of safety and clinical performance. Those implementing acts shall be adopted in accordance with the advisory procedure referred to in Article\u00a0114(2).\n\n\n\nArticle\u00a033\n\nEuropean database on medical devices\n\n\n1.\u00a0\u00a0\u00a0The Commission, after consulting the MDCG, shall set up, maintain and manage the European database on medical devices (\u2018Eudamed\u2019) for the following purposes:\n\n\n\n\n\n\n(a)\n\n\nto enable the public to be adequately informed about devices placed on the market, the corresponding certificates issued by notified bodies and about the relevant economic operators;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nto enable unique identification of devices within the internal market and to facilitate their traceability;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nto enable the public to be adequately informed about clinical investigations and to enable sponsors of clinical investigations to comply with obligations under Articles\u00a062 to 80, Article\u00a082, and any acts adopted pursuant to Article\u00a081;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nto enable manufacturers to comply with the information obligations laid down in Articles\u00a087 to 90 or in any acts adopted pursuant to Article\u00a091;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nto enable the competent authorities of the Member\u00a0States and the Commission to carry out their tasks relating to this Regulation on a well-informed basis and to enhance the cooperation between them.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0Eudamed shall include the following electronic systems:\n\n\n\n\n\n\n(a)\n\n\nthe electronic system for registration of devices referred to in Article\u00a029(4);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe UDI-database referred to in Article\u00a028;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe electronic system on registration of economic operators referred to in Article\u00a030;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe electronic system on notified bodies and on certificates referred to in Article\u00a057;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe electronic system on clinical investigations referred to in Article\u00a073;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe electronic system on vigilance and post-market surveillance referred to in Article\u00a092;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthe electronic system on market surveillance referred to in Article\u00a0100.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0When designing Eudamed the Commission shall give due consideration to compatibility with national databases and national web-interfaces to allow for import and export of data.\n\n\n4.\u00a0\u00a0\u00a0The data shall be entered into Eudamed by the Member\u00a0States, notified bodies, economic operators and sponsors as specified in the provisions on the electronic systems referred to in paragraph\u00a02. The Commission shall provide for technical and administrative support to users of Eudamed.\n\n\n5.\u00a0\u00a0\u00a0All the information collated and processed by Eudamed shall be accessible to the Member\u00a0States and to the Commission. The information shall be accessible to notified bodies, economic operators, sponsors and the public to the extent specified in the provisions on the electronic systems referred to in paragraph\u00a02.\nThe Commission shall ensure that public parts of Eudamed are presented in a user-friendly and easily-searchable format.\n\n\n6.\u00a0\u00a0\u00a0Eudamed shall contain personal data only insofar as necessary for the electronic systems referred to in paragraph\u00a02 of this Article\u00a0to collate and process information in accordance with this Regulation. Personal data shall be kept in a form which permits identification of data subjects for periods no longer than those referred to in Article\u00a010(8).\n\n\n7.\u00a0\u00a0\u00a0The Commission and the Member\u00a0States shall ensure that data subjects may effectively exercise their rights to information, of access, to rectification and to object in accordance with Regulation\u00a0(EC)\u00a0No\u00a045/2001 and Directive\u00a095/46/EC, respectively. They shall also ensure that data subjects may effectively exercise the right of access to data relating to them, and the right to have inaccurate or incomplete data corrected and erased. Within their respective responsibilities, the Commission and the Member\u00a0States shall ensure that inaccurate and unlawfully processed data are deleted, in accordance with the applicable legislation. Corrections and deletions shall be carried out as soon as possible, but no later than 60\u00a0days after a request is made by a data subject.\n\n\n8.\u00a0\u00a0\u00a0The Commission shall, by means of implementing acts, lay down the detailed arrangements necessary for the setting up and maintenance of Eudamed. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3). When adopting those implementing acts, the Commission shall ensure that, as far as possible, the system is developed in such a way as to avoid having to enter the same information twice within the same module or in different modules of the system.\n\n\n9.\u00a0\u00a0\u00a0In relation to its responsibilities under this Article\u00a0and the processing of personal data involved therein, the Commission shall be considered to be the controller of Eudamed and its electronic systems.\n\n\n\nArticle\u00a034\n\nFunctionality of Eudamed\n\n\n1.\u00a0\u00a0\u00a0The Commission shall, in collaboration with the MDCG, draw up the functional specifications for Eudamed. The Commission shall draw up a plan for the implementation of those specifications by 26 May 2018. That plan shall seek to ensure that Eudamed is fully functional at a date that allows the Commission to publish the notice referred to in paragraph\u00a03 of this Article\u00a0by 25 March 2020 and that all other relevant deadlines laid down in Article\u00a0123 of this Regulation and in Article\u00a0113 of Regulation\u00a0(EU)\u00a02017/746 are met.\n\n\n2.\u00a0\u00a0\u00a0The Commission shall, on the basis of an independent audit report, inform the MDCG when it has verified that Eudamed has achieved full functionality and Eudamed meets the functional specifications drawn up pursuant to paragraph\u00a01.\n\n\n3.\u00a0\u00a0\u00a0The Commission shall, after consultation with the MDCG and when it is satisfied that the conditions referred to in paragraph\u00a02 have been fulfilled, publish a notice to that effect in the Official Journal of the European Union.\n\n\n\n\nCHAPTER IV\n\n\nNOTIFIED BODIES\n\n\n\nArticle\u00a035\n\nAuthorities responsible for notified bodies\n\n\n1.\u00a0\u00a0\u00a0Any Member\u00a0State that intends to designate a conformity assessment body as a notified body, or has designated a notified body, to carry out conformity assessment activities under this Regulation shall appoint an authority (\u2018authority responsible for notified bodies\u2019), which may consist of separate constituent entities under national law and shall be responsible for setting up and carrying out the necessary procedures for the assessment, designation and notification of conformity assessment bodies and for the monitoring of notified bodies, including subcontractors and subsidiaries of those bodies.\n\n\n2.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall be established, organised and operated so as to safeguard the objectivity and impartiality of its activities and to avoid any conflicts of interests with conformity assessment bodies.\n\n\n3.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall be organised in a manner such that each decision relating to designation or notification is taken by personnel different from those who carried out the assessment.\n\n\n4.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall not perform any activities that notified bodies perform on a commercial or competitive basis.\n\n\n5.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall safeguard the confidential aspects of the information it obtains. However, it shall exchange information on notified bodies with other Member\u00a0States, the Commission and, when required, with other regulatory authorities.\n\n\n6.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall have a sufficient number of competent personnel permanently available for the proper performance of its tasks.\nWhere the authority responsible for notified bodies is a different authority from the national competent authority for medical devices, it shall ensure that the national authority responsible for medical devices is consulted on relevant matters.\n\n\n7.\u00a0\u00a0\u00a0Member\u00a0States shall make publicly available general information on their measures governing the assessment, designation and notification of conformity assessment bodies and for the monitoring of notified bodies, and on changes which have a significant impact on such tasks.\n\n\n8.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall participate in the peer-review activities provided for in Article\u00a048.\n\n\n\nArticle\u00a036\n\nRequirements relating to notified bodies\n\n\n1.\u00a0\u00a0\u00a0Notified bodies shall fulfil the tasks for which they are designated in accordance with this Regulation. They shall satisfy the organisational and general requirements and the quality management, resource and process requirements that are necessary to fulfil those tasks. In particular, notified bodies shall comply with Annex\u00a0VII.\nIn order to meet the requirements referred to in the first subparagraph, notified bodies shall have permanent availability of sufficient administrative, technical and scientific personnel in accordance with Section\u00a03.1.1 of Annex\u00a0VII and personnel with relevant clinical expertise in accordance with Section\u00a03.2.4 of Annex\u00a0VII, where possible employed by the notified body itself.\nThe personnel referred to in Sections 3.2.3 and 3.2.7 of Annex\u00a0VII shall be employed by the notified body itself and shall not be external experts or subcontractors.\n\n\n2.\u00a0\u00a0\u00a0Notified bodies shall make available and submit upon request all relevant documentation, including the manufacturer's documentation, to the authority responsible for notified bodies to allow it to conduct its assessment, designation, notification, monitoring and surveillance activities and to facilitate the assessment outlined in this Chapter.\n\n\n3.\u00a0\u00a0\u00a0In order to ensure the uniform application of the requirements set out in Annex\u00a0VII, the Commission may adopt implementing acts, to the extent necessary to resolve issues of divergent interpretation and of practical application. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a037\n\nSubsidiaries and subcontracting\n\n\n1.\u00a0\u00a0\u00a0Where a notified body subcontracts specific tasks connected with conformity assessment or has recourse to a subsidiary for specific tasks connected with conformity assessment, it shall verify that the subcontractor or the subsidiary meets the applicable requirements set out in Annex\u00a0VII and shall inform the authority responsible for notified bodies accordingly.\n\n\n2.\u00a0\u00a0\u00a0Notified bodies shall take full responsibility for the tasks performed on their behalf by subcontractors or subsidiaries.\n\n\n3.\u00a0\u00a0\u00a0Notified bodies shall make publicly available a list of their subsidiaries.\n\n\n4.\u00a0\u00a0\u00a0Conformity assessment activities may be subcontracted or carried out by a subsidiary provided that the legal or natural person that applied for conformity assessment has been informed accordingly.\n\n\n5.\u00a0\u00a0\u00a0Notified bodies shall keep at the disposal of the authority responsible for notified bodies all relevant documents concerning the verification of the qualifications of the subcontractor or the subsidiary and the work carried out by them under this Regulation.\n\n\n\nArticle\u00a038\n\nApplication by conformity assessment bodies for designation\n\n\n1.\u00a0\u00a0\u00a0Conformity assessment bodies shall submit an application for designation to the authority responsible for notified bodies.\n\n\n2.\u00a0\u00a0\u00a0The application shall specify the conformity assessment activities as defined in this Regulation, and the types of devices for which the body is applying to be designated, and shall be supported by documentation demonstrating compliance with Annex\u00a0VII.\nIn respect of the organisational and general requirements and the quality management requirements set out in Sections\u00a01 and 2 of Annex\u00a0VII, a valid accreditation certificate and the corresponding evaluation report delivered by a national accreditation body in accordance with Regulation\u00a0(EC)\u00a0No\u00a0765/2008 may be submitted and shall be taken into consideration during the assessment described in Article\u00a039. However, the applicant shall make available all the documentation referred to in the first subparagraph\u00a0to demonstrate compliance with those requirements upon request.\n\n\n3.\u00a0\u00a0\u00a0The notified body shall update the documentation referred to in paragraph\u00a02 whenever relevant changes occur, in order to enable the authority responsible for notified bodies to monitor and verify continuous compliance with all the requirements set out in Annex\u00a0VII.\n\n\n\nArticle\u00a039\n\nAssessment of the application\n\n\n1.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall within 30 days check that the application referred to in Article\u00a038 is complete and shall request the applicant to provide any missing information. Once the application is complete that authority shall send it to the Commission.\nThe authority responsible for notified bodies shall review the application and supporting documentation in accordance with its own procedures and shall draw up a preliminary assessment report.\n\n\n2.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall submit the preliminary assessment report to the Commission which shall immediately transmit it to the MDCG.\n\n\n3.\u00a0\u00a0\u00a0Within 14 days of the submission referred to in paragraph\u00a02 of this Article, the Commission, in conjunction with the MDCG, shall appoint a joint assessment team made up of three experts, unless the specific circumstances require a different number of experts, chosen from the list referred to in Article\u00a040(2). One of the experts shall be a representative of the Commission who shall coordinate the activities of the joint assessment team. The other two experts shall come from Member\u00a0States other than the one in which the applicant conformity assessment body is established.\nThe joint assessment team shall be comprised of experts who are competent to assess the conformity assessment activities and the types of devices which are the subject of the application or, in particular when the assessment procedure is initiated in accordance with Article\u00a047(3), to ensure that the specific concern can be appropriately assessed.\n\n\n4.\u00a0\u00a0\u00a0Within 90 days of its appointment, the joint assessment team shall review the documentation submitted with the application in accordance with Article\u00a038. The joint assessment team may provide feedback to, or require clarification from, the authority responsible for notified bodies on the application and on the planned on-site assessment.\nThe authority responsible for notified bodies together with the joint assessment team shall plan and conduct an on-site assessment of the applicant conformity assessment body and, where relevant, of any subsidiary or subcontractor, located inside or outside the Union, to be involved in the conformity assessment process.\nThe on-site assessment of the applicant body shall be led by the authority responsible for notified bodies.\n\n\n5.\u00a0\u00a0\u00a0Findings regarding non-compliance of an applicant conformity assessment body with the requirements set out in Annex\u00a0VII shall be raised during the assessment process and discussed between the authority responsible for notified bodies and the joint assessment team with a view to reaching consensus and resolving any diverging opinions, with respect to the assessment of the application.\nAt the end of the on-site assessment, the authority responsible for notified bodies shall list for the applicant conformity assessment body the non-compliances resulting from the assessment and summarise the assessment by the joint assessment team.\nWithin a specified timeframe, the applicant conformity assessment body shall submit to the national authority a corrective and preventive action plan to address the non-compliances.\n\n\n6.\u00a0\u00a0\u00a0The joint assessment team shall document any remaining diverging opinions with respect to the assessment within 30 days of completion of the on-site assessment and send them to the authority responsible for notified bodies.\n\n\n7.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall following receipt of a corrective and preventive action plan from the applicant body assess whether non-compliances identified during the assessment have been appropriately addressed. This plan shall indicate the root cause of the identified non-compliances and shall include a timeframe for implementation of the actions therein.\nThe authority responsible for notified bodies shall having confirmed the corrective and preventive action plan forward it and its opinion thereon to the joint assessment team. The joint assessment team may request of the authority responsible for notified bodies further clarification and modifications.\nThe authority responsible for notified bodies shall draw up its final assessment report which shall include:\n\n\n\n\n\n\n\u2014\n\n\nthe result of the assessment,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nconfirmation that the corrective and preventive actions have been appropriately addressed and, where required, implemented,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nany remaining diverging opinion with the joint assessment team, and, where applicable,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe recommended scope of designation.\n\n\n\n\n\n\n8.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall submit its final assessment report and, if applicable, the draft designation to the Commission, the MDCG and the joint assessment team.\n\n\n9.\u00a0\u00a0\u00a0The joint assessment team shall provide a final opinion regarding the assessment report prepared by the authority responsible for notified bodies and, if applicable, the draft designation within 21 days of receipt of those documents to the Commission, which shall immediately submit that final opinion to the MDCG. Within 42 days of receipt of the opinion of the joint assessment team, the MDCG shall issue a recommendation with regard to the draft designation, which the authority responsible for notified bodies shall duly take into consideration for its decision on the designation of the notified body.\n\n\n10.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, adopt measures setting out the detailed arrangements specifying procedures and reports for the application for designation referred to in Article\u00a038 and the assessment of the application set out in this Article. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a040\n\nNomination of experts for joint assessment of applications for notification\n\n\n1.\u00a0\u00a0\u00a0The Member\u00a0States and the Commission shall nominate experts qualified in the assessment of conformity assessment bodies in the field of medical devices to participate in the activities referred to in Articles\u00a039 and 48.\n\n\n2.\u00a0\u00a0\u00a0The Commission shall maintain a list of the experts nominated pursuant to paragraph\u00a01 of this Article, together with information on their specific field of competence and expertise. That list shall be made available to Member\u00a0States competent authorities through the electronic system referred to in Article\u00a057.\n\n\n\nArticle\u00a041\n\nLanguage requirements\n\nAll documents required pursuant to Articles\u00a038 and 39 shall be drawn up in a language or languages which shall be determined by the Member\u00a0State concerned.\nMember\u00a0States, in applying the first paragraph, shall consider accepting and using a commonly understood language in the medical field, for all or part of the documentation concerned.\nThe Commission shall provide translations of the documentation pursuant to Articles\u00a038 and 39, or parts thereof into an official Union language, such as is necessary for that documentation to be readily understood by the joint assessment team appointed in accordance with Article\u00a039(3).\n\n\nArticle\u00a042\n\nDesignation and notification procedure\n\n\n1.\u00a0\u00a0\u00a0Member\u00a0States may only designate conformity assessment bodies for which the assessment pursuant to Article\u00a039 was completed and which comply with Annex\u00a0VII.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States shall notify the Commission and the other Member\u00a0States of the conformity assessment bodies they have designated, using the electronic notification tool within the database of notified bodies developed and managed by the Commission\u00a0(NANDO).\n\n\n3.\u00a0\u00a0\u00a0The notification shall clearly specify, using the codes referred to in paragraph\u00a013 of this Article, the scope of the designation indicating the conformity assessment activities as defined in this Regulation and the types of devices which the notified body is authorised to assess and, without prejudice to Article\u00a044, any conditions associated with the designation.\n\n\n4.\u00a0\u00a0\u00a0The notification shall be accompanied by the final assessment report of the authority responsible for notified bodies, the final opinion of the joint assessment team referred to in Article\u00a039(9) and the recommendation of the MDCG. Where the notifying Member\u00a0State does not follow the recommendation of the MDCG, it shall provide a duly substantiated justification.\n\n\n5.\u00a0\u00a0\u00a0The notifying Member\u00a0State shall, without prejudice to Article\u00a044, inform the Commission and the other Member\u00a0States of any conditions associated with the designation and provide documentary evidence regarding the arrangements in place to ensure that the notified body will be monitored regularly and will continue to satisfy the requirements set out in Annex\u00a0VII.\n\n\n6.\u00a0\u00a0\u00a0Within 28 days of the notification referred to in paragraph\u00a02, a Member\u00a0State or the Commission may raise written objections, setting out its arguments, with regard either to the notified body or to its monitoring by the authority responsible for notified bodies. Where no objection is raised, the Commission shall publish in NANDO the notification within 42 days of its having been notified as referred to in paragraph\u00a02.\n\n\n7.\u00a0\u00a0\u00a0When a Member\u00a0State or the Commission raises objections in accordance with paragraph\u00a06, the Commission shall bring the matter before the MDCG within 10 days of the expiry of the period referred to in paragraph\u00a06. After consulting the parties involved, the MDCG shall give its opinion at the latest within 40 days of the matter having been brought before it. Where the MDCG is of the opinion that the notification can be accepted, the Commission shall publish in NANDO the notification within 14 days.\n\n\n8.\u00a0\u00a0\u00a0Where the MDCG, after having been consulted in accordance with paragraph\u00a07, confirms the existing objection or raises another objection, the notifying Member\u00a0State shall provide a written response to the MDCG opinion within 40\u00a0days of its receipt. The response shall address the objections raised in the opinion, and set out the reasons for the notifying Member\u00a0State's decision to designate or not designate the conformity assessment body.\n\n\n9.\u00a0\u00a0\u00a0Where the notifying Member\u00a0State decides to uphold its decision to designate the conformity assessment body, having given its reasons in accordance with paragraph\u00a08, the Commission shall publish in NANDO the notification within 14 days of being informed thereof.\n\n\n10.\u00a0\u00a0\u00a0When publishing the notification in NANDO, the Commission shall also add to the electronic system referred to in Article\u00a057 the information relating to the notification of the notified body along with the documents mentioned in paragraph\u00a04 of this Article\u00a0and the opinion and responses referred to in paragraphs 7 and 8 of this Article.\n\n\n11.\u00a0\u00a0\u00a0The designation shall become valid the day after the notification is published in NANDO. The published notification shall state the scope of lawful conformity assessment activity of the notified body.\n\n\n12.\u00a0\u00a0\u00a0The conformity assessment body concerned may perform the activities of a notified body only after the designation has become valid in accordance with paragraph\u00a011.\n\n\n13.\u00a0\u00a0\u00a0The Commission shall by 26 November 2017, by means of implementing acts, draw up a list of codes and corresponding types of devices for the purpose of specifying the scope of the designation of notified bodies. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3). The Commission, after consulting the MDCG, may update this list based, inter\u00a0alia, on information arising from the coordination activities described in Article\u00a048.\n\n\n\nArticle\u00a043\n\nIdentification number and list of notified bodies\n\n\n1.\u00a0\u00a0\u00a0The Commission shall assign an identification number to each notified body for which the notification becomes valid in accordance with Article\u00a042(11). It shall assign a single identification number even when the body is notified under several Union acts. If they are successfully designated in accordance with this Regulation, bodies notified pursuant to Directives\u00a090/385/EEC and 93/42/EEC shall retain the identification number assigned to them pursuant to those Directives.\n\n\n2.\u00a0\u00a0\u00a0The Commission shall make the list of the bodies notified under this Regulation, including the identification numbers that have been assigned to them and the conformity assessment activities as defined in this Regulation and the types of devices for which they have been notified, accessible to the public in NANDO. It shall also make this list available on the electronic system referred to in Article\u00a057. The Commission shall ensure that the list is kept up to date.\n\n\n\nArticle\u00a044\n\nMonitoring and re-assessment of notified bodies\n\n\n1.\u00a0\u00a0\u00a0Notified bodies shall, without delay, and at the latest within 15 days, inform the authority responsible for notified bodies of relevant changes which may affect their compliance with the requirements set out in Annex\u00a0VII or their ability to conduct the conformity assessment activities relating to the devices for which they have been designated.\n\n\n2.\u00a0\u00a0\u00a0The authorities responsible for notified bodies shall monitor the notified bodies established on their territory and their subsidiaries and subcontractors to ensure ongoing compliance with the requirements and the fulfilment of its obligations set out in this Regulation. Notified bodies shall, upon request by their authority responsible for notified bodies, supply all relevant information and documents, required to enable the authority, the Commission and other Member\u00a0States to verify compliance.\n\n\n3.\u00a0\u00a0\u00a0Where the Commission or the authority of a Member\u00a0State submits a request to a notified body established on the territory of another Member\u00a0State relating to a conformity assessment carried out by that notified body, it shall send a copy of that request to the authority responsible for notified bodies of that other Member\u00a0State. The notified body concerned shall respond without delay and within 15 days at the latest to the request. The authority responsible for notified bodies of the Member\u00a0State in which the body is established shall ensure that requests submitted by authorities of any other Member\u00a0State or by the Commission are resolved by the notified body unless there is a legitimate reason for not doing so in which case the matter may be referred to the MDCG.\n\n\n4.\u00a0\u00a0\u00a0At least once a year, the authorities responsible for notified bodies shall re-assess whether the notified bodies established on their respective territory and, where appropriate, the subsidiaries and subcontractors under the responsibility of those notified bodies still satisfy the requirements and fulfil their obligations set out in Annex\u00a0VII. That review shall include an on-site audit of each notified body and, where necessary, of its subsidiaries and subcontractors.\nThe authority responsible for notified bodies shall conduct its monitoring and assessment activities according to an annual assessment plan to ensure that it can effectively monitor the continued compliance of the notified body with the requirements of this Regulation. That plan shall provide a reasoned schedule for the frequency of assessment of the notified body and, in particular, associated subsidiaries and subcontractors. The authority shall submit its annual plan for monitoring or assessment for each notified body for which it is responsible to the MDCG and to the Commission.\n\n\n5.\u00a0\u00a0\u00a0The monitoring of notified bodies by the authority responsible for notified bodies shall include observed audits of notified body personnel, including where necessary any personnel from subsidiaries and subcontractors, as that personnel is in the process of conducting quality management system assessments at a manufacturer's facility.\n\n\n6.\u00a0\u00a0\u00a0The monitoring of notified bodies conducted by the authority responsible for notified bodies shall consider data arising from market surveillance, vigilance and post-market surveillance to help guide its activities.\nThe authority responsible for notified bodies shall provide for a systematic follow-up of complaints and other information, including from other Member\u00a0States, which may indicate non-fulfilment of the obligations by a notified body or its deviation from common or best practice.\n\n\n7.\u00a0\u00a0\u00a0The authority responsible for notified bodies may in addition to regular monitoring or on-site assessments conduct short-notice, unannounced or \u2018for-cause\u2019 reviews if needed to address a particular issue or to verify compliance.\n\n\n8.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall review the assessments by notified bodies of manufacturers' technical documentation, in particular the clinical evaluation documentation as further outlined in Article\u00a045.\n\n\n9.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall document and record any findings regarding non-compliance of the notified body with the requirements set out in Annex\u00a0VII and shall monitor the timely implementation of corrective and preventive actions.\n\n\n10.\u00a0\u00a0\u00a0Three years after notification of a notified body, and again every fourth year thereafter, a complete re-assessment to determine whether the notified body still satisfies the requirements set out in Annex\u00a0VII shall be conducted by the authority responsible for notified bodies of the Member\u00a0State in which the body is established and by a joint assessment team appointed for the purpose of the procedure described in Articles\u00a038 and\u00a039.\n\n\n11.\u00a0\u00a0\u00a0The Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 in order to amend paragraph\u00a010 to modify the frequency at which the complete re-assessment referred to in that paragraph\u00a0is to be carried out.\n\n\n12.\u00a0\u00a0\u00a0The Member\u00a0States shall report to the Commission and to the MDCG, at least once a year, on their monitoring and on-site assessment activities regarding notified bodies and, where applicable, subsidiaries and subcontractors. The report shall provide details of the outcome of those activities, including activities pursuant to paragraph\u00a07, and shall be treated as confidential by the MDCG and the Commission; however it shall contain a summary which shall be made publicly available.\nThe summary of the report shall be uploaded to the electronic system referred to in Article\u00a057.\n\n\n\nArticle\u00a045\n\nReview of notified body assessment of technical documentation and clinical evaluation documentation\n\n\n1.\u00a0\u00a0\u00a0The authority responsible for notified bodies, as part of its ongoing monitoring of notified bodies, shall review an appropriate number of notified body assessments of manufacturers' technical documentation, in particular the clinical evaluation documentation as referred to in points (c) and (d) of Section\u00a06.1 of Annex\u00a0II to verify the conclusions drawn by the notified body based on the information presented by the manufacturer. The reviews by the authority responsible for notified bodies shall be conducted both off-site and on-site.\n\n\n2.\u00a0\u00a0\u00a0The sampling of files to be reviewed in accordance with paragraph\u00a01 shall be planned and representative of the types and risk of devices certified by the notified body, in particular high-risk devices, and be appropriately justified and documented in a sampling plan, which shall be made available by the authority responsible for notified bodies to the MDCG upon request.\n\n\n3.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall review whether the assessment by the notified body was conducted appropriately and shall check the procedures used, associated documentation and the conclusions drawn by the notified body. Such checking shall include the technical documentation and clinical evaluation documentation of the manufacturer upon which the notified body has based its assessment. Such reviews shall be conducted utilising CS.\n\n\n4.\u00a0\u00a0\u00a0Those reviews shall also form part of the re-assessment of notified bodies in accordance with Article\u00a044(10) and the joint assessment activities referred to in Article\u00a047(3). The reviews shall be conducted utilising appropriate expertise.\n\n\n5.\u00a0\u00a0\u00a0Based on the reports of the reviews and assessments by the authority responsible for notified bodies or joint assessment teams, on input from the market surveillance, vigilance and post-market surveillance activities described in Chapter\u00a0VII, on the continuous monitoring of technical progress, or on the identification of concerns and emerging issues concerning the safety and performance of devices, the MDCG may recommend that the sampling, carried out under this Article, cover a greater or lesser proportion of the technical documentation and clinical evaluation documentation assessed by a notified body.\n\n\n6.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, adopt measures setting out the detailed arrangements, associated documents for, and coordination of, the review of assessments of technical documentation and clinical evaluation documentation, as referred to in this Article. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a046\n\nChanges to designations and notifications\n\n\n1.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall notify the Commission and the other Member\u00a0States of any relevant changes to the designation of a notified body.\nThe procedures described in Article\u00a039 and in Article\u00a042 shall apply to extensions of the scope of the designation.\nFor changes to the designation other than extensions of its scope, the procedures laid down in the following paragraphs shall apply.\n\n\n2.\u00a0\u00a0\u00a0The Commission shall immediately publish the amended notification in NANDO. The Commission shall immediately enter information on the changes to the designation of the notified body in the electronic system referred to in Article\u00a057.\n\n\n3.\u00a0\u00a0\u00a0Where a notified body decides to cease its conformity assessment activities it shall inform the authority responsible for notified bodies and the manufacturers concerned as soon as possible and in the case of a planned cessation one year before ceasing its activities. The certificates may remain valid for a temporary period of nine months after cessation of the notified body's activities on condition that another notified body has confirmed in writing that it will assume responsibilities for the devices covered by those certificates. The new notified body shall complete a full assessment of the devices affected by the end of that period before issuing new certificates for those devices. Where the notified body has ceased its activity, the authority responsible for notified bodies shall withdraw the designation.\n\n\n4.\u00a0\u00a0\u00a0Where a authority responsible for notified bodies has ascertained that a notified body no longer meets the requirements set out in Annex\u00a0VII, or that it is failing to fulfil its obligations or has not implemented the necessary corrective measures, the authority shall suspend, restrict, or fully or partially withdraw the designation, depending on the seriousness of the failure to meet those requirements or fulfil those obligations. A\u00a0suspension shall not exceed a period of one year, renewable once for the same period.\nThe authority responsible for notified bodies shall immediately inform the Commission and the other Member\u00a0States of any suspension, restriction or withdrawal of a designation.\n\n\n5.\u00a0\u00a0\u00a0Where its designation has been suspended, restricted, or fully or partially withdrawn, the notified body shall inform the manufacturers concerned at the latest within 10 days.\n\n\n6.\u00a0\u00a0\u00a0In the event of restriction, suspension or withdrawal of a designation, the authority responsible for notified bodies shall take appropriate steps to ensure that the files of the notified body concerned are kept and make them available to authorities in other Member\u00a0States responsible for notified bodies and to authorities responsible for market surveillance at their request.\n\n\n7.\u00a0\u00a0\u00a0In the event of restriction, suspension or withdrawal of a designation, the authority responsible for notified bodies shall:\n\n\n\n\n\n\n(a)\n\n\nassess the impact on the certificates issued by the notified body;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nsubmit a report on its findings to the Commission and the other Member\u00a0States within three months of having notified the changes to the designation;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nrequire the notified body to suspend or withdraw, within a reasonable period of time determined by the authority, any certificates which were unduly issued to ensure the safety of devices on the market;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nenter into the electronic system referred to in Article\u00a057 information in relation to certificates of which it has required their suspension or withdrawal;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\ninform the competent authority for medical devices of the Member\u00a0State in which the manufacturer has its registered place of business through the electronic system referred to in Article\u00a057 of the certificates for which it has required suspension or withdrawal. That competent authority shall take the appropriate measures, where necessary to avoid a potential risk to the health or safety of patients, users or others.\n\n\n\n\n\n\n8.\u00a0\u00a0\u00a0With the exception of certificates unduly issued, and where a designation has been suspended or restricted, the certificates shall remain valid in the following circumstances:\n\n\n\n\n\n\n(a)\n\n\nthe authority responsible for notified bodies has confirmed, within one month of the suspension or restriction, that there is no safety issue in relation to certificates affected by the suspension or restriction, and the authority responsible for notified bodies has outlined a timeline and actions anticipated to remedy the suspension or restriction; or\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe authority responsible for notified bodies has confirmed that no certificates relevant to the suspension will be issued, amended or re-issued during the course of the suspension or restriction, and states whether the notified body has the capability of continuing to monitor and remain responsible for existing certificates issued for the period of the suspension or restriction. In the event that the authority responsible for notified bodies determines that the notified body does not have the capability to support existing certificates issued, the manufacturer shall provide, to the competent authority for medical devices of the Member\u00a0State in which the manufacturer of the device covered by the certificate has its registered place of business, within three months of the suspension or restriction, a written confirmation that another qualified notified body is temporarily assuming the functions of the notified body to monitor and remain responsible for the certificates during the period of suspension or restriction.\n\n\n\n\n\n\n9.\u00a0\u00a0\u00a0With the exception of certificates unduly issued, and where a designation has been withdrawn, the certificates shall remain valid for a period of nine months in the following circumstances:\n\n\n\n\n\n\n(a)\n\n\nwhere the competent authority for medical devices of the Member\u00a0State in which the manufacturer of the device covered by the certificate has its registered place of business has confirmed that there is no safety issue associated with the devices in question; and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nanother notified body has confirmed in writing that it will assume immediate responsibilities for those devices and will have completed assessment of them within twelve months of the withdrawal of the designation.\n\n\n\n\nIn the circumstances referred to in the first subparagraph, the competent authority for medical devices of the Member\u00a0State in which the manufacturer of the device covered by the certificate has its place of business may extend the provisional validity of the certificates for further periods of three months, which altogether shall not exceed twelve\u00a0months.\nThe authority or the notified body assuming the functions of the notified body affected by the change of designation shall immediately inform the Commission, the other Member\u00a0States and the other notified bodies thereof.\n\n\n\nArticle\u00a047\n\nChallenge to the competence of notified bodies\n\n\n1.\u00a0\u00a0\u00a0The Commission, in conjunction with the MDCG, shall investigate all cases where concerns have been brought to its attention regarding the continued fulfilment by a notified body, or of one or more of its subsidiaries or subcontractors, of the requirements set out in Annex\u00a0VII or the obligations to which they are subject. It shall ensure that the relevant authority responsible for notified bodies is informed and is given an opportunity to investigate those concerns.\n\n\n2.\u00a0\u00a0\u00a0The notifying Member\u00a0State shall provide the Commission, on request, with all information regarding the designation of the notified body concerned.\n\n\n3.\u00a0\u00a0\u00a0The Commission, in conjunction with the MDCG, may initiate, as applicable, the assessment procedure described in Article\u00a039(3) and (4), where there is reasonable concern about the ongoing compliance of a notified body or a subsidiary or subcontractor of the notified body with the requirements set out in Annex\u00a0VII and where the investigation by the authority responsible for notified bodies is not deemed to have fully addressed the concerns or upon request of the authority responsible for notified bodies. The reporting and outcome of that assessment shall follow the principles of Article\u00a039. Alternatively, depending on the severity of the issue, the Commission, in conjunction with the MDCG, may request that the authority responsible for notified bodies allow the participation of up to two experts from the list established pursuant to Article\u00a040 in an on-site assessment as part of the planned monitoring and assessment activities in accordance with Article\u00a044 and as outlined in the annual assessment plan described in Article\u00a044(4).\n\n\n4.\u00a0\u00a0\u00a0Where the Commission ascertains that a notified body no longer meets the requirements for its designation, it shall inform the notifying Member\u00a0State accordingly and request it to take the necessary corrective measures, including the suspension, restriction or withdrawal of the designation if necessary.\nWhere the Member\u00a0State fails to take the necessary corrective measures, the Commission may, by means of implementing acts, suspend, restrict or withdraw the designation. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3). It shall notify the Member\u00a0State concerned of its decision and update NANDO and the electronic system referred to in Article\u00a057.\n\n\n5.\u00a0\u00a0\u00a0The Commission shall ensure that all confidential information obtained in the course of its investigations is treated accordingly.\n\n\n\nArticle\u00a048\n\nPeer review and exchange of experience between authorities responsible for notified bodies\n\n\n1.\u00a0\u00a0\u00a0The Commission shall provide for the organisation of exchange of experience and coordination of administrative practice between the authorities responsible for notified bodies. Such exchange shall cover elements including:\n\n\n\n\n\n\n(a)\n\n\ndevelopment of best practice documents relating to the activities of the authorities responsible for notified bodies;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ndevelopment of guidance documents for notified bodies in relation to the implementation of this Regulation;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\ntraining and qualification of the experts referred to in Article\u00a040;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nmonitoring of trends relating to changes to notified body designations and notifications and trends in certificate withdrawals and transfers between notified bodies;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nmonitoring of the application and applicability of scope codes referred to in Article\u00a042(13);\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\ndevelopment of a mechanism for peer reviews between authorities and the Commission;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nmethods of communication to the public on the monitoring and surveillance activities of authorities and the Commission on notified bodies.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The authorities responsible for notified bodies shall participate in a peer review every third year through the mechanism developed pursuant to paragraph\u00a01 of this\u00a0Article. Such reviews shall normally be conducted in parallel with the on-site joint assessments described in Article\u00a039. Alternatively, an authority may make the choice of having such reviews take place as part of its monitoring activities referred to in Article\u00a044.\n\n\n3.\u00a0\u00a0\u00a0The Commission shall participate in the organisation and provide support to the implementation of the peer review mechanism.\n\n\n4.\u00a0\u00a0\u00a0The Commission shall compile an annual summary report of the peer review activities, which shall be made publicly available.\n\n\n5.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, adopt measures setting out the detailed arrangements and related documents for the peer review mechanism and training and qualification as referred to in paragraph\u00a01 of this Article. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a049\n\nCoordination of notified bodies\n\nThe Commission shall ensure that appropriate coordination and cooperation between notified bodies is put in place and operated in the form of a coordination group of notified bodies in the field of medical devices, including in vitro diagnostic medical devices. This group shall meet on a regular basis and at least annually.\nThe bodies notified under this Regulation shall participate in the work of that group.\nThe Commission may establish the specific arrangements for the functioning of the coordination group of notified bodies.\n\n\nArticle\u00a050\n\nList of standard fees\n\nNotified bodies shall establish lists of their standard fees for the conformity assessment activities that they carry out and shall make those lists publicly available.\n\n\n\nCHAPTER V\n\n\nCLASSIFICATION AND CONFORMITY ASSESSMENT\n\n\n\n\nSECTION\u00a01\n\n\n\n\nClassification\n\n\n\n\nArticle\u00a051\n\nClassification of devices\n\n\n1.\u00a0\u00a0\u00a0Devices shall be divided into classes I, IIa, IIb and III, taking into account the intended purpose of the devices and their inherent risks. Classification shall be carried out in accordance with Annex\u00a0VIII.\n\n\n2.\u00a0\u00a0\u00a0Any dispute between the manufacturer and the notified body concerned, arising from the application of Annex\u00a0VIII, shall be referred for a decision to the competent authority of the Member\u00a0State in which the manufacturer has its registered place of business. In cases where the manufacturer has no registered place of business in the Union and has not yet designated an authorised representative, the matter shall be referred to the competent authority of the Member\u00a0State in which the authorised representative referred to in the last indent of point\u00a0(b) of the second paragraph\u00a0of Section\u00a02.2 of Annex\u00a0IX has its registered place of business. Where the notified body concerned is established in a Member\u00a0State other than that of the manufacturer, the competent authority shall adopt its decision after consultation with the competent authority of the Member\u00a0State that designated the notified body.\nThe competent authority of the Member\u00a0State in which the manufacturer has its registered place of business shall notify the MDCG and the Commission of its decision. The decision shall be made available upon request.\n\n\n3.\u00a0\u00a0\u00a0At the request of a Member\u00a0State the Commission shall after consulting the MDCG, decide, by means of implementing acts, on the following:\n\n\n\n\n\n\n(a)\n\n\napplication of Annex\u00a0VIII to a given device, or category or group of devices, with a view to determining the classification of such devices;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthat a device, or category or group of devices, shall for reasons of public health based on new scientific evidence, or based on any information which becomes available in the course of the vigilance and market surveillance activities be reclassified, by way of derogation from Annex\u00a0VIII.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0The Commission may also, on its own initiative and after consulting the MDCG, decide, by means of implementing acts, on the issues referred to in points (a) and (b) of paragraph\u00a03.\n\n\n5.\u00a0\u00a0\u00a0In order to ensure the uniform application of Annex\u00a0VIII, and taking account of the relevant scientific opinions of the relevant scientific committees, the Commission may adopt implementing acts to the extent necessary to resolve issues of divergent interpretation and of practical application.\n\n\n6.\u00a0\u00a0\u00a0The implementing acts referred to in paragraphs 3, 4 and 5 of this Article\u00a0shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\n\n\nSECTION\u00a02\n\n\n\n\nConformity assessment\n\n\n\n\nArticle\u00a052\n\nConformity assessment procedures\n\n\n1.\u00a0\u00a0\u00a0Prior to placing a device on the market, manufacturers shall undertake an assessment of the conformity of that device, in accordance with the applicable conformity assessment procedures set out in Annexes\u00a0IX to XI.\n\n\n2.\u00a0\u00a0\u00a0Prior to putting into service a device that is not placed on the market, manufacturers shall undertake an assessment of the conformity of that device, in accordance with the applicable conformity assessment procedures set out in Annexes\u00a0IX to XI.\n\n\n3.\u00a0\u00a0\u00a0Manufacturers of class\u00a0III devices, other than custom-made or investigational devices, shall be subject to a conformity assessment as specified in Annex\u00a0IX. Alternatively, the manufacturer may choose to apply a conformity assessment as specified in Annex\u00a0X coupled with a conformity assessment as specified in Annex\u00a0XI.\n\n\n4.\u00a0\u00a0\u00a0Manufacturers of class IIb devices, other than custom-made or investigational devices, shall be subject to a conformity assessment as specified in Chapters\u00a0I and III of Annex\u00a0IX, and including an assessment of the technical documentation as specified in Section\u00a04 of that Annex\u00a0of at least one representative device per generic device group.\nHowever, for class\u00a0IIb implantable devices, except sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips and connectors, the assessment of the technical documentation as specified in Section 4 of Annex IX shall apply for every device.\nAlternatively, the manufacturer may choose to apply a conformity assessment based on type examination as specified in Annex\u00a0X coupled with a conformity assessment based on product conformity verification as specified in Annex\u00a0XI.\n\n\n5.\u00a0\u00a0\u00a0Where justified in view of well-established technologies, similar to those used in the exempted devices listed in the second subparagraph\u00a0of paragraph\u00a04 of this Article, being used in other class IIb implantable devices, or where justified in order to protect the health and safety of patients, users or other persons or other aspects of public health, the Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 to amend that list by adding other types of class IIb implantable devices to that list or removing devices therefrom.\n\n\n6.\u00a0\u00a0\u00a0Manufacturers of class IIa devices, other than custom-made or investigational devices, shall be subject to a conformity assessment as specified in Chapters\u00a0I and III of Annex\u00a0IX, and including an assessment of the technical documentation as specified in Section\u00a04 of that Annex\u00a0of at least one representative device for each category of devices.\nAlternatively, the manufacturer may choose to draw up the technical documentation set out in Annexes\u00a0II and III coupled with a conformity assessment as specified in Section\u00a010 or Section\u00a018 of Annex\u00a0XI. The assessment of the technical documentation shall apply for at least one representative device for each category of devices.\n\n\n7.\u00a0\u00a0\u00a0Manufacturers of class I devices, other than custom-made or investigational devices, shall declare the conformity of their products by issuing the EU\u00a0declaration of conformity referred to in Article\u00a019 after drawing up the technical documentation set out in Annexes\u00a0II and III. If those devices are placed on the market in sterile condition, have a measuring function or are reusable surgical instruments, the manufacturer shall apply the procedures set out in Chapters\u00a0I and III of Annex\u00a0IX, or in Part\u00a0A of Annex\u00a0XI. However, the involvement of the notified body in those procedures shall be limited:\n\n\n\n\n\n\n(a)\n\n\nin the case of devices placed on the market in sterile condition, to the aspects relating to establishing, securing and maintaining sterile conditions;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nin the case of devices with a measuring function, to the aspects relating to the conformity of the devices with the metrological requirements;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nin the case of reusable surgical instruments, to the aspects relating to the reuse of the device, in particular cleaning, disinfection, sterilization, maintenance and functional testing and the related instructions for use.\n\n\n\n\n\n\n8.\u00a0\u00a0\u00a0Manufacturers of custom-made devices shall follow the procedure set out in Annex\u00a0XIII and draw up the statement set out in Section\u00a01 of that Annex\u00a0before placing such devices on the market.\nIn addition to the procedure applicable pursuant to the first subparagraph, manufacturers of class III custom-made implantable devices shall be subject to the conformity assessment as specified in Chapter\u00a0I of Annex\u00a0IX. Alternatively, the manufacturer may choose to apply a conformity assessment as specified in Part A of Annex\u00a0XI.\n\n\n9.\u00a0\u00a0\u00a0In addition to the procedures applicable pursuant to paragraph\u00a03, 4, 6, or 7 of this Article, in the case of devices referred to in the first subparagraph\u00a0of Article\u00a01(8), the procedure specified in Section\u00a05.2 of Annex\u00a0IX or Section\u00a06 of Annex\u00a0X, as applicable, shall also apply.\n\n\n10.\u00a0\u00a0\u00a0In addition to the procedures applicable pursuant to paragraph\u00a03, 4, 6, or 7 of this Article, in the case of devices that are covered by this Regulation in accordance with point\u00a0(f) or (g) of Article\u00a01(6) and with the first subparagraph\u00a0of Article\u00a01(10), the procedure specified in Section\u00a05.3 of Annex\u00a0IX or Section\u00a06 of Annex\u00a0X, as applicable, shall also apply.\n\n\n11.\u00a0\u00a0\u00a0In addition to the procedures applicable pursuant to paragraph\u00a03, 4, 6, or 7, in the case of devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed by or locally dispersed in the human body, the procedure specified in Section\u00a05.4 of Annex\u00a0IX or Section\u00a06 of Annex\u00a0X, as applicable, shall also apply.\n\n\n12.\u00a0\u00a0\u00a0The Member\u00a0State in which the notified body is established may require that all or certain documents, including the technical documentation, audit, assessment and inspection reports, relating to the procedures referred to in paragraphs 1 to 7 and 9 to 11 be made available in an official Union language(s) determined by that Member\u00a0State. In the absence of such requirement, those documents shall be available in any official Union language acceptable to the notified body.\n\n\n13.\u00a0\u00a0\u00a0Investigational devices shall be subject to the requirements set out in Articles\u00a062 to\u00a081.\n\n\n14.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, specify detailed arrangements and procedural aspects with a view to ensuring the harmonised application of the conformity assessment procedures by the notified bodies for any of the following aspects:\n\n\n\n\n\n\n(a)\n\n\nthe frequency and the sampling basis of the assessment of the technical documentation on a representative basis as set out in the third paragraph\u00a0of Section\u00a02.3 and in Section\u00a03.5 of Annex\u00a0IX in the case of class\u00a0IIa and class\u00a0IIb devices, and in Section\u00a010.2 of Annex\u00a0XI in the case of class\u00a0IIa devices;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe minimum frequency of unannounced on-site audits and sample tests to be conducted by notified bodies in accordance with Section\u00a03.4 of Annex\u00a0IX, taking into account the risk-class and the type of device;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe physical, laboratory or other tests to be carried out by notified bodies in the context of sample tests, assessment of the technical documentation and type examination in accordance with Sections 3.4 and 4.3 of Annex\u00a0IX, Section\u00a03 of Annex\u00a0X and Section\u00a015 of Annex\u00a0XI.\n\n\n\n\nThe implementing acts referred to in the first subparagraph\u00a0shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a053\n\nInvolvement of notified bodies in conformity assessment procedures\n\n\n1.\u00a0\u00a0\u00a0Where the conformity assessment procedure requires the involvement of a notified body, the manufacturer may apply to a notified body of its choice, provided that the chosen notified body is designated for conformity assessment activities related to the types of devices concerned. The manufacturer may not lodge an application in parallel with another notified body for the same conformity assessment procedure.\n\n\n2.\u00a0\u00a0\u00a0The notified body concerned shall, by means of the electronic system referred to in Article\u00a057, inform the other notified bodies of any manufacturer that withdraws its application prior to the notified body's decision regarding the conformity assessment.\n\n\n3.\u00a0\u00a0\u00a0When applying to a notified body under paragraph\u00a01, manufacturers shall declare whether they have withdrawn an application with another notified body prior to the decision of that notified body and provide information about any previous application for the same conformity assessment that has been refused by another notified body.\n\n\n4.\u00a0\u00a0\u00a0The notified body may require any information or data from the manufacturer, which is necessary in order to properly conduct the chosen conformity assessment procedure.\n\n\n5.\u00a0\u00a0\u00a0Notified bodies and the personnel of notified bodies shall carry out their conformity assessment activities with the highest degree of professional integrity and the requisite technical and scientific competence in the specific field and shall be free from all pressures and inducements, particularly financial, which might influence their judgement or the results of their conformity assessment activities, especially as regards persons or groups with an interest in the results of those activities.\n\n\n\nArticle\u00a054\n\nClinical evaluation consultation procedure for certain class III and class IIb devices\n\n\n1.\u00a0\u00a0\u00a0In addition to the procedures applicable pursuant to Article\u00a052, a notified body shall also follow the procedure regarding clinical evaluation consultation as specified in Section\u00a05.1 of Annex\u00a0IX or as referred to in Section\u00a06 of Annex\u00a0X, as applicable, when performing a conformity assessment of the following devices:\n\n\n\n\n\n\n(a)\n\n\nclass III implantable devices, and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nclass IIb active devices intended to administer and/or remove a medicinal product, as referred to in Section\u00a06.4 of Annex\u00a0VIII (Rule 12).\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The procedure referred to in paragraph\u00a01 shall not be required for the devices referred to therein:\n\n\n\n\n\n\n(a)\n\n\nin the case of renewal of a certificate issued under this Regulation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nwhere the device has been designed by modifying a device already marketed by the same manufacturer for the same intended purpose, provided that the manufacturer has demonstrated to the satisfaction of the notified body that the modifications do not adversely affect the benefit-risk ratio of the device; or\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nwhere the principles of the clinical evaluation of the device type or category have been addressed in a CS referred to in Article\u00a09 and the notified body confirms that the clinical evaluation of the manufacturer for this device is in compliance with the relevant CS for clinical evaluation of that kind of device.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0The notified body shall notify the competent authorities, the authority responsible for notified bodies and the Commission through the electronic system referred to in Article\u00a057 of whether or not the procedure referred to in paragraph\u00a01 of this Article\u00a0is to be applied. That notification shall be accompanied by the clinical evaluation assessment report.\n\n\n4.\u00a0\u00a0\u00a0The Commission shall draw up an annual overview of devices which have been subject to the procedure specified in Section\u00a05.1 of Annex\u00a0IX and referred to in Section\u00a06 of Annex\u00a0X. The annual overview shall include the notifications in accordance with paragraph\u00a03 of this Article\u00a0and point\u00a0(e) of Section\u00a05.1 of Annex\u00a0IX and a listing of the cases where the notified body did not follow the advice from the expert panel. The Commission shall submit this overview to the European Parliament, to the Council and to the MDCG.\n\n\n5.\u00a0\u00a0\u00a0The Commission shall by 27 May 2025 draw up a report on the operation of this Article\u00a0and submit it to the European Parliament and to the Council. The report shall take into account the annual overviews and any available relevant recommendations from the MDCG. On the basis of that report the Commission shall, if appropriate, make proposals for amendments to this Regulation.\n\n\n\nArticle\u00a055\n\nMechanism for scrutiny of conformity assessments of certain class III and class IIb devices\n\n\n1.\u00a0\u00a0\u00a0A notified body shall notify the competent authorities of certificates it has granted to devices for which the conformity assessment has been performed pursuant to Article\u00a054(1). Such notification shall take place through the electronic system referred to in Article\u00a057 and shall include the summary of safety and clinical performance pursuant to Article\u00a032, the assessment report by the notified body, the instructions for use referred to in Section\u00a023.4 of Annex\u00a0I, and, where applicable, the scientific opinion of the expert panels referred to in Section\u00a05.1 of Annex\u00a0IX or Section\u00a06 of Annex\u00a0X, as applicable. In the case of divergent views between the notified body and the expert panels, a full justification shall also be included.\n\n\n2.\u00a0\u00a0\u00a0A competent authority and, where applicable, the Commission may, based on reasonable concerns apply further procedures in accordance with Article\u00a044, 45, 46, 47 or 94 and, where deemed necessary, take appropriate measures in accordance with Articles\u00a095 and\u00a097.\n\n\n3.\u00a0\u00a0\u00a0The MDCG and, where applicable, the Commission, may, based on reasonable concerns, request scientific advice from the expert panels in relation to the safety and performance of any device.\n\n\n\nArticle\u00a056\n\nCertificates of conformity\n\n\n1.\u00a0\u00a0\u00a0The certificates issued by the notified bodies in accordance with Annexes\u00a0IX, X and XI shall be in an official Union language determined by the Member\u00a0State in which the notified body is established or otherwise in an official Union language acceptable to the notified body. The minimum content of the certificates shall be as set out in Annex\u00a0XII.\n\n\n2.\u00a0\u00a0\u00a0The certificates shall be valid for the period they indicate, which shall not exceed five years. On application by the manufacturer, the validity of the certificate may be extended for further periods, each not exceeding five years, based on a re-assessment in accordance with the applicable conformity assessment procedures. Any supplement to a certificate shall remain valid as long as the certificate which it supplements is valid.\n\n\n3.\u00a0\u00a0\u00a0Notified bodies may impose restrictions to the intended purpose of a device to certain groups of patients or require manufacturers to undertake specific PMCF studies pursuant to Part B of Annex\u00a0XIV.\n\n\n4.\u00a0\u00a0\u00a0Where a notified body finds that the requirements of this Regulation are no longer met by the manufacturer, it shall, taking account of the principle of proportionality, suspend or withdraw the certificate issued or impose any restrictions on it unless compliance with such requirements is ensured by appropriate corrective action taken by the manufacturer within an appropriate deadline set by the notified body. The notified body shall give the reasons for its decision.\n\n\n5.\u00a0\u00a0\u00a0The notified body shall enter in the electronic system referred to in Article\u00a057 any information regarding certificates issued, including amendments and supplements thereto, and regarding suspended, reinstated, withdrawn or refused certificates and restrictions imposed on certificates. Such information shall be accessible to the public.\n\n\n6.\u00a0\u00a0\u00a0In the light of technical progress, the Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 amending the minimum content of the certificates set out in Annex\u00a0XII.\n\n\n\nArticle\u00a057\n\nElectronic system on notified bodies and on certificates of conformity\n\n\n1.\u00a0\u00a0\u00a0The Commission, after consulting the MDCG, shall set up and manage an electronic system to collate and process the following information:\n\n\n\n\n\n\n(a)\n\n\nthe list of subsidiaries referred to in Article\u00a037(3);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe list of experts referred to in Article\u00a040(2);\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe information relating to the notification referred to in Article\u00a042(10) and the amended notifications referred to in Article\u00a046(2);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe list of notified bodies referred to in Article\u00a043(2);\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe summary of the report referred to in Article\u00a044(12);\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe notifications for conformity assessments and certificates referred to in Articles\u00a054(3) and 55(1);\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nwithdrawal or refusals of applications for the certificates as referred to in Article\u00a053(2) and Section\u00a04.3 of Annex\u00a0VII;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe information regarding certificates referred to in Article\u00a056(5);\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nthe summary of safety and clinical performance referred to in Article\u00a032.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The information collated and processed by the electronic system shall be accessible to the competent authorities of the Member\u00a0States, to the Commission, where appropriate to the notified bodies and where provided elsewhere in this regulation or in Regulation\u00a0(EU)\u00a02017/746 to the public.\n\n\n\nArticle\u00a058\n\nVoluntary change of notified body\n\n\n1.\u00a0\u00a0\u00a0In cases where a manufacturer terminates its contract with a notified body and enters into a contract with another notified body in respect of the conformity assessment of the same device, the detailed arrangements for the change of notified body shall be clearly defined in an agreement between the manufacturer, the incoming notified body and, where practicable the outgoing notified body. That agreement shall cover at least the following aspects:\n\n\n\n\n\n\n(a)\n\n\nthe date on which the certificates issued by the outgoing notified body become invalid;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe date until which the identification number of the outgoing notified body may be indicated in the information supplied by the manufacturer, including any promotional material;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe transfer of documents, including confidentiality aspects and property rights;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe date after which the conformity assessment tasks of the outgoing notified body is assigned to the incoming notified body;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe last serial number or lot number for which the outgoing notified body is responsible.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The outgoing notified body shall withdraw the certificates it has issued for the device concerned on the date on which they become invalid.\n\n\n\nArticle\u00a059\n\nDerogation from the conformity assessment procedures\n\n\n1.\u00a0\u00a0\u00a0By way of derogation from Article\u00a052, any competent authority may authorise, on a duly justified request, the placing on the market or putting into service within the territory of the Member\u00a0State concerned, of a specific device for which the procedures referred to in that Article\u00a0have not been carried out but use of which is in the interest of public health or patient safety or health.\n\n\n2.\u00a0\u00a0\u00a0The Member\u00a0State shall inform the Commission and the other Member\u00a0States of any decision to authorise the placing on the market or putting into service of a device in accordance with paragraph\u00a01 where such authorisation is granted for use other than for a single patient.\n\n\n3.\u00a0\u00a0\u00a0Following a notification pursuant to paragraph\u00a02 of this Article, the Commission, in exceptional cases relating to public health or patient safety or health, may, by means of implementing acts, extend for a limited period of time the validity of an authorisation granted by a Member\u00a0State in accordance with paragraph\u00a01 of this Article\u00a0to the territory of the Union and set the conditions under which the device may be placed on the market or put into service. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\nOn duly justified imperative grounds of urgency relating to the health and safety of humans, the Commission shall adopt immediately applicable implementing acts in accordance with the procedure referred to in Article\u00a0114(4).\n\n\n\nArticle\u00a060\n\nCertificate of free sale\n\n\n1.\u00a0\u00a0\u00a0For the purpose of export and upon request by a manufacturer or an authorised representative, the Member\u00a0State in which the manufacturer or the authorised representative has its registered place of business shall issue a certificate of free sale declaring that the manufacturer or the authorised representative, as applicable, has its registered place of business on its territory and that the device in question bearing the CE\u00a0marking in accordance with this Regulation may be marketed in the Union. The certificate of free sale shall set out the Basic UDI-DI of the device as provided to the UDI\u00a0database under Article\u00a029. Where a notified body has issued a certificate pursuant to Article\u00a056, the certificate of free sale shall set out the unique number identifying the certificate issued by the notified body, as referred to in Section\u00a03 of Chapter\u00a0II of Annex\u00a0XII.\n\n\n2.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, establish a model for certificates of free sale, taking into account international practice as regards the use of certificates of free sale. Those implementing acts shall be adopted in accordance with the advisory procedure referred to in Article\u00a0114(2).\n\n\n\n\n\nCHAPTER VI\n\n\nCLINICAL EVALUATION AND CLINICAL INVESTIGATIONS\n\n\n\nArticle\u00a061\n\nClinical evaluation\n\n\n1.\u00a0\u00a0\u00a0Confirmation of conformity with relevant general safety and performance requirements set out in Annex\u00a0I under the normal conditions of the intended use of the device, and the evaluation of the undesirable side-effects and of the acceptability of the benefit-risk- ratio referred to in Sections 1 and 8 of Annex\u00a0I, shall be based on clinical data providing sufficient clinical evidence, including where applicable relevant data as referred to in Annex\u00a0III.\nThe manufacturer shall specify and justify the level of clinical evidence necessary to demonstrate conformity with the relevant general safety and performance requirements. That level of clinical evidence shall be appropriate in view of the characteristics of the device and its intended purpose.\nTo that end, manufacturers shall plan, conduct and document a clinical evaluation in accordance with this Article\u00a0and Part A of Annex\u00a0XIV.\n\n\n2.\u00a0\u00a0\u00a0For all class III devices and for the class IIb devices referred to in point\u00a0(b) of Article\u00a054(1), the manufacturer may, prior to its clinical evaluation and/or investigation, consult an expert panel as referred to in Article\u00a0106, with the aim of reviewing the manufacturer's intended clinical development strategy and proposals for clinical investigation. The manufacturer shall give due consideration to the views expressed by the expert panel. Such consideration shall be documented in the clinical evaluation report referred to in paragraph\u00a012 of this Article.\nThe manufacturer may not invoke any rights to the views expressed by the expert panel with regard to any future conformity assessment procedure.\n\n\n3.\u00a0\u00a0\u00a0A clinical evaluation shall follow a defined and methodologically sound procedure based on the following:\n\n\n\n\n\n\n(a)\n\n\na critical evaluation of the relevant scientific literature currently available relating to the safety, performance, design characteristics and intended purpose of the device, where the following conditions are satisfied:\n\n\n\n\n\n\n\u2014\n\n\nit is demonstrated that the device subject to clinical evaluation for the intended purpose is equivalent to the device to which the data relate, in accordance with Section\u00a03 of Annex\u00a0XIV, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe data adequately demonstrate compliance with the relevant general safety and performance requirements;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\na critical evaluation of the results of all available clinical investigations, taking duly into consideration whether the investigations were performed under Articles\u00a062 to\u00a080, any acts adopted pursuant to Article\u00a081, and Annex\u00a0XV; and\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\na consideration of currently available alternative treatment options for that purpose, if any.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0In the case of implantable devices and class III devices, clinical investigations shall be performed, except if:\n\n\n\n\n\n\n\u2014\n\n\nthe device has been designed by modifications of a device already marketed by the same manufacturer,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe modified device has been demonstrated by the manufacturer to be equivalent to the marketed device, in accordance with Section\u00a03 of Annex\u00a0XIV and this demonstration has been endorsed by the notified body, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe clinical evaluation of the marketed device is sufficient to demonstrate conformity of the modified device with the relevant safety and performance requirements.\n\n\n\n\nIn this case, the notified body shall check that the PMCF plan is appropriate and includes post market studies to demonstrate the safety and performance of the device.\nIn addition, clinical investigations need not be performed in the cases referred to in paragraph\u00a06.\n\n\n5.\u00a0\u00a0\u00a0A manufacturer of a device demonstrated to be equivalent to an already marketed device not manufactured by him, may also rely on paragraph\u00a04 in order not to perform a clinical investigation provided that the following conditions are fulfilled in addition to what is required in that paragraph:\n\n\n\n\n\n\n\u2014\n\n\nthe two manufacturers have a contract in place that explicitly allows the manufacturer of the second device full access to the technical documentation on an ongoing basis, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe original clinical evaluation has been performed in compliance with the requirements of this Regulation,\n\n\n\n\nand the manufacturer of the second device provides clear evidence thereof to the notified body.\n\n\n6.\u00a0\u00a0\u00a0The requirement to perform clinical investigations pursuant to paragraph\u00a04 shall not apply to implantable devices and class III devices:\n\n\n\n\n\n\n(a)\n\n\nwhich have been lawfully placed on the market or put into service in accordance with Directive\u00a090/385/EEC or Directive\u00a093/42/EEC and for which the clinical evaluation:\n\n\n\n\n\n\n\u2014\n\n\nis based on sufficient clinical data, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nis in compliance with the relevant product-specific CS for the clinical evaluation of that kind of device, where such a CS is available; or\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthat are sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips or connectors for which the clinical evaluation is based on sufficient clinical data and is in compliance with the relevant product-specific CS, where such a CS is available.\n\n\n\n\n\n\n7.\u00a0\u00a0\u00a0Cases in which paragraph\u00a04 is not applied by virtue of paragraph\u00a06 shall be justified in the clinical evaluation report by the manufacturer and in the clinical evaluation assessment report by the notified body.\n\n\n8.\u00a0\u00a0\u00a0Where justified in view of well-established technologies, similar to those used in the exempted devices listed in point\u00a0(b) of paragraph\u00a06 of this Article, being used in other devices, or where justified in order to protect the health and safety of patients, users or other persons or other aspects of public health, the Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 to amend the list of exempted devices referred to in the second subparagraph\u00a0of Article\u00a052(4) and in point\u00a0(b) of paragraph\u00a06 of this Article, by adding other types of implantable or class III devices to that list or removing devices therefrom.\n\n\n9.\u00a0\u00a0\u00a0In the case of the products without an intended medical purpose listed in Annex\u00a0XVI, the requirement to demonstrate a clinical benefit in accordance with this Chapter and Annexes\u00a0XIV and XV shall be understood as a requirement to demonstrate the performance of the device. Clinical evaluations of those products shall be based on relevant data concerning safety, including data from post-market surveillance, PMCF, and, where applicable, specific clinical investigation. Clinical investigations shall be performed for those products unless reliance on existing clinical data from an analogous medical device is duly justified.\n\n\n10.\u00a0\u00a0\u00a0Without prejudice to paragraph\u00a04, where the demonstration of conformity with general safety and performance requirements based on clinical data is not deemed appropriate, adequate justification for any such exception shall be given based on the results of the manufacturer's risk management and on consideration of the specifics of the interaction between the device and the human body, the clinical performance intended and the claims of the manufacturer. In such a case, the manufacturer shall duly substantiate in the technical documentation referred to in Annex\u00a0II why it considers a demonstration of conformity with general safety and performance requirements that is based on the results of non-clinical testing methods alone, including performance evaluation, bench testing and pre-clinical evaluation, to be adequate.\n\n\n11.\u00a0\u00a0\u00a0The clinical evaluation and its documentation shall be updated throughout the life cycle of the device concerned with clinical data obtained from the implementation of the manufacturer's PMCF plan in accordance with Part B of Annex\u00a0XIV and the post-market surveillance plan referred to in Article\u00a084.\nFor class III devices and implantable devices, the PMCF evaluation report and, if indicated, the summary of safety and clinical performance referred to in Article\u00a032 shall be updated at least annually with such data.\n\n\n12.\u00a0\u00a0\u00a0The clinical evaluation, its results and the clinical evidence derived from it shall be documented in a clinical evaluation report as referred to in Section\u00a04 of Annex\u00a0XIV, which, except for custom-made devices, shall be part of the technical documentation referred to in Annex\u00a0II relating to the device concerned.\n\n\n13.\u00a0\u00a0\u00a0Where necessary to ensure the uniform application of Annex\u00a0XIV, the Commission may, having due regard to technical and scientific progress, adopt implementing acts to the extent necessary to resolve issues of divergent interpretation and of practical application. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a062\n\nGeneral requirements regarding clinical investigations conducted to demonstrate conformity of devices\n\n\n1.\u00a0\u00a0\u00a0Clinical investigations shall be designed, authorised, conducted, recorded and reported in accordance with the provisions of this Article\u00a0and of Articles\u00a063 to 80, the acts adopted pursuant to Article\u00a081, and Annex\u00a0XV, where carried out as part of the clinical evaluation for conformity assessment purposes, for one or more of the following purposes:\n\n\n\n\n\n\n(a)\n\n\nto establish and verify that, under normal conditions of use, a device is designed, manufactured and packaged in such a way that it is suitable for one or more of the specific purposes listed in point\u00a0(1) of Article\u00a02, and achieves the performance intended as specified by its manufacturer;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nto establish and verify the clinical benefits of a device as specified by its manufacturer;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nto establish and verify the clinical safety of the device and to determine any undesirable side-effects, under normal conditions of use of the device, and assess whether they constitute acceptable risks when weighed against the benefits to be achieved by the device.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0Where the sponsor of a clinical investigation is not established in the Union, that sponsor shall ensure that a natural or legal person is established in the Union as its legal representative. Such legal representative shall be responsible for ensuring compliance with the sponsor's obligations pursuant to this Regulation, and shall be the addressee for all communications with the sponsor provided for in this Regulation. Any communication with that legal representative shall be deemed to be a communication with the sponsor.\nMember\u00a0States may choose not to apply the first subparagraph\u00a0to clinical investigations to be conducted solely on their territory, or on their territory and the territory of a third country, provided that they ensure that the sponsor establishes at least a contact person on their territory in respect of that clinical investigation who shall be the addressee for all communications with the sponsor provided for in this Regulation.\n\n\n3.\u00a0\u00a0\u00a0Clinical investigations shall be designed and conducted in such a way that the rights, safety, dignity and well-being of the subjects participating in a clinical investigation are protected and prevail over all other interests and the clinical data generated are scientifically valid, reliable and robust.\nClinical investigations shall be subject to scientific and ethical review. The ethical review shall be performed by an ethics committee in accordance with national law. Member\u00a0States shall ensure that the procedures for review by ethics committees are compatible with the procedures set out in this Regulation for the assessment of the application for authorisation of a clinical investigation. At least one lay person shall participate in the ethical review.\n\n\n4.\u00a0\u00a0\u00a0A clinical investigation as referred to in paragraph\u00a01 may be conducted only where all of the following conditions are met:\n\n\n\n\n\n\n(a)\n\n\nthe clinical investigation is the subject of an authorisation by the Member\u00a0State(s) in which the clinical investigation is to be conducted, in accordance with this Regulation, unless otherwise stated;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nan ethics committee, set up in accordance with national law, has not issued a negative opinion in relation to the clinical investigation, which is valid for that entire Member\u00a0State under its national law;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe sponsor, or its legal representative or a contact person pursuant to paragraph\u00a02, is established in the Union;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nvulnerable populations and subjects are appropriately protected in accordance with Articles\u00a064 to 68;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe anticipated benefits to the subjects or to public health justify the foreseeable risks and inconveniences and compliance with this condition is constantly monitored;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe subject or, where the subject is not able to give informed consent, his or her legally designated representative has given informed consent in accordance with Article\u00a063;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthe subject or, where the subject is not able to give informed consent, his or her legally designated representative, has been provided with the contact details of an entity where further information can be received in case of need;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe rights of the subject to physical and mental integrity, to privacy and to the protection of the data concerning him or her in accordance with Directive\u00a095/46/EC are safeguarded;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nthe clinical investigation has been designed to involve as little pain, discomfort, fear and any other foreseeable risk as possible for the subjects, and both the risk threshold and the degree of distress are specifically defined in the clinical investigation plan and constantly monitored;\n\n\n\n\n\n\n\n\n\n\n(j)\n\n\nthe medical care provided to the subjects is the responsibility of an appropriately qualified medical doctor or, where appropriate, a qualified dental practitioner or any other person entitled by national law to provide the relevant patient care under clinical investigation conditions;\n\n\n\n\n\n\n\n\n\n\n(k)\n\n\nno undue influence, including that of a financial nature, is exerted on the subject, or, where applicable, on his or her legally designated representatives, to participate in the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(l)\n\n\nthe investigational device(s) in question conform(s) to the applicable general safety and performance requirements set out in Annex\u00a0I apart from the aspects covered by the clinical investigation and that, with regard to those aspects, every precaution has been taken to protect the health and safety of the subjects. This includes, where appropriate, technical and biological safety testing and pre-clinical evaluation, as well as provisions in the field of occupational safety and accident prevention, taking into consideration the state of the art;\n\n\n\n\n\n\n\n\n\n\n(m)\n\n\nthe requirements of Annex\u00a0XV are fulfilled.\n\n\n\n\n\n\n5.\u00a0\u00a0\u00a0Any subject, or, where the subject is not able to give informed consent, his or her legally designated representative, may, without any resulting detriment and without having to provide any justification, withdraw from the clinical investigation at any time by revoking his or her informed consent. Without prejudice to Directive\u00a095/46/EC, the withdrawal of the informed consent shall not affect the activities already carried out and the use of data obtained based on informed consent before its withdrawal.\n\n\n6.\u00a0\u00a0\u00a0The investigator shall be a person exercising a profession which is recognised in the Member\u00a0State concerned as qualifying for the role of investigator on account of having the necessary scientific knowledge and experience in patient care. Other personnel involved in conducting a clinical investigation shall be suitably qualified, by education, training or experience in the relevant medical field and in clinical research methodology, to perform their tasks.\n\n\n7.\u00a0\u00a0\u00a0The facilities where the clinical investigation is to be conducted shall be suitable for the clinical investigation and shall be similar to the facilities where the device is intended to be used.\n\n\n\nArticle\u00a063\n\nInformed consent\n\n\n1.\u00a0\u00a0\u00a0Informed consent shall be written, dated and signed by the person performing the interview referred to in point\u00a0(c) of paragraph\u00a02, and by the subject or, where the subject is not able to give informed consent, his or her legally designated representative after having been duly informed in accordance with paragraph\u00a02. Where the subject is unable to write, consent may be given and recorded through appropriate alternative means in the presence of at least one impartial witness. In that case, the witness shall sign and date the informed consent document. The subject or, where the subject is not able to give informed consent, his or her legally designated representative shall be provided with a copy of the document or the record, as appropriate, by which informed consent has been given. The informed consent shall be documented. Adequate time shall be given for the subject or his or her legally designated representative to consider his or her decision to participate in the clinical investigation.\n\n\n2.\u00a0\u00a0\u00a0Information given to the subject or, where the subject is not able to give informed consent, his or her legally designated representative for the purposes of obtaining his or her informed consent shall:\n\n\n\n\n\n\n(a)\n\n\nenable the subject or his or her legally designated representative to understand:\n\n\n\n\n\n\n(i)\n\n\nthe nature, objectives, benefits, implications, risks and inconveniences of the clinical investigations;\n\n\n\n\n\n\n\n\n\n\n(ii)\n\n\nthe subject's rights and guarantees regarding his or her protection, in particular his or her right to refuse to participate in and the right to withdraw from the clinical investigation at any time without any resulting detriment and without having to provide any justification;\n\n\n\n\n\n\n\n\n\n\n(iii)\n\n\nthe conditions under which the clinical investigations is to be conducted, including the expected duration of the subject's participation in the clinical investigation; and\n\n\n\n\n\n\n\n\n\n\n(iv)\n\n\nthe possible treatment alternatives, including the follow-up measures if the participation of the subject in the clinical investigation is discontinued;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nbe kept comprehensive, concise, clear, relevant, and understandable to the subject or his or her legally designated representative;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nbe provided in a prior interview with a member of the investigating team who is appropriately qualified under national law;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\ninclude information about the applicable damage compensation system referred to in Article\u00a069; and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\ninclude the Union-wide unique single identification number of the clinical investigation referred to in Article\u00a070(1) and information about the availability of the clinical investigation results in accordance with paragraph\u00a06 of this Article.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0The information referred to in paragraph\u00a02 shall be prepared in writing and be available to the subject or, where the subject is not able to give informed consent, his or her legally designated representative.\n\n\n4.\u00a0\u00a0\u00a0In the interview referred to in point\u00a0(c) of paragraph\u00a02, special attention shall be paid to the information needs of specific patient populations and of individual subjects, as well as to the methods used to give the information.\n\n\n5.\u00a0\u00a0\u00a0In the interview referred to in point\u00a0(c) of paragraph\u00a02, it shall be verified that the subject has understood the information.\n\n\n6.\u00a0\u00a0\u00a0The subject shall be informed that a clinical investigation report and a summary presented in terms understandable to the intended user will be made available pursuant to Article\u00a077(5) in the electronic system on clinical investigations referred to in Article\u00a073 irrespective of the outcome of the clinical investigation, and shall be informed, to the extent possible, when they have become available.\n\n\n7.\u00a0\u00a0\u00a0This Regulation is without prejudice to national law requiring that, in addition to the informed consent given by the legally designated representative, a minor who is capable of forming an opinion and assessing the information given to him or her, shall also assent in order to participate in a clinical investigation.\n\n\n\nArticle\u00a064\n\nClinical investigations on incapacitated subjects\n\n\n1.\u00a0\u00a0\u00a0In the case of incapacitated subjects who have not given, or have not refused to give, informed consent before the onset of their incapacity, a clinical investigation may be conducted only where, in addition to the conditions set out in Article\u00a062(4), all of the following conditions are met:\n\n\n\n\n\n\n(a)\n\n\nthe informed consent of their legally designated representative has been obtained;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe incapacitated subjects have received the information referred to in Article\u00a063(2) in a way that is adequate in view of their capacity to understand it;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe explicit wish of an incapacitated subject who is capable of forming an opinion and assessing the information referred to in Article\u00a063(2) to refuse participation in, or to withdraw from, the clinical investigation at any time, is respected by the investigator;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nno incentives or financial inducements are given to subjects or their legally designated representatives, except for compensation for expenses and loss of earnings directly related to the participation in the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe clinical investigation is essential with respect to incapacitated subjects and data of comparable validity cannot be obtained in clinical investigations on persons able to give informed consent, or by other research methods;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe clinical investigation relates directly to a medical condition from which the subject suffers;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthere are scientific grounds for expecting that participation in the clinical investigation will produce a direct benefit to the incapacitated subject outweighing the risks and burdens involved.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The subject shall as far as possible take part in the informed consent procedure.\n\n\n\nArticle\u00a065\n\nClinical investigations on minors\n\nA clinical investigation on minors may be conducted only where, in addition to the conditions set out in Article\u00a062(4), all of the following conditions are met:\n\n\n\n\n\n\n(a)\n\n\nthe informed consent of their legally designated representative has been obtained;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe minors have received the information referred to in Article\u00a063(2) in a way adapted to their age and mental maturity and from investigators or members of the investigating team who are trained or experienced in working with children;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe explicit wish of a minor who is capable of forming an opinion and assessing the information referred to in Article\u00a063(2) to refuse participation in, or to withdraw from, the clinical investigation at any time, is respected by the investigator;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nno incentives or financial inducements are given to the subject or his or her legally designated representative except for compensation for expenses and loss of earnings directly related to the participation in the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe clinical investigation is intended to investigate treatments for a medical condition that only occurs in minors or the clinical investigation is essential with respect to minors to validate data obtained in clinical investigations on persons able to give informed consent or by other research methods;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe clinical investigation either relates directly to a medical condition from which the minor concerned suffers or is of such a nature that it can only be carried out on minors;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthere are scientific grounds for expecting that participation in the clinical investigation will produce a direct benefit to the minor subject outweighing the risks and burdens involved;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe minor shall take part in the informed consent procedure in a way adapted to his or her age and mental maturity;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nif during a clinical investigation the minor reaches the age of legal competence to give informed consent as defined in national law, his or her express informed consent shall be obtained before that subject can continue to participate in the clinical investigation.\n\n\n\n\n\n\nArticle\u00a066\n\nClinical investigations on pregnant or breastfeeding women\n\nA clinical investigation on pregnant or breastfeeding women may be conducted only where, in addition to the conditions set out in Article\u00a062(4), all of the following conditions are met:\n\n\n\n\n\n\n(a)\n\n\nthe clinical investigation has the potential to produce a direct benefit for the pregnant or breastfeeding woman concerned, or her embryo, foetus or child after birth, outweighing the risks and burdens involved;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nwhere research is undertaken on breastfeeding women, particular care is taken to avoid any adverse impact on the health of the child;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nno incentives or financial inducements are given to the subject except for compensation for expenses and loss of earnings directly related to the participation in the clinical investigation.\n\n\n\n\n\n\nArticle\u00a067\n\nAdditional national measures\n\nMember\u00a0States may maintain additional measures regarding persons performing mandatory military service, persons deprived of liberty, persons who, due to a judicial decision, cannot take part in clinical investigations, or persons in residential care institutions.\n\n\nArticle\u00a068\n\nClinical investigations in emergency situations\n\n\n1.\u00a0\u00a0\u00a0By way of derogation from point\u00a0(f) of Article\u00a062(4), from points (a) and (b) of Article\u00a064(1) and from points (a) and (b) of Article\u00a065, informed consent to participate in a clinical investigation may be obtained, and information on the clinical investigation may be given, after the decision to include the subject in the clinical investigation, provided that that decision is taken at the time of the first intervention on the subject, in accordance with the clinical investigation plan for that clinical investigation and that all of the following conditions are fulfilled:\n\n\n\n\n\n\n(a)\n\n\ndue to the urgency of the situation, caused by a sudden life-threatening or other sudden serious medical condition, the subject is unable to provide prior informed consent and to receive prior information on the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthere are scientific grounds to expect that participation of the subject in the clinical investigation will have the potential to produce a direct clinically relevant benefit for the subject resulting in a measurable health-related improvement alleviating the suffering and/or improving the health of the subject, or in the diagnosis of its condition;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nit is not possible within the therapeutic window to supply all prior information to and obtain prior informed consent from his or her legally designated representative;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe investigator certifies that he or she is not aware of any objections to participate in the clinical investigation previously expressed by the subject;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe clinical investigation relates directly to the subject's medical condition because of which it is not possible within the therapeutic window to obtain prior informed consent from the subject or from his or her legally designated representative and to supply prior information, and the clinical investigation is of such a nature that it may be conducted exclusively in emergency situations;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe clinical investigation poses a minimal risk to, and imposes a minimal burden on, the subject in comparison with the standard treatment of the subject's condition.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0Following an intervention pursuant to paragraph\u00a01 of this Article, informed consent in accordance with Article\u00a063 shall be sought to continue the participation of the subject in the clinical investigation, and information on the clinical investigation shall be given, in accordance with the following requirements:\n\n\n\n\n\n\n(a)\n\n\nregarding incapacitated subjects and minors, the informed consent shall be sought by the investigator from his or her legally designated representative without undue delay and the information referred to in Article\u00a063(2) shall be given as soon as possible to the subject and to his or her legally designated representative;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nregarding other subjects, the informed consent shall be sought by the investigator without undue delay from the subject or his or her legally designated representative, whichever can be done sooner, and the information referred to in Article\u00a063(2) shall be given as soon as possible to the subject or his or her legally designated representative, as applicable.\n\n\n\n\nFor the purposes of point\u00a0(b) where informed consent has been obtained from the legally designated representative, informed consent to continue the participation in the clinical investigation shall be obtained from the subject as soon as he or she is capable of giving informed consent.\n\n\n3.\u00a0\u00a0\u00a0If the subject or, where applicable, his or her legally designated representative does not give consent, he or she shall be informed of the right to object to the use of data obtained from the clinical investigation.\n\n\n\nArticle\u00a069\n\nDamage compensation\n\n\n1.\u00a0\u00a0\u00a0Member\u00a0States shall ensure that systems for compensation for any damage suffered by a subject resulting from participation in a clinical investigation conducted on their territory are in place in the form of insurance, a guarantee, or a similar arrangement that is equivalent as regards its purpose and which is appropriate to the nature and the extent of the risk.\n\n\n2.\u00a0\u00a0\u00a0The sponsor and the investigator shall make use of the system referred to in paragraph\u00a01 in the form appropriate for the Member\u00a0State in which the clinical investigation is conducted.\n\n\n\nArticle\u00a070\n\nApplication for clinical investigations\n\n\n1.\u00a0\u00a0\u00a0The sponsor of a clinical investigation shall submit an application to the Member\u00a0State(s) in which the clinical investigation is to be conducted (referred to for the purposes of this Article\u00a0as \u2018Member\u00a0State concerned\u2019) accompanied by the documentation referred to in Chapter II of Annex\u00a0XV.\nThe application shall be submitted by means of the electronic system referred to in Article\u00a073, which shall generate a Union-wide unique single identification number for the clinical investigation, which shall be used for all relevant communication in relation to that clinical investigation. Within 10 days of it receiving the application, the Member\u00a0State concerned shall notify the sponsor as to whether the clinical investigation falls within the scope of this Regulation and as to whether the application dossier is complete in accordance with Chapter II of Annex\u00a0XV.\n\n\n2.\u00a0\u00a0\u00a0Within one week of any change occurring in relation to the documentation referred to in Chapter II of Annex\u00a0XV, the sponsor shall update the relevant data in the electronic system referred to in Article\u00a073 and make that change to the documentation clearly identifiable. The Member\u00a0State concerned shall be notified of the update by means of that electronic system.\n\n\n3.\u00a0\u00a0\u00a0Where the Member\u00a0State concerned finds that the clinical investigation applied for does not fall within the scope of this Regulation or that the application dossier is not complete, it shall inform the sponsor thereof and shall set a time limit of maximum 10 days for the sponsor to comment or to complete the application by means of the electronic system referred to in Article\u00a073. The Member\u00a0State concerned may extend this period by a maximum of 20 days where appropriate.\nWhere the sponsor has not provided comments nor completed the application within the time limit referred to in the first subparagraph, the application shall be deemed to have lapsed. Where the sponsor considers the application does fall under the scope of this Regulation and/or is complete but the Member\u00a0State concerned does not, the application shall be considered to have been rejected. The Member\u00a0State concerned shall provide for an appeal procedure in respect of such refusal.\nThe Member\u00a0State concerned shall notify the sponsor within five days of receipt of the comments or of the requested additional information, whether the clinical investigation is considered as falling within the scope of this Regulation and the application is complete.\n\n\n4.\u00a0\u00a0\u00a0The Member\u00a0State concerned may also extend the period referred to in paragraph\u00a01 and\u00a03 each by a further five\u00a0days.\n\n\n5.\u00a0\u00a0\u00a0For the purposes of this Chapter, the date on which the sponsor is notified in accordance with paragraph\u00a01 or 3 shall be the validation date of the application. Where the sponsor is not notified, the validation date shall be the last day of the periods referred to in paragraphs\u00a01, 3 and 4 respectively.\n\n\n6.\u00a0\u00a0\u00a0During the period when the application is being assessed, the Member\u00a0State may request additional information from the sponsor. The expiry of the period laid down in point\u00a0(b) of paragraph\u00a07 shall be suspended from the date of the first request until such time as the additional information has been received.\n\n\n7.\u00a0\u00a0\u00a0The sponsor may start the clinical investigation in the following circumstances:\n\n\n\n\n\n\n(a)\n\n\nin the case of investigational class I devices or in the case of non-invasive class\u00a0IIa and class\u00a0IIb devices, unless otherwise stated by national law, immediately after the validation date of the application pursuant to paragraph\u00a05, and provided that a negative opinion which is valid for the entire Member\u00a0State, under national law, has not been issued by an ethics committee in the Member\u00a0State concerned in respect of the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nin the case of investigational devices, other than those referred to in point\u00a0(a), as soon as the Member\u00a0State concerned has notified the sponsor of its authorisation, and provided that a negative opinion which is valid for the entire Member\u00a0State, under national law, has not been issued by an ethics committee in the Member\u00a0State concerned in respect of the clinical investigation. The Member\u00a0State shall notify the sponsor of the authorisation within 45\u00a0days of the validation date referred to in paragraph\u00a05. The Member\u00a0State may extend this period by a further 20\u00a0days for the purpose of consulting with experts.\n\n\n\n\n\n\n8.\u00a0\u00a0\u00a0The Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 amending, in the light of technical progress and global regulatory developments, the requirements laid down in Chapter\u00a0II of Annex\u00a0XV.\n\n\n9.\u00a0\u00a0\u00a0In order to ensure the uniform application of the requirements laid down in Chapter\u00a0II of Annex\u00a0XV, the Commission may adopt implementing acts to the extent necessary to resolve issues of divergent interpretation and of practical application. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a071\n\nAssessment by Member\u00a0States\n\n\n1.\u00a0\u00a0\u00a0Member\u00a0States shall ensure that the persons validating and assessing the application, or deciding on it, do not have conflicts of interest, are independent of the sponsor, the investigators involved and of natural or legal persons financing the clinical investigation, as well as free of any other undue influence.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States shall ensure that the assessment is done jointly by an appropriate number of persons who collectively have the necessary qualifications and experience.\n\n\n3.\u00a0\u00a0\u00a0Member\u00a0States shall assess whether the clinical investigation is designed in such a way that potential remaining risks to subjects or third persons, after risk minimization, are justified, when weighed against the clinical benefits to be expected. They shall, while taking into account applicable CS or harmonised standards, examine in particular:\n\n\n\n\n\n\n(a)\n\n\nthe demonstration of compliance of the investigational device(s) with the applicable general safety and performance requirements, apart from the aspects covered by the clinical investigation, and whether, with regard to those aspects, every precaution has been taken to protect the health and safety of the subjects. This includes, where appropriate, assurance of technical and biological safety testing and pre-clinical evaluation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nwhether the risk-minimisation solutions employed by the sponsor are described in harmonised standards and, in those cases where the sponsor does not use harmonised standards, whether the risk-minimisation solutions provide a level of protection that is equivalent to that provided by harmonised standards;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nwhether the measures planned for the safe installation, putting into service and maintenance of the investigational device are adequate;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe reliability and robustness of the data generated in the clinical investigation, taking account of statistical approaches, design of the investigation and methodological aspects, including sample size, comparator and endpoints;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nwhether the requirements of Annex\u00a0XV are met;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nin the case of devices for sterile use, evidence of the validation of the manufacturer's sterilisation procedures or information on the reconditioning and sterilisation procedures which have to be conducted by the investigation site;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthe demonstration of the safety, quality and usefulness of any components of animal or human origin or of substances, which may be considered medicinal products in accordance with Directive\u00a02001/83/EC.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0Member\u00a0States shall refuse the authorisation of the clinical investigation if:\n\n\n\n\n\n\n(a)\n\n\nthe application dossier submitted pursuant to Article\u00a070(1) remains incomplete;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe device or the submitted documents, especially the investigation plan and the investigator's brochure, do not correspond to the state of scientific knowledge, and the clinical investigation, in particular, is not suitable for providing evidence for the safety, performance characteristics or benefit of the device on subjects or patients,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe requirements of Article\u00a062 are not met, or\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nany assessment under paragraph\u00a03 is negative.\n\n\n\n\nMember\u00a0States shall provide for an appeal procedure in respect of a refusal pursuant to the first subparagraph.\n\n\n\nArticle\u00a072\n\nConduct of a clinical investigation\n\n\n1.\u00a0\u00a0\u00a0The sponsor and the investigator shall ensure that the clinical investigation is conducted in accordance with the approved clinical investigation plan.\n\n\n2.\u00a0\u00a0\u00a0In order to verify that the rights, safety and well-being of subjects are protected, that the reported data are reliable and robust, and that the conduct of the clinical investigation is in compliance with the requirements of this Regulation, the sponsor shall ensure adequate monitoring of the conduct of a clinical investigation. The extent and nature of the monitoring shall be determined by the sponsor on the basis of an assessment that takes into consideration all characteristics of the clinical investigation including the following:\n\n\n\n\n\n\n(a)\n\n\nthe objective and methodology of the clinical investigation; and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe degree of deviation of the intervention from normal clinical practice.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0All clinical investigation information shall be recorded, processed, handled, and stored by the sponsor or investigator, as applicable, in such a way that it can be accurately reported, interpreted and verified while the confidentiality of records and the personal data of the subjects remain protected in accordance with the applicable law on personal data protection.\n\n\n4.\u00a0\u00a0\u00a0Appropriate technical and organisational measures shall be implemented to protect information and personal data processed against unauthorised or unlawful access, disclosure, dissemination, alteration, or destruction or accidental loss, in particular where the processing involves transmission over a network.\n\n\n5.\u00a0\u00a0\u00a0Member\u00a0States shall inspect, at an appropriate level, investigation site(s) to check that clinical investigations are conducted in accordance with the requirements of this Regulation and with the approved investigation plan.\n\n\n6.\u00a0\u00a0\u00a0The sponsor shall establish a procedure for emergency situations which enables the immediate identification and, where necessary, an immediate recall of the devices used in the investigation.\n\n\n\nArticle\u00a073\n\nElectronic system on clinical investigations\n\n\n1.\u00a0\u00a0\u00a0The Commission shall, in collaboration with the Member\u00a0States, set up, manage and maintain an electronic system:\n\n\n\n\n\n\n(a)\n\n\nto create the single identification numbers for clinical investigations referred to in Article\u00a070(1);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nto be used as an entry point for the submission of all applications or notifications for clinical investigations referred to in Articles\u00a070, 74, 75 and 78 and for all other submission of data, or processing of data in this context;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nfor the exchange of information relating to clinical investigations in accordance with this Regulation between the Member\u00a0States and between them and the Commission including the exchange of information referred to in Articles\u00a070 and\u00a076;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nfor information to be provided by the sponsor in accordance with Article\u00a077, including the clinical investigation report and its summary as required in paragraph\u00a05 of that Article;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nfor reporting on serious adverse events and device deficiencies and related updates referred to in Article\u00a080.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0When setting up the electronic system referred in paragraph\u00a01 of this Article, the Commission shall ensure that it is interoperable with the EU database for clinical trials on medicinal products for human use set up in accordance with Article\u00a081 of Regulation\u00a0(EU)\u00a0No\u00a0536/2014 of the European Parliament and of the Council\u00a0(37) as concerns combined clinical investigations of devices with a clinical trial under that Regulation.\n\n\n3.\u00a0\u00a0\u00a0The information referred to in point\u00a0(c) of paragraph\u00a01 shall only be accessible to the Member\u00a0States and the Commission. The information referred to in the other points of that paragraph\u00a0shall be accessible to the public, unless, for all or parts of that information, confidentiality of the information is justified on any of the following grounds:\n\n\n\n\n\n\n(a)\n\n\nprotection of personal data in accordance with Regulation\u00a0(EC)\u00a0No\u00a045/2001;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nprotection of commercially confidential information, especially in the investigators brochure, in particular through taking into account the status of the conformity assessment for the device, unless there is an overriding public interest in disclosure;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\neffective supervision of the conduct of the clinical investigation by the Member\u00a0State(s) concerned.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0No\u00a0personal data of subjects shall be publicly available.\n\n\n5.\u00a0\u00a0\u00a0The user interface of the electronic system referred to in paragraph\u00a01 shall be available in all official languages of the Union.\n\n\n\nArticle\u00a074\n\nClinical investigations regarding devices bearing the CE marking\n\n\n1.\u00a0\u00a0\u00a0Where a clinical investigation is to be conducted to further assess, within the scope of its intended purpose, a device which already bears the CE marking in accordance with Article\u00a020(1), (\u2018PMCF investigation\u2019), and where the investigation would involve submitting subjects to procedures additional to those performed under the normal conditions of use of the device and those additional procedures are invasive or burdensome, the sponsor shall notify the Member\u00a0States concerned at least 30 days prior to its commencement by means of the electronic system referred to in Article\u00a073. The sponsor shall include the documentation referred to in Chapter II of Annex\u00a0XV as part of the notification. Points (b) to (k) and (m) of Article\u00a062(4), Article\u00a075, Article\u00a076, Article\u00a077, Article\u00a080(5) and the relevant provisions of Annex\u00a0XV shall apply to PMCF\u00a0investigations.\n\n\n2.\u00a0\u00a0\u00a0Where a clinical investigation is to be conducted to assess, outside the scope of its intended purpose, a device which already bears the CE marking in accordance with Article\u00a020(1), Articles\u00a062 to 81 shall apply.\n\n\n\nArticle\u00a075\n\nSubstantial modifications to clinical investigations\n\n\n1.\u00a0\u00a0\u00a0If a sponsor intends to introduce modifications to a clinical investigation that are likely to have a substantial impact on the safety, health or rights of the subjects or on the robustness or reliability of the clinical data generated by the investigation, it shall notify, within one week, by means of the electronic system referred to in Article\u00a073 the Member\u00a0State(s) in which the clinical investigation is being or is to be conducted of the reasons for and the nature of those modifications. The sponsor shall include an updated version of the relevant documentation referred to in Chapter\u00a0II of Annex\u00a0XV as part of the notification. Changes to the relevant documentation shall be clearly identifiable.\n\n\n2.\u00a0\u00a0\u00a0The Member\u00a0State shall assess any substantial modification to the clinical investigation in accordance with the procedure laid down in Article\u00a071.\n\n\n3.\u00a0\u00a0\u00a0The sponsor may implement the modifications referred to in paragraph\u00a01 at the earliest 38\u00a0days after the notification referred to in that paragraph, unless:\n\n\n\n\n\n\n(a)\n\n\nthe Member\u00a0State in which the clinical investigation is being or is to be conducted has notified the sponsor of its refusal based on the grounds referred to in Article\u00a071(4) or on considerations of public health, subject and user safety or health, of public policy, or\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nan ethics committee in that Member\u00a0State has issued a negative opinion in relation to the substantial modification to the clinical investigation, which, in accordance with national law, is valid for that entire Member\u00a0State.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0The Member\u00a0State(s) concerned may extend the period referred to in paragraph\u00a03 by a further seven days, for the purpose of consulting with experts.\n\n\n\nArticle\u00a076\n\nCorrective measures to be taken by Member\u00a0States and information exchange between Member\u00a0States\n\n\n1.\u00a0\u00a0\u00a0Where a Member\u00a0State in which a clinical investigation is being or is to be conducted has grounds for considering that the requirements set out in this Regulation are not met, it may take at least any of the following measures on its territory:\n\n\n\n\n\n\n(a)\n\n\nrevoke the authorisation for the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nsuspend or terminate the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nrequire the sponsor to modify any aspect of the clinical investigation.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0Before the Member\u00a0State concerned takes any of the measures referred to in paragraph\u00a01 it shall, except where immediate action is required, ask the sponsor or the investigator or both for their opinion. That opinion shall be delivered within seven days.\n\n\n3.\u00a0\u00a0\u00a0Where a Member\u00a0State has taken a measure referred to in paragraph\u00a01 of this Article\u00a0or has refused a clinical investigation, or has been notified by the sponsor of the early termination of a clinical investigation on safety grounds, that Member\u00a0State shall communicate the corresponding decision and the grounds therefor to all Member\u00a0States and the Commission by means of the electronic system referred to in Article\u00a073.\n\n\n4.\u00a0\u00a0\u00a0Where an application is withdrawn by the sponsor prior to a decision by a Member\u00a0State, that information shall be made available through the electronic system referred to in Article\u00a073 to all Member\u00a0States and the Commission.\n\n\n\nArticle\u00a077\n\nInformation from the sponsor at the end of a clinical investigation or in the event of a temporary halt or early termination\n\n\n1.\u00a0\u00a0\u00a0If the sponsor has temporarily halted a clinical investigation or has terminated a clinical investigation early, it shall inform within 15 days the Member\u00a0State in which that clinical investigation has been temporarily halted or terminated early, through the electronic system referred to in Article\u00a073, of the temporary halt or early termination, providing a justification. In the event that the sponsor has temporarily halted or terminated early the clinical investigation on safety grounds, it shall inform all Member\u00a0States in which that clinical investigation is being conducted thereof within 24 hours.\n\n\n2.\u00a0\u00a0\u00a0The end of a clinical investigation shall be deemed to coincide with the last visit of the last subject unless another point in time for such end is set out in the clinical investigation plan.\n\n\n3.\u00a0\u00a0\u00a0The sponsor shall notify each Member\u00a0State in which a clinical investigation was being conducted of the end of that clinical investigation in that Member\u00a0State. That notification shall be made within 15 days of the end of the clinical investigation in relation to that Member\u00a0State.\n\n\n4.\u00a0\u00a0\u00a0If an investigation is conducted in more than one Member\u00a0State, the sponsor shall notify all Member\u00a0States in which that clinical investigation was conducted of the end of the clinical investigation in all Member\u00a0States. That notification shall be made within 15 days of that end of the clinical investigation.\n\n\n5.\u00a0\u00a0\u00a0Irrespective of the outcome of the clinical investigation, within one year of the end of the clinical investigation or within three months of the early termination or temporary halt, the sponsor shall submit to the Member\u00a0States in which a clinical investigation was conducted a clinical investigation report as referred to in Section\u00a02.8 of Chapter I and Section\u00a07 of Chapter III of Annex\u00a0XV.\nThe clinical investigation report shall be accompanied by a summary presented in terms that are easily understandable to the intended user. Both the report and summary shall be submitted by the sponsor by means of the electronic system referred to in Article\u00a073.\nWhere, for scientific reasons, it is not possible to submit the clinical investigation report within one year of the end of the investigation, it shall be submitted as soon as it is available. In such case, the clinical investigation plan referred to in Section\u00a03 of Chapter\u00a0II of Annex\u00a0XV shall specify when the results of the clinical investigation are going to be available, together with a justification.\n\n\n6.\u00a0\u00a0\u00a0The Commission shall issue guidelines regarding the content and structure of the summary of the clinical investigation report.\nIn addition, the Commission may issue guidelines for the formatting and sharing of raw data, for cases where the sponsor decides to share raw data on a voluntary basis. Those guidelines may take as a basis and adapt, where possible, existing guidelines for sharing of raw data in the field of clinical investigations.\n\n\n7.\u00a0\u00a0\u00a0The summary and the clinical investigation report referred to in paragraph\u00a05 of this Article\u00a0shall become publicly accessible through the electronic system referred to in Article\u00a073, at the latest when the device is registered in accordance with Article\u00a029 and before it is placed on the market. In cases of early termination or temporary halt, the summary and the report shall become publicly accessible immediately after submission.\nIf the device is not registered in accordance with Article\u00a029 within one year of the summary and the report having been entered into the electronic system pursuant to paragraph\u00a05 of this Article, they shall become publicly accessible at that point in time.\n\n\n\nArticle\u00a078\n\nCoordinated assessment procedure for clinical investigations\n\n\n1.\u00a0\u00a0\u00a0By means of the electronic system referred to in Article\u00a073, the sponsor of a clinical investigation to be conducted in more than one Member\u00a0State may submit, for the purpose of Article\u00a070, a single application that, upon receipt, is transmitted electronically to all Member\u00a0States in which the clinical investigation is to be conducted.\n\n\n2.\u00a0\u00a0\u00a0The sponsor shall propose in the single application referred to in paragraph\u00a01 that one of the Member\u00a0States in which the clinical investigation is to be conducted acts as coordinating Member\u00a0State. The Member\u00a0States in which the clinical investigation is to be conducted shall, within six days of submission of the application, agree on one of them taking the role of the coordinating Member\u00a0State. If they do not agree on a coordinating Member\u00a0State, the coordinating Member\u00a0State proposed by the sponsor shall assume that role.\n\n\n3.\u00a0\u00a0\u00a0Under the direction of the coordinating Member\u00a0State referred to in paragraph\u00a02, the Member\u00a0States concerned shall coordinate their assessment of the application, in particular of the documentation referred to in Chapter II of Annex\u00a0XV.\nHowever, the completeness of the documentation referred to in Sections 1.13, 3.1.3, 4.2, 4.3 and 4.4 of Chapter II of Annex\u00a0XV shall be assessed separately by each Member\u00a0State concerned in accordance with Article\u00a070(1) to (5).\n\n\n4.\u00a0\u00a0\u00a0With regard to documentation other than that referred to in the second subparagraph\u00a0of paragraph\u00a03, the coordinating Member\u00a0State shall:\n\n\n\n\n\n\n(a)\n\n\nwithin six days of receipt of the single application, notify the sponsor that it is the coordinating Member\u00a0State (\u2018notification date\u2019);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nfor the purpose of the validation of the application, take into account any considerations submitted within seven days of the notification date by any Member\u00a0State concerned;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nwithin 10 days of the notification date, assess whether the clinical investigation falls within the scope of this Regulation and whether the application is complete, and shall notify the sponsor accordingly. Article\u00a070(1) and (3) to (5) shall apply to the coordinating Member\u00a0State in relation to that assessment;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nestablish the results of its assessment in a draft assessment report to be transmitted within 26\u00a0days of the validation date to the Member\u00a0States concerned. By day\u00a038 after the validation date, the other Member\u00a0States concerned shall transmit their comments and proposals on the draft assessment report and the underlying application to the coordinating Member\u00a0State which shall take due account of those comments and proposals in its finalisation of the final assessment report, to be transmitted within 45\u00a0days of the validation date to the sponsor and the other Member\u00a0States concerned.\n\n\n\n\nThe final assessment report shall be taken into account by all Member\u00a0States concerned when deciding on the sponsor's application in accordance with Article\u00a070(7).\n\n\n5.\u00a0\u00a0\u00a0As regards the assessment of the documentation referred to in the second subparagraph\u00a0of paragraph\u00a03, each Member\u00a0State concerned may request, on a single occasion, additional information from the sponsor. The sponsor shall submit the requested additional information within the period set by the Member\u00a0State concerned, which shall not exceed 12\u00a0days from the receipt of the request. The expiry of the last deadline pursuant to point\u00a0(d) of paragraph\u00a04 shall be suspended from the date of the request until such time as the additional information has been received.\n\n\n6.\u00a0\u00a0\u00a0For class\u00a0IIb and class\u00a0III devices, the coordinating Member\u00a0State may also extend the periods referred to in paragraph\u00a04 by a further 50 days, for the purpose of consulting with experts.\n\n\n7.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, further specify the procedures and timescales for coordinated assessments to be taken into account by Member\u00a0States concerned when deciding on the sponsor's application. Such implementing acts may also set out the procedures and timescales for coordinated assessment in the case of substantial modifications pursuant to paragraph\u00a012 of this Article, in the case of reporting of adverse events pursuant to Article\u00a080(4) and in the case of clinical investigations of combination products between medical devices and medicinal products, where the latter are under a concurrent coordinated assessment of a clinical trial under Regulation\u00a0(EU)\u00a0No\u00a0536/2014. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n8.\u00a0\u00a0\u00a0Where the conclusion of the coordinating Member\u00a0State concerning the area of coordinated assessment is that the conduct of the clinical investigation is acceptable or acceptable subject to compliance with specific conditions, that conclusion shall be deemed to be the conclusion of all Member\u00a0States concerned.\nNotwithstanding the first subparagraph, a Member\u00a0State concerned may only disagree with the conclusion of the coordinating Member\u00a0State concerning the area of coordinated assessment on the following grounds:\n\n\n\n\n\n\n(a)\n\n\nwhen it considers that participation in the clinical investigation would lead to a subject receiving treatment inferior to that received in normal clinical practice in that Member\u00a0State concerned;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ninfringement of national law; or\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nconsiderations as regards subject safety and data reliability and robustness submitted under point\u00a0(b) of paragraph\u00a04.\n\n\n\n\nWhere one of the Member\u00a0States concerned disagrees with the conclusion on the basis of the second subparagraph\u00a0of this paragraph, it shall communicate its disagreement, together with a detailed justification, through the electronic system referred to in Article\u00a073, to the Commission, to all other Member\u00a0States concerned and to the sponsor.\n\n\n9.\u00a0\u00a0\u00a0Where the conclusion of the coordinating Member\u00a0State concerning the area of coordinated assessment is that the clinical investigation is not acceptable, that conclusion shall be deemed to be the conclusion of all Member\u00a0States concerned.\n\n\n10.\u00a0\u00a0\u00a0A Member\u00a0State concerned shall refuse to authorise a clinical investigation if it disagrees with the conclusion of the coordinating Member\u00a0State as regards any of the grounds referred to in the second subparagraph\u00a0of paragraph\u00a08, or if it finds, on duly justified grounds, that the aspects addressed in Sections 1.13, 3.1.3, 4.2, 4.3 and 4.4 of Chapter\u00a0II of Annex\u00a0XV are not complied with, or where an ethics committee has issued a negative opinion in relation to that clinical investigation, which is valid, in accordance with national law, for that entire Member\u00a0State. That Member\u00a0State shall provide for an appeal procedure in respect of such refusal.\n\n\n11.\u00a0\u00a0\u00a0Each Member\u00a0State concerned shall notify the sponsor through the electronic system referred to in Article\u00a073 as to whether the clinical investigation is authorised, whether it is authorised subject to conditions, or whether authorisation has been refused. Notification shall be done by way of one single decision within five days of the transmission, pursuant to point\u00a0(d) of paragraph\u00a04, by the coordinating Member\u00a0State of the final assessment report. Where an authorisation of a clinical investigation is subject to conditions, those conditions may only be such that, by their nature, they cannot be fulfilled at the time of that authorisation.\n\n\n12.\u00a0\u00a0\u00a0Any substantial modifications as referred to in Article\u00a075 shall be notified to the Member\u00a0States concerned by means of the electronic system referred to in Article\u00a073. Any assessment as to whether there are grounds for disagreement as referred to in the second subparagraph\u00a0of paragraph\u00a08 of this Article\u00a0shall be carried out under the direction of the coordinating Member\u00a0State, except for substantial modifications concerning Sections 1.13, 3.1.3, 4.2, 4.3 and 4.4 of Chapter II of Annex\u00a0XV, which shall be assessed separately by each Member\u00a0State concerned.\n\n\n13.\u00a0\u00a0\u00a0The Commission shall provide administrative support to the coordinating Member\u00a0State in the accomplishment of its tasks under this Chapter.\n\n\n14.\u00a0\u00a0\u00a0The procedure set out in this Article\u00a0shall, until 27 May 2027, be applied only by those of the Member\u00a0States in which the clinical investigation is to be conducted which have agreed to apply it. After 27 May 2027, all Member\u00a0States shall be required to apply that procedure.\n\n\n\nArticle\u00a079\n\nReview of coordinated assessment procedure\n\nBy 27 May 2026, the Commission shall submit to the European Parliament and to the Council a report on experience gained from the application of Article\u00a078 and, if necessary, propose a review of Article\u00a078(14) and point\u00a0(h) of Article\u00a0123(3).\n\n\nArticle\u00a080\n\nRecording and reporting of adverse events that occur during clinical investigations\n\n\n1.\u00a0\u00a0\u00a0The sponsor shall fully record all of the following:\n\n\n\n\n\n\n(a)\n\n\nany adverse event of a type identified in the clinical investigation plan as being critical to the evaluation of the results of that clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nany serious adverse event;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nany device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention had not occurred, or circumstances had been less fortunate;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nany new findings in relation to any event referred to in points (a) to (c).\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The sponsor shall report, without delay to all Member\u00a0States in which the clinical investigation is being conducted, all of the following by means of the electronic system referred to in Article\u00a073:\n\n\n\n\n\n\n(a)\n\n\nany serious adverse event that has a causal relationship with the investigational device, the comparator or the investigation procedure or where such causal relationship is reasonably possible;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nany device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention had not occurred, or circumstances had been less fortunate;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nany new findings in relation to any event referred to in points (a) and (b).\n\n\n\n\nThe period for reporting shall take account of the severity of the event. Where necessary to ensure timely reporting, the sponsor may submit an initial report that is incomplete followed up by a complete report.\nUpon request by any Member\u00a0State in which the clinical investigation is being conducted, the sponsor shall provide all information referred to in paragraph\u00a01.\n\n\n3.\u00a0\u00a0\u00a0The sponsor shall also report to the Member\u00a0States in which the clinical investigation is being conducted any event referred to in paragraph\u00a02 of this Article\u00a0that occurred in third countries in which a clinical investigation is performed under the same clinical investigation plan as the one applying to a clinical investigation covered by this Regulation by means of the electronic system referred to in Article\u00a073.\n\n\n4.\u00a0\u00a0\u00a0In the case of a clinical investigation for which the sponsor has used the single application referred to in Article\u00a078, the sponsor shall report any event as referred to in paragraph\u00a02 of this Article\u00a0by means of the electronic system referred to in Article\u00a073. Upon receipt, this report shall be transmitted electronically to all Member\u00a0States in which the clinical investigation is being conducted.\nUnder the direction of the coordinating Member\u00a0State referred to in Article\u00a078(2), the Member\u00a0States shall coordinate their assessment of serious adverse events and device deficiencies to determine whether to modify, suspend or terminate the clinical investigation or whether to revoke the authorisation for that clinical investigation.\nThis paragraph\u00a0shall not affect the rights of the other Member\u00a0States to perform their own evaluation and to adopt measures in accordance with this Regulation in order to ensure the protection of public health and patient safety. The coordinating Member\u00a0State and the Commission shall be kept informed of the outcome of any such evaluation and the adoption of any such measures.\n\n\n5.\u00a0\u00a0\u00a0In the case of PMCF investigations referred to in Article\u00a074(1), the provisions on vigilance laid down in Articles\u00a087 to 90 and in the acts adopted pursuant to Article\u00a091 shall apply instead of this Article.\n\n\n6.\u00a0\u00a0\u00a0Notwithstanding paragraph\u00a05, this Article\u00a0shall apply where a causal relationship between the serious adverse event and the preceding investigational procedure has been established.\n\n\n\nArticle\u00a081\n\nImplementing acts\n\nThe Commission may, by means of implementing acts, establish the detailed arrangements and procedural aspects necessary for the implementation of this Chapter as regards the following:\n\n\n\n\n\n\n(a)\n\n\nharmonised electronic forms for the application for clinical investigations and their assessment as referred to in Articles\u00a070 and 78, taking into account specific categories or groups of devices;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe functioning of the electronic system referred to in Article\u00a073;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nharmonised electronic forms for the notification of PMCF investigations as referred to in Article\u00a074(1), and of substantial modifications as referred to in Article\u00a075;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe exchange of information between Member\u00a0States as referred to in Article\u00a076;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nharmonised electronic forms for the reporting of serious adverse events and device deficiencies as referred to in Article\u00a080;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe timelines for the reporting of serious adverse events and device deficiencies, taking into account the severity of the event to be reported as referred to in Article\u00a080;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nuniform application of the requirements regarding the clinical evidence or data needed to demonstrate compliance with the general safety and performance requirements set out in Annex\u00a0I.\n\n\n\n\nThe implementing acts referred to in the first paragraph\u00a0shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\nArticle\u00a082\n\nRequirements regarding other clinical investigations\n\n\n1.\u00a0\u00a0\u00a0Clinical investigations, not performed pursuant to any of the purposes listed in Article\u00a062(1), shall comply with the provisions of Article\u00a062 (2) and (3), points (b), (c), (d), (f), (h), and (l) of Article\u00a062(4) and Article\u00a062(6).\n\n\n2.\u00a0\u00a0\u00a0In order to protect the rights, safety, dignity and well-being of subjects and the scientific and ethical integrity of clinical investigations not performed for any of the purposes listed in Article\u00a062(1), each Member\u00a0State shall define any additional requirements for such investigations, as appropriate for each Member\u00a0State concerned.\n\n\n\n\nCHAPTER VII\n\n\nPOST-MARKET SURVEILLANCE, VIGILANCE AND MARKET SURVEILLANCE\n\n\n\n\nSECTION 1\n\n\n\n\nPost-market surveillance\n\n\n\n\nArticle\u00a083\n\nPost-market surveillance system of the manufacturer\n\n\n1.\u00a0\u00a0\u00a0For each device, manufacturers shall plan, establish, document, implement, maintain and update a post-market surveillance system in a manner that is proportionate to the risk class and appropriate for the type of device. That system shall be an integral part of the manufacturer's quality management system referred to in Article\u00a010(9).\n\n\n2.\u00a0\u00a0\u00a0The post-market surveillance system shall be suited to actively and systematically gathering, recording and analysing relevant data on the quality, performance and safety of a device throughout its entire lifetime, and to drawing the necessary conclusions and to determining, implementing and monitoring any preventive and corrective actions.\n\n\n3.\u00a0\u00a0\u00a0Data gathered by the manufacturer's post-market surveillance system shall in particular be used:\n\n\n\n\n\n\n(a)\n\n\nto update the benefit-risk determination and to improve the risk management as referred to in Chapter I of Annex\u00a0I;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nto update the design and manufacturing information, the instructions for use and the labelling;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nto update the clinical evaluation;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nto update the summary of safety and clinical performance referred to in Article\u00a032;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nfor the identification of needs for preventive, corrective or field safety corrective action;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nfor the identification of options to improve the usability, performance and safety of the device;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nwhen relevant, to contribute to the post-market surveillance of other devices; and\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nto detect and report trends in accordance with Article\u00a088.\n\n\n\n\nThe technical documentation shall be updated accordingly.\n\n\n4.\u00a0\u00a0\u00a0If, in the course of the post-market surveillance, a need for preventive or corrective action or both is identified, the manufacturer shall implement the appropriate measures and inform the competent authorities concerned and, where applicable, the notified body. Where a serious incident is identified or a field safety corrective action is implemented, it shall be reported in accordance with Article\u00a087.\n\n\n\nArticle\u00a084\n\nPost-market surveillance plan\n\nThe post-market surveillance system referred to in Article\u00a083 shall be based on a post-market surveillance plan, the requirements for which are set out in Section\u00a01.1 of Annex\u00a0III. For devices other than custom-made devices, the post-market surveillance plan shall be part of the technical documentation specified in Annex\u00a0II.\n\n\nArticle\u00a085\n\nPost-market surveillance report\n\nManufacturers of class I devices shall prepare a post-market surveillance report summarising the results and conclusions of the analyses of the post-market surveillance data gathered as a result of the post-market surveillance plan referred to in Article\u00a084 together with a rationale and description of any preventive and corrective actions taken. The report shall be updated when necessary and made available to the competent authority upon request.\n\n\nArticle\u00a086\n\nPeriodic safety update report\n\n\n1.\u00a0\u00a0\u00a0Manufacturers of class IIa, class IIb and class III devices shall prepare a periodic safety update report (\u2018PSUR\u2019) for each device and where relevant for each category or group of devices summarising the results and conclusions of the analyses of the post-market surveillance data gathered as a result of the post-market surveillance plan referred to in Article\u00a084 together with a rationale and description of any preventive and corrective actions taken. Throughout the lifetime of the device concerned, that PSUR shall set out:\n\n\n\n\n\n\n(a)\n\n\nthe conclusions of the benefit-risk determination;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe main findings of the PMCF; and\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe volume of sales of the device and an estimate evaluation of the size and other characteristics of the population using the device and, where practicable, the usage frequency of the device.\n\n\n\n\nManufacturers of class IIb and class III devices shall update the PSUR at least annually. That PSUR shall, except in the case of custom-made devices, be part of the technical documentation as specified in Annexes\u00a0II and\u00a0III.\nManufacturers of class IIa devices shall update the PSUR when necessary and at least every two years. That PSUR shall, except in the case of custom-made devices, be part of the technical documentation as specified in Annexes\u00a0II and\u00a0III.\nFor custom-made devices, the PSUR shall be part of the documentation referred to in Section\u00a02 of Annex\u00a0XIII.\n\n\n2.\u00a0\u00a0\u00a0For class III devices or implantable devices, manufacturers shall submit PSURs by means of the electronic system referred to in Article\u00a092 to the notified body involved in the conformity assessment in accordance with Article\u00a052. The notified body shall review the report and add its evaluation to that electronic system with details of any action taken. Such PSURs and the evaluation by the notified body shall be made available to competent authorities through that electronic system.\n\n\n3.\u00a0\u00a0\u00a0For devices other than those referred to in paragraph\u00a02, manufacturers shall make PSURs available to the notified body involved in the conformity assessment and, upon request, to competent authorities.\n\n\n\n\n\nSECTION 2\n\n\n\n\nVigilance\n\n\n\n\nArticle\u00a087\n\nReporting of serious incidents and field safety corrective actions\n\n\n1.\u00a0\u00a0\u00a0Manufacturers of devices made available on the Union market, other than investigational devices, shall report, to the relevant competent authorities, in accordance with Articles\u00a092(5) and (7), the following:\n\n\n\n\n\n\n(a)\n\n\nany serious incident involving devices made available on the Union market, except expected side-effects which are clearly documented in the product information and quantified in the technical documentation and are subject to trend reporting pursuant to Article\u00a088;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nany field safety corrective action in respect of devices made available on the Union market, including any field safety corrective action undertaken in a third country in relation to a device which is also legally made available on the Union market, if the reason for the field safety corrective action is not limited to the device made available in the third country.\n\n\n\n\nThe reports referred to in the first subparagraph\u00a0shall be submitted through the electronic system referred to in Article\u00a092.\n\n\n2.\u00a0\u00a0\u00a0As a general rule, the period for the reporting referred to in paragraph\u00a01 shall take account of the severity of the serious incident.\n\n\n3.\u00a0\u00a0\u00a0Manufacturers shall report any serious incident as referred to in point\u00a0(a) of paragraph\u00a01 immediately after they have established the causal relationship between that incident and their device or that such causal relationship is reasonably possible and not later than 15\u00a0days after they become aware of the incident.\n\n\n4.\u00a0\u00a0\u00a0Notwithstanding paragraph\u00a03, in the event of a serious public health threat the report referred to in paragraph\u00a01 shall be provided immediately, and not later than 2 days after the manufacturer becomes aware of that threat.\n\n\n5.\u00a0\u00a0\u00a0Notwithstanding paragraph\u00a03, in the event of death or an unanticipated serious deterioration in a person's state of health the report shall be provided immediately after the manufacturer has established or as soon as it suspects a causal relationship between the device and the serious incident but not later than 10 days after the date on which the manufacturer becomes aware of the serious incident.\n\n\n6.\u00a0\u00a0\u00a0Where necessary to ensure timely reporting, the manufacturer may submit an initial report that is incomplete followed up by a complete report.\n\n\n7.\u00a0\u00a0\u00a0If, after becoming aware of a potentially reportable incident, the manufacturer is uncertain about whether the incident is reportable, it shall nevertheless submit a report within the timeframe required in accordance with paragraphs\u00a02 to 5.\n\n\n8.\u00a0\u00a0\u00a0Except in cases of urgency in which the manufacturer needs to undertake field safety corrective action immediately, the manufacturer shall, without undue delay, report the field safety corrective action referred to in point\u00a0(b) of paragraph\u00a01 in advance of the field safety corrective action being undertaken.\n\n\n9.\u00a0\u00a0\u00a0For similar serious incidents that occur with the same device or device type and for which the root cause has been identified or a field safety corrective action implemented or where the incidents are common and well documented, the manufacturer may provide periodic summary reports instead of individual serious incident reports, on condition that the coordinating competent authority referred to in Article\u00a089(9), in consultation with the competent authorities referred to in point\u00a0(a) of Article\u00a092(8), has agreed with the manufacturer on the format, content and frequency of the periodic summary reporting. Where a single competent authority is referred to in points (a) and (b) of Article\u00a092(8), the manufacturer may provide periodic summary reports following agreement with that competent authority.\n\n\n10.\u00a0\u00a0\u00a0The Member\u00a0States shall take appropriate measures such as organising targeted information campaigns, to encourage and enable healthcare professionals, users and patients to report to the competent authorities suspected serious incidents referred to in point\u00a0(a) of paragraph\u00a01.\nThe competent authorities shall record centrally at national level reports they receive from healthcare professionals, users and patients.\n\n\n11.\u00a0\u00a0\u00a0Where a competent authority of a Member\u00a0State obtains such reports on suspected serious incidents referred to in point\u00a0(a) of paragraph\u00a01 from healthcare professionals, users or patients, it shall take the necessary steps to ensure that the manufacturer of the device concerned is informed of the suspected serious incident without delay.\nWhere the manufacturer of the device concerned considers that the incident is a serious incident, it shall provide a report in accordance with paragraphs 1 to 5 of this Article\u00a0on that serious incident to the competent authority of the Member\u00a0State in which that serious incident occurred and shall take the appropriate follow-up action in accordance with Article\u00a089.\nWhere the manufacturer of the device concerned considers that the incident is not a serious incident or is an expected undesirable side-effect, which will be covered by trend reporting in accordance with Article\u00a088, it shall provide an explanatory statement. If the competent authority does not agree with the conclusion of the explanatory statement, it may require the manufacturer to provide a report in accordance with paragraphs 1 to 5 of this Article\u00a0and require it to ensure that appropriate follow-up action is taken in accordance with Article\u00a089.\n\n\n\nArticle\u00a088\n\nTrend reporting\n\n\n1.\u00a0\u00a0\u00a0Manufacturers shall report, by means of the electronic system referred to in Article\u00a092, any statistically significant increase in the frequency or severity of incidents that are not serious incidents or that are expected undesirable side-effects that could have a significant impact on the benefit-risk analysis referred to in Sections 1 and 5 of Annex\u00a0I and which have led or may lead to risks to the health or safety of patients, users or other persons that are unacceptable when weighed against the intended benefits. The significant increase shall be established in comparison to the foreseeable frequency or severity of such incidents in respect of the device, or category or group of devices, in question during a specific period as specified in the technical documentation and product information.\nThe manufacturer shall specify how to manage the incidents referred to in the first subparagraph\u00a0and the methodology used for determining any statistically significant increase in the frequency or severity of such incidents, as well as the observation period, in the post-market surveillance plan referred to in Article\u00a084.\n\n\n2.\u00a0\u00a0\u00a0The competent authorities may conduct their own assessments on the trend reports referred to in paragraph\u00a01 and require the manufacturer to adopt appropriate measures in accordance with this Regulation in order to ensure the protection of public health and patient safety. Each competent authority shall inform the Commission, the other competent authorities and the notified body that issued the certificate, of the results of such assessment and of the adoption of such measures.\n\n\n\nArticle\u00a089\n\nAnalysis of serious incidents and field safety corrective actions\n\n\n1.\u00a0\u00a0\u00a0Following the reporting of a serious incident pursuant to Article\u00a087(1), the manufacturer shall, without delay, perform the necessary investigations in relation to the serious incident and the devices concerned. This shall include a risk assessment of the incident and field safety corrective action taking into account criteria as referred to in paragraph\u00a03 of this Article\u00a0as appropriate.\nThe manufacturer shall co-operate with the competent authorities and where relevant with the notified body concerned during the investigations referred to in the first subparagraph\u00a0and shall not perform any investigation which involves altering the device or a sample of the batch concerned in a way which may affect any subsequent evaluation of the causes of the incident, prior to informing the competent authorities of such action.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States shall take the necessary steps to ensure that any information regarding a serious incident that has occurred within their territory, or a field safety corrective action that has been or is to be undertaken within their territory, and that is brought to their knowledge in accordance with Article\u00a087 is evaluated centrally at national level by their competent authority, if possible together with the manufacturer, and, where relevant, the notified body concerned.\n\n\n3.\u00a0\u00a0\u00a0In the context of the evaluation referred to in paragraph\u00a02, the competent authority shall evaluate the risks arising from the reported serious incident and evaluate any related field safety corrective actions, taking into account the protection of public health and criteria such as causality, detectability and probability of recurrence of the problem, frequency of use of the device, probability of occurrence of direct or indirect harm, the severity of that harm, the clinical benefit of the device, intended and potential users, and population affected. The competent authority shall also evaluate the adequacy of the field safety corrective action envisaged or undertaken by the manufacturer and the need for, and kind of, any other corrective action, in particular taking into account the principle of inherent safety contained in Annex\u00a0I.\nUpon request by the national competent authority, manufacturers shall provide all documents necessary for the risk assessment.\n\n\n4.\u00a0\u00a0\u00a0The competent authority shall monitor the manufacturer's investigation of a serious incident. Where necessary, a competent authority may intervene in a manufacturer's investigation or initiate an independent investigation.\n\n\n5.\u00a0\u00a0\u00a0The manufacturer shall provide a final report to the competent authority setting out its findings from the investigation by means of the electronic system referred to in Article\u00a092. The report shall set out conclusions and where relevant indicate corrective actions to be taken.\n\n\n6.\u00a0\u00a0\u00a0In the case of devices referred to in the first subparagraph\u00a0of Article\u00a01(8) and where the serious incident or field safety corrective action may be related to a substance which, if used separately, would be considered to be a medicinal product, the evaluating competent authority or the coordinating competent authority referred to in paragraph\u00a09 of this Article\u00a0shall, inform the national competent authority or the EMA, depending on which issued the scientific opinion on that substance under Article\u00a052(9), of that serious incident or field safety corrective action.\nIn the case of devices covered by this Regulation in accordance with point\u00a0(g) of Article\u00a01(6) and where the serious incident or field safety corrective action may be related to the derivatives of tissues or cells of human origin utilised for\u00a0the manufacture of the device, and in the case of devices falling under this Regulation pursuant to Article\u00a01(10), the\u00a0competent authority or the coordinating competent authority referred to in paragraph\u00a09 of this Article\u00a0shall inform the competent authority for human tissues and cells that was consulted by the notified body in accordance with Article\u00a052(10).\n\n\n7.\u00a0\u00a0\u00a0After carrying out the evaluation in accordance with paragraph\u00a03 of this Article, the evaluating competent authority shall, through the electronic system referred to in Article\u00a092, inform, without delay, the other competent authorities of the corrective action taken or envisaged by the manufacturer or required of it to minimise the risk of recurrence of the serious incident, including information on the underlying events and the outcome of its assessment.\n\n\n8.\u00a0\u00a0\u00a0The manufacturer shall ensure that information about the field safety corrective action taken is brought without delay to the attention of users of the device in question by means of a field safety notice. The field safety notice shall be edited in an official Union language or languages determined by the Member\u00a0State in which the field safety corrective action is taken. Except in cases of urgency, the content of the draft field safety notice shall be submitted to the evaluating competent authority or, in the cases referred to in paragraph\u00a09, to the coordinating competent authority to allow it to make comments. Unless duly justified by the situation of the individual Member\u00a0State, the content of the field safety notice shall be consistent in all Member\u00a0States.\nThe field safety notice shall allow the correct identification of the device or devices involved, in particular by including the relevant UDIs, and the correct identification, in particular, by including the SRN, if already issued, of the manufacturer that has undertaken the field safety corrective action. The field safety notice shall explain, in a clear manner, without understating the level of risk, the reasons for the field safety corrective action with reference to the device malfunction and associated risks for patients, users or other persons, and shall clearly indicate all the actions to be taken by users.\nThe manufacturer shall enter the field safety notice in the electronic system referred to in Article\u00a092 through which that notice shall be accessible to the public.\n\n\n9.\u00a0\u00a0\u00a0The competent authorities shall actively participate in a procedure in order to coordinate their assessments referred to in paragraph\u00a03 in the following cases:\n\n\n\n\n\n\n(a)\n\n\nwhere there is concern regarding a particular serious incident or cluster of serious incidents relating to the same device or type of device of the same manufacturer in more than one Member\u00a0State;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nwhere the appropriateness of a field safety corrective action that is proposed by a manufacturer in more than one Member\u00a0State is in question.\n\n\n\n\nThat coordinated procedure shall cover the following:\n\n\n\n\n\n\n\u2014\n\n\ndesignation of a coordinating competent authority on a case by case basis, when required;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndefining the coordinated assessment process, including the tasks and responsibilities of the coordinating competent authority and the involvement of other competent authorities.\n\n\n\n\nUnless otherwise agreed between the competent authorities, the coordinating competent authority shall be the competent authority of the Member\u00a0State in which the manufacturer has its registered place of business.\nThe coordinating competent authority shall, through the electronic system referred to in Article\u00a092, inform the manufacturer, the other competent authorities and the Commission that it has assumed the role of coordinating authority.\n\n\n10.\u00a0\u00a0\u00a0The designation of a coordinating competent authority shall not affect the rights of the other competent authorities to perform their own assessment and to adopt measures in accordance with this Regulation in order to ensure the protection of public health and patient safety. The coordinating competent authority and the Commission shall be kept informed of the outcome of any such assessment and the adoption of any such measures.\n\n\n11.\u00a0\u00a0\u00a0The Commission shall provide administrative support to the coordinating competent authority in the accomplishment of its tasks under this Chapter.\n\n\n\nArticle\u00a090\n\nAnalysis of vigilance data\n\nThe Commission shall, in collaboration with the Member\u00a0States, put in place systems and processes to actively monitor the data available in the electronic system referred to in Article\u00a092, in order to identify trends, patterns or signals in the data that may reveal new risks or safety concerns.\nWhere a previously unknown risk is identified or the frequency of an anticipated risk significantly and adversely changes the benefit-risk determination, the competent authority or, where appropriate, the coordinating competent authority shall inform the manufacturer, or where applicable the authorised representative, which shall then take the necessary corrective actions.\n\n\nArticle\u00a091\n\nImplementing acts\n\nThe Commission may, by means of implementing acts, and after consultation of the MDCG, adopt the detailed arrangements and procedural aspects necessary for the implementation of Articles\u00a085 to\u00a090 and 92 as regards the following:\n\n\n\n\n\n\n(a)\n\n\nthe typology of serious incidents and field safety corrective actions in relation to specific devices, or categories or groups of devices;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe reporting of serious incidents and field safety corrective actions and field safety notices, and the provision of periodic summary reports, post-market surveillance reports, PSURs and trend reports by manufacturers as referred to in Articles\u00a085, 86, 87, 88 and 89 respectively;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nstandard structured forms for electronic and non-electronic reporting, including a minimum data set for reporting of suspected serious incidents by healthcare professionals, users and patients;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\ntimelines for the reporting of field safety corrective actions, and for the provision by manufacturers of periodic summary reports and trend reports, taking into account the severity of the incident to be reported as referred to in Article\u00a087;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nharmonised forms for the exchange of information between competent authorities as referred to in Article\u00a089;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nprocedures for the designation of a coordinating competent authority; the coordinated evaluation process, including tasks and responsibilities of the coordinating competent authority and involvement of other competent authorities in this process.\n\n\n\n\nThe implementing acts referred to in the first paragraph\u00a0shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\nArticle\u00a092\n\nElectronic system on vigilance and on post-market surveillance\n\n\n1.\u00a0\u00a0\u00a0The Commission shall, in collaboration with the Member\u00a0States, set up and manage an electronic system to collate and process the following information:\n\n\n\n\n\n\n(a)\n\n\nthe reports by manufacturers on serious incidents and field safety corrective actions referred to in Article\u00a087(1) and Article\u00a089(5);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe periodic summary reports by manufacturers referred to in Article\u00a087(9);\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe reports by manufacturers on trends referred to in Article\u00a088;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe PSURs referred to in Article\u00a086;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe field safety notices by manufacturers referred to in Article\u00a089(8);\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe information to be exchanged between the competent authorities of the Member\u00a0States and between them and the Commission in accordance with Article\u00a089(7) and\u00a0(9).\n\n\n\n\nThat electronic system shall include relevant links to the UDI database.\n\n\n2.\u00a0\u00a0\u00a0The information referred to in paragraph\u00a01 of this Article\u00a0shall be made available through the electronic system to the competent authorities of the Member\u00a0States and to the Commission. The notified bodies shall also have access to that information to the extent that it relates to devices for which they issued a certificate in accordance with Article\u00a053.\n\n\n3.\u00a0\u00a0\u00a0The Commission shall ensure that healthcare professionals and the public have appropriate levels of access to the electronic system referred to in paragraph\u00a01.\n\n\n4.\u00a0\u00a0\u00a0On the basis of arrangements between the Commission and competent authorities of third countries or international organisations, the Commission may grant those competent authorities or international organisations access to the electronic system referred to in paragraph\u00a01 at the appropriate level. Those arrangements shall be based on reciprocity and make provision for confidentiality and data protection equivalent to those applicable in the Union.\n\n\n5.\u00a0\u00a0\u00a0The reports on serious incidents referred to in point\u00a0(a) of Article\u00a087(1) shall be automatically transmitted, upon receipt, via the electronic system referred to in paragraph\u00a01 of this Article, to the competent authority of the Member\u00a0State in which the incident occurred.\n\n\n6.\u00a0\u00a0\u00a0The trend reports referred to in Article\u00a088(1) shall be automatically transmitted upon receipt via the electronic system referred to in paragraph\u00a01 of this Article\u00a0to the competent authorities of the Member\u00a0State in which the incidents occurred.\n\n\n7.\u00a0\u00a0\u00a0The reports on field safety corrective actions referred to in point\u00a0(b) of Article\u00a087(1) shall be automatically transmitted upon receipt via the electronic system referred to in paragraph\u00a01 of this Article\u00a0to the competent authorities of the following Member\u00a0States:\n\n\n\n\n\n\n(a)\n\n\nthe Member\u00a0States in which the field safety corrective action is being or is to be undertaken;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe Member\u00a0State in which the manufacturer has its registered place of business.\n\n\n\n\n\n\n8.\u00a0\u00a0\u00a0The periodic summary reports referred to in Article\u00a087(9) shall be automatically transmitted upon receipt via the electronic system referred to in paragraph\u00a01 of this Article\u00a0to the competent authority of:\n\n\n\n\n\n\n(a)\n\n\nthe Member\u00a0State or Member\u00a0States participating in the coordination procedure in accordance with Article\u00a089(9) and which have agreed on the periodic summary report;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe Member\u00a0State in which the manufacturer has its registered place of business.\n\n\n\n\n\n\n9.\u00a0\u00a0\u00a0The information referred to in paragraphs 5 to 8 of this Article\u00a0shall be automatically transmitted, upon receipt, through the electronic system referred to in paragraph\u00a01 of this Article, to the notified body that issued the certificate for the device in question in accordance with Article\u00a056.\n\n\n\n\n\nSECTION 3\n\n\n\n\nMarket surveillance\n\n\n\n\nArticle\u00a093\n\nMarket surveillance activities\n\n\n1.\u00a0\u00a0\u00a0The competent authorities shall perform appropriate checks on the conformity characteristics and performance of devices including, where appropriate, a review of documentation and physical or laboratory checks on the basis of adequate samples. The competent authorities shall, in particular, take account of established principles regarding risk assessment and risk management, vigilance data and complaints.\n\n\n2.\u00a0\u00a0\u00a0The competent authorities shall draw up annual surveillance activity plans and allocate a sufficient number of material and competent human resources in order to carry out those activities taking into account the European market surveillance programme developed by the MDCG pursuant to Article\u00a0105 and local circumstances.\n\n\n3.\u00a0\u00a0\u00a0In order to fulfil the obligations laid down in paragraph\u00a01, the competent authorities:\n\n\n\n\n\n\n(a)\n\n\nmay require economic operators to, inter\u00a0alia, make available the documentation and information necessary for the purpose of carrying out the authorities' activities and, where justified, to provide the necessary samples of devices or access to devices free of charge; and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nshall carry out both announced and, if necessary, unannounced inspections of the premises of economic operators, as well as suppliers and/or subcontractors, and, where necessary, at the facilities of professional users.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0The competent authorities shall prepare an annual summary of the results of their surveillance activities and make it accessible to other competent authorities by means of the electronic system referred to in Article\u00a0100.\n\n\n5.\u00a0\u00a0\u00a0The competent authorities may confiscate, destroy or otherwise render inoperable devices that present an unacceptable risk or falsified devices where they deem it necessary to do so in the interests of the protection of public health.\n\n\n6.\u00a0\u00a0\u00a0Following each inspection carried out for the purposes referred to in paragraph\u00a01, the competent authority shall draw up a report on the findings of the inspection that concern compliance with the legal and technical requirements applicable under this Regulation. The report shall set out any corrective actions needed.\n\n\n7.\u00a0\u00a0\u00a0The competent authority which carried out the inspection shall communicate the content of the report referred to in paragraph\u00a06 of this Article\u00a0to the economic operator that has been the subject of the inspection. Before adopting the final report, the competent authority shall give that economic operator the opportunity to submit comments. That final inspection report shall be entered in the electronic system provided for in Article\u00a0100.\n\n\n8.\u00a0\u00a0\u00a0The Member\u00a0States shall review and assess the functioning of their market surveillance activities. Such reviews and assessments shall be carried out at least every four years and the results thereof shall be communicated to the other Member\u00a0States and the Commission. Each Member\u00a0State shall make a summary of the results accessible to the public by means of the electronic system referred to in Article\u00a0100.\n\n\n9.\u00a0\u00a0\u00a0The competent authorities of the Member\u00a0States shall coordinate their market surveillance activities, cooperate with each other and share with each other and with the Commission the results thereof, to provide for a harmonised and high level of market surveillance in all Member\u00a0States.\nWhere appropriate, the competent authorities of the Member\u00a0States shall agree on work-sharing, joint market surveillance activities and specialisation.\n\n\n10.\u00a0\u00a0\u00a0Where more than one authority in a Member\u00a0State is responsible for market surveillance and external border controls, those authorities shall cooperate with each other, by sharing information relevant to their role and functions.\n\n\n11.\u00a0\u00a0\u00a0Where appropriate, the competent authorities of the Member\u00a0States shall cooperate with the competent authorities of third countries with a view to exchanging information and technical support and promoting activities relating to market surveillance.\n\n\n\nArticle\u00a094\n\nEvaluation of devices suspected of presenting an unacceptable risk or other non-compliance\n\nWhere the competent authorities of a Member\u00a0State, based on data obtained by vigilance or market surveillance activities or on other information, have reason to believe that a device:\n\n\n\n\n\n\n(a)\n\n\nmay present an unacceptable risk to the health or safety of patients, users or other persons, or to other aspects of the protection of public health; or\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\notherwise does not comply with the requirements laid down in this Regulation,\n\n\n\n\nthey shall carry out an evaluation of the device concerned covering all requirements laid down in this Regulation relating to the risk presented by the device, or to any other non-compliance of the device.\nThe relevant economic operators shall cooperate with the competent authorities.\n\n\nArticle\u00a095\n\nProcedure for dealing with devices presenting an unacceptable risk to health and safety\n\n\n1.\u00a0\u00a0\u00a0Where, having performed an evaluation pursuant to Article\u00a094, the competent authorities find that the device presents an unacceptable risk to the health or safety of patients, users or other persons, or to other aspects of the protection of public health, they shall without delay require the manufacturer of the devices concerned, its authorised representative and all other relevant economic operators to take all appropriate and duly justified corrective action to bring the device into compliance with the requirements of this Regulation relating to the risk presented by the device and, in a manner that is proportionate to the nature of the risk, to restrict the making available of the device on the market, to subject the making available of the device to specific requirements, to withdraw the device from the market, or to recall it, within a reasonable period that is clearly defined and communicated to the relevant economic operator.\n\n\n2.\u00a0\u00a0\u00a0The competent authorities shall, without delay, notify the Commission, the other Member\u00a0States and, where a certificate has been issued in accordance with Article\u00a056 for the device concerned, the notified body that issued that certificate, of the results of the evaluation and of the actions which they have required the economic operators to take, by means of the electronic system referred to in Article\u00a0100.\n\n\n3.\u00a0\u00a0\u00a0The economic operators as referred to in paragraph\u00a01 shall, without delay, ensure that all appropriate corrective action is taken throughout the Union in respect of all the devices concerned that they have made available on the market.\n\n\n4.\u00a0\u00a0\u00a0Where the economic operator as referred to in paragraph\u00a01 does not take adequate corrective action within the period referred to in paragraph\u00a01, the competent authorities shall take all appropriate measures to prohibit or restrict the making available of the device on their national market, to withdraw the device from that market or to recall it.\nThe competent authorities shall notify the Commission, the other Member\u00a0States and the notified body referred to in paragraph\u00a02 of this Article, without delay, of those measures, by means of the electronic system referred to in Article\u00a0100.\n\n\n5.\u00a0\u00a0\u00a0The notification referred to in paragraph\u00a04 shall include all available details, in particular the data necessary for the identification and tracing of the non-compliant device, the origin of the device, the nature of and the reasons for the non-compliance alleged and the risk involved, the nature and duration of the national measures taken and the arguments put forward by the relevant economic operator.\n\n\n6.\u00a0\u00a0\u00a0Member\u00a0States other than the Member\u00a0State initiating the procedure shall, without delay, inform the Commission and the other Member\u00a0States, by means of the electronic system referred to in Article\u00a0100, of any additional relevant information at their disposal relating to the non-compliance of the device concerned and of any measures adopted by them in relation to the device concerned.\nIn the event of disagreement with the notified national measure, they shall, without delay, inform the Commission and the other Member\u00a0States of their objections, by means of the electronic system referred to in Article\u00a0100.\n\n\n7.\u00a0\u00a0\u00a0Where, within two months of receipt of the notification referred to in paragraph\u00a04, no objection has been raised by either a Member\u00a0State or the Commission in respect of any measures taken by a Member\u00a0State, those measures shall be deemed to be justified.\nIn that case, all Member\u00a0States shall ensure that corresponding appropriate restrictive or prohibitive measures, including withdrawing, recalling or limiting the availability of the device on their national market, are taken without delay in respect of the device concerned.\n\n\n\nArticle\u00a096\n\nProcedure for evaluating national measures at Union level\n\n\n1.\u00a0\u00a0\u00a0Where, within two months of receipt of the notification referred to in Article\u00a095(4), objections are raised by a Member\u00a0State against a measure taken by another Member\u00a0State, or where the Commission considers the measure to be contrary to Union law, the Commission shall, after consulting the competent authorities concerned and, where necessary, the economic operators concerned, evaluate that national measure. On the basis of the results of that evaluation, the Commission may decide, by means of implementing acts, whether or not the national measure is justified. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n2.\u00a0\u00a0\u00a0Where the Commission considers the national measure to be justified as referred to in paragraph\u00a01 of this Article, the second subparagraph\u00a0of Article\u00a095(7) shall apply. If the Commission considers the national measure to be unjustified, the Member\u00a0State concerned shall withdraw the measure.\nWhere the Commission does not adopt a decision pursuant to paragraph\u00a01 of this Article\u00a0within eight months of receipt of the notification referred to in Article\u00a095(4), the national measure shall be considered to be justified.\n\n\n3.\u00a0\u00a0\u00a0Where a Member\u00a0State or the Commission considers that the risk to health and safety emanating from a device cannot be mitigated satisfactorily by means of measures taken by the Member\u00a0State or Member\u00a0States concerned, the Commission, at the request of a Member\u00a0State or on its own initiative, may take, by means of implementing acts, the necessary and duly justified measures to ensure the protection of health and safety, including measures restricting or prohibiting the placing on the market and putting into service of the device concerned. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a097\n\nOther non-compliance\n\n\n1.\u00a0\u00a0\u00a0Where, having performed an evaluation pursuant to Article\u00a094, the competent authorities of a Member\u00a0State find that a device does not comply with the requirements laid down in this Regulation but does not present an unacceptable risk to the health or safety of patients, users or other persons, or to other aspects of the protection of public health, they shall require the relevant economic operator to bring the non-compliance concerned to an end within a reasonable period that is clearly defined and communicated to the economic operator and that is proportionate to the non-compliance.\n\n\n2.\u00a0\u00a0\u00a0Where the economic operator does not bring the non-compliance to an end within the period referred to in paragraph\u00a01 of this Article, the Member\u00a0State concerned shall, without delay, take all appropriate measures to restrict or prohibit the product being made available on the market or to ensure that it is recalled or withdrawn from the market. That Member\u00a0State shall inform the Commission and the other Member\u00a0States, without delay, of those measures, by means of the electronic system referred to in Article\u00a0100.\n\n\n3.\u00a0\u00a0\u00a0In order to ensure the uniform application of this Article, the Commission may, by means of implementing acts, specify appropriate measures to be taken by competent authorities to address given types of non-compliance. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a098\n\nPreventive health protection measures\n\n\n1.\u00a0\u00a0\u00a0Where a Member\u00a0State, after having performed an evaluation which indicates a potential risk related to a device or a specific category or group of devices, considers that, in order to protect the health and safety of patients, users or other persons or other aspects of public health, the making available on the market or putting into service of a device or a specific category or group of devices should be prohibited, restricted or made subject to particular requirements or that such device or category or group of devices should be withdrawn from the market or recalled, it may take any necessary and justified measures.\n\n\n2.\u00a0\u00a0\u00a0The Member\u00a0State referred to in paragraph\u00a01 shall immediately notify the Commission and all other Member\u00a0States, giving the reasons for its decision, by means of the electronic system referred to in Article\u00a0100.\n\n\n3.\u00a0\u00a0\u00a0The Commission, in consultation with the MDCG and, where necessary, the economic operators concerned, shall assess the national measures taken. The Commission may decide, by means of implementing acts, whether the national measures are justified or not. In the absence of a Commission decision within six months of their notification, the national measures shall be considered to be justified. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n4.\u00a0\u00a0\u00a0Where the assessment referred to in paragraph\u00a03 of this Article\u00a0demonstrates that the making available on the market or putting into service of a device, specific category or group of devices should be prohibited, restricted or made subject to particular requirements or that such device or category or group of devices should be withdrawn from the market or recalled in all Member\u00a0States in order to protect the health and safety of patients, users or other persons or other aspects of public health, the Commission may adopt implementing acts to take the necessary and duly justified measures. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a099\n\nGood administrative practice\n\n\n1.\u00a0\u00a0\u00a0Any measure adopted by the competent authorities of the Member\u00a0States pursuant to Articles\u00a095 to 98 shall state the exact grounds on which it is based. Where such a measure is addressed to a specific economic operator, the competent authority shall notify without delay the economic operator concerned of that measure, and shall at the same time inform that economic operator of the remedies available under the law or the administrative practice of the Member\u00a0State concerned and of the time limits to which such remedies are subject. Where the measure is of general applicability, it shall be appropriately published.\n\n\n2.\u00a0\u00a0\u00a0Except in cases where immediate action is necessary for reasons of unacceptable risk to human health or safety, the economic operator concerned shall be given the opportunity to make submissions to the competent authority within an appropriate period of time that is clearly defined before any measure is adopted.\nWhere action has been taken without the economic operator having had the opportunity to make submissions as referred to in the first subparagraph, it shall be given the opportunity to make submissions as soon as possible and the action taken shall be reviewed promptly thereafter.\n\n\n3.\u00a0\u00a0\u00a0Any measure adopted shall be immediately withdrawn or amended upon the economic operator's demonstrating that it has taken effective corrective action and that the device is in compliance with the requirements of this Regulation.\n\n\n4.\u00a0\u00a0\u00a0Where a measure adopted pursuant to Articles\u00a095 to 98 concerns a device for which a notified body has been involved in the conformity assessment, the competent authorities shall by means of the electronic system referred to in Article\u00a0100 inform the relevant notified body and the authority responsible for the notified body of the measure taken.\n\n\n\nArticle\u00a0100\n\nElectronic system on market surveillance\n\n\n1.\u00a0\u00a0\u00a0The Commission, in collaboration with the Member\u00a0States, shall set up and manage an electronic system to collate and process the following information:\n\n\n\n\n\n\n(a)\n\n\nsummaries of the results of the surveillance activities referred to in Article\u00a093(4);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe final inspection report referred to in Article\u00a093(7);\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\ninformation in relation to devices presenting an unacceptable risk to health and safety as referred to in Article\u00a095(2), (4) and (6);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\ninformation in relation to non-compliance of products as referred to in Article\u00a097(2);\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\ninformation in relation to the preventive health protection measures referred to in Article\u00a098(2);\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nsummaries of the results of the reviews and assessments of the market surveillance activities of the Member\u00a0States referred to in 93(8).\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The information referred to in paragraph\u00a01 of this Article\u00a0shall be immediately transmitted through the electronic system to all competent authorities concerned and, where applicable, to the notified body that issued a certificate in accordance with Article\u00a056 for the device concerned and be accessible to the Member\u00a0States and to the Commission.\n\n\n3.\u00a0\u00a0\u00a0Information exchanged between Member\u00a0States shall not be made public where to do so might impair market surveillance activities and co-operation between Member\u00a0States.\n\n\n\n\n\nCHAPTER VIII\n\n\nCOOPERATION BETWEEN MEMBER\u00a0STATES, MEDICAL DEVICE COORDINATION GROUP, EXPERT LABORATORIES, EXPERT PANELS AND DEVICE REGISTERS\n\n\n\nArticle\u00a0101\n\nCompetent authorities\n\nThe Member\u00a0States shall designate the competent authority or authorities responsible for the implementation of this Regulation. They shall entrust their authorities with the powers, resources, equipment and knowledge necessary for the proper performance of their tasks pursuant to this Regulation. The Member\u00a0States shall communicate the names and contact details of the competent authorities to the Commission which shall publish a list of competent authorities.\n\n\nArticle\u00a0102\n\nCooperation\n\n\n1.\u00a0\u00a0\u00a0The competent authorities of the Member\u00a0States shall cooperate with each other and with the Commission. The Commission shall provide for the organisation of exchanges of information necessary to enable this Regulation to be applied uniformly.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States shall, with the support of the Commission, participate, where appropriate, in initiatives developed at international level with the aim of ensuring cooperation between regulatory authorities in the field of medical devices.\n\n\n\nArticle\u00a0103\n\nMedical Device Coordination Group\n\n\n1.\u00a0\u00a0\u00a0A Medical Device Coordination Group (\u2018MDCG\u2019) is hereby established.\n\n\n2.\u00a0\u00a0\u00a0Each Member\u00a0State shall appoint to the MDCG, for a three-year term which may be renewed, one member and one alternate each with expertise in the field of medical devices, and one member and one alternate with expertise in the field of in vitro diagnostic medical devices. A Member\u00a0State may choose to appoint only one member and one alternate, each with expertise in both fields.\nThe members of the MDCG shall be chosen for their competence and experience in the field of medical devices and in vitro diagnostic medical devices. They shall represent the competent authorities of the Member\u00a0States. The names and affiliation of members shall be made public by the Commission.\nThe alternates shall represent and vote for the members in their absence.\n\n\n3.\u00a0\u00a0\u00a0The MDCG shall meet at regular intervals and, where the situation requires, upon request by the Commission or a Member\u00a0State. The meetings shall be attended either by the members appointed for their role and expertise in the field of medical devices, or by the members appointed for their expertise in the field of in vitro diagnostic medical devices, or by the members appointed for their expertise in both fields, or their alternates, as appropriate.\n\n\n4.\u00a0\u00a0\u00a0The MDCG shall use its best endeavours to reach consensus. If such consensus cannot be reached, the MDCG shall decide by a majority of its members. Members with diverging positions may request that their positions and the grounds on which they are based be recorded in the MDCG's position.\n\n\n5.\u00a0\u00a0\u00a0The MDCG shall be chaired by a representative of the Commission. The chair shall not take part in votes of the MDCG.\n\n\n6.\u00a0\u00a0\u00a0The MDCG may invite, on a case-by-case basis, experts and other third parties to attend meetings or provide written contributions.\n\n\n7.\u00a0\u00a0\u00a0The MDCG may establish standing or temporary sub-groups. Where appropriate, organisations representing the interests of the medical device industry, healthcare professionals, laboratories, patients and consumers at Union level shall be invited to such sub-groups in the capacity of observers.\n\n\n8.\u00a0\u00a0\u00a0The MDCG shall establish its rules of procedure which shall, in particular, lay down procedures for the following:\n\n\n\n\n\n\n\u2014\n\n\nthe adoption of opinions or recommendations or other positions, including in cases of urgency;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe delegation of tasks to reporting and co-reporting members;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe implementation of Article\u00a0107 regarding conflict of interests;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe functioning of sub-groups.\n\n\n\n\n\n\n9.\u00a0\u00a0\u00a0The MDCG shall have the tasks laid down in Article\u00a0105 of this Regulation and Article\u00a099 of Regulation (EU)\u00a02017/746.\n\n\n\nArticle\u00a0104\n\nSupport by the Commission\n\nThe Commission shall support the functioning of the cooperation between national competent authorities. It shall, in particular, provide for the organisation of exchanges of experience between the competent authorities and provide technical, scientific and logistic support to the MDCG and its sub-groups. It shall organise the meetings of the MDCG and its sub-groups, participate in those meetings and ensure the appropriate follow-up.\n\n\nArticle\u00a0105\n\nTasks of the MDCG\n\nUnder this Regulation, the MDCG shall have the following tasks:\n\n\n\n\n\n\n(a)\n\n\nto contribute to the assessment of applicant conformity assessment bodies and notified bodies pursuant to the provisions set out in Chapter IV;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nto advise the Commission, at its request, in matters concerning the coordination group of notified bodies as established pursuant to Article\u00a049;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nto contribute to the development of guidance aimed at ensuring effective and harmonised implementation of this Regulation, in particular regarding the designation and monitoring of notified bodies, application of the general safety and performance requirements and conduct of clinical evaluations and investigations by manufacturers, assessment by notified bodies and vigilance activities;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nto contribute to the continuous monitoring of technical progress and assessment of whether the general safety and performance requirements laid down in this Regulation and Regulation\u00a0(EU)\u00a02017/746 are adequate to ensure safety and performance of devices, and thereby contribute to identifying whether there is a need to amend Annex\u00a0I to this Regulation;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nto contribute to the development of device standards, of CS and of scientific guidelines, including product specific guidelines, on clinical investigation of certain devices in particular implantable devices and class III devices;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nto assist the competent authorities of the Member\u00a0States in their coordination activities in particular in the fields of classification and the determination of the regulatory status of devices, clinical investigations, vigilance and market surveillance including the development and maintenance of a framework for a European market surveillance programme with the objective of achieving efficiency and harmonisation of market surveillance in the Union, in accordance with Article\u00a093;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nto provide advice, either on its own initiative or at request of the Commission, in the assessment of any issue related to the implementation of this Regulation;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nto contribute to harmonised administrative practice with regard to devices in the Member\u00a0States.\n\n\n\n\n\n\nArticle\u00a0106\n\nProvision of scientific, technical and clinical opinions and advice\n\n\n1.\u00a0\u00a0\u00a0The Commission shall, by means of implementing acts and in consultation with the MDCG, make provision for expert panels to be designated for the assessment of the clinical evaluation in relevant medical fields as referred to in paragraph\u00a09 of this Article\u00a0and to provide views in accordance with Article\u00a048(6) of Regulation\u00a0(EU)\u00a02017/746 on the performance evaluation of certain in vitro diagnostic medical devices and, where necessary, for categories or groups of devices, or for specific hazards relating to categories or groups of devices, observing the principles of highest scientific competence, impartiality, independence and transparency. The same principles shall apply where the Commission decides to appoint expert laboratories in accordance with paragraph\u00a07 of this Article.\n\n\n2.\u00a0\u00a0\u00a0Expert panels and expert laboratories may be designated in areas where the Commission, in consultation with the MDCG, has identified a need for the provision of consistent scientific, technical and/or clinical advice or laboratory expertise in relation to the implementation of this Regulation. Expert panels and expert laboratories may be appointed on a standing or temporary basis.\n\n\n3.\u00a0\u00a0\u00a0Expert panels shall consist of advisors appointed by the Commission on the basis of up-to-date clinical, scientific or technical expertise in the field and with a geographical distribution that reflects the diversity of scientific and clinical approaches in the Union. The Commission shall determine the number of members of each panel in accordance with the requisite needs.\nThe members of expert panels shall perform their tasks with impartiality and objectivity. They shall neither seek nor take instructions from notified bodies or manufacturers. Each member shall draw up a declaration of interests, which shall be made publicly available.\nThe Commission shall establish systems and procedures to actively manage and prevent potential conflicts of interest.\n\n\n4.\u00a0\u00a0\u00a0Expert panels shall take into account relevant information provided by stakeholders including patients' organisations and healthcare professionals when preparing their scientific opinions.\n\n\n5.\u00a0\u00a0\u00a0The Commission, following consultation with the MDCG, may appoint advisors to expert panels following publication in the Official Journal of the European Union and on the Commission website following a call for expressions of interest. Depending on the type of task and the need for specific expertise, advisors may be appointed to the expert panels for a maximum period of three years and their appointment may be renewed.\n\n\n6.\u00a0\u00a0\u00a0The Commission, following consultation with the MDCG, may include advisors on a central list of available experts who, whilst not being formally appointed to a panel, are available to provide advice and to support the work of the expert panel as needed. That list shall be published on the Commission website.\n\n\n7.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts and following consultation with the MDCG, designate expert laboratories, on the basis of their expertise in:\n\n\n\n\n\n\n\u2014\n\n\nphysico-chemical characterisation, or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmicrobiological, biocompatibility, mechanical, electrical, electronic or non-clinical biological and toxicological testing\n\n\n\n\nof specific devices, categories or groups of devices.\nThe Commission shall only designate expert laboratories for which a Member\u00a0State or the Joint Research Centre has submitted an application for designation.\n\n\n8.\u00a0\u00a0\u00a0Expert laboratories shall satisfy the following criteria:\n\n\n\n\n\n\n(a)\n\n\nhave adequate and appropriately qualified staff with adequate knowledge and experience in the field of the devices for which they are designated;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\npossess the necessary equipment to carry out the tasks assigned to them;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nhave the necessary knowledge of international standards and best practices;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nhave an appropriate administrative organisation and structure;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nensure that their staff observe the confidentiality of information and data obtained in carrying out their tasks.\n\n\n\n\n\n\n9.\u00a0\u00a0\u00a0Expert panels appointed for clinical evaluation in relevant medical fields shall fulfil the tasks provided for in Article\u00a054(1) and Article\u00a061(2) and Section\u00a05.1 of Annex\u00a0IX or Section\u00a06 of Annex\u00a0X, as applicable.\n\n\n10.\u00a0\u00a0\u00a0Expert panels and expert laboratories may have the following tasks, depending on the requisite needs:\n\n\n\n\n\n\n(a)\n\n\nto provide scientific, technical and clinical assistance to the Commission and the MDCG in relation to the implementation of this Regulation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nto contribute to the development and maintenance of appropriate guidance and CS for:\n\n\n\n\n\n\n\u2014\n\n\nclinical investigations,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclinical evaluation and PMCF,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nperformance studies,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nperformance evaluation and post-market performance follow-up,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nphysico-chemical characterisation, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmicrobiological, biocompatibility, mechanical, electrical, electronic or non-clinical toxicological testing\n\n\n\n\nfor specific devices, or a category or group of devices, or for specific hazards related to a category or group of devices;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nto develop and review clinical evaluation guidance and performance evaluation guidance for performance of conformity assessment in line with the state of the art with regard to clinical evaluation, performance evaluation, physico-chemical characterisation, and microbiological, biocompatibility, mechanical, electrical, electronic or non-clinical toxicological testing;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nto contribute to the development of standards at international level, ensuring that such standards reflect the state of the art;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nto provide opinions in response to consultations by manufacturers in accordance with Article\u00a061(2), notified bodies and Member\u00a0States in accordance with paragraphs\u00a011 to 13 of this Article.\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nto contribute to identification of concerns and emerging issues on the safety and performance of medical devices;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nto provide views in accordance with Article\u00a048(4) of Regulation\u00a0(EU)\u00a02017/746 on the performance evaluation of certain in vitro diagnostic medical devices.\n\n\n\n\n\n\n11.\u00a0\u00a0\u00a0The Commission, shall facilitate the access of Member\u00a0States and notified bodies and manufacturers to advice provided by expert panels and expert laboratories concerning, inter\u00a0alia, the criteria for an appropriate data set for assessment of the conformity of a device, in particular with regard to the clinical data required for clinical evaluation, with regard to physico-chemical characterisation, and with regard to microbiological, biocompatibility, mechanical, electrical, electronic and non-clinical toxicological testing.\n\n\n12.\u00a0\u00a0\u00a0When adopting its scientific opinion in accordance with paragraph\u00a09, the members of the expert panels shall use their best endeavours to reach consensus. If consensus cannot be reached, the expert panels shall decide by a majority of their members, and the scientific opinion shall mention the divergent positions and the grounds on which they are based.\nThe Commission shall publish the scientific opinion and advice delivered in accordance with paragraphs 9 and 11 of this Article, ensuring consideration of aspects of confidentiality as set out in Article\u00a0109. The clinical evaluation guidance referred to in point\u00a0(c) of paragraph\u00a010 shall be published following consultation with the MDCG.\n\n\n13.\u00a0\u00a0\u00a0The Commission may require manufacturers and notified bodies to pay fees for the advice provided by expert panels and expert laboratories. The structure and the level of fees as well as the scale and structure of recoverable costs shall be adopted by the Commission by means of implementing acts, taking into account the objectives of the adequate implementation of this Regulation, protection of health and safety, support of innovation and cost-effectiveness and the necessity to achieve active participation in the expert panels. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n14.\u00a0\u00a0\u00a0The fees payable to the Commission in accordance with the procedure under paragraph\u00a013 of this Article\u00a0shall be set in a transparent manner and on the basis of the costs for the services provided. The fees payable shall be reduced in the case of a clinical evaluation consultation procedure initiated in accordance with point\u00a0(c) of Section\u00a05.1 of Annex\u00a0IX involving a manufacturer who is a micro, small or medium-sized enterprise within the meaning of Recommendation\u00a02003/361/EC.\n\n\n15.\u00a0\u00a0\u00a0The Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 to amend the tasks of expert panels and expert laboratories referred to in paragraph\u00a010 of this Article.\n\n\n\nArticle\u00a0107\n\nConflict of interests\n\n\n1.\u00a0\u00a0\u00a0Members of the MDCG, its sub-groups, and members of expert panels and expert laboratories shall not have financial or other interests in the medical device industry which could affect their impartiality. They shall undertake to act in the public interest and in an independent manner. They shall declare any direct or indirect interests they may have in the medical device industry and update that declaration whenever a relevant change occurs. The declaration of interests shall be made publicly available on the Commission website. This Article\u00a0shall not apply to the representatives of stakeholder organisations participating in the sub-groups of the MDCG.\n\n\n2.\u00a0\u00a0\u00a0Experts and other third parties invited by the MDCG on a case-by-case basis shall declare any interests they may have in the issue in question.\n\n\n\nArticle\u00a0108\n\nDevice registers and databanks\n\nThe Commission and the Member\u00a0States shall take all appropriate measures to encourage the establishment of registers and databanks for specific types of devices setting common principles to collect comparable information. Such registers and databanks shall contribute to the independent evaluation of the long-term safety and performance of devices, or the traceability of implantable devices, or all of such characteristics.\n\n\n\nCHAPTER IX\n\n\nCONFIDENTIALITY, DATA PROTECTION, FUNDING AND PENALTIES\n\n\n\nArticle\u00a0109\n\nConfidentiality\n\n\n1.\u00a0\u00a0\u00a0Unless otherwise provided for in this Regulation and without prejudice to existing national provisions and practices in the Member\u00a0States on confidentiality, all parties involved in the application of this Regulation shall respect the confidentiality of information and data obtained in carrying out their tasks in order to protect the following:\n\n\n\n\n\n\n(a)\n\n\npersonal data, in accordance with Article\u00a0110;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ncommercially confidential information and trade secrets of a natural or legal person, including intellectual property rights; unless disclosure is in the public interest;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe effective implementation of this Regulation, in particular for the purpose of inspections, investigations or audits.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0Without prejudice to paragraph\u00a01, information exchanged on a confidential basis between competent authorities and between competent authorities and the Commission shall not be disclosed without the prior agreement of the originating authority.\n\n\n3.\u00a0\u00a0\u00a0Paragraphs 1 and 2 shall not affect the rights and obligations of the Commission, Member\u00a0States and notified bodies with regard to exchange of information and the dissemination of warnings, nor the obligations of the persons concerned to provide information under criminal law.\n\n\n4.\u00a0\u00a0\u00a0The Commission and Member\u00a0States may exchange confidential information with regulatory authorities of third countries with which they have concluded bilateral or multilateral confidentiality arrangements.\n\n\n\nArticle\u00a0110\n\nData protection\n\n\n1.\u00a0\u00a0\u00a0Member\u00a0States shall apply Directive\u00a095/46/EC to the processing of personal data carried out in the Member\u00a0States pursuant to this Regulation.\n\n\n2.\u00a0\u00a0\u00a0Regulation\u00a0(EC)\u00a0No\u00a045/2001 shall apply to the processing of personal data carried out by the Commission pursuant to this Regulation.\n\n\n\nArticle\u00a0111\n\nLevying of fees\n\n\n1.\u00a0\u00a0\u00a0This Regulation shall be without prejudice to the possibility for Member\u00a0States to levy fees for the activities set out in this Regulation, provided that the level of the fees is set in a transparent manner and on the basis of cost-recovery principles.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States shall inform the Commission and the other Member\u00a0States at least three months before the structure and level of fees is to be adopted. The structure and level of fees shall be made publicly available on request.\n\n\n\nArticle\u00a0112\n\nFunding of activities related to designation and monitoring of notified bodies\n\nThe costs associated with joint assessment activities shall be covered by the Commission. The Commission shall, by means of implementing acts, lay down the scale and structure of recoverable costs and other necessary implementing rules. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\nArticle\u00a0113\n\nPenalties\n\nThe Member\u00a0States shall lay down the rules on penalties applicable for infringement of the provisions of this Regulation and shall take all measures necessary to ensure that they are implemented. The penalties provided for shall be effective, proportionate, and dissuasive. The Member\u00a0States shall notify the Commission of those rules and of those measures by 25 February 2020 and shall notify it, without delay, of any subsequent amendment affecting them.\n\n\n\nCHAPTER X\n\n\nFINAL PROVISIONS\n\n\n\nArticle\u00a0114\n\nCommittee procedure\n\n\n1.\u00a0\u00a0\u00a0The Commission shall be assisted by a Committee on Medical Devices. That Committee shall be a committee within the meaning of Regulation\u00a0(EU)\u00a0No\u00a0182/2011.\n\n\n2.\u00a0\u00a0\u00a0Where reference is made to this paragraph, Article\u00a04 of Regulation\u00a0(EU)\u00a0No\u00a0182/2011 shall apply.\n\n\n3.\u00a0\u00a0\u00a0Where reference is made to this paragraph, Article\u00a05 of Regulation\u00a0(EU)\u00a0No\u00a0182/2011 shall apply.\nWhere the committee delivers no opinion, the Commission shall not adopt the draft implementing act and the third subparagraph\u00a0of Article\u00a05(4) of Regulation\u00a0(EU)\u00a0No\u00a0182/2011 shall apply.\n\n\n4.\u00a0\u00a0\u00a0Where reference is made to this paragraph, Article\u00a08 of Regulation\u00a0(EU)\u00a0No\u00a0182/2011, in conjunction with Article\u00a04 or 5 thereof, as appropriate, shall apply.\n\n\n\nArticle\u00a0115\n\nExercise of the delegation\n\n\n1.\u00a0\u00a0\u00a0The power to adopt delegated acts is conferred on the Commission subject to the conditions laid down in this Article.\n\n\n2.\u00a0\u00a0\u00a0The power to adopt delegated acts referred to in Articles\u00a01(5), 3, 10(4), 18(3), 19(4), 27(10), 44(11), 52(5), 56(6), 61(8), 70(8) and 106(15) shall be conferred on the Commission for a period of five years from 25 May 2017. The Commission shall draw up a report in respect of the delegation of power not later than nine months before the end of the five-year period. The delegation of power shall be tacitly extended for periods of an identical duration, unless the European Parliament or the Council opposes such extension not later than three months before the end of each period.\n\n\n3.\u00a0\u00a0\u00a0The delegation of power referred to in Articles\u00a01(5), 3, 10(4), 18(3), 19(4), 27(10), 44(11), 52(5), 56(6), 61(8), 70(8) and 106(15) may be revoked at any time by the European Parliament or by the Council. A decision to revoke shall put an end to the delegation of the power specified in that decision. It shall take effect the day following the publication of the decision in the Official Journal of the European Union or at a later date specified therein. It shall not affect the validity of any delegated acts already in force.\n\n\n4.\u00a0\u00a0\u00a0Before adopting a delegated act, the Commission shall consult experts designated by each Member\u00a0State in accordance with the principles laid down in the Interinstitutional Agreement of 13 April 2016 on Better Law-Making.\n\n\n5.\u00a0\u00a0\u00a0As soon as it adopts a delegated act, the Commission shall notify it simultaneously to the European Parliament and to the Council.\n\n\n6.\u00a0\u00a0\u00a0A delegated act adopted pursuant to Articles\u00a01(5), 3, 10(4), 18(3), 19(4), 27(10), 44(11), 52(5), 56(6), 61(8), 70(8) and 106(15) shall enter into force only if no objection has been expressed either by the European Parliament or by the Council within a period of three months of notification of that act to the European Parliament and the Council or if, before the expiry of that period, the European Parliament and the Council have both informed the Commission that they will not object. That period shall be extended by three months at the initiative of the European Parliament or of the Council.\n\n\n\nArticle\u00a0116\n\nSeparate delegated acts for different delegated powers\n\nThe Commission shall adopt a separate delegated act in respect of each power delegated to it pursuant to this Regulation.\n\n\nArticle\u00a0117\n\nAmendment to Directive\u00a02001/83/EC\n\nIn Annex\u00a0I to Directive\u00a02001/83/EC, point 12 of Section\u00a03.2. is replaced by the following:\n\n\n\n\n\n\n\n\u2018(12)\n\n\nWhere, in accordance with the second subparagraph\u00a0of Article\u00a01(8) or the second subparagraph\u00a0of Article\u00a01(9) of Regulation\u00a0(EU)\u00a02017/745 of the European Parliament and of the Council\u00a0(*1), a product is governed by this Directive, the marketing authorisation dossier shall include, where available, the results of the assessment of the conformity of the device part with the relevant general safety and performance requirements set out in Annex\u00a0I to that Regulation contained in the manufacturer's EU declaration of conformity or the relevant certificate issued by a notified body allowing the manufacturer to affix a CE\u00a0marking to the medical device.\nIf the dossier does not include the results of the conformity assessment referred to in the first subparagraph\u00a0and where for the conformity assessment of the device, if used separately, the involvement of a notified body is required in accordance with Regulation\u00a0(EU)\u00a02017/745, the authority shall require the applicant to provide an opinion on the conformity of the device part with the relevant general safety and performance requirements set out in Annex\u00a0I to that Regulation issued by a notified body designated in accordance with that Regulation for the type of device in question.\n\n\n\n\n\n\n\nArticle\u00a0118\n\nAmendment to Regulation\u00a0(EC)\u00a0No\u00a0178/2002\n\nIn the third paragraph\u00a0of Article\u00a02 of Regulation\u00a0(EC)\u00a0No\u00a0178/2002, the following point is added:\n\n\n\n\n\n\n\n\u2018(i)\n\n\nmedical devices within the meaning of Regulation\u00a0(EU)\u00a02017/745 of the European Parliament and of the Council\u00a0(*2).\n\n\n\n\n\n\n\nArticle\u00a0119\n\nAmendment to Regulation\u00a0(EC)\u00a0No\u00a01223/2009\n\nIn Article\u00a02 of Regulation\u00a0(EC)\u00a0No\u00a01223/2009, the following paragraph\u00a0is added:\n\n\n\u20184.\u00a0\u00a0\u00a0The Commission may, at the request of a Member\u00a0State or on its own initiative, adopt the necessary measures to determine whether or not a specific product or group of products falls within the definition \u2018cosmetic product\u2019. Those measures shall be adopted in accordance with the regulatory procedure referred to in Article\u00a032(2).\u2019.\n\n\n\n\nArticle\u00a0120\n\nTransitional provisions\n\n\n1.\u00a0\u00a0\u00a0From 26 May 2020, any publication of a notification in respect of a notified body in accordance with Directives\u00a090/385/EEC and 93/42/EEC shall become void.\n\n\n2.\u00a0\u00a0\u00a0Certificates issued by notified bodies in accordance with Directives\u00a090/385/EEC and 93/42/EEC prior to 25 May 2017 shall remain valid until the end of the period indicated on the certificate, except for certificates issued in accordance with Annex\u00a04 to Directive\u00a090/385/EEC or Annex\u00a0IV to Directive\u00a093/42/EEC which shall become void at the latest on 27 May 2022.\nCertificates issued by notified bodies in accordance with Directives\u00a090/385/EEC and 93/42/EEC from 25 May 2017 shall remain valid until the end of the period indicated on the certificate, which shall not exceed five years from its issuance. They shall however become void at the latest on 27 May 2024.\n\n\n3.\u00a0\u00a0\u00a0By way of derogation from Article\u00a05 of this Regulation, a device with a certificate that was issued in accordance with Directive\u00a090/385/EEC or Directive\u00a093/42/EEC and which is valid by virtue of paragraph\u00a02 of this Article\u00a0may only be placed on the market or put into service provided that from the date of application of this Regulation it continues to comply with either of those Directives, and provided there are no significant changes in the design and intended purpose. However, the requirements of this Regulation relating to post-market surveillance, market surveillance, vigilance, registration of economic operators and of devices shall apply in place of the corresponding requirements in those\u00a0Directives.\nWithout prejudice to Chapter\u00a0IV and paragraph\u00a01 of this Article, the notified body that issued the certificate referred to in the first subparagraph\u00a0shall continue to be responsible for the appropriate surveillance in respect of all of the applicable requirements relating to the devices it has certified.\n\n\n4.\u00a0\u00a0\u00a0Devices lawfully placed on the market pursuant to Directives\u00a090/385/EEC and 93/42/EEC prior to 26 May 2020, and devices placed on the market from 26 May 2020 by virtue of a certificate as referred to in paragraph\u00a02 of this Article, may continue to be made available on the market or put into service until 27 May 2025.\n\n\n5.\u00a0\u00a0\u00a0By way of derogation from Directives\u00a090/385/EEC and 93/42/EEC, devices which comply with this Regulation may be placed on the market prior to 26 May 2020.\n\n\n6.\u00a0\u00a0\u00a0By way of derogation from Directives\u00a090/385/EEC and 93/42/EEC, conformity assessment bodies which comply with this Regulation may be designated and notified prior 26 May 2020. Notified bodies which are designated and notified in accordance with this Regulation may carry out the conformity assessment procedures laid down in this Regulation and issue certificates in accordance with this Regulation prior to 26 May 2020.\n\n\n7.\u00a0\u00a0\u00a0As regards devices subject to the consultation procedure laid down in Article\u00a054, paragraph\u00a05 of this Article\u00a0shall apply provided that the necessary appointments to the MDCG and expert panels have been made.\n\n\n8.\u00a0\u00a0\u00a0By way of derogation from Article\u00a010a and point\u00a0(a) of Article\u00a010b(1) of Directive\u00a090/385/EEC and Article\u00a014(1) and (2) and points (a) and (b) of Article\u00a014a(1) of Directive\u00a093/42/EEC, manufacturers, authorised representatives, importers and notified bodies which, during the period starting on the later of the dates referred to point\u00a0(d) of Article\u00a0123(3) and ending 18 months later, comply with Article\u00a029(4) and Article\u00a056(5) of this Regulation shall be considered to comply with the laws and regulations adopted by Member\u00a0States in accordance with, respectively, Article\u00a010a of Directive\u00a090/385/EEC or Article\u00a014(1) and (2) of Directive\u00a093/42/EEC and with, respectively, point\u00a0(a) of Article\u00a010b(1) of Directive\u00a090/385/EEC or points (a) and (b) of Article\u00a014a(1) of Directive\u00a093/42/EEC as specified in Decision 2010/227/EU.\n\n\n9.\u00a0\u00a0\u00a0Authorisations granted by the competent authorities of the Member\u00a0States in accordance with Article\u00a09(9) of Directive\u00a090/385/EEC or Article\u00a011(13) of Directive\u00a093/42/EEC shall keep the validity indicated in the authorisation.\n\n\n10.\u00a0\u00a0\u00a0Devices falling within the scope of this Regulation in accordance with points (f) and (g) of Article\u00a01(6) which have been legally placed on the market or put into service in accordance with the rules in force in the Member\u00a0States prior to 26 May 2020 may continue to be placed on the market and put into service in the Member\u00a0States concerned.\n\n\n11.\u00a0\u00a0\u00a0Clinical investigations which have started to be conducted in accordance with Article\u00a010 of Directive\u00a090/385/EEC or Article\u00a015 of Directive\u00a093/42/EEC prior to 26 May 2020 may continue to be conducted. As of 26 May 2020, however, the reporting of serious adverse events and device deficiencies shall be carried out in accordance with this Regulation.\n\n\n12.\u00a0\u00a0\u00a0Until the Commission has designated, pursuant to Article\u00a027(2), issuing entities, GS1, HIBCC and ICCBBA shall be considered to be designated issuing entities.\n\n\n\nArticle\u00a0121\n\nEvaluation\n\nBy 27 May 2027, the Commission shall assess the application of this Regulation and produce an evaluation report on the progress towards achievement of the objectives contained herein including an assessment of the resources required to implement this Regulation. Special attention shall be given to the traceability of medical devices through the storage, pursuant to Article\u00a027, of the UDI by economic operators, health institutions and health professionals.\n\n\nArticle\u00a0122\n\nRepeal\n\nWithout prejudice to Articles\u00a0120(3) and (4) of this Regulation, and without prejudice to the obligations of the Member\u00a0States and manufacturers as regards vigilance and to the obligations of manufacturers as regards the making available of documentation, under Directives\u00a090/385/EEC and 93/42/EEC, those Directives are repealed with effect from 26 May 2020, with the exception of:\n\n\n\n\n\n\n\u2014\n\n\nArticles\u00a08 and 10, points (b) and (c) of Article\u00a010b(1), Article\u00a010b(2) and Article\u00a010b(3) of Directive\u00a090/385/EEC, and the obligations relating to vigilance and clinical investigations provided for in the corresponding Annexes, which are repealed with effect from the later of the dates referred to in point\u00a0(d) of Article\u00a0123(3) of this Regulation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a010a and point\u00a0(a) of Article\u00a010b(1) of Directive\u00a090/385/EEC, and the obligations relating to registration of devices and economic operators, and to certificate notifications, provided for in the corresponding Annexes, which are repealed with effect from 18\u00a0months after the later of the dates referred to in point\u00a0(d) of Article\u00a0123(3) of this Regulation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a010, points (c) and (d) of Article\u00a014a(1), Article\u00a014a(2), Article\u00a014a(3) and Article\u00a015 of Directive\u00a093/42/EEC, and the obligations relating to vigilance and clinical investigations provided for in the corresponding Annexes, which are repealed with effect from the later of the dates referred to in point\u00a0(d) of Article\u00a0123(3) of this Regulation; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a014(1) and (2) and points (a) and (b) of Article\u00a014a(1) of Directive\u00a093/42/EEC, and the obligations relating to registration of devices and economic operators, and to certificate notifications, provided for in the corresponding Annexes, which are repealed with effect from 18 months after the later of the dates referred to in point\u00a0(d) of Article\u00a0123(3) of this Regulation.\n\n\n\n\nAs regards the devices referred to in Article\u00a0120 (3) and (4) of this Regulation, the Directives referred to in the first\u00a0paragraph\u00a0shall continue to apply until 27 May 2025 to the extent necessary for the application of those paragraphs.\nNotwithstanding the first paragraph, Regulations (EU)\u00a0No\u00a0207/2012 and (EU)\u00a0No\u00a0722/2012 shall remain in force and continue to apply unless and until repealed by implementing acts adopted by the Commission pursuant to this Regulation.\nReferences to the repealed Directives shall be understood as references to this Regulation and shall be read in accordance with the correlation table laid down in Annex\u00a0XVII to this Regulation.\n\n\nArticle\u00a0123\n\nEntry into force and date of application\n\n\n1.\u00a0\u00a0\u00a0This Regulation shall enter into force on the twentieth day following that of its publication in the Official Journal of the European Union.\n\n\n2.\u00a0\u00a0\u00a0It shall apply from 26 May 2020.\n\n\n3.\u00a0\u00a0\u00a0By way of derogation from paragraph\u00a02:\n\n\n\n\n\n\n(a)\n\n\nArticles\u00a035 to 50 shall apply from 26 November 2017. However, from that date until 26 May 2020, the obligations on notified bodies pursuant to Articles\u00a035 to 50 shall apply only to those bodies which submit an application for designation in accordance with Article\u00a038;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nArticles\u00a0101 and 103 shall apply from 26 November 2017;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nArticle\u00a0102 shall apply from 26 May 2018;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nwithout prejudice to the obligations on the Commission pursuant to Article\u00a034, where, due to circumstances that could not reasonably have been foreseen when drafting the plan referred to in Article\u00a034(1), Eudamed is not fully functional on 26\u00a0May 2020, the obligations and requirements that relate to Eudamed shall apply from the date corresponding to six\u00a0months after the date of publication of the notice referred to in Article\u00a034(3). The provisions referred to in the preceding sentence are:\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a029,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a031,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a032,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a033(4),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe second sentence of Article\u00a040(2),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a042(10),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a043(2),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe second subparagraph\u00a0of Article\u00a044(12),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npoints (d) and (e) of Article\u00a046(7),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a053(2),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a054(3),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a055(1),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticles\u00a070 to 77,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nparagraphs 1 to 13 of Article\u00a078,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticles\u00a079 to 82,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a086(2),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticles\u00a087 and 88,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a089(5) and (7), and the third subparagraph\u00a0of Article\u00a089(8),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a090,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a093(4), (7) and (8),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a095(2) and (4),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe last sentence of Article\u00a097(2),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a099(4),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe second sentence of the first subparagraph\u00a0of Article\u00a0120(3).\n\n\n\n\nUntil Eudamed is fully functional, the corresponding provisions of Directives\u00a090/385/EEC and 93/42/EEC shall continue to apply for the purpose of meeting the obligations laid down in the provisions listed in the first paragraph\u00a0of this point regarding exchange of information including, and in particular, information regarding vigilance reporting, clinical investigations, registration of devices and economic operators, and certificate notifications.\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nArticle\u00a029(4) and Article\u00a056(5) shall apply from 18 months after the later of the dates referred to in point\u00a0(d);\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nfor implantable devices and for class III devices Article\u00a027(4) shall apply from 26\u00a0May 2021. For class\u00a0IIa and class\u00a0IIb devices Article\u00a027(4) shall apply from 26\u00a0May 2023. For class I devices Article\u00a027(4) shall apply from 26\u00a0May 2025;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nfor reusable devices that shall bear the UDI carrier on the device itself, Article\u00a027(4) shall apply from two years after the date referred to in point\u00a0(f) of this paragraph\u00a0for the respective class of devices in that point;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nThe procedure set out in Article\u00a078 shall apply from 26 May 2027, without prejudice to Article\u00a078(14);\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nArticle\u00a0120(12) shall apply from 26 May 2019.\n\n\n\n\n\n\n\n\n\n\nThis Regulation shall be binding in its entirety and directly applicable in all Member\u00a0States.\nDone at Strasbourg, 5 April 2017.\n\n\nFor the European Parliament\n\n\nThe President\n\nA. TAJANI\n            \n\n\n\nFor the Council\n\n\nThe President\n\nI. BORG\n            \n\n\n\n\n\n(1)\u00a0\u00a0Opinion of 14 February 2013 (OJ\u00a0C\u00a0133, 9.5.2013, p.\u00a052).\n\n(2)\u00a0\u00a0Position of the European Parliament of 2 April 2014 (not yet published in the Official Journal) and position of the Council at first reading of 7 March 2017 (not yet published in the Official Journal).\n\n(3)\u00a0\u00a0Council Directive\u00a090/385/EEC of 20 June 1990 on the approximation of the laws of the Member\u00a0States relating to active implantable medical devices (OJ\u00a0L\u00a0189, 20.7.1990, p.\u00a017).\n\n(4)\u00a0\u00a0Council Directive\u00a093/42/EEC of 14 June 1993 concerning medical devices (OJ\u00a0L\u00a0169, 12.7.1993, p.\u00a01).\n\n(5)\u00a0\u00a0Regulation (EC)\u00a0No\u00a0178/2002 of the European Parliament and of the Council of 28\u00a0January\u00a02002 laying down the general principles and requirements of food law, establishing the European Food Safety Authority and laying down procedures in matters of food safety (OJ\u00a0L\u00a031, 1.2.2002, p.\u00a01).\n\n(6)\u00a0\u00a0Regulation (EC)\u00a0No\u00a01223/2009 of the European Parliament and of the Council of 30\u00a0November 2009 on cosmetic products (OJ\u00a0L\u00a0342, 22.12.2009, p.\u00a059).\n\n(7)\u00a0\u00a0Directive\u00a02001/83/EC of the European Parliament and of the Council of 6\u00a0November\u00a02001 on the Community code relating to medicinal products for human use (OJ\u00a0L\u00a0311, 28.11.2001, p.\u00a067).\n\n(8)\u00a0\u00a0Regulation (EC)\u00a0No\u00a01394/2007 of the European Parliament and of the Council of 13\u00a0November\u00a02007 on advanced therapy medicinal products and amending Directive\u00a02001/83/EC and Regulation (EC)\u00a0No\u00a0726/2004 (OJ\u00a0L\u00a0324, 10.12.2007, p.\u00a0121).\n\n(9)\u00a0\u00a0Directive\u00a02004/23/EC of the European Parliament and of the Council of 31\u00a0March\u00a02004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells (OJ\u00a0L\u00a0102, 7.4.2004, p.\u00a048).\n\n(10)\u00a0\u00a0Directive\u00a02002/98/EC of the European Parliament and of the Council of 27\u00a0January\u00a02003 setting standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components (OJ\u00a0L\u00a033, 8.2.2003, p.\u00a030).\n\n(11)\u00a0\u00a0Commission Recommendation 2011/696/EU of 18 October 2011 on the definition of nanomaterial (OJ\u00a0L\u00a0275, 20.10.2011, p.\u00a038).\n\n(12)\u00a0\u00a0Directive\u00a02014/30/EU of the European Parliament and of the Council of 26\u00a0February\u00a02014 on the harmonisation of the laws of the Member\u00a0States relating to electromagnetic compatibility (OJ\u00a0L\u00a096, 29.3.2014. p.\u00a079).\n\n(13)\u00a0\u00a0Council Directive\u00a02013/59/Euratom of 5\u00a0December\u00a02013 laying down basic safety standards for protection against the dangers arising from exposure to ionising radiation, and repealing Directives\u00a089/618/Euratom, 90/641/Euratom, 96/29/Euratom, 97/43/Euratom and 2003/122/Euratom (OJ\u00a0L\u00a013, 17.1.2014, p.\u00a01).\n\n(14)\u00a0\u00a0Directive\u00a0(EU)\u00a02015/1535 of the European Parliament and of the Council of 9\u00a0September\u00a02015 laying down a procedure for the provision of information in the field of technical regulations and of rules on Information Society services (OJ\u00a0L\u00a0241, 17.9.2015, p.\u00a01).\n\n(15)\u00a0\u00a0Regulation (EU)\u00a0No\u00a01025/2012 of the European Parliament and of the Council of 25\u00a0October 2012 on European standardisation, amending Council Directives 89/686/EEC and 93/15/EEC and Directives 94/9/EC, 94/25/EC, 95/16/EC, 97/23/EC, 98/34/EC, 2004/22/EC, 2007/23/EC, 2009/23/EC and 2009/105/EC of the European Parliament and of the Council and repealing Council Decision 87/95/EEC and Decision No\u00a01673/2006/EC of the European Parliament and of the Council (OJ\u00a0L\u00a0316, 14.11.2012, p.\u00a012).\n\n(16)\u00a0\u00a0Directive\u00a098/79/EC of the European Parliament and of the Council of 27\u00a0October\u00a01998 on in\u00a0vitro diagnostic medical devices (OJ\u00a0L\u00a0331, 7.12.1998, p.\u00a01).\n\n(17)\u00a0\u00a0Regulation (EC)\u00a0No\u00a0765/2008 of the European Parliament and of the Council of 9\u00a0July\u00a02008 setting out the requirements for accreditation and market surveillance relating to the marketing of products and repealing Regulation (EEC) No\u00a0339/93 (OJ\u00a0L\u00a0218, 13.8.2008, p.\u00a030).\n\n(18)\u00a0\u00a0Decision No\u00a0768/2008/EC of the European Parliament and of the Council of 9\u00a0July\u00a02008 on a common framework for the marketing of products, and repealing Council Decision\u00a093/465/EEC (OJ\u00a0L\u00a0218, 13.8.2008, p.\u00a082).\n\n(19)\u00a0\u00a0Council Directive\u00a085/374/EEC of 25\u00a0July\u00a01985 on the approximation of the laws, regulations and administrative provisions of the Member\u00a0States concerning liability for defective products (OJ\u00a0L\u00a0210, 7.8.1985, p.\u00a029).\n\n(20)\u00a0\u00a0Judgment of 28\u00a0July\u00a02011 in Orifarm and Paranova, joined cases C-400/09 and C-207/10, ECLI:EU:C:2011:519.\n\n(21)\u00a0\u00a0Commission Decision\u00a02010/227/EU of 19 April 2010 on the European Databank for Medical Devices (OJ\u00a0L\u00a0102, 23.4.2010, p.\u00a045).\n\n(22)\u00a0\u00a0Directive\u00a095/46/EC of the European Parliament and of the Council of 24\u00a0October\u00a01995 on the protection of individuals with regard to the processing of personal data and on the free movement of such data (OJ\u00a0L\u00a0281, 23.11.1995, p.\u00a031).\n\n(23)\u00a0\u00a0Regulation (EC)\u00a0No\u00a045/2001 of the European Parliament and of the Council of 18\u00a0December\u00a02000 on the protection of individuals with regard to the processing of personal data by the Community institutions and bodies and on the free movement of such data (OJ\u00a0L\u00a08, 12.1.2001, p.\u00a01).\n\n(24)\u00a0\u00a0Directive\u00a02010/63/EU of the European Parliament and of the Council of 22\u00a0September\u00a02010 on the protection of animals used for scientific purposes (OJ\u00a0L\u00a0276, 20.10.2010, p.\u00a033).\n\n(25)\u00a0\u00a0Regulation (EU)\u00a02017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision\u00a02010/227/EU (see page 176 of this Official Journal).\n\n(26)\u00a0\u00a0\n            OJ\u00a0L\u00a0123, 12.5.2016, p.\u00a01.\n\n(27)\u00a0\u00a0Regulation (EU)\u00a0No\u00a0182/2011 of the European Parliament and of the Council of 16\u00a0February 2011 laying down the rules and general principles concerning mechanisms for control by Member\u00a0States of the Commission's exercise of implementing powers (OJ\u00a0L\u00a055, 28.2.2011, p.\u00a013).\n\n(28)\u00a0\u00a0Commission Regulation (EU)\u00a0No\u00a0207/2012 of 9\u00a0March\u00a02012 on electronic instructions for use of medical devices (OJ\u00a0L\u00a072, 10.3.2012, p.\u00a028).\n\n(29)\u00a0\u00a0Commission Regulation (EU)\u00a0No\u00a0722/2012 of 8 August 2012 concerning particular requirements as regards the requirements laid down in Council Directives 90/385/EEC and 93/42/EEC with respect to active implantable medical devices and medical devices manufactured utilising tissues of animal origin (OJ\u00a0L\u00a0212, 9.8.2012, p.\u00a03).\n\n(30)\u00a0\u00a0Commission Directive\u00a02003/12/EC of 3 February 2003 on the reclassification of breast implants in the framework of Directive\u00a093/42/EEC concerning medical devices (OJ\u00a0L\u00a028, 4.2.2003, p.\u00a043).\n\n(31)\u00a0\u00a0Commission Directive\u00a02005/50/EC of 11 August 2005 on the reclassification of hip, knee and shoulder joint replacements in the framework of Council Directive\u00a093/42/EEC concerning medical devices (OJ\u00a0L\u00a0210, 12.8.2005, p.\u00a041).\n\n(32)\u00a0\u00a0Commission Implementing Regulation (EU)\u00a0No\u00a0920/2013 of 24 September 2013 on the designation and the supervision of notified bodies under Council Directive\u00a090/385/EEC on active implantable medical devices and Council Directive\u00a093/42/EEC on medical devices (OJ\u00a0L\u00a0253, 25.9.2013, p.\u00a08).\n\n(33)\u00a0\u00a0\n            OJ\u00a0C 358, 7.12.2013, p.\u00a010.\n\n(34)\u00a0\u00a0Regulation\u00a0(EC)\u00a0No\u00a0726/2004 of the European Parliament and of the Council of 31\u00a0March\u00a02004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (OJ\u00a0L\u00a0136, 30.4.2004, p.\u00a01).\n\n(35)\u00a0\u00a0Directive\u00a02006/42/EC of the European Parliament and of the Council of 17\u00a0May\u00a02006 on machinery, and amending Directive\u00a095/16/EC (OJ\u00a0L\u00a0157, 9.6.2006, p.\u00a024).\n\n(36)\u00a0\u00a0Commission Recommendation 2003/361/\u0395C of 6\u00a0May\u00a02003 concerning the definition of micro, small and medium-sized enterprises (OJ\u00a0L\u00a0124, 20.5.2003, p.\u00a036).\n\n(37)\u00a0\u00a0Regulation (EU)\u00a0No\u00a0536/2014 of the European Parliament and of the Council of 16\u00a0April\u00a02014 on clinical trials on medicinal products for human use, and repealing Directive\u00a02001/20/EC (OJ\u00a0L\u00a0158, 27.5.2014, p.\u00a01).\n\n\n\n\nANNEXES\n\nI\u00a0\u00a0\u00a0\n\nGeneral safety and performance requirements\n\n\n\nII\u00a0\u00a0\u00a0\n\nTechnical documentation\n\n\n\nIII\u00a0\u00a0\u00a0\n\nTechnical documentation on post-market surveillance\n\n\n\nIV\u00a0\u00a0\u00a0\n\nEU declaration of conformity\n\n\n\nV\u00a0\u00a0\u00a0\n\nCE marking of conformity\n\n\n\nVI\u00a0\u00a0\u00a0\n\nInformation to be submitted upon the registration of devices and economic operators in accordance with Articles\u00a029(4) and 31; core data elements to be provided to the UDI\u00a0database together with the UDI-DI in accordance with Articles\u00a028 and 29;and the UDI\u00a0system\n\n\n\nVII\u00a0\u00a0\u00a0\n\nRequirements to be met by notified bodies\n\n\n\nVIII\u00a0\u00a0\u00a0\n\nClassification rules\n\n\n\nIX\u00a0\u00a0\u00a0\n\nConformity assessment based on a quality management system and assessment of the technical documentation\n\n\n\nX\u00a0\u00a0\u00a0\n\nConformity assessment based on type examination\n\n\n\nXI\u00a0\u00a0\u00a0\n\nConformity assessment based on product conformity verification\n\n\n\nXII\u00a0\u00a0\u00a0\n\nCertificates issued by a notified body\n\n\n\nXIII\u00a0\u00a0\u00a0\n\nProcedure for custom-made devices\n\n\n\nXIV\u00a0\u00a0\u00a0\n\nClinical evaluation and post-market clinical follow-up\n\n\n\nXV\u00a0\u00a0\u00a0\n\nClinical investigations\n\n\n\nXVI\u00a0\u00a0\u00a0\n\nList of groups of products without an intended medical purpose referred to in Article\u00a01(2)\n\n\n\nXVII\u00a0\u00a0\u00a0\n\nCorrelation table\n\n\n\n\n\n\n\nANNEX I\n\nGENERAL SAFETY AND PERFORMANCE REQUIREMENTS\n\nCHAPTER I\n\n\nGENERAL REQUIREMENTS\n\n\n1.\u00a0\u00a0\u00a0Devices shall achieve the performance intended by their manufacturer and shall be designed and manufactured in such a way that, during normal conditions of use, they are suitable for their intended purpose. They shall be safe and effective and shall not compromise the clinical condition or the safety of patients, or the safety and health of users or, where applicable, other persons, provided that any risks which may be associated with their use constitute acceptable risks when weighed against the benefits to the patient and are compatible with a high level of protection of health and safety, taking into account the generally acknowledged state of the art.\n2.\u00a0\u00a0\u00a0The requirement in this Annex\u00a0to reduce risks as far as possible means the reduction of risks as far as possible without adversely affecting the benefit-risk ratio.\n3.\u00a0\u00a0\u00a0Manufacturers shall establish, implement, document and maintain a risk management system.\nRisk management shall be understood as a continuous iterative process throughout the entire lifecycle of a device, requiring regular systematic updating. In carrying out risk management manufacturers shall:\n\n\n\n\n\n\n(a)\n\n\nestablish and document a risk management plan for each device;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nidentify and analyse the known and foreseeable hazards associated with each device;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nestimate and evaluate the risks associated with, and occurring during, the intended use and during reasonably foreseeable misuse;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\neliminate or control the risks referred to in point\u00a0(c) in accordance with the requirements of Section\u00a04;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nevaluate the impact of information from the production phase and, in particular, from the post-market surveillance system, on hazards and the frequency of occurrence thereof, on estimates of their associated risks, as well as on the overall risk, benefit-risk ratio and risk acceptability; and\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nbased on the evaluation of the impact of the information referred to in point\u00a0(e), if necessary amend control measures in line with the requirements of Section\u00a04.\n\n\n\n\n4.\u00a0\u00a0\u00a0Risk control measures adopted by manufacturers for the design and manufacture of the devices shall conform to safety principles, taking account of the generally acknowledged state of the art. To reduce risks, Manufacturers shall manage risks so that the residual risk associated with each hazard as well as the overall residual risk is judged acceptable. In selecting the most appropriate solutions, manufacturers shall, in the following order of priority:\n\n\n\n\n\n\n(a)\n\n\neliminate or reduce risks as far as possible through safe design and manufacture;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nwhere appropriate, take adequate protection measures, including alarms if necessary, in relation to risks that cannot be eliminated; and\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nprovide information for safety (warnings/precautions/contra-indications) and, where appropriate, training to users.\n\n\n\n\nManufacturers shall inform users of any residual risks.\n5.\u00a0\u00a0\u00a0In eliminating or reducing risks related to use error, the manufacturer shall:\n\n\n\n\n\n\n(a)\n\n\nreduce as far as possible the risks related to the ergonomic features of the device and the environment in which the device is intended to be used (design for patient safety), and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ngive consideration to the technical knowledge, experience, education, training and use environment, where applicable, and the medical and physical conditions of intended users (design for lay, professional, disabled or other users).\n\n\n\n\n6.\u00a0\u00a0\u00a0The characteristics and performance of a device shall not be adversely affected to such a degree that the health or safety of the patient or the user and, where applicable, of other persons are compromised during the lifetime of the device, as indicated by the manufacturer, when the device is subjected to the stresses which can occur during normal conditions of use and has been properly maintained in accordance with the manufacturer's instructions.\n7.\u00a0\u00a0\u00a0Devices shall be designed, manufactured and packaged in such a way that their characteristics and performance during their intended use are not adversely affected during transport and storage, for example, through fluctuations of temperature and humidity, taking account of the instructions and information provided by the manufacturer.\n8.\u00a0\u00a0\u00a0All known and foreseeable risks, and any undesirable side-effects, shall be minimised and be acceptable when weighed against the evaluated benefits to the patient and/or user arising from the achieved performance of the device during normal conditions of use.\n9.\u00a0\u00a0\u00a0For the devices referred to in Annex\u00a0XVI, the general safety requirements set out in Sections 1 and 8 shall be understood to mean that the device, when used under the conditions and for the purposes intended, does not present a risk at all or presents a risk that is no more than the maximum acceptable risk related to the product's use which is consistent with a high level of protection for the safety and health of persons.\nCHAPTER II\n\n\nREQUIREMENTS REGARDING DESIGN AND MANUFACTURE\n\n\n10.\u00a0\u00a0\u00a0Chemical, physical and biological properties\n10.1.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to ensure that the characteristics and performance requirements referred to in Chapter I are fulfilled. Particular attention shall be paid to:\n\n\n\n\n\n\n(a)\n\n\nthe choice of materials and substances used, particularly as regards toxicity and, where relevant, flammability;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe compatibility between the materials and substances used and biological tissues, cells and body fluids, taking account of the intended purpose of the device and, where relevant, absorption, distribution, metabolism and excretion;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe compatibility between the different parts of a device which consists of more than one implantable part;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe impact of processes on material properties;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nwhere appropriate, the results of biophysical or modelling research the validity of which has been demonstrated beforehand;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe mechanical properties of the materials used, reflecting, where appropriate, matters such as strength, ductility, fracture resistance, wear resistance and fatigue resistance;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nsurface properties; and\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe confirmation that the device meets any defined chemical and/or physical specifications.\n\n\n\n\n10.2.\u00a0\u00a0\u00a0Devices shall be designed, manufactured and packaged in such a way as to minimise the risk posed by contaminants and residues to patients, taking account of the intended purpose of the device, and to the persons involved in the transport, storage and use of the devices. Particular attention shall be paid to tissues exposed to those contaminants and residues and to the duration and frequency of exposure.\n10.3.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way that they can be used safely with the materials and substances, including gases, with which they enter into contact during their intended use; if the devices are intended to administer medicinal products they shall be designed and manufactured in such a way as to be compatible with the medicinal products concerned in accordance with the provisions and restrictions governing those medicinal products and that the performance of both the medicinal products and of the devices is maintained in accordance with their respective indications and intended use.\n10.4.\u00a0\u00a0\u00a0Substances\n10.4.1.\u00a0\u00a0\u00a0Design and manufacture of devices\nDevices shall be designed and manufactured in such a way as to reduce as far as possible the risks posed by substances or particles, including wear debris, degradation products and processing residues, that may be released from the device.\nDevices, or those parts thereof or those materials used therein that:\n\n\n\n\n\n\n\u2014\n\n\nare invasive and come into direct contact with the human body,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\n(re)administer medicines, body liquids or other substances, including gases, to/from the body, or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntransport or store such medicines, body fluids or substances, including gases, to be (re)administered to the body,\n\n\n\n\nshall only contain the following substances in a concentration that is above 0,1 % weight by weight (w/w) where justified pursuant to Section\u00a010.4.2:\n\n\n\n\n\n\n(a)\n\n\nsubstances which are carcinogenic, mutagenic or toxic to reproduction (\u2018CMR\u2019), of category\u00a01A or 1B, in accordance with Part 3 of Annex\u00a0VI to Regulation (EC)\u00a0No\u00a01272/2008 of the European Parliament and of the Council\u00a0(1), or\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nsubstances having endocrine-disrupting properties for which there is scientific evidence of probable serious effects to human health and which are identified either in accordance with the procedure set out in Article\u00a059 of Regulation\u00a0(EC)\u00a0No\u00a01907/2006 of the European Parliament and of the Council\u00a0(2) or, once a delegated act has been adopted by the Commission pursuant to the first subparagraph\u00a0of Article\u00a05(3) of Regulation\u00a0(EU)\u00a0No\u00a0528/2012 of the European Parliament and the Council\u00a0(3), in accordance with the criteria that are relevant to human health amongst the criteria established therein.\n\n\n\n\n10.4.2.\u00a0\u00a0\u00a0Justification regarding the presence of CMR and/or endocrine-disrupting substances\nThe justification for the presence of such substances shall be based upon:\n\n\n\n\n\n\n(a)\n\n\nan analysis and estimation of potential patient or user exposure to the substance;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nan analysis of possible alternative substances, materials or designs, including, where available, information about independent research, peer-reviewed studies, scientific opinions from relevant scientific committees and an analysis of the availability of such alternatives;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nargumentation as to why possible substance and/ or material substitutes, if available, or design changes, if feasible, are inappropriate in relation to maintaining the functionality, performance and the benefit-risk ratios of the product; including taking into account if the intended use of such devices includes treatment of children or treatment of pregnant or breastfeeding women or treatment of other patient groups considered particularly vulnerable to such substances and/or materials; and\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nwhere applicable and available, the latest relevant scientific committee guidelines in accordance with Sections 10.4.3. and 10.4.4.\n\n\n\n\n10.4.3.\u00a0\u00a0\u00a0Guidelines on phthalates\nFor the purposes of Section\u00a010.4., the Commission shall, as soon as possible and by 26 May 2018, provide the relevant scientific committee with a mandate to prepare guidelines that shall be ready before 26 May 2020. The mandate for the committee shall encompass at least a benefit-risk assessment of the presence of phthalates which belong to either of the groups of substances referred to in points (a) and (b) of Section\u00a010.4.1. The benefit-risk assessment shall take into account the intended purpose and context of the use of the device, as well as any available alternative substances and alternative materials, designs or medical treatments. When deemed appropriate on the basis of the latest scientific evidence, but at least every five years, the guidelines shall be updated.\n10.4.4.\u00a0\u00a0\u00a0Guidelines on other CMR and endocrine-disrupting substances\nSubsequently, the Commission shall mandate the relevant scientific committee to prepare guidelines as referred to in Section\u00a010.4.3. also for other substances referred to in points\u00a0(a) and (b) of Section\u00a010.4.1., where appropriate.\n10.4.5.\u00a0\u00a0\u00a0Labelling\nWhere devices, parts thereof or materials used therein as referred to in Section\u00a010.4.1. contain substances referred to in points (a) or (b) of Section\u00a010.4.1. in a concentration above 0,1 % weight by weight (w/w), the presence of those substances shall be labelled on the device itself and/or on the packaging for each unit or, where appropriate, on the sales packaging, with the list of such substances. If the intended use of such devices includes treatment of children or treatment of pregnant or breastfeeding women or treatment of other patient groups considered particularly vulnerable to such substances and/or materials, information on residual risks for those patient groups and, if applicable, on appropriate precautionary measures shall be given in the instructions for use.\n10.5.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks posed by the unintentional ingress of substances into the device taking into account the device and the nature of the environment in which it is intended to be used.\n10.6.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks linked to the size and the properties of particles which are or can be released into the patient's or user's body, unless they come into contact with intact skin only. Special attention shall be given to nanomaterials.\n11.\u00a0\u00a0\u00a0Infection and microbial contamination\n11.1.\u00a0\u00a0\u00a0Devices and their manufacturing processes shall be designed in such a way as to eliminate or to reduce as far as possible the risk of infection to patients, users and, where applicable, other persons. The design shall:\n\n\n\n\n\n\n(a)\n\n\nreduce as far as possible and appropriate the risks from unintended cuts and pricks, such as needle stick injuries,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nallow easy and safe handling,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nreduce as far as possible any microbial leakage from the device and/or microbial exposure during use, and\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nprevent microbial contamination of the device or its content such as specimens or fluids.\n\n\n\n\n11.2.\u00a0\u00a0\u00a0Where necessary devices shall be designed to facilitate their safe cleaning, disinfection, and/or re-sterilisation.\n11.3.\u00a0\u00a0\u00a0Devices labelled as having a specific microbial state shall be designed, manufactured and packaged to ensure that they remain in that state when placed on the market and remain so under the transport and storage conditions specified by the manufacturer.\n11.4.\u00a0\u00a0\u00a0Devices delivered in a sterile state shall be designed, manufactured and packaged in accordance with appropriate procedures, to ensure that they are sterile when placed on the market and that, unless the packaging which is intended to maintain their sterile condition is damaged, they remain sterile, under the transport and storage conditions specified by the manufacturer, until that packaging is opened at the point of use. It shall be ensured that the integrity of that packaging is clearly evident to the final user.\n11.5.\u00a0\u00a0\u00a0Devices labelled as sterile shall be processed, manufactured, packaged and, sterilised by means of appropriate, validated methods.\n11.6.\u00a0\u00a0\u00a0Devices intended to be sterilised shall be manufactured and packaged in appropriate and controlled conditions and facilities.\n11.7.\u00a0\u00a0\u00a0Packaging systems for non-sterile devices shall maintain the integrity and cleanliness of the product and, where the devices are to be sterilised prior to use, minimise the risk of microbial contamination; the packaging system shall be suitable taking account of the method of sterilisation indicated by the manufacturer.\n11.8.\u00a0\u00a0\u00a0The labelling of the device shall distinguish between identical or similar devices placed on the market in both a sterile and a non-sterile condition additional to the symbol used to indicate that devices are sterile.\n12.\u00a0\u00a0\u00a0Devices incorporating a substance considered to be a medicinal product and devices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body.\n12.1.\u00a0\u00a0\u00a0In the case of devices referred to in the first subparagraph\u00a0of Article\u00a01(8), the quality, safety and usefulness of the substance which, if used separately, would be considered to be a medicinal product within the meaning of point\u00a0(2) of Article\u00a01 of Directive\u00a02001/83/EC, shall be verified by analogy with the methods specified in Annex\u00a0I to Directive\u00a02001/83/EC, as required by the applicable conformity assessment procedure under this Regulation.\n12.2.\u00a0\u00a0\u00a0Devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body, and that are absorbed by or locally dispersed in the human body shall comply, where applicable and in a manner limited to the aspects not covered by this Regulation, with the relevant requirements laid down in Annex\u00a0I to Directive\u00a02001/83/EC for the evaluation of absorption, distribution, metabolism, excretion, local tolerance, toxicity, interaction with other devices, medicinal products or other substances and potential for adverse reactions, as required by the applicable conformity assessment procedure under this Regulation.\n13.\u00a0\u00a0\u00a0Devices incorporating materials of biological origin\n13.1.\u00a0\u00a0\u00a0For devices manufactured utilising derivatives of tissues or cells of human origin which are non-viable or are rendered non-viable covered by this Regulation in accordance with point\u00a0(g) of Article\u00a01(6), the following shall apply:\n\n\n\n\n\n\n(a)\n\n\ndonation, procurement and testing of the tissues and cells shall be done in accordance with Directive\u00a02004/23/EC;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nprocessing, preservation and any other handling of those tissues and cells or their derivatives shall be carried out so as to provide safety for patients, users and, where applicable, other persons. In particular, safety with regard to viruses and other transmissible agents shall be addressed by appropriate methods of sourcing and by implementation of validated methods of elimination or inactivation in the course of the manufacturing process;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe traceability system for those devices shall be complementary and compatible with the traceability and data protection requirements laid down in Directive\u00a02004/23/EC and in Directive\u00a02002/98/EC.\n\n\n\n\n13.2.\u00a0\u00a0\u00a0For devices manufactured utilising tissues or cells of animal origin, or their derivatives, which are non-viable or rendered non-viable the following shall apply:\n\n\n\n\n\n\n(a)\n\n\nwhere feasible taking into account the animal species, tissues and cells of animal origin, or their derivatives, shall originate from animals that have been subjected to veterinary controls that are adapted to the intended use of the tissues. Information on the geographical origin of the animals shall be retained by manufacturers;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nsourcing, processing, preservation, testing and handling of tissues, cells and substances of animal origin, or their derivatives, shall be carried out so as to provide safety for patients, users and, where applicable, other persons. In particular safety with regard to viruses and other transmissible agents shall be addressed by implementation of validated methods of elimination or viral inactivation in the course of the manufacturing process, except when the use of such methods would lead to unacceptable degradation compromising the clinical benefit of the device;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nin the case of devices manufactured utilising tissues or cells of animal origin, or their derivatives, as referred to in Regulation\u00a0(EU)\u00a0No\u00a0722/2012 the particular requirements laid down in that Regulation shall apply.\n\n\n\n\n13.3.\u00a0\u00a0\u00a0For devices manufactured utilising non-viable biological substances other than those referred to in Sections\u00a013.1 and 13.2, the processing, preservation, testing and handling of those substances shall be carried out so as to provide safety for patients, users and, where applicable, other persons, including in the waste disposal chain. In particular, safety with regard to viruses and other transmissible agents shall be addressed by appropriate methods of sourcing and by implementation of validated methods of elimination or inactivation in the course of the manufacturing process.\n14.\u00a0\u00a0\u00a0Construction of devices and interaction with their environment\n14.1.\u00a0\u00a0\u00a0If the device is intended for use in combination with other devices or equipment the whole combination, including the connection system shall be safe and shall not impair the specified performance of the devices. Any restrictions on use applying to such combinations shall be indicated on the label and/or in the instructions for use. Connections which the user has to handle, such as fluid, gas transfer, electrical or mechanical coupling, shall be designed and constructed in such a way as to minimise all possible risks, such as misconnection.\n14.2.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to remove or reduce as far as possible:\n\n\n\n\n\n\n(a)\n\n\nthe risk of injury, in connection with their physical features, including the volume/pressure ratio, dimensional and where appropriate ergonomic features;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nrisks connected with reasonably foreseeable external influences or environmental conditions, such as magnetic fields, external electrical and electromagnetic effects, electrostatic discharge, radiation associated with diagnostic or therapeutic procedures, pressure, humidity, temperature, variations in pressure and acceleration or radio signal interferences;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe risks associated with the use of the device when it comes into contact with materials, liquids, and substances, including gases, to which it is exposed during normal conditions of use;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe risks associated with the possible negative interaction between software and the IT environment within which it operates and interacts;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe risks of accidental ingress of substances into the device;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe risks of reciprocal interference with other devices normally used in the investigations or for the treatment given; and\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nrisks arising where maintenance or calibration are not possible (as with implants), from ageing of materials used or loss of accuracy of any measuring or control mechanism.\n\n\n\n\n14.3.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to minimise the risks of fire or explosion during normal use and in single fault condition. Particular attention shall be paid to devices the intended use of which includes exposure to or use in association with flammable or explosive substances or substances which could cause combustion.\n14.4.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way that adjustment, calibration, and maintenance can be done safely and effectively.\n14.5.\u00a0\u00a0\u00a0Devices that are intended to be operated together with other devices or products shall be designed and manufactured in such a way that the interoperability and compatibility are reliable and safe.\n14.6\u00a0\u00a0\u00a0Any measurement, monitoring or display scale shall be designed and manufactured in line with ergonomic principles, taking account of the intended purpose, users and the environmental conditions in which the devices are intended to be used.\n14.7.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to facilitate their safe disposal and the safe disposal of related waste substances by the user, patient or other person. To that end, manufacturers shall identify and test procedures and measures as a result of which their devices can be safely disposed after use. Such procedures shall be described in the instructions for use.\n15.\u00a0\u00a0\u00a0Devices with a diagnostic or measuring function\n15.1.\u00a0\u00a0\u00a0Diagnostic devices and devices with a measuring function, shall be designed and manufactured in such a way as to provide sufficient accuracy, precision and stability for their intended purpose, based on appropriate scientific and technical methods. The limits of accuracy shall be indicated by the manufacturer.\n15.2.\u00a0\u00a0\u00a0The measurements made by devices with a measuring function shall be expressed in legal units conforming to the provisions of Council Directive\u00a080/181/EEC\u00a0(4).\n16.\u00a0\u00a0\u00a0Protection against radiation\n16.1.\u00a0\u00a0\u00a0General\n\n\n\n\n\n\n(a)\n\n\nDevices shall be designed, manufactured and packaged in such a way that exposure of patients, users and other persons to radiation is reduced as far as possible, and in a manner that is compatible with the intended purpose, whilst not restricting the application of appropriate specified levels for therapeutic and diagnostic purposes.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nThe operating instructions for devices emitting hazardous or potentially hazardous radiation shall contain detailed information as to the nature of the emitted radiation, the means of protecting the patient and the user, and on ways of avoiding misuse and of reducing the risks inherent to installation as far as possible and appropriate. Information regarding the acceptance and performance testing, the acceptance criteria, and the maintenance procedure shall also be specified.\n\n\n\n\n16.2.\u00a0\u00a0\u00a0Intended radiation\n\n\n\n\n\n\n(a)\n\n\nWhere devices are designed to emit hazardous, or potentially hazardous, levels of ionizing and/or non-ionizing radiation necessary for a specific medical purpose the benefit of which is considered to outweigh the risks inherent to the emission, it shall be possible for the user to control the emissions. Such devices shall be designed and manufactured to ensure reproducibility of relevant variable parameters within an acceptable tolerance.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nWhere devices are intended to emit hazardous, or potentially hazardous, ionizing and/or non-ionizing radiation, they shall be fitted, where possible, with visual displays and/or audible warnings of such emissions.\n\n\n\n\n16.3.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way that exposure of patients, users and other persons to the emission of unintended, stray or scattered radiation is reduced as far as possible. Where possible and appropriate, methods shall be selected which reduce the exposure to radiation of patients, users and other persons who may be affected.\n16.4.\u00a0\u00a0\u00a0Ionising radiation\n\n\n\n\n\n\n(a)\n\n\nDevices intended to emit ionizing radiation shall be designed and manufactured taking into account the requirements of the Directive\u00a02013/59/Euratom laying down basic safety standards for protection against the dangers arising from exposure to ionising radiation.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nDevices intended to emit ionising radiation shall be designed and manufactured in such a way as to ensure that, where possible, taking into account the intended use, the quantity, geometry and quality of the radiation emitted can be varied and controlled, and, if possible, monitored during treatment.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nDevices emitting ionising radiation intended for diagnostic radiology shall be designed and manufactured in such a way as to achieve an image and/or output quality that are appropriate to the intended medical purpose whilst minimising radiation exposure of the patient and user.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nDevices that emit ionising radiation and are intended for therapeutic radiology shall be designed and manufactured in such a way as to enable reliable monitoring and control of the delivered dose, the beam type, energy and, where appropriate, the quality of radiation.\n\n\n\n\n17.\u00a0\u00a0\u00a0Electronic programmable systems \u2014 devices that incorporate electronic programmable systems and software that are devices in themselves\n17.1.\u00a0\u00a0\u00a0Devices that incorporate electronic programmable systems, including software, or software that are devices in themselves, shall be designed to ensure repeatability, reliability and performance in line with their intended use. In the event of a single fault condition, appropriate means shall be adopted to eliminate or reduce as far as possible consequent risks or impairment of performance.\n17.2.\u00a0\u00a0\u00a0For devices that incorporate software or for software that are devices in themselves, the software shall be developed and manufactured in accordance with the state of the art taking into account the principles of development life cycle, risk management, including information security, verification and validation.\n17.3.\u00a0\u00a0\u00a0Software referred to in this Section\u00a0that is intended to be used in combination with mobile computing platforms shall be designed and manufactured taking into account the specific features of the mobile platform (e.g. size and contrast ratio of the screen) and the external factors related to their use (varying environment as regards level of light or noise).\n17.4.\u00a0\u00a0\u00a0Manufacturers shall set out minimum requirements concerning hardware, IT networks characteristics and IT security measures, including protection against unauthorised access, necessary to run the software as intended.\n18.\u00a0\u00a0\u00a0Active devices and devices connected to them\n18.1.\u00a0\u00a0\u00a0For non-implantable active devices, in the event of a single fault condition, appropriate means shall be adopted to eliminate or reduce as far as possible consequent risks.\n18.2.\u00a0\u00a0\u00a0Devices where the safety of the patient depends on an internal power supply shall be equipped with a means of determining the state of the power supply and an appropriate warning or indication for when the capacity of the power supply becomes critical. If necessary, such warning or indication shall be given prior to the power supply becoming critical.\n18.3.\u00a0\u00a0\u00a0Devices where the safety of the patient depends on an external power supply shall include an alarm system to signal any power failure.\n18.4.\u00a0\u00a0\u00a0Devices intended to monitor one or more clinical parameters of a patient shall be equipped with appropriate alarm systems to alert the user of situations which could lead to death or severe deterioration of the patient's state of health.\n18.5.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks of creating electromagnetic interference which could impair the operation of the device in question or other devices or equipment in the intended environment.\n18.6.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to provide a level of intrinsic immunity to electromagnetic interference such that is adequate to enable them to operate as\u00a0intended.\n18.7.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to avoid, as far as possible, the risk of accidental electric shocks to the patient, user or any other person, both during normal use of the device and in the event of a single fault condition in the device, provided the device is installed and maintained as indicated by the manufacturer.\n18.8.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to protect, as far as possible, against unauthorised access that could hamper the device from functioning as intended.\n19.\u00a0\u00a0\u00a0Particular requirements for active implantable devices\n19.1.\u00a0\u00a0\u00a0Active implantable devices shall be designed and manufactured in such a way as to remove or minimize as far as possible:\n\n\n\n\n\n\n(a)\n\n\nrisks connected with the use of energy sources with particular reference, where electricity is used, to insulation, leakage currents and overheating of the devices,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nrisks connected with medical treatment, in particular those resulting from the use of defibrillators or high-frequency surgical equipment, and\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nrisks which may arise where maintenance and calibration are impossible, including:\n\n\n\n\n\n\n\u2014\n\n\nexcessive increase of leakage currents,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nageing of the materials used,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nexcess heat generated by the device,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndecreased accuracy of any measuring or control mechanism.\n\n\n\n\n\n\n\n\n19.2.\u00a0\u00a0\u00a0Active implantable devices shall be designed and manufactured in such a way as to ensure\n\n\n\n\n\n\n\u2014\n\n\nif applicable, the compatibility of the devices with the substances they are intended to administer, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe reliability of the source of energy.\n\n\n\n\n19.3.\u00a0\u00a0\u00a0Active implantable devices and, if appropriate, their component parts shall be identifiable to allow any necessary measure to be taken following the discovery of a potential risk in connection with the devices or their component parts.\n19.4.\u00a0\u00a0\u00a0Active implantable devices shall bear a code by which they and their manufacturer can be unequivocally identified (particularly with regard to the type of device and its year of manufacture); it shall be possible to read this code, if necessary, without the need for a surgical operation.\n20.\u00a0\u00a0\u00a0Protection against mechanical and thermal risks\n20.1.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to protect patients and users against mechanical risks connected with, for example, resistance to movement, instability and moving parts.\n20.2.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to reduce to the lowest possible level the risks arising from vibration generated by the devices, taking account of technical progress and of the means available for limiting vibrations, particularly at source, unless the vibrations are part of the specified performance.\n20.3.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to reduce to the lowest possible level the risks arising from the noise emitted, taking account of technical progress and of the means available to reduce noise, particularly at source, unless the noise emitted is part of the specified performance.\n20.4.\u00a0\u00a0\u00a0Terminals and connectors to the electricity, gas or hydraulic and pneumatic energy supplies which the user or other person has to handle, shall be designed and constructed in such a way as to minimise all possible risks.\n20.5.\u00a0\u00a0\u00a0Errors likely to be made when fitting or refitting certain parts which could be a source of risk shall be made impossible by the design and construction of such parts or, failing this, by information given on the parts themselves and/or their housings.\nThe same information shall be given on moving parts and/or their housings where the direction of movement needs to be known in order to avoid a risk.\n20.6.\u00a0\u00a0\u00a0Accessible parts of devices (excluding the parts or areas intended to supply heat or reach given temperatures) and their surroundings shall not attain potentially dangerous temperatures under normal conditions of use.\n21.\u00a0\u00a0\u00a0Protection against the risks posed to the patient or user by devices supplying energy or substances\n21.1.\u00a0\u00a0\u00a0Devices for supplying the patient with energy or substances shall be designed and constructed in such a way that the amount to be delivered can be set and maintained accurately enough to ensure the safety of the patient and of the user.\n21.2.\u00a0\u00a0\u00a0Devices shall be fitted with the means of preventing and/or indicating any inadequacies in the amount of energy delivered or substances delivered which could pose a danger. Devices shall incorporate suitable means to prevent, as far as possible, the accidental release of dangerous levels of energy or substances from an energy and/or substance source.\n21.3.\u00a0\u00a0\u00a0The function of the controls and indicators shall be clearly specified on the devices. Where a device bears instructions required for its operation or indicates operating or adjustment parameters by means of a visual system, such information shall be understandable to the user and, as appropriate, the patient.\n22.\u00a0\u00a0\u00a0Protection against the risks posed by medical devices intended by the manufacturer for use by lay persons\n22.1.\u00a0\u00a0\u00a0Devices for use by lay persons shall be designed and manufactured in such a way that they perform appropriately for their intended purpose taking into account the skills and the means available to lay persons and the influence resulting from variation that can be reasonably anticipated in the lay person's technique and environment. The information and instructions provided by the manufacturer shall be easy for the lay person to understand and apply.\n22.2.\u00a0\u00a0\u00a0Devices for use by lay persons shall be designed and manufactured in such a way as to:\n\n\n\n\n\n\n\u2014\n\n\nensure that the device can be used safely and accurately by the intended user at all stages of the procedure, if necessary after appropriate training and/or information,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreduce, as far as possible and appropriate, the risk from unintended cuts and pricks such as needle stick injuries, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreduce as far as possible the risk of error by the intended user in the handling of the device and, if applicable, in the interpretation of the results.\n\n\n\n\n22.3.\u00a0\u00a0\u00a0Devices for use by lay persons shall, where appropriate, include a procedure by which the lay person:\n\n\n\n\n\n\n\u2014\n\n\ncan verify that, at the time of use, the device will perform as intended by the manufacturer, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif applicable, is warned if the device has failed to provide a valid result.\n\n\n\n\nCHAPTER III\n\n\nREQUIREMENTS REGARDING THE INFORMATION SUPPLIED WITH THE DEVICE\n\n\n23.\u00a0\u00a0\u00a0Label and instructions for use\n23.1.\u00a0\u00a0\u00a0General requirements regarding the information supplied by the manufacturer\nEach device shall be accompanied by the information needed to identify the device and its manufacturer, and by any safety and performance information relevant to the user, or any other person, as appropriate. Such information may appear on the device itself, on the packaging or in the instructions for use, and shall, if the manufacturer has a website, be made available and kept up to date on the website, taking into account the following:\n\n\n\n\n\n\n(a)\n\n\nThe medium, format, content, legibility, and location of the label and instructions for use shall be appropriate to the particular device, its intended purpose and the technical knowledge, experience, education or training of the intended user(s). In particular, instructions for use shall be written in terms readily understood by the intended user and, where appropriate, supplemented with drawings and diagrams.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nThe information required on the label shall be provided on the device itself. If this is not practicable or appropriate, some or all of the information may appear on the packaging for each unit, and/or on the packaging of multiple devices.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nLabels shall be provided in a human-readable format and may be supplemented by machine-readable information, such as radio-frequency identification (\u2018RFID\u2019) or bar codes.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nInstructions for use shall be provided together with devices. By way of exception, instructions for use shall not be required for class I and class IIa devices if such devices can be used safely without any such instructions and unless otherwise provided for elsewhere in this Section.\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nWhere multiple devices are supplied to a single user and/or location, a single copy of the instructions for use may be provided if so agreed by the purchaser who in any case may request further copies to be provided free of charge.\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nInstructions for use may be provided to the user in non-paper format (e.g.\u00a0electronic) to the extent, and only under the conditions, set out in Regulation\u00a0(EU)\u00a0No\u00a0207/2012 or in any subsequent implementing rules adopted pursuant to this Regulation.\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nResidual risks which are required to be communicated to the user and/or other person shall be included as limitations, contra-indications, precautions or warnings in the information supplied by the manufacturer.\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nWhere appropriate, the information supplied by the manufacturer shall take the form of internationally recognised symbols. Any symbol or identification colour used shall conform to the harmonised standards or CS. In areas for which no harmonised standards or CS exist, the symbols and colours shall be described in the documentation supplied with the device.\n\n\n\n\n23.2.\u00a0\u00a0\u00a0Information on the label\nThe label shall bear all of the following particulars:\n\n\n\n\n\n\n(a)\n\n\nthe name or trade name of the device;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe details strictly necessary for a user to identify the device, the contents of the packaging and, where it is not obvious for the user, the intended purpose of the device;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe name, registered trade name or registered trade mark of the manufacturer and the address of its registered place of business;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nif the manufacturer has its registered place of business outside the Union, the name of the authorised representative and address of the registered place of business of the authorised representative;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nwhere applicable, an indication that the device contains or incorporates:\n\n\n\n\n\n\n\u2014\n\n\na medicinal substance, including a human blood or plasma derivative, or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntissues or cells, or their derivatives, of human origin, or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntissues or cells of animal origin, or their derivatives, as referred to in Regulation\u00a0(EU)\u00a0No\u00a0722/2012;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nwhere applicable, information labelled in accordance with Section\u00a010.4.5.;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthe lot number or the serial number of the device preceded by the words LOT NUMBER or SERIAL NUMBER or an equivalent symbol, as appropriate;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe UDI carrier referred to in Article\u00a027(4) and Part C of Annex\u00a0VII;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nan unambiguous indication of t the time limit for using or implanting the device safely, expressed at least in terms of year and month, where this is relevant;\n\n\n\n\n\n\n\n\n\n\n(j)\n\n\nwhere there is no indication of the date until when it may be used safely, the date of manufacture. This date of manufacture may be included as part of the lot number or serial number, provided the date is clearly identifiable;\n\n\n\n\n\n\n\n\n\n\n(k)\n\n\nan indication of any special storage and/or handling condition that applies;\n\n\n\n\n\n\n\n\n\n\n(l)\n\n\nif the device is supplied sterile, an indication of its sterile state and the sterilisation method;\n\n\n\n\n\n\n\n\n\n\n(m)\n\n\nwarnings or precautions to be taken that need to be brought to the immediate attention of the user of the device, and to any other person. This information may be kept to a minimum in which case more detailed information shall appear in the instructions for use, taking into account the intended users;\n\n\n\n\n\n\n\n\n\n\n(n)\n\n\nif the device is intended for single use, an indication of that fact. A manufacturer's indication of single use shall be consistent across the Union;\n\n\n\n\n\n\n\n\n\n\n(o)\n\n\nif the device is a single-use device that has been reprocessed, an indication of that fact, the number of reprocessing cycles already performed, and any limitation as regards the number of reprocessing cycles;\n\n\n\n\n\n\n\n\n\n\n(p)\n\n\nif the device is custom-made, the words \u2018custom-made device\u2019;\n\n\n\n\n\n\n\n\n\n\n(q)\n\n\nan indication that the device is a medical device. If the device is intended for clinical investigation only, the words \u2018exclusively for clinical investigation\u2019;\n\n\n\n\n\n\n\n\n\n\n(r)\n\n\nin the case of devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed by or locally dispersed in the human body, the overall qualitative composition of the device and quantitative information on the main constituent or constituents responsible for achieving the principal intended action;\n\n\n\n\n\n\n\n\n\n\n(s)\n\n\nfor active implantable devices, the serial number, and for other implantable devices, the serial number or the lot number.\n\n\n\n\n23.3.\u00a0\u00a0\u00a0Information on the packaging which maintains the sterile condition of a device (\u2018sterile packaging\u2019)\nThe following particulars shall appear on the sterile packaging:\n\n\n\n\n\n\n(a)\n\n\nan indication permitting the sterile packaging to be recognised as such,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\na declaration that the device is in a sterile condition,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe method of sterilisation,\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe name and address of the manufacturer,\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\na description of the device,\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nif the device is intended for clinical investigations, the words \u2018exclusively for clinical investigations\u2019,\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nif the device is custom-made, the words \u2018custom-made device\u2019,\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe month and year of manufacture,\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nan unambiguous indication of the time limit for using or implanting the device safely expressed at least in terms of year and month, and\n\n\n\n\n\n\n\n\n\n\n(j)\n\n\nan instruction to check the instructions for use for what to do if the sterile packaging is damaged or unintentionally opened before use.\n\n\n\n\n23.4.\u00a0\u00a0\u00a0Information in the instructions for use\nThe instructions for use shall contain all of the following particulars:\n\n\n\n\n\n\n(a)\n\n\nthe particulars referred to in points (a), (c), (e), (f), (k), (l), (n) and (r) of Section\u00a023.2;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe device's intended purpose with a clear specification of indications, contra-indications, the patient target group or groups, and of the intended users, as appropriate;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nwhere applicable, a specification of the clinical benefits to be expected.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nwhere applicable, links to the summary of safety and clinical performance referred to in Article\u00a032;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe performance characteristics of the device;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nwhere applicable, information allowing the healthcare professional to verify if the device is suitable and select the corresponding software and accessories;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nany residual risks, contra-indications and any undesirable side-effects, including information to be conveyed to the patient in this regard;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nspecifications the user requires to use the device appropriately, e.g. if the device has a measuring function, the degree of accuracy claimed for it;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\ndetails of any preparatory treatment or handling of the device before it is ready for use or during its use, such as sterilisation, final assembly, calibration, etc., including the levels of disinfection required to ensure patient safety and all available methods for achieving those levels of disinfection;\n\n\n\n\n\n\n\n\n\n\n(j)\n\n\nany requirements for special facilities, or special training, or particular qualifications of the device user and/or other persons;\n\n\n\n\n\n\n\n\n\n\n(k)\n\n\nthe information needed to verify whether the device is properly installed and is ready to perform safely and as intended by the manufacturer, together with, where relevant:\n\n\n\n\n\n\n\u2014\n\n\ndetails of the nature, and frequency, of preventive and regular maintenance, and of any preparatory cleaning or disinfection,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nidentification of any consumable components and how to replace them,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation on any necessary calibration to ensure that the device operates properly and safely during its intended lifetime, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmethods for eliminating the risks encountered by persons involved in installing, calibrating or servicing devices;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(l)\n\n\nif the device is supplied sterile, instructions in the event of the sterile packaging being damaged or unintentionally opened before use;\n\n\n\n\n\n\n\n\n\n\n(m)\n\n\nif the device is supplied non-sterile with the intention that it is sterilised before use, the appropriate instructions for sterilisation;\n\n\n\n\n\n\n\n\n\n\n(n)\n\n\nif the device is reusable, information on the appropriate processes for allowing reuse, including cleaning, disinfection, packaging and, where appropriate, the validated method of re-sterilisation appropriate to the Member\u00a0State or Member\u00a0States in which the device has been placed on the market. Information shall be provided to identify when the device should no longer be reused, e.g. signs of material degradation or the maximum number of allowable reuses;\n\n\n\n\n\n\n\n\n\n\n(o)\n\n\nan indication, if appropriate, that a device can be reused only if it is reconditioned under the responsibility of the manufacturer to comply with the general safety and performance requirements;\n\n\n\n\n\n\n\n\n\n\n(p)\n\n\nif the device bears an indication that it is for single use, information on known characteristics and technical factors known to the manufacturer that could pose a risk if the device were to be re-used. This information shall be based on a specific section of the manufacturer's risk management documentation, where such characteristics and technical factors shall be addressed in detail. If in accordance with point\u00a0(d) of Section\u00a023.1. no instructions for use are required, this information shall be made available to the user upon request;\n\n\n\n\n\n\n\n\n\n\n(q)\n\n\nfor devices intended for use together with other devices and/or general purpose equipment:\n\n\n\n\n\n\n\u2014\n\n\ninformation to identify such devices or equipment, in order to obtain a safe combination, and/or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation on any known restrictions to combinations of devices and equipment;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(r)\n\n\nif the device emits radiation for medical purposes:\n\n\n\n\n\n\n\u2014\n\n\ndetailed information as to the nature, type and where appropriate, the intensity and distribution of the emitted radiation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe means of protecting the patient, user, or other person from unintended radiation during use of the device;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(s)\n\n\ninformation that allows the user and/or patient to be informed of any warnings, precautions, contra-indications, measures to be taken and limitations of use regarding the device. That information shall, where relevant, allow the user to brief the patient about any warnings, precautions, contra-indications, measures to be taken and limitations of use regarding the device. The information shall cover, where appropriate:\n\n\n\n\n\n\n\u2014\n\n\nwarnings, precautions and/or measures to be taken in the event of malfunction of the device or changes in its performance that may affect safety,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwarnings, precautions and/or measures to be taken as regards the exposure to reasonably foreseeable external influences or environmental conditions, such as magnetic fields, external electrical and electromagnetic effects, electrostatic discharge, radiation associated with diagnostic or therapeutic procedures, pressure, humidity, or temperature,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwarnings, precautions and/or measures to be taken as regards the risks of interference posed by the reasonably foreseeable presence of the device during specific diagnostic investigations, evaluations, or therapeutic treatment or other procedures such as electromagnetic interference emitted by the device affecting other equipment,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif the device is intended to administer medicinal products, tissues or cells of human or animal origin, or their derivatives, or biological substances, any limitations or incompatibility in the choice of substances to be delivered,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwarnings, precautions and/or limitations related to the medicinal substance or biological material that is incorporated into the device as an integral part of the device; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nprecautions related to materials incorporated into the device that contain or consist of CMR substances or endocrine-disrupting substances, or that could result in sensitisation or an allergic reaction by the patient or user;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(t)\n\n\nin the case of devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body and that are absorbed by or locally dispersed in the human body, warnings and precautions, where appropriate, related to the general profile of interaction of the device and its products of metabolism with other devices, medicinal products and other substances as well as contra-indications, undesirable side-effects and risks relating to overdose;\n\n\n\n\n\n\n\n\n\n\n(u)\n\n\nin the case of implantable devices, the overall qualitative and quantitative information on the materials and substances to which patients can be exposed;\n\n\n\n\n\n\n\n\n\n\n(v)\n\n\nwarnings or precautions to be taken in order to facilitate the safe disposal of the device, its accessories and the consumables used with it, if any. This information shall cover, where appropriate:\n\n\n\n\n\n\n\u2014\n\n\ninfection or microbial hazards such as explants, needles or surgical equipment contaminated with potentially infectious substances of human origin, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nphysical hazards such as from sharps.\n\n\n\n\nIf in accordance with the point\u00a0(d) of Section\u00a023.1 no instructions for use are required, this information shall be made available to the user upon request;\n\n\n\n\n\n\n\n\n\n\n(w)\n\n\nfor devices intended for use by lay persons, the circumstances in which the user should consult a healthcare professional;\n\n\n\n\n\n\n\n\n\n\n(x)\n\n\nfor the devices covered by this Regulation pursuant to Article\u00a01(2), information regarding the absence of a clinical benefit and the risks related to use of the device;\n\n\n\n\n\n\n\n\n\n\n(y)\n\n\ndate of issue of the instructions for use or, if they have been revised, date of issue and identifier of the latest revision of the instructions for use;\n\n\n\n\n\n\n\n\n\n\n(z)\n\n\na notice to the user and/or patient that any serious incident that has occurred in relation to the device should be reported to the manufacturer and the competent authority of the Member\u00a0State in which the user and/or patient is established;\n\n\n\n\n\n\n\n\n\n\n(aa)\n\n\ninformation to be supplied to the patient with an implanted device in accordance with Article\u00a018;\n\n\n\n\n\n\n\n\n\n\n(ab)\n\n\nfor devices that incorporate electronic programmable systems, including software, or software that are devices in themselves, minimum requirements concerning hardware, IT networks characteristics and IT security measures, including protection against unauthorised access, necessary to run the software as intended.\n\n\n\n\n\n\n(1)\u00a0\u00a0Regulation (EC)\u00a0No\u00a01272/2008 of the European Parliament and of the Council of 16\u00a0December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation\u00a0(EC)\u00a0No\u00a01907/2006 ( OJ\u00a0L\u00a0353, 31.12.2008, p.\u00a01).\n\n(2)\u00a0\u00a0Regulation (EC)\u00a0No\u00a01907/2006 of the European Parliament and of the Council of 18\u00a0December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) (OJ\u00a0L\u00a0396, 30.12.2006, p.\u00a01).\n\n(3)\u00a0\u00a0Regulation (EU)\u00a0No\u00a0528/2012 of the European Parliament and the Council of 22\u00a0May\u00a02012 concerning the making available on the market of and use of biocidal products (OJ\u00a0L\u00a0167, 27.6.2012, p.\u00a01).\n\n(4)\u00a0\u00a0Council Directive\u00a080/181/EEC of 20 December 1979 on the approximation of the laws of the Member\u00a0States relating to units of measurement and on the repeal of Directive\u00a071/354/EEC (OJ\u00a0L\u00a039, 15.2.1980, p.\u00a040).\n\n\n\n\n\nANNEX II\n\nTECHNICAL DOCUMENTATION\n\nThe technical documentation and, if applicable, the summary thereof to be drawn up by the manufacturer shall be presented in a clear, organised, readily searchable and unambiguous manner and shall include in particular the elements listed in this Annex.\n1.\u00a0\u00a0\u00a0DEVICE DESCRIPTION AND SPECIFICATION, INCLUDING VARIANTS AND ACCESSORIES\n1.1.\u00a0\u00a0\u00a0Device description and specification\n\n\n\n\n\n\n(a)\n\n\nproduct or trade name and a general description of the device including its intended purpose and intended users;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe Basic UDI-DI as referred to in Part C of Annex\u00a0VI assigned by the manufacturer to the device in question, as soon as identification of this device becomes based on a UDI system, or otherwise a clear identification by means of product code, catalogue number or other unambiguous reference allowing traceability;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe intended patient population and medical conditions to be diagnosed, treated and/or monitored and other considerations such as patient selection criteria, indications, contra-indications, warnings;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nprinciples of operation of the device and its mode of action, scientifically demonstrated if necessary;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe rationale for the qualification of the product as a device;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe risk class of the device and the justification for the classification rule(s) applied in accordance with Annex\u00a0VIII;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nan explanation of any novel features;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\na description of the accessories for a device, other devices and other products that are not devices, which are intended to be used in combination with it;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\na description or complete list of the various configurations/variants of the device that are intended to be made available on the market;\n\n\n\n\n\n\n\n\n\n\n(j)\n\n\na general description of the key functional elements, e.g. its parts/components (including software if appropriate), its formulation, its composition, its functionality and, where relevant, its qualitative and quantitative composition. Where appropriate, this shall include labelled pictorial representations (e.g. diagrams, photographs, and drawings), clearly indicating key parts/components, including sufficient explanation to understand the drawings and diagrams;\n\n\n\n\n\n\n\n\n\n\n(k)\n\n\na description of the raw materials incorporated into key functional elements and those making either direct contact with the human body or indirect contact with the body, e.g., during extracorporeal circulation of body fluids;\n\n\n\n\n\n\n\n\n\n\n(l)\n\n\ntechnical specifications, such as features, dimensions and performance attributes, of the device and any variants/configurations and accessories that would typically appear in the product specification made available to the user, for example in brochures, catalogues and similar publications.\n\n\n\n\n1.2.\u00a0\u00a0\u00a0Reference to previous and similar generations of the device\n\n\n\n\n\n\n(a)\n\n\nan overview of the previous generation or generations of the device produced by the manufacturer, where such devices exist;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nan overview of identified similar devices available on the Union or international markets, where such devices exist.\n\n\n\n\n2.\u00a0\u00a0\u00a0INFORMATION TO BE SUPPLIED BY THE MANUFACTURER\nA complete set of:\n\n\n\n\n\n\n\u2014\n\n\nthe label or labels on the device and on its packaging, such as single unit packaging, sales packaging, transport packaging in case of specific management conditions, in the languages accepted in the Member\u00a0States where the device is envisaged to be sold; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe instructions for use in the languages accepted in the Member\u00a0States where the device is envisaged to be sold.\n\n\n\n\n3.\u00a0\u00a0\u00a0DESIGN AND MANUFACTURING INFORMATION\n\n\n\n\n\n\n(a)\n\n\ninformation to allow the design stages applied to the device to be understood;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ncomplete information and specifications, including the manufacturing processes and their validation, their adjuvants, the continuous monitoring and the final product testing. Data shall be fully included in the technical documentation;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nidentification of all sites, including suppliers and sub-contractors, where design and manufacturing activities are performed.\n\n\n\n\n4.\u00a0\u00a0\u00a0GENERAL SAFETY AND PERFORMANCE REQUIREMENTS\nThe documentation shall contain information for the demonstration of conformity with the general safety and performance requirements set out in Annex\u00a0I that are applicable to the device taking into account its intended purpose, and shall include a justification, validation and verification of the solutions adopted to meet those requirements. The demonstration of conformity shall include:\n\n\n\n\n\n\n(a)\n\n\nthe general safety and performance requirements that apply to the device and an explanation as to why others do not apply;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe method or methods used to demonstrate conformity with each applicable general safety and performance requirement;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe harmonised standards, CS or other solutions applied; and\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe precise identity of the controlled documents offering evidence of conformity with each harmonised standard, CS or other method applied to demonstrate conformity with the general safety and performance requirements. The information referred to under this point shall incorporate a cross-reference to the location of such evidence within the full technical documentation and, if applicable, the summary technical documentation.\n\n\n\n\n5.\u00a0\u00a0\u00a0BENEFIT-RISK ANALYSIS AND RISK MANAGEMENT\nThe documentation shall contain information on:\n\n\n\n\n\n\n(a)\n\n\nthe benefit-risk analysis referred to in Sections 1 and 8 of Annex\u00a0I, and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe solutions adopted and the results of the risk management referred to in Section\u00a03 of Annex\u00a0I.\n\n\n\n\n6.\u00a0\u00a0\u00a0PRODUCT VERIFICATION AND VALIDATION\nThe documentation shall contain the results and critical analyses of all verifications and validation tests and/or studies undertaken to demonstrate conformity of the device with the requirements of this Regulation and in particular the applicable general safety and performance requirements.\n6.1.\u00a0\u00a0\u00a0Pre-clinical and clinical data\n\n\n\n\n\n\n(a)\n\n\nresults of tests, such as engineering, laboratory, simulated use and animal tests, and evaluation of published literature applicable to the device, taking into account its intended purpose, or to similar devices, regarding the pre-clinical safety of the device and its conformity with the specifications;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ndetailed information regarding test design, complete test or study protocols, methods of data analysis, in addition to data summaries and test conclusions regarding in particular:\n\n\n\n\n\n\n\u2014\n\n\nthe biocompatibility of the device including the identification of all materials in direct or indirect contact with the patient or user;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nphysical, chemical and microbiological characterisation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nelectrical safety and electromagnetic compatibility;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsoftware verification and validation (describing the software design and development process and evidence of the validation of the software, as used in the finished device. This information shall typically include the summary results of all verification, validation and testing performed both in-house and in a simulated or actual user environment prior to final release. It shall also address all of the different hardware configurations and, where applicable, operating systems identified in the information supplied by the manufacturer);\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nstability, including shelf life; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nperformance and safety.\n\n\n\n\nWhere applicable, conformity with the provisions of Directive\u00a02004/10/EC of the European Parliament and of the Council\u00a0(1) shall be demonstrated.\nWhere no new testing has been undertaken, the documentation shall incorporate a rationale for that decision. An example of such a rationale would be that biocompatibility testing on identical materials was conducted when those materials were incorporated in a previous version of the device that has been legally placed on the market or put into service;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe clinical evaluation report and its updates and the clinical evaluation plan referred to in Article\u00a061(12) and Part A of Annex\u00a0XIV;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe PMCF plan and PMCF evaluation report referred to in Part B of Annex\u00a0XIV or a justification why a PMCF is not applicable.\n\n\n\n\n6.2.\u00a0\u00a0\u00a0Additional information required in specific cases\n\n\n\n\n\n\n(a)\n\n\nWhere a device incorporates, as an integral part, a substance which, if used separately, may be considered to be a medicinal product within the meaning of point 2 of Article\u00a01 of Directive\u00a02001/83/EC, including a medicinal product derived from human blood or human plasma, as referred to in the first subparagraph\u00a0of Article\u00a01(8), a statement indicating this fact. In this case, the documentation shall identify the source of that substance and contain the data of the tests conducted to assess its safety, quality and usefulness, taking account of the intended purpose of the device.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nWhere a device is manufactured utilising tissues or cells of human or animal origin, or their derivatives, and is covered by this Regulation in accordance with points\u00a0(f) and (g) of Article\u00a01(6, and where a device incorporates, as an integral part, tissues or cells of human origin or their derivatives that have an action ancillary to that of the device and is covered by this Regulation in accordance with the first subparagraph\u00a0of Article\u00a01(10), a statement indicating this fact. In such a case, the documentation shall identify all materials of human or animal origin used and provide detailed information concerning the conformity with Sections 13.1. or 13.2., respectively, of Annex\u00a0I.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nIn the case of devices that are composed of substances or combinations of substances that are intended to be introduced into the human body and that are absorbed by or locally dispersed in the human body, detailed information, including test design, complete test or study protocols, methods of data analysis, and data summaries and test conclusions, regarding studies in relation to:\n\n\n\n\n\n\n\u2014\n\n\nabsorption, distribution, metabolism and excretion;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npossible interactions of those substances, or of their products of metabolism in the human body, with other devices, medicinal products or other substances, considering the target population, and its associated medical conditions;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nlocal tolerance; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntoxicity, including single-dose toxicity, repeat-dose toxicity, genotoxicity, carcinogenicity and reproductive and developmental toxicity, as applicable depending on the level and nature of exposure to the device.\n\n\n\n\nIn the absence of such studies, a justification shall be provided.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nIn the case of devices containing CMR or endocrine-disrupting substances referred to in Section\u00a010.4.1 of Annex\u00a0I, the justification referred to in Section\u00a010.4.2 of that Annex.\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nIn the case of devices placed on the market in a sterile or defined microbiological condition, a description of the environmental conditions for the relevant manufacturing steps. In the case of devices placed on the market in a sterile condition, a description of the methods used, including the validation reports, with respect to packaging, sterilisation and maintenance of sterility. The validation report shall address bioburden testing, pyrogen testing and, if applicable, testing for sterilant residues.\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nIn the case of devices placed on the market with a measuring function, a description of the methods used in order to ensure the accuracy as given in the specifications.\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nIf the device is to be connected to other device(s) in order to operate as intended, a description of this combination/configuration including proof that it conforms to the general safety and performance requirements when connected to any such device(s) having regard to the characteristics specified by the manufacturer.\n\n\n\n\n\n\n(1)\u00a0\u00a0Directive\u00a02004/10/EC of the European Parliament and of the Council of 11\u00a0February\u00a02004 on the harmonisation of laws, regulations and administrative provisions relating to the application of the principles of good laboratory practice and the verification of their applications for tests on chemical substances (OJ\u00a0L\u00a050, 20.2.2004, p.\u00a044).\n\n\n\n\n\nANNEX III\n\nTECHNICAL DOCUMENTATION ON POST-MARKET SURVEILLANCE\n\nThe technical documentation on post-market surveillance to be drawn up by the manufacturer in accordance with Articles\u00a083 to 86 shall be presented in a clear, organised, readily searchable and unambiguous manner and shall include in particular the elements described in this Annex.\n1.1.\u00a0\u00a0\u00a0The post-market surveillance plan drawn up in accordance with Article\u00a084.\nThe manufacturer shall prove in a post-market surveillance plan that it complies with the obligation referred to in Article\u00a083.\n\n\n\n\n\n\n(a)\n\n\nThe post-market surveillance plan shall address the collection and utilization of available information, in particular:\n\n\n\n\n\n\n\u2014\n\n\ninformation concerning serious incidents, including information from PSURs, and field safety corrective actions;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nrecords referring to non-serious incidents and data on any undesirable side-effects;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation from trend reporting;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nrelevant specialist or technical literature, databases and/or registers;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation, including feedbacks and complaints, provided by users, distributors and importers; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npublicly available information about similar medical devices.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nThe post-market surveillance plan shall cover at least:\n\n\n\n\n\n\n\u2014\n\n\na proactive and systematic process to collect any information referred to in point\u00a0(a). The process shall allow a correct characterisation of the performance of the devices and shall also allow a comparison to be made between the device and similar products available on the market;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\neffective and appropriate methods and processes to assess the collected data;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsuitable indicators and threshold values that shall be used in the continuous reassessment of the benefit-risk analysis and of the risk management as referred to in Section\u00a03 of Annex\u00a0I;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\neffective and appropriate methods and tools to investigate complaints and analyse market-related experience collected in the field;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmethods and protocols to manage the events subject to the trend report as provided for in Article\u00a088, including the methods and protocols to be used to establish any statistically significant increase in the frequency or severity of incidents as well as the observation period;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmethods and protocols to communicate effectively with competent authorities, notified bodies, economic operators and users;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreference to procedures to fulfil the manufacturers obligations laid down in Articles\u00a083, 84 and 86;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsystematic procedures to identify and initiate appropriate measures including corrective actions;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\neffective tools to trace and identify devices for which corrective actions might be necessary; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na PMCF plan as referred to in Part B of Annex\u00a0XIV, or a justification as to why a PMCF is not applicable.\n\n\n\n\n\n\n\n\n1.2.\u00a0\u00a0\u00a0The PSUR referred to in Article\u00a086 and the post-market surveillance report referred to in Article\u00a085.\n\n\n\n\n\nANNEX IV\n\nEU DECLARATION OF CONFORMITY\n\nThe EU declaration of conformity shall contain all of the following information:\n\n\n\n\n\n\n1.\n\n\nName, registered trade name or registered trade mark and, if already issued, SRN as referred to in Article\u00a031 of the manufacturer, and, if applicable, its authorised representative, and the address of their registered place of business where they can be contacted and their location be established;\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nA statement that the EU declaration of conformity is issued under the sole responsibility of the manufacturer;\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nThe Basic UDI-DI as referred to in Part C of Annex\u00a0VI;\n\n\n\n\n\n\n\n\n\n\n4.\n\n\nProduct and trade name, product code, catalogue number or other unambiguous reference allowing identification and traceability of the device covered by the EU declaration of conformity, such as a photograph, where appropriate, as well as its intended purpose. Except for the product or trade name, the information allowing identification and traceability may be provided by the Basic UDI-DI referred to in point 3;\n\n\n\n\n\n\n\n\n\n\n5.\n\n\nRisk class of the device in accordance with the rules set out in Annex\u00a0VIII;\n\n\n\n\n\n\n\n\n\n\n6.\n\n\nA statement that the device that is covered by the present declaration is in conformity with this Regulation and, if applicable, with any other relevant Union legislation that provides for the issuing of an EU declaration of conformity;\n\n\n\n\n\n\n\n\n\n\n7.\n\n\nReferences to any CS used and in relation to which conformity is declared;\n\n\n\n\n\n\n\n\n\n\n8.\n\n\nWhere applicable, the name and identification number of the notified body, a description of the conformity assessment procedure performed and identification of the certificate or certificates issued;\n\n\n\n\n\n\n\n\n\n\n9.\n\n\nWhere applicable, additional information;\n\n\n\n\n\n\n\n\n\n\n10.\n\n\nPlace and date of issue of the declaration, name and function of the person who signed it as well as an indication for, and on behalf of whom, that person signed, signature.\n\n\n\n\n\n\n\n\n\nANNEX V\n\nCE MARKING OF CONFORMITY\n\n\n\n\n\n\n\n\n\n1.\n\n\nThe CE marking shall consist of the initials \u2018CE\u2019 taking the following form:\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nIf the CE marking is reduced or enlarged, the proportions given in the above graduated drawing shall be respected.\n\n\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nThe various components of the CE marking shall have substantially the same vertical dimension, which may not be less than 5 mm. This minimum dimension may be waived for small-scale devices.\n\n\n\n\n\n\n\n\n\nANNEX VI\n\nINFORMATION TO BE SUBMITTED UPON THE REGISTRATION OF DEVICES AND ECONOMIC OPERATORS IN ACCORDANCE WITH ARTICLES 29(4) AND 31, CORE DATA ELEMENTS TO BE PROVIDED TO THE UDI DATABASE TOGETHER WITH THE UDI-DI IN ACCORDANCE WITH ARTICLES 28 AND 29, AND THE UDI SYSTEM\n\nPART A\n\nINFORMATION TO BE SUBMITTED UPON THE REGISTRATION OF DEVICES AND ECONOMIC OPERATORS IN ACCORDANCE WITH ARTICLES 29(4) AND 31\n\nManufacturers or, when applicable, authorised representatives, and, when applicable, importers shall submit the information referred to in Section\u00a01 and shall ensure that the information on their devices referred to in Section\u00a02 is complete, correct and updated by the relevant party.\n1.\u00a0\u00a0\u00a0Information relating to the economic operator\n\n\n\n\n\n\n1.1.\n\n\ntype of economic operator(manufacturer, authorised representative, or importer),\n\n\n\n\n\n\n\n\n\n\n1.2.\n\n\nname, address and contact details of the economic operator,\n\n\n\n\n\n\n\n\n\n\n1.3.\n\n\nwhere submission of information is carried out by another person on behalf of any of the economic operators mentioned under Section 1.1, the name, address and contact details of that person,\n\n\n\n\n\n\n\n\n\n\n1.4.\n\n\nname address and contact details of the person or persons responsible for regulatory compliance referred to in Article\u00a015.\n\n\n\n\n2.\u00a0\u00a0\u00a0Information relating to the device\n\n\n\n\n\n\n2.1.\n\n\nBasic UDI-DI,\n\n\n\n\n\n\n\n\n\n\n2.2.\n\n\ntype, number and expiry date of the certificate issued by the notified body and the name or identification number of that notified body and the link to the information that appears on the certificate and was entered by the notified body in the electronic system on notified bodies and certificates,\n\n\n\n\n\n\n\n\n\n\n2.3.\n\n\nMember\u00a0State in which the device is to or has been placed on the market in the Union,\n\n\n\n\n\n\n\n\n\n\n2.4.\n\n\nin the case of class IIa, class IIb or class III devices: Member\u00a0States where the device is or is to be made available,\n\n\n\n\n\n\n\n\n\n\n2.5.\n\n\nrisk class of the device,\n\n\n\n\n\n\n\n\n\n\n2.6.\n\n\nreprocessed single-use device (y/n),\n\n\n\n\n\n\n\n\n\n\n2.7.\n\n\npresence of a substance which, if used separately, may be considered to be a medicinal product and name of that substance,\n\n\n\n\n\n\n\n\n\n\n2.8.\n\n\npresence of a substance which, if used separately, may be considered to be a medicinal product derived from human blood or human plasma and name of this substance,\n\n\n\n\n\n\n\n\n\n\n2.9.\n\n\npresence of tissues or cells of human origin, or their derivatives (y/n),\n\n\n\n\n\n\n\n\n\n\n2.10.\n\n\npresence of tissues or cells of animal origin, or their derivatives, as referred to in Regulation\u00a0(EU)\u00a0No\u00a0722/2012 (y/n),\n\n\n\n\n\n\n\n\n\n\n2.11.\n\n\nwhere applicable, the single identification number of the clinical investigation or investigations conducted in relation to the device or a link to the clinical investigation registration in the electronic system on clinical investigations,\n\n\n\n\n\n\n\n\n\n\n2.12.\n\n\nin the case of devices listed in Annex\u00a0XVI, specification as to whether the intended purpose of the device is other than a medical purpose,\n\n\n\n\n\n\n\n\n\n\n2.13.\n\n\nin the case of devices designed and manufactured by another legal or natural person as referred in Article\u00a010(15), the name, address and contact details of that legal or natural person,\n\n\n\n\n\n\n\n\n\n\n2.14.\n\n\nin the case of class III or implantable devices, the summary of safety and clinical performance,\n\n\n\n\n\n\n\n\n\n\n2.15.\n\n\nstatus of the device (on the market, no longer placed on the market, recalled, field safety corrective action initiated).\n\n\n\n\nPART B\n\nCORE DATA ELEMENTS TO BE PROVIDED TO THE UDI DATABASE TOGETHER WITH THE UDI-DI IN ACCORDANCE WITH ARTICLES 28 AND 29\n\nThe manufacturer shall provide to the UDI database the UDI-DI and all of the following information relating to the manufacturer and the device:\n\n\n\n\n\n\n1.\n\n\nquantity per package configuration,\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nthe Basic UDI-DI as referred to in Article\u00a029 and any additional UDI-DIs,\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nthe manner in which production of the device is controlled (expiry date or manufacturing date, lot number, serial number),\n\n\n\n\n\n\n\n\n\n\n4.\n\n\nif applicable, the unit of use UDI-DI (where a UDI is not labelled on the device at the level of its unit of use, a \u2018unit of use\u2019 DI shall be assigned so as to associate the use of a device with a patient),\n\n\n\n\n\n\n\n\n\n\n5.\n\n\nname and address of the manufacturer (as indicated on the label),\n\n\n\n\n\n\n\n\n\n\n6.\n\n\nthe SRN issued in accordance with Article\u00a031(2),\n\n\n\n\n\n\n\n\n\n\n7.\n\n\nif applicable, name and address of the authorised representative (as indicated on the label),\n\n\n\n\n\n\n\n\n\n\n8.\n\n\nthe medical device nomenclature code as provided for in Article\u00a026,\n\n\n\n\n\n\n\n\n\n\n9.\n\n\nrisk class of the device,\n\n\n\n\n\n\n\n\n\n\n10.\n\n\nif applicable, name or trade name,\n\n\n\n\n\n\n\n\n\n\n11.\n\n\nif applicable, device model, reference, or catalogue number,\n\n\n\n\n\n\n\n\n\n\n12.\n\n\nif applicable, clinical size (including volume, length, gauge, diameter),\n\n\n\n\n\n\n\n\n\n\n13.\n\n\nadditional product description (optional),\n\n\n\n\n\n\n\n\n\n\n14.\n\n\nif applicable, storage and/or handling conditions (as indicated on the label or in the instructions for use),\n\n\n\n\n\n\n\n\n\n\n15.\n\n\nif applicable, additional trade names of the device,\n\n\n\n\n\n\n\n\n\n\n16.\n\n\nlabelled as a single-use device (y/n),\n\n\n\n\n\n\n\n\n\n\n17.\n\n\nif applicable, the maximum number of reuses,\n\n\n\n\n\n\n\n\n\n\n18.\n\n\ndevice labelled sterile (y/n),\n\n\n\n\n\n\n\n\n\n\n19.\n\n\nneed for sterilisation before use (y/n),\n\n\n\n\n\n\n\n\n\n\n20.\n\n\ncontaining latex (y/n),\n\n\n\n\n\n\n\n\n\n\n21.\n\n\nwhere applicable, information labelled in accordance with Section\u00a010.4.5 of Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n22.\n\n\nURL for additional information, such as electronic instructions for use (optional),\n\n\n\n\n\n\n\n\n\n\n23.\n\n\nif applicable, critical warnings or contra-indications,\n\n\n\n\n\n\n\n\n\n\n24.\n\n\nstatus of the device (on the market, no longer placed on the market, recalled, field safety corrective action initiated).\n\n\n\n\nPART C\n\nTHE UDI SYSTEM\n\n1.\u00a0\u00a0\u00a0Definitions\nAutomatic identification and data capture (\u2018AIDC\u2019)\nAIDC is a technology used to automatically capture data. AIDC technologies include bar codes, smart cards, biometrics and RFID.\nBasic UDI-DI\nThe Basic UDI-DI is the primary identifier of a device model. It is the DI assigned at the level of the device unit of use. It is the main key for records in the UDI database and is referenced in relevant certificates and EU declarations of conformity.\nUnit of Use DI\nThe Unit of Use DI serves to associate the use of a device with a patient in instances in which a UDI is not labelled on the individual device at the level of its unit of use, for example in the event of several units of the same device being packaged together.\nConfigurable device\nA configurable device is a device that consists of several components which can be assembled by the manufacturer in multiple configurations. Those individual components may be devices in themselves.\nConfigurable devices include computed tomography (CT) systems, ultrasound systems, anaesthesia systems, physiological Monitoring systems, radiology information systems\u00a0(RIS).\nConfiguration\nConfiguration is a combination of items of equipment, as specified by the manufacturer, that operate together as a device to achieve an intended purpose. The combination of items may be modified, adjusted or customized to meet specific needs.\nConfigurations include inter alia:\n\n\n\n\n\n\n\u2014\n\n\ngantries, tubes, tables, consoles and other items of equipment that can be configured/combined to deliver an intended function in computed tomography.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nventilators, breathing circuits, vaporizers combined to deliver an intended function in anaesthesia.\n\n\n\n\nUDI-DI\nThe UDI-DI is a unique numeric or alphanumeric code specific to a model of device and that is also used as the \u2018access key\u2019 to information stored in a UDI database.\nHuman Readable Interpretation (\u2018HRI\u2019)\nHRI is a legible interpretation of the data characters encoded in the UDI carrier.\nPackaging levels\nPackaging levels means the various levels of device packaging that contain a defined quantity of devices, such as a carton or case.\nUDI-PI\nThe UDI-PI is a numeric or alphanumeric code that identifies the unit of device production.\nThe different types of UDI-PIs include serial number, lot number, software identification and manufacturing or expiry date or both types of date.\nRadio Frequency Identification RFID\nRFID is a technology that uses communication through the use of radio waves to exchange data between a reader and an electronic tag attached to an object, for the purpose of identification.\nShipping containers\nA shipping container is a container in relation to which traceability is controlled by a process specific to logistics systems.\nUnique Device Identifier (\u2018UDI\u2019)\nThe UDI is a series of numeric or alphanumeric characters that is created through a globally accepted device identification and coding standard. It allows the unambiguous identification of a specific device on the market. The UDI is comprised of the UDI-DI and the UDI-PI.\nThe word \u2018Unique\u2019 does not imply serialisation of individual production units.\nUDI carrier\nThe UDI carrier is the means of conveying the UDI by using AIDC and, if applicable, its\u00a0HRI.\nUDI carriers include, inter alia, ID/linear bar code, 2D/Matrix bar code, RFID.\n2.\u00a0\u00a0\u00a0General requirements\n2.1.\u00a0\u00a0\u00a0The affixing of the UDI is an additional requirement \u2014 it does not replace any other marking or labelling requirements laid down in Annex\u00a0I to this Regulation.\n2.2.\u00a0\u00a0\u00a0The manufacturer shall assign and maintain unique UDIs for its devices.\n2.3.\u00a0\u00a0\u00a0Only the manufacturer may place the UDI on the device or its packaging.\n2.4.\u00a0\u00a0\u00a0Only coding standards provided by issuing entities designated by the Commission pursuant to Article\u00a027(2) may be used.\n3.\u00a0\u00a0\u00a0The UDI\n3.1.\u00a0\u00a0\u00a0A UDI shall be assigned to the device itself or its packaging. Higher levels of packaging shall have their own UDI.\n3.2.\u00a0\u00a0\u00a0Shipping containers shall be exempted from the requirement in Section\u00a03.1. By way of example, a UDI shall not be required on a logistics unit; where a healthcare provider orders multiple devices using the UDI or model number of individual devices and the manufacturer places those devices in a container for shipping or to protect the individually packaged devices, the container (logistics unit) shall not be subject to UDI requirements.\n3.3.\u00a0\u00a0\u00a0The UDI shall contain two parts: a UDI-DI and a UDI-PI.\n3.4.\u00a0\u00a0\u00a0The UDI-DI shall be unique at each level of device packaging.\n3.5.\u00a0\u00a0\u00a0If a lot number, serial number, software identification or expiry date appears on the label, it shall be part of the UDI-PI. If there is also a manufacturing date on the label, it does not need to be included in the UDI-PI. If there is only a manufacturing date on the label, this shall be used as the UDI-PI.\n3.6.\u00a0\u00a0\u00a0Each component that is considered to be a device and is commercially available on its own shall be assigned a separate UDI unless the components are part of a configurable device that is marked with its own UDI.\n3.7.\u00a0\u00a0\u00a0Systems and procedure packs as referred to in Article\u00a022 shall be assigned and bear their own UDI.\n3.8.\u00a0\u00a0\u00a0The manufacturer shall assign the UDI to a device following the relevant coding standard.\n3.9.\u00a0\u00a0\u00a0A new UDI-DI shall be required whenever there is a change that could lead to misidentification of the device and/or ambiguity in its traceability; in particular, any change of one of the following UDI database data elements shall require a new UDI-DI:\n\n\n\n\n\n\n(a)\n\n\nname or trade name,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ndevice version or model,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nlabelled as single use,\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\npackaged sterile,\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nneed for sterilization before use,\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nquantity of devices provided in a package,\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\ncritical warnings or contra-indications: e.g. containing latex or DEHP.\n\n\n\n\n3.10.\u00a0\u00a0\u00a0Manufacturers that repackage and/or relabel devices, with their own label shall retain a record of the original device manufacturer's UDI.\n4.\u00a0\u00a0\u00a0UDI carrier\n4.1.\u00a0\u00a0\u00a0The UDI carrier (AIDC and HRI representation of the UDI) shall be placed on the label or on the device itself and on all higher levels of device packaging. Higher levels do not include shipping containers.\n4.2.\u00a0\u00a0\u00a0In the event of there being significant space constraints on the unit of use packaging, the UDI carrier may be placed on the next higher packaging level.\n4.3.\u00a0\u00a0\u00a0For single-use devices of classes I and IIa packaged and labelled individually, the UDI\u00a0carrier shall not be required to appear on the packaging but it shall appear on a higher level of packaging, e.g. a carton containing several individually packaged devices. However, when the healthcare provider is not expected to have access, in cases such as in home healthcare settings, to the higher level of device packaging, the UDI shall be placed on the packaging of the individual device.\n4.4.\u00a0\u00a0\u00a0For devices exclusively intended for retail point of sale the UDI-PIs in AIDC shall not be required to appear on the point of sale packaging.\n4.5.\u00a0\u00a0\u00a0When AIDC carriers other than the UDI carrier are part of the product labelling, the UDI\u00a0carrier shall be readily identifiable.\n4.6.\u00a0\u00a0\u00a0If linear bar codes are used, the UDI-DI and UDI-PI may be concatenated or non-concatenated in two or more bar codes. All parts and elements of the linear bar code shall be distinguishable and identifiable.\n4.7.\u00a0\u00a0\u00a0If there are significant constraints limiting the use of both AIDC and HRI on the label, only the AIDC format shall be required to appear on the label. For devices intended to be used outside healthcare facilities, such as devices for home care, the HRI shall however appear on the label even if this results in there being no space for the AIDC.\n4.8.\u00a0\u00a0\u00a0The HRI format shall follow the rules of the UDI code-issuing entity.\n4.9.\u00a0\u00a0\u00a0If the manufacturer is using RFID technology, a linear or 2D bar code in line with the standard provided by the issuing entities shall also be provided on the label.\n4.10.\u00a0\u00a0\u00a0Devices that are reusable shall bear a UDI carrier on the device itself. The UDI carrier for reusable devices that require cleaning, disinfection, sterilisation or refurbishing between patient uses shall be permanent and readable after each process performed to make the device ready for the subsequent use throughout the intended lifetime of the device. The requirement of this Section\u00a0shall not apply to devices in the following circumstances:\n\n\n\n\n\n\n(a)\n\n\nany type of direct marking would interfere with the safety or performance of the device;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe device cannot be directly marked because it is not technologically feasible.\n\n\n\n\n4.11.\u00a0\u00a0\u00a0The UDI carrier shall be readable during normal use and throughout the intended lifetime of the device.\n4.12.\u00a0\u00a0\u00a0If the UDI carrier is readily readable or, in the case of AIDC, scannable, through the device's packaging, the placing of the UDI carrier on the packaging shall not be required.\n4.13.\u00a0\u00a0\u00a0In the case of single finished devices made up of multiple parts that must be assembled before their first use, it shall be sufficient to place the UDI carrier on only one part of each device.\n4.14.\u00a0\u00a0\u00a0The UDI carrier shall be placed in a manner such that the AIDC can be accessed during normal operation or storage.\n4.15.\u00a0\u00a0\u00a0Bar code carriers that include both a UDI-DI and a UDI-PI may also include essential data for the device to operate or other data.\n5.\u00a0\u00a0\u00a0General principles of the UDI database\n5.1.\u00a0\u00a0\u00a0The UDI database shall support the use of all core UDI database data elements referred to in Part B of this Annex.\n5.2.\u00a0\u00a0\u00a0Manufacturers shall be responsible for the initial submission and updates of the identifying information and other device data elements in the UDI database.\n5.3.\u00a0\u00a0\u00a0Appropriate methods/procedures for validation of the data provided shall be implemented.\n5.4.\u00a0\u00a0\u00a0Manufacturers shall periodically verify the correctness of all of the data relevant to devices they have placed on the market, except for devices that are no longer available on the market.\n5.5.\u00a0\u00a0\u00a0The presence of the device UDI-DI in the UDI database shall not be assumed to mean that the device is in conformity with this Regulation.\n5.6.\u00a0\u00a0\u00a0The database shall allow for the linking of all the packaging levels of the device.\n5.7.\u00a0\u00a0\u00a0The data for new UDI-DIs shall be available at the time the device is placed on the market.\n5.8.\u00a0\u00a0\u00a0Manufacturers shall update the relevant UDI database record within 30 days of a change being made to an element, which does not require a new UDI-DI.\n5.9.\u00a0\u00a0\u00a0Internationally-accepted standards for data submission and updates shall, wherever possible, be used by the UDI database.\n5.10.\u00a0\u00a0\u00a0The user interface of the UDI database shall be available in all official languages of the Union. The use of free-text fields shall, however, be minimized in order to reduce translations.\n5.11.\u00a0\u00a0\u00a0Data relating to devices that are no longer available on the market shall be retained in the UDI database.\n6.\u00a0\u00a0\u00a0Rules for specific device types\n6.1.\u00a0\u00a0\u00a0Implantable devices:\n\n\n\n\n\n\n6.1.1.\n\n\nImplantable devices shall, at their lowest level of packaging (\u2018unit packs\u2019), be identified, or marked using AIDC, with a UDI (UDI-DI + UDI-PI);\n\n\n\n\n\n\n\n\n\n\n6.1.2.\n\n\nThe UDI-PI shall have at least the following characteristics:\n\n\n\n\n\n\n(a)\n\n\nthe serial number for active implantable devices,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe serial number or lot number for other implantable devices.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n6.1.3.\n\n\nThe UDI of the implantable device shall be identifiable prior to implantation.\n\n\n\n\n6.2.\u00a0\u00a0\u00a0Reusable devices requiring cleaning, disinfection, sterilisation or refurbishing between uses\n6.2.1.\u00a0\u00a0\u00a0The UDI of such devices shall be placed on the device and be readable after each procedure to make the device ready for the next use.\n6.2.2.\u00a0\u00a0\u00a0The UDI-PI characteristics such as the lot or serial number shall be defined by the manufacturer.\n6.3.\u00a0\u00a0\u00a0Systems and procedure packs as referred to in Article\u00a022\n6.3.1.\u00a0\u00a0\u00a0The natural or legal person referred to in Article\u00a022 shall be responsible for identifying the system or procedure pack with a UDI including both UDI-DI and UDI-PI.\n6.3.2.\u00a0\u00a0\u00a0Device contents of system or procedure packs shall bear a UDI carrier on their packaging or on the device itself.\nExemptions:\n\n\n\n\n\n\n(a)\n\n\nindividual single-use disposable devices, the uses of which are generally known to the persons by whom they are intended to be used, which are contained within a system or procedure pack, and which are not intended for individual use outside the context of the system or procedure pack, shall not be required to bear their own UDI\u00a0carrier;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ndevices that are exempted from bearing a UDI carrier on the relevant level of packaging shall not be required to bear a UDI carrier when included within a system or procedure pack.\n\n\n\n\n6.3.3.\u00a0\u00a0\u00a0Placement of the UDI carrier on systems or procedure packs\n\n\n\n\n\n\n(a)\n\n\nThe system or procedure pack UDI carrier shall as a general rule be affixed to the outside of the packaging.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nThe UDI carrier shall be readable, or, in the case of AIDC, scannable, whether placed on the outside of the packaging of the system or procedure pack or inside transparent packaging.\n\n\n\n\n6.4.\u00a0\u00a0\u00a0Configurable devices:\n6.4.1.\u00a0\u00a0\u00a0A UDI shall be assigned to the configurable device in its entirety and shall be called the configurable device UDI.\n6.4.2.\u00a0\u00a0\u00a0The configurable device UDI-DI shall be assigned to groups of configurations, not per configuration within the group.\u00a0A group of configurations is defined as the collection of possible configurations for a given device as described in the technical documentation.\n6.4.3.\u00a0\u00a0\u00a0A configurable device UDI-PI shall be assigned to each individual configurable device.\n6.4.4.\u00a0\u00a0\u00a0The carrier of the configurable device UDI shall be placed on the assembly that is most unlikely to be exchanged during the lifetime of the system and shall be identified as the configurable device UDI.\n6.4.5.\u00a0\u00a0\u00a0Each component that is considered a device and is commercially available on its own shall be assigned a separate UDI.\n6.5.\u00a0\u00a0\u00a0Device Software\n6.5.1.\u00a0\u00a0\u00a0UDI assignment Criteria\nThe UDI shall be assigned at the system level of the software. Only software which is commercially available on its own and software which constitutes a device in itself shall be subject to that requirement.\nThe software identification shall be considered to be the manufacturing control mechanism and shall be displayed in the UDI-PI.\n6.5.2.\u00a0\u00a0\u00a0A new UDI-DI shall be required whenever there is a modification that changes:\n\n\n\n\n\n\n(a)\n\n\nthe original performance;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe safety or the intended use of the software;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\ninterpretation of data.\n\n\n\n\nSuch modifications include new or modified algorithms, database structures, operating platform, architecture or new user interfaces or new channels for interoperability.\n6.5.3.\u00a0\u00a0\u00a0Minor software revisions shall require a new UDI-PI and not a new UDI-DI.\nMinor software revisions are generally associated with bug fixes, usability enhancements that are not for safety purposes, security patches or operating efficiency.\nMinor software revisions shall be identified by a manufacturer-specific form of identification.\n6.5.4.\u00a0\u00a0\u00a0UDI placement criteria for software\n\n\n\n\n\n\n(a)\n\n\nwhere the software is delivered on a physical medium, e.g. CD or DVD, each packaging level shall bear the human readable and AIDC representation of the complete UDI. The UDI that is applied to the physical medium containing the software and its packaging shall be identical to the UDI assigned to the system level software;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe UDI shall be provided on a readily accessible screen for the user in an easily-readable plain-text format, such as an \u2018about\u2019 file, or included on the start-up screen;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nsoftware lacking a user interface such as middleware for image conversion, shall be capable of transmitting the UDI through an application programming interface (API);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nonly the human readable portion of the UDI shall be required in electronic displays of the software. The marking of UDI using AIDC shall not be required in the electronic displays, such as \u2018about\u2019 menu, splash screen etc.;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe human readable format of the UDI for the software shall include the Application Identifiers (AI) for the standard used by the issuing entities, so as to assist the user in identifying the UDI and determining which standard is being used to create the UDI.\n\n\n\n\n\n\n\n\n\nANNEX VII\n\nREQUIREMENTS TO BE MET BY NOTIFIED BODIES\n\n1.\u00a0\u00a0\u00a0ORGANISATIONAL AND GENERAL REQUIREMENTS\n1.1.\u00a0\u00a0\u00a0Legal status and organisational structure\n1.1.1.\u00a0\u00a0\u00a0Each notified body shall be established under the national law of a Member\u00a0State, or under the law of a third country with which the Union has concluded an agreement in this respect. Its legal personality and status shall be fully documented. Such documentation shall include information about ownership and the legal or natural persons exercising control over the notified body.\n1.1.2.\u00a0\u00a0\u00a0If the notified body is a legal entity that is part of a larger organisation, the activities of that organisation as well as its organisational structure and governance, and the relationship with the notified body shall be clearly documented. In such cases, the requirements of Section\u00a01.2 are applicable to both the notified body and the organisation to which it belongs.\n1.1.3.\u00a0\u00a0\u00a0If a notified body wholly or partly owns legal entities established in a Member\u00a0State or in a third country or is owned by another legal entity, the activities and responsibilities of those entities, as well as their legal and operational relationships with the notified body, shall be clearly defined and documented. Personnel of those entities performing conformity assessment activities under this Regulation shall be subject to the applicable requirements of this Regulation.\n1.1.4.\u00a0\u00a0\u00a0The organisational structure, allocation of responsibilities, reporting lines and operation of the notified body shall be such that they ensure that there is confidence in the performance by the notified body and in the results of the conformity assessment activities it conducts.\n1.1.5.\u00a0\u00a0\u00a0The notified body shall clearly document its organisational structure and the functions, responsibilities and authority of its top-level management and of other personnel who may have an influence upon the performance by the notified body and upon the results of its conformity assessment activities.\n1.1.6.\u00a0\u00a0\u00a0The notified body shall identify the persons in top-level management that have overall authority and responsibility for each of the following:\n\n\n\n\n\n\n\u2014\n\n\nthe provision of adequate resources for conformity assessment activities;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe development of procedures and policies for the operation of the notified body;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe supervision of implementation of the procedures, policies and quality management systems of the notified body;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe supervision of the notified body's finances;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe activities and decisions taken by the notified body, including contractual agreements;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe delegation of authority to personnel and/or committees, where necessary, for the performance of defined activities;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe interaction with the authority responsible for notified bodies and the obligations regarding communications with other competent authorities, the Commission and other notified bodies.\n\n\n\n\n1.2.\u00a0\u00a0\u00a0Independence and impartiality\n1.2.1.\u00a0\u00a0\u00a0The notified body shall be a third-party body that is independent of the manufacturer of the device in relation to which it performs conformity assessment activities. The notified body shall also be independent of any other economic operator having an interest in the device as well as of any competitors of the manufacturer. This does not preclude the notified body from carrying out conformity assessment activities for competing manufacturers.\n1.2.2.\u00a0\u00a0\u00a0The notified body shall be organised and operated so as to safeguard the independence, objectivity and impartiality of its activities. The notified body shall document and implement a structure and procedures for safeguarding impartiality and for promoting and applying the principles of impartiality throughout its organisation, personnel and assessment activities. Such procedures shall provide for the identification, investigation and resolution of any case in which a conflict of interest may arise, including involvement in consultancy services in the field of devices prior to taking up employment with the notified body. The investigation, outcome and its resolution shall be documented.\n1.2.3.\u00a0\u00a0\u00a0The notified body, its top-level management and the personnel responsible for carrying out the conformity assessment tasks shall not:\n\n\n\n\n\n\n(a)\n\n\nbe the designer, manufacturer, supplier, installer, purchaser, owner or maintainer of devices which they assess, nor the authorised representative of any of those parties. Such restriction shall not preclude the purchase and use of assessed devices that are necessary for the operations of the notified body and the conduct of the conformity assessment, or the use of such devices for personal purposes;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nbe involved in the design, manufacture or construction, marketing, installation and use, or maintenance of the devices for which they are designated, nor represent the parties engaged in those activities;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nengage in any activity that may conflict with their independence of judgement or integrity in relation to conformity assessment activities for which they are designated;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\noffer or provide any service which may jeopardise the confidence in their independence, impartiality or objectivity. In particular, they shall not offer or provide consultancy services to the manufacturer, its authorised representative, a supplier or a commercial competitor as regards the design, construction, marketing or maintenance of devices or processes under assessment, and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nbe linked to any organisation which itself provides consultancy services as referred to in point\u00a0(d). Such restriction does not preclude general training activities that are not client specific and that relate to regulation of devices or to related standards.\n\n\n\n\n1.2.4.\u00a0\u00a0\u00a0Involvement in consultancy services in the field of devices prior to taking up employment with a notified body shall be fully documented at the time of employment and potential conflicts of interest shall be monitored and resolved in accordance with this Annex. Personnel who were formerly employed by a specific client, or provided consultancy services in the field of devices to that specific client prior to taking up employment with a notified body, shall not be assigned for conformity assessment activities for that specific client or companies belonging to the same group for a period of three years.\n1.2.5.\u00a0\u00a0\u00a0The impartiality of notified bodies, of their top-level management and of the assessment personnel shall be guaranteed. The level of the remuneration of the top-level management and assessment personnel of a notified body and subcontractors, involved in assessment activities shall not depend on the results of the assessments. Notified bodies shall make publicly available the declarations of interest of their top-level management.\n1.2.6.\u00a0\u00a0\u00a0If a notified body is owned by a public entity or institution, independence and absence of any conflict of interest shall be ensured and documented between, on the one hand, the authority responsible for notified bodies and/or the competent authority and, on the other hand, the notified body.\n1.2.7.\u00a0\u00a0\u00a0The notified body shall ensure and document that the activities of its subsidiaries or subcontractors, or of any associated body, including the activities of its owners do not affect its independence, impartiality or the objectivity of its conformity assessment activities.\n1.2.8.\u00a0\u00a0\u00a0The notified body shall operate in accordance with a set of consistent, fair and reasonable terms and conditions, taking into account the interests of small and medium-sized enterprises as defined in Recommendation\u00a02003/361/EC in relation to fees.\n1.2.9.\u00a0\u00a0\u00a0The requirements laid down in this Section\u00a0in no way preclude exchanges of technical information and regulatory guidance between a notified body and a manufacturer applying for conformity assessment.\n1.3.\u00a0\u00a0\u00a0Confidentiality\n1.3.1.\u00a0\u00a0\u00a0The notified body shall have documented procedures in place ensuring that its personnel, committees, subsidiaries, subcontractors, and any associated body or personnel of external bodies respect the confidentiality of the information which comes into its possession during the performance of conformity assessment activities, except when disclosure is required by law.\n1.3.2.\u00a0\u00a0\u00a0The personnel of a notified body shall observe professional secrecy in carrying out their tasks under this Regulation or any provision of national law giving effect to it, except in relation to the authorities responsible for notified bodies, competent authorities for medical devices in the Member\u00a0States or the Commission. Proprietary rights shall be protected. The notified body shall have documented procedures in place in respect of the requirements of this Section.\n1.4.\u00a0\u00a0\u00a0Liability\n1.4.1.\u00a0\u00a0\u00a0The notified body shall take out appropriate liability insurance for its conformity assessment activities, unless liability is assumed by the Member\u00a0State in question in accordance with national law or that Member\u00a0State is directly responsible for the conformity assessment.\n1.4.2.\u00a0\u00a0\u00a0The scope and overall financial value of the liability insurance shall correspond to the level and geographic scope of activities of the notified body and be commensurate with the risk profile of the devices certified by the notified body. The liability insurance shall cover cases where the notified body may be obliged to withdraw, restrict or suspend certificates.\n1.5.\u00a0\u00a0\u00a0Financial requirements\nThe notified body shall have at its disposal the financial resources required to conduct its conformity assessment activities within its scope of designation and related business operations. It shall document and provide evidence of its financial capacity and its long-term economic viability, taking into account, where relevant, any specific circumstances during an initial start-up phase.\n1.6.\u00a0\u00a0\u00a0Participation in coordination activities\n1.6.1.\u00a0\u00a0\u00a0The notified body shall participate in, or ensure that its assessment personnel is informed of, any relevant standardisation activities and in the activities of the notified body coordination group referred to in Article\u00a049 and that its assessment and decision-making personnel are informed of all relevant legislation, guidance and best practice documents adopted in the framework of this Regulation.\n1.6.2.\u00a0\u00a0\u00a0The notified body shall take into consideration guidance and best practice documents.\n2.\u00a0\u00a0\u00a0QUALITY MANAGEMENT REQUIREMENTS\n2.1.\u00a0\u00a0\u00a0The notified body shall establish, document, implement, maintain and operate a quality management system that is appropriate to the nature, area and scale of its conformity assessment activities and is capable of supporting and demonstrating the consistent fulfilment of the requirements of this Regulation.\n2.2.\u00a0\u00a0\u00a0The quality management system of the notified body shall address at least the following:\n\n\n\n\n\n\n\u2014\n\n\nmanagement system structure and documentation, including policies and objectives for its activities;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npolicies for assignment of activities and responsibilities to personnel;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nassessment and decision-making processes in accordance with the tasks, responsibilities and role of the notified body's personnel and top-level management;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe planning, conduct, evaluation and, if necessary, adaptation of its conformity assessment procedures;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncontrol of documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncontrol of records;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmanagement reviews;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninternal audits;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncorrective and preventive actions;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncomplaints and appeals; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncontinuous training.\n\n\n\n\nWhere documents are used in various languages, the notified body shall ensure and control that they have the same content.\n2.3.\u00a0\u00a0\u00a0The top-level management of the notified body shall ensure that the quality management system is fully understood, implemented and maintained throughout the notified body organisation including subsidiaries and subcontractors involved in conformity assessment activities pursuant to this Regulation.\n2.4.\u00a0\u00a0\u00a0The notified body shall require all personnel to formally commit themselves by a signature or equivalent to comply with the procedures defined by the notified body. That commitment shall cover aspects relating to confidentiality and to independence from commercial and other interests, and any existing or prior association with clients. The personnel shall be required to complete written statements indicating their compliance with confidentiality, independence and impartiality principles.\n3.\u00a0\u00a0\u00a0RESOURCE REQUIREMENTS\n3.1.\u00a0\u00a0\u00a0General\n3.1.1.\u00a0\u00a0\u00a0Notified bodies shall be capable of carrying out all the tasks falling to them under this Regulation with the highest degree of professional integrity and the requisite competence in the specific field, whether those tasks are carried out by notified bodies themselves or on their behalf and under their responsibility.\nIn particular, notified bodies shall have the necessary personnel and possess or have access to all equipment, facilities and competence needed to perform properly the technical, scientific and administrative tasks entailed in the conformity assessment activities in relation to which they have been designated.\nSuch requirement presupposes at all times and for each conformity assessment procedure and each type of devices in relation to which they have been designated, that the notified body has permanent availability of sufficient administrative, technical and scientific personnel who possess experience and knowledge relating to the relevant devices and the corresponding technologies. Such personnel shall be in sufficient numbers to ensure that the notified body in question can perform the conformity assessment tasks, including the assessment of the medical functionality, clinical evaluations and the performance and safety of devices, for which it has been designated, having regard to the requirements of this Regulation, in particular, those set out in Annex\u00a0I.\nA notified body's cumulative competences shall be such as to enable it to assess the types of devices for which it is designated. The notified body shall have sufficient internal competence to critically evaluate assessments conducted by external expertise. Tasks which a notified body is precluded from subcontracting are set out in Section\u00a04.1.\nPersonnel involved in the management of the operation of a notified body's conformity assessment activities for devices shall have appropriate knowledge to set up and operate a system for the selection of assessment and verification staff, for verification of their competence, for authorisation and allocation of their tasks, for organisation of their initial and ongoing training and for the assignment of their duties and the monitoring of those staff, in order to ensure that personnel who carry out and perform assessment and verification operations are competent to fulfil the tasks required of them.\nThe notified body shall identify at least one individual within its top-level management as having overall responsibility for all conformity assessment activities in relation to devices.\n3.1.2.\u00a0\u00a0\u00a0The notified body shall ensure that personnel involved in conformity assessment activities maintain their qualification and expertise by implementing a system for exchange of experience and a continuous training and education programme.\n3.1.3.\u00a0\u00a0\u00a0The notified body shall clearly document the extent and limits of duties and responsibilities and the level of authorisation of the personnel, including any subcontractors and external experts, involved in conformity assessment activities and inform those personnel accordingly.\n3.2.\u00a0\u00a0\u00a0Qualification criteria in relation to personnel\n3.2.1.\u00a0\u00a0\u00a0The Notified Body shall establish and document qualification criteria and procedures for selection and authorisation of persons involved in conformity assessment activities, including as regards knowledge, experience and other competence required, and the required initial and ongoing training. The qualification criteria shall address the various functions within the conformity assessment process, such as auditing, product evaluation or testing, technical documentation review and decision-making, as well as the devices, technologies and areas, such as biocompatibility, sterilisation, tissues and cells of human and animal origin and clinical evaluation, covered by the scope of designation.\n3.2.2.\u00a0\u00a0\u00a0The qualification criteria referred to in Section\u00a03.2.1 shall refer to the scope of a notified body's designation in accordance with the scope description used by the Member\u00a0State for the notification referred to in Article\u00a042(3), providing a sufficient level of detail for the required qualification within the subdivisions of the scope description.\nSpecific qualification criteria shall be defined at least for the assessment of:\n\n\n\n\n\n\n\u2014\n\n\nthe pre-clinical evaluation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclinical evaluation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntissues and cells of human and animal origin,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nfunctional safety,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsoftware,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npackaging,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndevices that incorporate as an integral part a medicinal product,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndevices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe different types of sterilisation processes.\n\n\n\n\n3.2.3.\u00a0\u00a0\u00a0The personnel responsible for establishing qualification criteria and for authorising other personnel to perform specific conformity assessment activities shall be employed by the notified body itself and shall not be external experts or subcontracted. They shall have proven knowledge and experience in all of the following:\n\n\n\n\n\n\n\u2014\n\n\nUnion devices legislation and relevant guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe conformity assessment procedures provided for in this Regulation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na broad base of knowledge of device technologies and the design and manufacture of devices;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe notified body's quality management system, related procedures and the required qualification criteria;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntraining relevant to personnel involved in conformity assessment activities in relation to devices;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nadequate experience in conformity assessments under this Regulation or previously applicable law within a notified body.\n\n\n\n\n3.2.4.\u00a0\u00a0\u00a0The notified body shall have permanent availability of personnel with relevant clinical expertise and where possible such personnel shall be employed by the notified body itself. Such personnel shall be integrated throughout the notified body's assessment and decision-making process in order to:\n\n\n\n\n\n\n\u2014\n\n\nidentify when specialist input is required for the assessment of the clinical evaluation conducted by the manufacturer and identify appropriately qualified experts;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriately train external clinical experts in the relevant requirements of this Regulation, CS, guidance and harmonised standards and ensure that the external clinical experts are fully aware of the context and implications of their assessment and the advice they provide;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbe able to review and scientifically challenge the clinical data contained within the clinical evaluation, and any associated clinical investigations, and appropriately guide external clinical experts in the assessment of the clinical evaluation presented by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbe able to scientifically evaluate and, if necessary, challenge the clinical evaluation presented, and the results of the external clinical experts' assessment of the manufacturer's clinical evaluation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbe able to ascertain the comparability and consistency of the assessments of clinical evaluations conducted by clinical experts;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbe able to make an assessment of the manufacturer's clinical evaluation and a clinical judgement of the opinion provided by any external expert and make a recommendation to the notified body's decision maker; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbe able to draw up records and reports demonstrating that the relevant conformity assessment activities have been appropriately carried out.\n\n\n\n\n3.2.5.\u00a0\u00a0\u00a0The personnel responsible for carrying out product-related reviews (product reviewers), such as technical documentation reviews or type examination, including aspects such as clinical evaluation, biological safety, sterilisation and software validation, shall have all of the following proven qualifications:\n\n\n\n\n\n\n\u2014\n\n\nsuccessful completion of a university or a technical college degree or equivalent qualification in relevant studies, e.g. medicine, pharmacy, engineering or other relevant sciences;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nfour years' professional experience in the field of healthcare products or related activities, such as in manufacturing, auditing or research, of which two years shall be in the design, manufacture, testing or use of the device or technology to be assessed or related to the scientific aspects to be assessed;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nknowledge of device legislation, including the general safety and performance requirements set out in Annex\u00a0I;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge and experience of relevant harmonised standards, CS and guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge and experience of risk management and related device standards and guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge and experience of clinical evaluation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge of the devices which they are assessing;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge and experience of the conformity assessment procedures laid down in Annexes\u00a0IX to\u00a0XI, in particular of the aspects of those procedures for which they are responsible, and adequate authorisation for carrying out those assessments;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe ability to draw up records and reports demonstrating that the relevant conformity assessment activities have been appropriately carried out.\n\n\n\n\n3.2.6.\u00a0\u00a0\u00a0The personnel responsible for carrying out audits of the manufacturer's quality management system (site auditors) shall have all of the following proven qualifications:\n\n\n\n\n\n\n\u2014\n\n\nsuccessful completion of a university or a technical college degree or equivalent qualification in relevant studies, such as medicine, pharmacy, engineering or other relevant sciences;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nfour years' professional experience in the field of healthcare products or related activities, such as in manufacturing, auditing or research, of which two years shall be in the area of quality management;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge of devices legislation as well as related harmonised standards, CS and guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge and experience of risk management and related device standards and guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge of quality management systems and related standards and guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge and experience of the conformity assessment procedures laid down in Annexes\u00a0IX to\u00a0XI, in particular of the aspects of those procedures for which they are responsible, and adequate authorisation for carrying out those audits;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntraining in auditing techniques enabling them to challenge quality management systems;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe ability to draw up records and reports demonstrating that the relevant conformity assessment activities have been appropriately carried out.\n\n\n\n\n3.2.7.\u00a0\u00a0\u00a0The personnel with overall responsibility for final reviews and decision-making on certification shall be employed by the notified body itself and shall not be external experts or be subcontracted. Those personnel shall, as a group, have proven knowledge and comprehensive experience of all of the following:\n\n\n\n\n\n\n\u2014\n\n\ndevices legislation and relevant guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe device conformity assessments relevant to this Regulation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe types of qualifications, experience and expertise relevant to device conformity assessment;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na broad base of knowledge of device technologies, including sufficient experience of conformity assessment of devices being reviewed for certification, the device industry and the design and manufacture of devices;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe notified body's quality management system, related procedures and the required qualifications for personnel involved;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe ability to draw up records and reports demonstrating that the conformity assessment activities have been appropriately carried out.\n\n\n\n\n3.3.\u00a0\u00a0\u00a0Documentation of qualification, training and authorisation of personnel\n3.3.1.\u00a0\u00a0\u00a0The notified body shall have a procedure in place to fully document the qualification of each member of personnel involved in conformity assessment activities and the satisfaction of the qualification criteria referred to in Section\u00a03.2. Where in exceptional circumstances the fulfilment of the qualification criteria set out in Section\u00a03.2. cannot be fully demonstrated, the notified body shall justify to the authority responsible for notified bodies the authorisation of those members of personnel to carry out specific conformity assessment activities.\n3.3.2.\u00a0\u00a0\u00a0For all of its personnel referred to in Sections 3.2.3 to 3.2.7, the notified body shall establish and maintain up to date:\n\n\n\n\n\n\n\u2014\n\n\na matrix detailing the authorisations and responsibilities of the personnel in respect of conformity assessment activities; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nrecords attesting to the required knowledge and experience for the conformity assessment activity for which they are authorised. The records shall contain a rationale for defining the scope of the responsibilities for each of the assessment personnel and records of the conformity assessment activities carried out by each of them.\n\n\n\n\n3.4.\u00a0\u00a0\u00a0Subcontractors and external experts\n3.4.1.\u00a0\u00a0\u00a0Notified bodies may, without prejudice to Section\u00a03.2, subcontract certain clearly defined component parts of a conformity assessment activity.\nThe subcontracting of the auditing of quality management systems or of product related reviews as a whole shall not be permitted; nevertheless parts of those activities may be conducted by subcontractors and external auditors and experts working on behalf of the notified body. The notified body in question shall retain full responsibility for being able to produce appropriate evidence of the competence of subcontractors and experts to fulfil their specific tasks, for making a decision based on a subcontractor's assessment and for the work conducted by subcontractors and experts on its behalf.\nThe following activities may not be subcontracted by notified bodies:\n\n\n\n\n\n\n\u2014\n\n\nreview of the qualifications and monitoring of the performance of external experts;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nauditing and certification activities where the subcontracting in question is to auditing or certification organisations;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nallocation of work to external experts for specific conformity assessment activities; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nfinal review and decision making functions.\n\n\n\n\n3.4.2.\u00a0\u00a0\u00a0Where a notified body subcontracts certain conformity assessment activities either to an organisation or an individual, it shall have a policy describing the conditions under which subcontracting may take place, and shall ensure that:\n\n\n\n\n\n\n\u2014\n\n\nthe subcontractor meets the relevant requirements of this Annex;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsubcontractors and external experts do not further subcontract work to organisations or personnel; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe natural or legal person that applied for conformity assessment has been informed of the requirements referred to in the first and second indent.\n\n\n\n\nAny subcontracting or consultation of external personnel shall be properly documented, shall not involve any intermediaries and shall be subject to a written agreement covering, among other things, confidentiality and conflicts of interest. The notified body in question shall take full responsibility for the tasks performed by subcontractors.\n3.4.3.\u00a0\u00a0\u00a0Where subcontractors or external experts are used in the context of a conformity assessment, in particular regarding novel, invasive and implantable devices or technologies, the notified body in question shall have internal competence in each product area for which it is designated that is adequate for the purpose of leading the overall conformity assessment, verifying the appropriateness and validity of expert opinions and making decisions on certification.\n3.5.\u00a0\u00a0\u00a0Monitoring of competences, training and exchange of experience\n3.5.1.\u00a0\u00a0\u00a0The notified body shall establish procedures for the initial evaluation and on-going monitoring of the competence, conformity assessment activities and performance of all internal and external personnel, and subcontractors, involved in conformity assessment activities.\n3.5.2.\u00a0\u00a0\u00a0Notified bodies shall review at regular intervals, the competence of their personnel, identify training needs and draw up a training plan to maintain the required level of qualification and knowledge of individual personnel. That review shall at a minimum, verify that personnel:\n\n\n\n\n\n\n\u2014\n\n\nare aware of Union and national law in force on devices, relevant harmonised standards, CS, guidance documents and the results of the coordination activities referred to in Section\u00a01.6; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntake part in the internal exchange of experience and the continuous training and education programme referred to in Section\u00a03.1.2.\n\n\n\n\n4.\u00a0\u00a0\u00a0PROCESS REQUIREMENTS\n4.1.\u00a0\u00a0\u00a0General\nThe notified body shall have in place documented processes and sufficiently detailed procedures for the conduct of each conformity assessment activity for which it is designated, comprising the individual steps from pre-application activities up to decision making and surveillance and taking into account, when necessary, the respective specificities of the devices.\nThe requirements laid down in Sections 4.3, 4.4, 4.7 and 4.8 shall be fulfilled as part of the internal activities of notified bodies and shall not be subcontracted.\n4.2.\u00a0\u00a0\u00a0Notified body quotations and pre-application activities\nThe notified body shall:\n\n\n\n\n\n\n(a)\n\n\npublish a publicly available description of the application procedure by which manufacturers can obtain certification from it. That description shall include which languages are acceptable for submission of documentation and for any related correspondence;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nhave documented procedures relating to, and documented details about, fees charged for specific conformity assessment activities and any other financial conditions relating to notified bodies' assessment activities for devices;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nhave documented procedures in relation to advertising of their conformity assessment services. Those procedures shall ensure that advertising or promotional activities in no way imply or are capable of leading to an inference that their conformity assessment will offer manufacturers earlier market access or be quicker, easier or less stringent than that of other notified bodies;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nhave documented procedures requiring the review of pre-application information, including the preliminary verification that the product is covered by this Regulation and its classification, prior to issuing any quotation to the manufacturer relating to a specific conformity assessment; and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nensure that all contracts relating to the conformity assessment activities covered by this Regulation are concluded directly between the manufacturer and the notified body and not with any other organisation.\n\n\n\n\n4.3.\u00a0\u00a0\u00a0Application review and contract\nThe notified body shall require a formal application signed by a manufacturer or an authorised representative containing all of the information and the manufacturer's declarations required by the relevant conformity assessment as referred to in Annexes\u00a0IX to\u00a0XI.\nThe contract between a notified body and a manufacturer shall take the form of a written agreement signed by both parties. It shall be kept by the notified body. This contract shall have clear terms and conditions and contain obligations that enable the notified body to act as required under this Regulation, including an obligation on the manufacturer to inform the notified body of vigilance reports, the right of the notified body to suspend, restrict or withdraw certificates issued and the duty of the notified body to fulfil its information obligations.\nThe notified body shall have documented procedures to review applications, addressing:\n\n\n\n\n\n\n(a)\n\n\nthe completeness of those applications with respect to the requirements of the relevant conformity assessment procedure, as referred to in the corresponding Annex, under which approval has been sought,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe verification of the qualification of products covered by those applications as devices and their respective classifications,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nwhether the conformity assessment procedures chosen by the applicant are applicable to the device in question under this Regulation,\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe ability of the notified body to assess the application based on its designation, and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe availability of sufficient and appropriate resources.\n\n\n\n\nThe outcome of each review of an application shall be documented. Refusals or withdrawals of applications shall be notified to the electronic system referred to in Article\u00a057 and shall be accessible to other notified bodies.\n4.4.\u00a0\u00a0\u00a0Allocation of resources\nThe notified body shall have documented procedures to ensure that all conformity assessment activities are conducted by appropriately authorised and qualified personnel who are sufficiently experienced in the evaluation of the devices, systems and processes and related documentation that are subject to conformity assessment.\nFor each application, the notified body shall determine the resources needed and identify one individual responsible for ensuring that the assessment of that application is conducted in accordance with the relevant procedures and for ensuring that the appropriate resources including personnel are utilised for each of the tasks of the assessment. The allocation of tasks required to be carried out as part of the conformity assessment and any changes subsequently made to this allocation shall be documented.\n4.5.\u00a0\u00a0\u00a0Conformity assessment activities\n4.5.1.\u00a0\u00a0\u00a0General\nThe notified body and its personnel shall carry out the conformity assessment activities with the highest degree of professional integrity and the requisite technical and scientific competence in the specific fields.\nThe notified body shall have expertise, facilities and documented procedures that are sufficient to effectively conduct the conformity assessment activities for which the notified body in question is designated, taking account of the relevant requirements set out in Annexes\u00a0IX to XI, and in particular all of the following requirements:\n\n\n\n\n\n\n\u2014\n\n\nappropriately plan the conduct of each individual project,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure that the composition of the assessment teams is such that there is sufficient experience in relation to the technology concerned, and that there is continuous objectivity and independence, and to provide for rotation of the members of the assessment team at appropriate intervals,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nspecify the rationale for fixing time limits for completion of conformity assessment activities,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nassess the manufacturer's technical documentation and the solutions adopted to meet the requirements laid down in Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreview the manufacturer's procedures and documentation relating to the evaluation of pre-clinical aspects,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreview the manufacturer's procedures and documentation relating to clinical evaluation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\naddress the interface between the manufacturer's risk management process and its appraisal and analysis of the pre-clinical and clinical evaluation and to evaluate their relevance for the demonstration of conformity with the relevant requirements in Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncarry out the specific procedures referred to in Sections 5.2 to 5.4 of Annex\u00a0IX,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nin the case of class IIa or class IIb devices, assess the technical documentation of devices selected on a representative basis,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nplan and periodically carry out appropriate surveillance audits and assessments, carry out or request certain tests to verify the proper functioning of the quality management system and to perform unannounced on site audits,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nrelating to the sampling of devices, verify that the manufactured device is in conformity with the technical documentation; such requirements shall define the relevant sampling criteria and testing procedure prior to sampling,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nevaluate and verify a manufacturer's compliance with relevant Annexes.\n\n\n\n\nThe notified body shall, where relevant, take into consideration available CS, guidance and best practice documents and harmonised standards, even if the manufacturer does not claim to be in compliance.\n4.5.2.\u00a0\u00a0\u00a0Quality management system auditing\n\n\n\n\n\n\n(a)\n\n\nAs part of the assessment of the quality management system, a notified body shall prior to an audit and in accordance with its documented procedures:\n\n\n\n\n\n\n\u2014\n\n\nassess the documentation submitted in accordance with the relevant conformity assessment Annex, and draw up an audit programme which clearly identifies the number and sequence of activities required to demonstrate complete coverage of a manufacturer's quality management system and to determine whether it meets the requirements of this Regulation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nidentify links between, and allocation of responsibilities among, the various manufacturing sites, and identify relevant suppliers and/or subcontractors of the manufacturer, and consider the need to specifically audit any of those suppliers or subcontractors or both,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclearly define, for each audit identified in the audit programme, the objectives, criteria and scope of the audit, and draw up an audit plan that adequately addresses and takes account of the specific requirements for the devices, technologies and processes involved,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndraw up and keep up to date, for class IIa and class IIb devices, a sampling plan for the assessment of technical documentation as referred to in Annexes\u00a0II and III covering the range of such devices covered by the manufacturer's application. That plan shall ensure that all devices covered by the certificate are sampled over the period of validity of the certificate, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nselect and assign appropriately qualified and authorised personnel for conducting the individual audits. The respective roles, responsibilities and authorities of the team members shall be clearly defined and documented.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nBased on the audit programme it has drawn up, the notified body shall, in accordance with its documented procedures:\n\n\n\n\n\n\n\u2014\n\n\naudit the manufacturer's quality management system, in order to verify that the quality management system ensures that the devices covered conform to the relevant provisions of this Regulation which apply to devices at every stage, from design through final quality control to ongoing surveillance, and shall determine whether the requirements of this Regulation are met,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbased on relevant technical documentation and in order to determine whether the manufacturer meets the requirements referred to in the relevant conformity assessment Annex, review and audit the manufacturer's processes and subsystems, in particular for:\n\n\n\n\n\n\n\u2014\n\n\ndesign and development,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nproduction and process controls,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nproduct documentation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npurchasing controls including verification of purchased devices,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncorrective and preventive actions, including for post-market surveillance, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nPMCF,\n\n\n\n\nand review and audit requirements and provisions adopted by the manufacturer, including those in relation to fulfilling the general safety and performance requirements set out in Annex\u00a0I.\nThe documentation shall be sampled in such a manner as to reflect the risks associated with the intended use of the device, the complexity of the manufacturing technologies, the range and classes of devices produced and any available post-market surveillance information,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif not already covered by the audit programme, audit the control of processes on the premises of the manufacturer's suppliers, when the conformity of finished devices is significantly influenced by the activity of suppliers and, in particular when the manufacturer cannot demonstrate sufficient control over its suppliers,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nconduct assessments of the technical documentation based on its sampling plan and taking account of Sections 4.5.4. and\u00a04.5.5. for pre-clinical and clinical evaluations, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe notified body shall ensure that audit findings are appropriately and consistently classified in accordance with the requirements of this Regulation and with relevant standards, or with best practice documents developed or adopted by the MDCG.\n\n\n\n\n\n\n\n\n4.5.3.\u00a0\u00a0\u00a0Product verification\nAssessment of the technical documentation\nFor assessment of the technical documentation conducted in accordance with Chapter\u00a0II of Annex\u00a0IX, notified bodies shall have sufficient expertise, facilities and documented procedures for:\n\n\n\n\n\n\n\u2014\n\n\nthe allocation of appropriately qualified and authorised personnel for the examination of individual aspects such as use of the device, biocompatibility, clinical evaluation, risk management, and sterilisation, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe assessment of conformity of the design with this Regulation, and for taking account of Sections 4.5.4. to\u00a04.5.6. That assessment shall include examination of the implementation by manufacturers of incoming, in-process and final checks and the results thereof. If further tests or other evidence is required for the assessment of conformity with the requirements of this Regulation, the notified body in question shall carry out adequate physical or laboratory tests in relation to the device or request the manufacturer to carry out such tests.\n\n\n\n\nType-examinations\nThe notified body shall have documented procedures, sufficient expertise and facilities for the type-examination of devices in accordance with Annex\u00a0X including the capacity to:\n\n\n\n\n\n\n\u2014\n\n\nexamine and assess the technical documentation taking account of Sections 4.5.4. to\u00a04.5.6., and verify that the type has been manufactured in conformity with that documentation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nestablish a test plan identifying all relevant and critical parameters which need to be tested by the notified body or under its responsibility;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndocument its rationale for the selection of those parameters;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncarry out the appropriate examinations and tests in order to verify that the solutions adopted by the manufacturer meet the general safety and performance requirements set out in Annex\u00a0I. Such examinations and tests shall include all tests necessary to verify that the manufacturer has in fact applied the relevant standards it has opted to use;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nagree with the applicant as to where the necessary tests will be performed if they are not to be carried out directly by the notified body; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nassume full responsibility for test results. Test reports submitted by the manufacturer shall only be taken into account if they have been issued by conformity assessment bodies which are competent and independent of the manufacturer.\n\n\n\n\nVerification by examination and testing of every product\nThe notified body shall:\n\n\n\n\n\n\n(a)\n\n\nhave documented procedures, sufficient expertise and facilities for the verification by examination and testing of every product in accordance with Part B of Annex\u00a0XI;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nestablish a test plan identifying all relevant and critical parameters which need to be tested by the notified body or under its responsibility in order to:\n\n\n\n\n\n\n\u2014\n\n\nverify, for class IIb devices, the conformity of the device with the type described in the EU type-examination certificate and with the requirements of this Regulation which apply to those devices,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nconfirm, for class IIa devices, the conformity with the technical documentation referred to in Annexes\u00a0II and III and with the requirements of this Regulation which apply to those devices;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\ndocument its rationale for the selection of the parameters referred to in point\u00a0(b);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nhave documented procedures to carry out the appropriate assessments and tests in order to verify the conformity of the device with the requirements of this Regulation by examining and testing every product as specified in Section\u00a015 of Annex\u00a0XI;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nhave documented procedures providing for the reaching of an agreement with the applicant concerning when and where necessary tests that are not to be carried out by the notified body itself are to be performed; and\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nassume full responsibility for test results in accordance with documented procedures; test reports submitted by the manufacturer shall only be taken into account if they have been issued by conformity assessment bodies which are competent and independent of the manufacturer.\n\n\n\n\n4.5.4.\u00a0\u00a0\u00a0Pre-clinical evaluation assessment\nThe notified body shall have documented procedures in place for the review of the manufacturer's procedures and documentation relating to the evaluation of pre-clinical aspects. The notified body shall examine, validate and verify that the manufacturer's procedures and documentation adequately address:\n\n\n\n\n\n\n(a)\n\n\nthe planning, conduct, assessment, reporting and, where appropriate, updating of the pre-clinical evaluation, in particular of\n\n\n\n\n\n\n\u2014\n\n\nthe scientific pre-clinical literature search, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe pre-clinical testing, for example laboratory testing, simulated use testing, computer modelling, the use of animal models,\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe nature and duration of body contact and the specific associated biological risks,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe interface with the risk management process, and\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe appraisal and analysis of the available pre-clinical data and its relevance with regard to demonstrating conformity with the relevant requirements in Annex\u00a0I.\n\n\n\n\nThe notified body's assessment of pre-clinical evaluation procedures and documentation shall address the results of literature searches and all validation, verification and testing performed and conclusions drawn, and shall typically include considering the use of alternative materials and substances and take account of the packaging, stability, including shelf life, of the finished device. Where no new testing has been undertaken by a manufacturer or where there are deviations from procedures, the notified body in question shall critically examine the justification presented by the manufacturer.\n4.5.5.\u00a0\u00a0\u00a0Clinical evaluation assessment\nThe notified body shall have documented procedures in place relating to the assessment of a manufacturer's procedures and documentation relating to clinical evaluation both for initial conformity assessment and on an ongoing basis. The notified body shall examine, validate and verify that manufacturers' procedures and documentation adequately address:\n\n\n\n\n\n\n\u2014\n\n\nthe planning, conduct, assessment, reporting and updating of the clinical evaluation as referred to in Annex\u00a0XIV,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npost-market surveillance and PMCF,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe interface with the risk management process,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe appraisal and analysis of the available data and its relevance with regard to demonstrating conformity with the relevant requirements in Annex\u00a0I, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe conclusions drawn with regard to the clinical evidence and drawing up of the clinical evaluation report.\n\n\n\n\nThese procedures referred to in the first paragraph\u00a0shall take into consideration available CS, guidance and best practice documents.\nThe notified body's assessment of clinical evaluations as referred to in Annex\u00a0XIV shall cover:\n\n\n\n\n\n\n\u2014\n\n\nthe intended use specified by the manufacturer and claims for the device defined by it,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe planning of the clinical evaluation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe methodology for the literature search,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nrelevant documentation from the literature search,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe clinical investigation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nvalidity of equivalence claimed in relation to other devices, the demonstration of equivalence, the suitability and conclusions data from equivalent and similar devices,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npost-market surveillance and PMCF,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe clinical evaluation report, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\njustifications in relation to non-performance of clinical investigations or PMCF.\n\n\n\n\nIn relation to clinical data from clinical investigations included within the clinical evaluation, the notified body in question shall ensure that the conclusions drawn by the manufacturer are valid in the light of the approved clinical investigation plan.\nThe notified body shall ensure that the clinical evaluation adequately addresses the relevant safety and performance requirements provided for in Annex\u00a0I, that it is appropriately aligned with the risk management requirements, that it is conducted in accordance with Annex\u00a0XIV and that it is appropriately reflected in the information provided relating to the device.\n4.5.6.\u00a0\u00a0\u00a0Specific Procedures\nThe notified body shall have documented procedures, sufficient expertise and facilities for the procedures referred to in Sections 5 and 6 of Annex\u00a0IX, Section\u00a06 of Annex\u00a0X and Section\u00a016 of Annex\u00a0XI, for which they are designated.\nIn the case of devices manufactured utilising tissues or cells of animal origin or their derivatives, such as from TSE susceptible species, as referred to in Regulation\u00a0(EU)\u00a0No\u00a0722/2012, the notified body shall have documented procedures in place that fulfil the requirements laid down in that Regulation, including for the preparation of a summary evaluation report for the relevant competent authority.\n4.6.\u00a0\u00a0\u00a0Reporting\nThe notified body shall:\n\n\n\n\n\n\n\u2014\n\n\nensure that all steps of the conformity assessment are documented so that the conclusions of the assessment are clear and demonstrate compliance with the requirements of this Regulation and can represent objective evidence of such compliance to persons that are not themselves involved in the assessment, for example personnel in designating authorities,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure that records that are sufficient to provide a discernible audit trail are available for quality management system audits,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclearly document the conclusions of its assessment of clinical evaluation in a clinical evaluation assessment report, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nfor each specific project, provide a detailed report which shall be based on a standard format containing a minimum set of elements determined by the MDCG.\n\n\n\n\nThe report of the notified body shall:\n\n\n\n\n\n\n\u2014\n\n\nclearly document the outcome of its assessment and draw clear conclusions from the verification of the manufacturer's conformity with the requirements of this Regulation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmake a recommendation for a final review and for a final decision to be taken by the notified body; this recommendation shall be signed off by the member of personnel responsible in the notified body, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbe provided to the manufacturer in question.\n\n\n\n\n4.7.\u00a0\u00a0\u00a0Final review\nThe notified body shall prior to making a final decision:\n\n\n\n\n\n\n\u2014\n\n\nensure that the personnel assigned for the final review and decision-making on specific projects are appropriately authorised and are different from the personnel who have conducted the assessments,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nverify that the report or reports and supporting documentation needed for decision making, including concerning resolution of non-conformities noted during assessment, are complete and sufficient with respect to the scope of the application, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nverify whether there are any unresolved non-conformities preventing issuance of a certificate.\n\n\n\n\n4.8.\u00a0\u00a0\u00a0Decisions and Certifications\nThe notified body shall have documented procedures for decision-making including as regards the allocation of responsibilities for the issuance, suspension, restriction and withdrawal of certificates. Those procedures shall include the notification requirements laid down in Chapter V of this Regulation. The procedures shall allow the notified body in question to:\n\n\n\n\n\n\n\u2014\n\n\ndecide, based on the assessment documentation and additional information available, whether the requirements of this Regulation are fulfilled,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndecide, based on the results of its assessment of the clinical evaluation and risk management, whether the post-market surveillance plan, including the PMCF plan, is adequate,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndecide on specific milestones for further review by the notified body of the up to date clinical evaluation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndecide whether specific conditions or provisions need to be defined for the certification,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndecide, based on the novelty, risk classification, clinical evaluation and conclusions from the risk analysis of the device, on a period of certification not exceeding five\u00a0years,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclearly document decision making and approval steps including approval by signature of the members of personnel responsible,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclearly document responsibilities and mechanisms for communication of decisions, in particular, where the final signatory of a certificate differs from the decision maker or decision makers or does not fulfil the requirements laid down in Section\u00a03.2.7,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nissue a certificate or certificates in accordance with the minimum requirements laid down in Annex\u00a0XII for a period of validity not exceeding five years and shall indicate whether there are specific conditions or limitations associated with the certification,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nissue a certificate or certificates for the applicant alone and shall not issue certificates covering multiple entities, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure that the manufacturer is notified of the outcome of the assessment and the resultant decision and that they are entered into the electronic system referred to in Article\u00a057.\n\n\n\n\n4.9.\u00a0\u00a0\u00a0Changes and modifications\nThe notified body shall have documented procedures and contractual arrangements with manufacturers in place relating to the manufacturers' information obligations and the assessment of changes to:\n\n\n\n\n\n\n\u2014\n\n\nthe approved quality management system or systems or to the product-range covered,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe approved design of a device,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe intended use of or claims made for the device,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe approved type of a device, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nany substance incorporated in or utilised for the manufacturing of a device and being subject to the specific procedures in accordance with Section\u00a04.5.6.\n\n\n\n\nThe procedures and contractual arrangements referred to in the first paragraph\u00a0shall include measures for checking the significance of the changes referred to in the first paragraph.\nIn accordance with its documented procedures, the notified body in question shall:\n\n\n\n\n\n\n\u2014\n\n\nensure that manufacturers submit for prior approval plans for changes as referred to in the first paragraph\u00a0and relevant information relating to such changes,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nassess the changes proposed and verify whether, after these changes, the quality management system, or the design of a device or type of a device, still meets the requirements of this Regulation, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nnotify the manufacturer of its decision and provide a report or as applicable a supplementary report, which shall contain the justified conclusions of its assessment.\n\n\n\n\n4.10.\u00a0\u00a0\u00a0Surveillance activities and post-certification monitoring\nThe notified body shall have documented procedures:\n\n\n\n\n\n\n\u2014\n\n\ndefining how and when surveillance activities of manufacturers are to be conducted. Those procedures shall include arrangements for unannounced on-site audits of manufacturers and, where applicable, subcontractors and suppliers carrying out product tests and the monitoring of compliance with any conditions binding manufacturers and associated with certification decisions, such as updates to clinical data at defined intervals,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nfor screening relevant sources of scientific and clinical data and post-market information relating to the scope of their designation. Such information shall be taken into account in the planning and conduct of surveillance activities, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nto review vigilance data to which they have access under Article\u00a092(2) in order to estimate its impact, if any, on the validity of existing certificates. The results of the evaluation and any decisions taken shall be thoroughly documented.\n\n\n\n\nThe notified body in question shall, upon receipt of information about vigilance cases from a manufacturer or competent authorities, decide which of the following options to apply:\n\n\n\n\n\n\n\u2014\n\n\nnot to take action on the basis that the vigilance case is clearly not related to the certification granted,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nobserve the manufacturer's and competent authority's activities and the results of the manufacturer's investigation so as to determine whether the certification granted is at risk or whether adequate corrective action has been taken,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nperform extraordinary surveillance measures, such as document reviews, short-notice or unannounced audits and product testing, where it is likely that the certification granted is at risk,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nincrease the frequency of surveillance audits,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreview specific products or processes on the occasion of the next audit of the manufacturer, or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntake any other relevant measure.\n\n\n\n\nIn relation to surveillance audits of manufacturers, the notified body shall have documented procedures to:\n\n\n\n\n\n\n\u2014\n\n\nconduct surveillance audits of the manufacturer on at least an annual basis which shall be planned and conducted in line with the relevant requirements in Section\u00a04.5,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure adequate assessment of the manufacturer's documentation on, and application of the provisions on, vigilance, the post-market surveillance, and PMCF,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsample and test devices and technical documentation, during audits, according to pre-defined sampling criteria and testing procedures to ensure that the manufacturer continuously applies the approved quality management system,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure that the manufacturer complies with the documentation and information obligations laid down in the relevant Annexes\u00a0and that its procedures take into account best practices in the implementation of quality management systems,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure that the manufacturer does not use quality management system or device approvals in a misleading manner,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ngather sufficient information to determine if the quality management system continues to comply with the requirements of this Regulation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nask the manufacturer, if non-conformities are detected, for corrections, corrective actions and, where applicable, preventive actions, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwhere necessary, impose specific restrictions on the relevant certificate, or suspend or withdraw it.\n\n\n\n\nThe notified body shall, if listed as part of the conditions for certification:\n\n\n\n\n\n\n\u2014\n\n\nconduct an in-depth review of the clinical evaluation as most recently updated by the manufacturer based on the manufacturer's post-market surveillance, on its PMCF and on clinical literature relevant to the condition being treated with the device or on clinical literature relevant to similar devices,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclearly document the outcome of the in-depth review and address any specific concerns to the manufacturer or impose any specific conditions on it, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure that the clinical evaluation as most recently updated, is appropriately reflected in the instructions for use and, where applicable, the summary of safety and performance.\n\n\n\n\n4.11.\u00a0\u00a0\u00a0Re-certification\nThe notified body shall have documented procedures in place relating to the re-certification reviews and the renewal of certificates. Re-certification of approved quality management systems or EU technical documentation assessment certificates or EU type-examination certificates shall occur at least every five years.\nThe notified body shall have documented procedures relating to renewals of EU technical documentation assessment certificates and EU type-examination certificates and those procedures shall require the manufacturer in question to submit a summary of changes and scientific findings for the device, including:\n\n\n\n\n\n\n(a)\n\n\nall changes to the originally approved device, including changes not yet notified,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nexperience gained from post-market surveillance,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nexperience from risk management,\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nexperience from updating the proof of compliance with the general safety and performance requirements set out in Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nexperience from reviews of the clinical evaluation, including the results of any clinical investigations and PMCF,\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nchanges to the requirements, to components of the device or to the scientific or regulatory environment,\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nchanges to applied or new harmonised standards, CS or equivalent documents, and\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nchanges in medical, scientific and technical knowledge, such as:\n\n\n\n\n\n\n\u2014\n\n\nnew treatments,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nchanges in test methods,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nnew scientific findings on materials and components, including findings on their biocompatibility,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nexperience from studies on comparable devices,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndata from registers and registries,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nexperience from clinical investigations with comparable devices.\n\n\n\n\n\n\n\n\nThe notified body shall have documented procedures to assess the information referred to in the second paragraph\u00a0and shall pay particular attention to clinical data from post-market surveillance and PMCF activities undertaken since the previous certification or re-certification, including appropriate updates to manufacturers' clinical evaluation reports.\nFor the decision on re-certification, the notified body in question shall use the same methods and principles as for the initial certification decision. If necessary, separate forms shall be established for re-certification taking into account the steps taken for certification such as application and application review.\n\n\n\n\n\nANNEX\u00a0VIII\n\nCLASSIFICATION RULES\n\nCHAPTER I\n\nDEFINITIONS SPECIFIC TO CLASSIFICATION RULES\n\n1.\u00a0\u00a0\u00a0DURATION OF USE\n1.1.\u00a0\u00a0\u00a0\n                     \u2018Transient\u2019 means normally intended for continuous use for less than 60 minutes.\n1.2.\u00a0\u00a0\u00a0\n                     \u2018Short term\u2019 means normally intended for continuous use for between 60 minutes and 30\u00a0days.\n1.3.\u00a0\u00a0\u00a0\n                     \u2018Long term\u2019 means normally intended for continuous use for more than 30 days.\n2.\u00a0\u00a0\u00a0INVASIVE AND ACTIVE DEVICES\n2.1.\u00a0\u00a0\u00a0\n                     \u2018Body orifice\u2019 means any natural opening in the body, as well as the external surface of the eyeball, or any permanent artificial opening, such as a stoma.\n2.2.\u00a0\u00a0\u00a0\n                     \u2018Surgically invasive device\u2019 means:\n\n\n\n\n\n\n(a)\n\n\nan invasive device which penetrates inside the body through the surface of the body, including through mucous membranes of body orifices with the aid or in the context of a surgical operation; and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\na device which produces penetration other than through a body orifice.\n\n\n\n\n2.3.\u00a0\u00a0\u00a0\n                     \u2018Reusable surgical instrument\u2019 means an instrument intended for surgical use in cutting, drilling, sawing, scratching, scraping, clamping, retracting, clipping or similar procedures, without a connection to an active device and which is intended by the manufacturer to be reused after appropriate procedures such as cleaning, disinfection and sterilisation have been carried out.\n2.4.\u00a0\u00a0\u00a0\n                     \u2018Active therapeutic device\u2019 means any active device used, whether alone or in combination with other devices, to support, modify, replace or restore biological functions or structures with a view to treatment or alleviation of an illness, injury or disability.\n2.5.\u00a0\u00a0\u00a0\n                     \u2018Active device intended for diagnosis and monitoring\u2019 means any active device used, whether alone or in combination with other devices, to supply information for detecting, diagnosing, monitoring or treating physiological conditions, states of health, illnesses or congenital deformities.\n2.6.\u00a0\u00a0\u00a0\n                     \u2018Central circulatory system\u2019 means the following blood vessels: arteriae pulmonales, aorta ascendens, arcus aortae, aorta descendens to the bifurcatio aortae, arteriae coronariae, arteria carotis communis, arteria carotis externa, arteria carotis interna, arteriae cerebrales, truncus brachiocephalicus, venae cordis, venae pulmonales, vena cava superior and vena cava inferior.\n2.7.\u00a0\u00a0\u00a0\n                     \u2018Central nervous system\u2019 means the brain, meninges and spinal cord.\n2.8.\u00a0\u00a0\u00a0\n                     \u2018Injured skin or mucous membrane\u2019 means an area of skin or a mucous membrane presenting a pathological change or change following disease or a wound.\nCHAPTER II\n\nIMPLEMENTING RULES\n\n3.1.\u00a0\u00a0\u00a0Application of the classification rules shall be governed by the intended purpose of the devices.\n3.2.\u00a0\u00a0\u00a0If the device in question is intended to be used in combination with another device, the classification rules shall apply separately to each of the devices. Accessories for a medical device and for a product listed in Annex\u00a0XVI shall be classified in their own right separately from the device with which they are used.\n3.3.\u00a0\u00a0\u00a0Software, which drives a device or influences the use of a device, shall fall within the same class as the device.\nIf the software is independent of any other device, it shall be classified in its own right.\n3.4.\u00a0\u00a0\u00a0If the device is not intended to be used solely or principally in a specific part of the body, it shall be considered and classified on the basis of the most critical specified use.\n3.5.\u00a0\u00a0\u00a0If several rules, or if, within the same rule, several sub-rules, apply to the same device based on the device's intended purpose, the strictest rule and sub-rule resulting in the higher classification shall apply.\n3.6.\u00a0\u00a0\u00a0In calculating the duration referred to in Section\u00a01, continuous use shall mean:\n\n\n\n\n\n\n(a)\n\n\nthe entire duration of use of the same device without regard to temporary interruption of use during a procedure or temporary removal for purposes such as cleaning or disinfection of the device. Whether the interruption of use or the removal is temporary shall be established in relation to the duration of the use prior to and after the period when the use is interrupted or the device removed; and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe accumulated use of a device that is intended by the manufacturer to be replaced immediately with another of the same type.\n\n\n\n\n3.7.\u00a0\u00a0\u00a0A device is considered to allow direct diagnosis when it provides the diagnosis of the disease or condition in question by itself or when it provides decisive information for the diagnosis.\nCHAPTER III\n\nCLASSIFICATION RULES\n\n4.\u00a0\u00a0\u00a0NON-INVASIVE DEVICES\n4.1.\u00a0\u00a0\u00a0Rule 1\nAll non-invasive devices are classified as class I, unless one of the rules set out hereinafter applies.\n4.2.\u00a0\u00a0\u00a0Rule 2\nAll non-invasive devices intended for channelling or storing blood, body liquids, cells or tissues, liquids or gases for the purpose of eventual infusion, administration or introduction into the body are classified as class IIa:\n\n\n\n\n\n\n\u2014\n\n\nif they may be connected to a class\u00a0IIa, class\u00a0IIb or class\u00a0III active device; or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif they are intended for use for channelling or storing blood or other body liquids or for storing organs, parts of organs or body cells and tissues, except for blood bags; blood bags are classified as class\u00a0IIb.\n\n\n\n\nIn all other cases, such devices are classified as class\u00a0I.\n4.3.\u00a0\u00a0\u00a0Rule 3\nAll non-invasive devices intended for modifying the biological or chemical composition of human tissues or cells, blood, other body liquids or other liquids intended for implantation or administration into the body are classified as class IIb, unless the treatment for which the device is used consists of filtration, centrifugation or exchanges of gas, heat, in which case they are classified as class\u00a0IIa.\nAll non-invasive devices consisting of a substance or a mixture of substances intended to be used in vitro in direct contact with human cells, tissues or organs taken from the human body or used in vitro with human embryos before their implantation or administration into the body are classified as class\u00a0III.\n4.4.\u00a0\u00a0\u00a0Rule 4\nAll non-invasive devices which come into contact with injured skin or mucous membrane are classified as:\n\n\n\n\n\n\n\u2014\n\n\nclass I if they are intended to be used as a mechanical barrier, for compression or for absorption of exudates;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIb if they are intended to be used principally for injuries to skin which have breached the dermis or mucous membrane and can only heal by secondary intent;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIa if they are principally intended to manage the micro-environment of injured skin or mucous membrane; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIa in all other cases.\n\n\n\n\nThis rule applies also to the invasive devices that come into contact with injured mucous membrane.\n5.\u00a0\u00a0\u00a0INVASIVE DEVICES\n5.1.\u00a0\u00a0\u00a0Rule 5\nAll invasive devices with respect to body orifices, other than surgically invasive devices, which are not intended for connection to an active device or which are intended for connection to a class I active device are classified as:\n\n\n\n\n\n\n\u2014\n\n\nclass I if they are intended for transient use;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass IIa if they are intended for short-term use, except if they are used in the oral cavity as far as the pharynx, in an ear canal up to the ear drum or in the nasal cavity, in which case they are classified as class I; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIb if they are intended for long-term use, except if they are used in the oral cavity as far as the pharynx, in an ear canal up to the ear drum or in the nasal cavity and are not liable to be absorbed by the mucous membrane, in which case they are classified as class\u00a0IIa.\n\n\n\n\nAll invasive devices with respect to body orifices, other than surgically invasive devices, intended for connection to a class\u00a0IIa, class\u00a0IIb or class\u00a0III active device, are classified as class\u00a0IIa.\n5.2.\u00a0\u00a0\u00a0Rule 6\nAll surgically invasive devices intended for transient use are classified as class\u00a0IIa unless they:\n\n\n\n\n\n\n\u2014\n\n\nare intended specifically to control, diagnose, monitor or correct a defect of the heart or of the central circulatory system through direct contact with those parts of the body, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare reusable surgical instruments, in which case they are classified as class\u00a0I;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended specifically for use in direct contact with the heart or central circulatory system or the central nervous system, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to supply energy in the form of ionising radiation in which case they are classified as class\u00a0IIb;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nhave a biological effect or are wholly or mainly absorbed in which case they are classified as class\u00a0IIb; or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to administer medicinal products by means of a delivery system, if such administration of a medicinal product is done in a manner that is potentially hazardous taking account of the mode of application, in which case they are classified as class\u00a0IIb.\n\n\n\n\n5.3.\u00a0\u00a0\u00a0Rule 7\nAll surgically invasive devices intended for short-term use are classified as class IIa unless they:\n\n\n\n\n\n\n\u2014\n\n\nare intended specifically to control, diagnose, monitor or correct a defect of the heart or of the central circulatory system through direct contact with those parts of the body, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended specifically for use in direct contact with the heart or central circulatory system or the central nervous system, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to supply energy in the form of ionizing radiation in which case they are classified as class\u00a0IIb;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nhave a biological effect or are wholly or mainly absorbed in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to undergo chemical change in the body in which case they are classified as class\u00a0IIb, except if the devices are placed in the teeth; or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to administer medicines, in which case they are classified as class\u00a0IIb.\n\n\n\n\n5.4.\u00a0\u00a0\u00a0Rule 8\nAll implantable devices and long-term surgically invasive devices are classified as class\u00a0IIb unless they:\n\n\n\n\n\n\n\u2014\n\n\nare intended to be placed in the teeth, in which case they are classified as class\u00a0IIa;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to be used in direct contact with the heart, the central circulatory system or the central nervous system, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nhave a biological effect or are wholly or mainly absorbed, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to undergo chemical change in the body in which case they are classified as class\u00a0III, except if the devices are placed in the teeth;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to administer medicinal products, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare active implantable devices or their accessories, in which cases they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare breast implants or surgical meshes, in which cases they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare total or partial joint replacements, in which case they are classified as class\u00a0III, with the exception of ancillary components such as screws, wedges, plates and instruments; or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare spinal disc replacement implants or are implantable devices that come into contact with the spinal column, in which case they are classified as class\u00a0III with the exception of components such as screws, wedges, plates and instruments.\n\n\n\n\n6.\u00a0\u00a0\u00a0ACTIVE DEVICES\n6.1.\u00a0\u00a0\u00a0Rule 9\nAll active therapeutic devices intended to administer or exchange energy are classified as class IIa unless their characteristics are such that they may administer energy to or exchange energy with the human body in a potentially hazardous way, taking account of the nature, the density and site of application of the energy, in which case they are classified as class\u00a0IIb.\nAll active devices intended to control or monitor the performance of active therapeutic class IIb devices, or intended directly to influence the performance of such devices are classified as class\u00a0IIb.\nAll active devices intended to emit ionizing radiation for therapeutic purposes, including devices which control or monitor such devices, or which directly influence their performance, are classified as class\u00a0IIb.\nAll active devices that are intended for controlling, monitoring or directly influencing the performance of active implantable devices are classified as class\u00a0III.\n6.2.\u00a0\u00a0\u00a0Rule 10\nActive devices intended for diagnosis and monitoring are classified as class\u00a0IIa:\n\n\n\n\n\n\n\u2014\n\n\nif they are intended to supply energy which will be absorbed by the human body, except for devices intended to illuminate the patient's body, in the visible spectrum, in which case they are classified as class I;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif they are intended to image in vivo distribution of radiopharmaceuticals; or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif they are intended to allow direct diagnosis or monitoring of vital physiological processes, unless they are specifically intended for monitoring of vital physiological parameters and the nature of variations of those parameters is such that it could result in immediate danger to the patient, for instance variations in cardiac performance, respiration, activity of the central nervous system, or they are intended for diagnosis in clinical situations where the patient is in immediate danger, in which cases they are classified as class\u00a0IIb.\n\n\n\n\nActive devices intended to emit ionizing radiation and intended for diagnostic or therapeutic radiology, including interventional radiology devices and devices which control or monitor such devices, or which directly influence their performance, are classified as class\u00a0IIb.\n6.3.\u00a0\u00a0\u00a0Rule 11\nSoftware intended to provide information which is used to take decisions with diagnosis or therapeutic purposes is classified as class IIa, except if such decisions have an impact that may cause:\n\n\n\n\n\n\n\u2014\n\n\ndeath or an irreversible deterioration of a person's state of health, in which case it is in class\u00a0III; or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na serious deterioration of a person's state of health or a surgical intervention, in which case it is classified as class\u00a0IIb.\n\n\n\n\nSoftware intended to monitor physiological processes is classified as class\u00a0IIa, except if it is intended for monitoring of vital physiological parameters, where the nature of variations of those parameters is such that it could result in immediate danger to the patient, in which case it is classified as class\u00a0IIb.\nAll other software is classified as class\u00a0I.\n6.4.\u00a0\u00a0\u00a0Rule 12\nAll active devices intended to administer and/or remove medicinal products, body liquids or other substances to or from the body are classified as class\u00a0IIa, unless this is done in a manner that is potentially hazardous, taking account of the nature of the substances involved, of the part of the body concerned and of the mode of application in which case they are classified as class\u00a0IIb.\n6.5.\u00a0\u00a0\u00a0Rule 13\nAll other active devices are classified as class\u00a0I.\n7.\u00a0\u00a0\u00a0SPECIAL RULES\n7.1.\u00a0\u00a0\u00a0Rule 14\nAll devices incorporating, as an integral part, a substance which, if used separately, can be considered to be a medicinal product, as defined in point\u00a02 of Article\u00a01 of Directive\u00a02001/83/EC, including a medicinal product derived from human blood or human plasma, as defined in point\u00a010 of Article\u00a01 of that Directive, and that has an action ancillary to that of the devices, are classified as class\u00a0III.\n7.2.\u00a0\u00a0\u00a0Rule 15\nAll devices used for contraception or prevention of the transmission of sexually transmitted diseases are classified as class\u00a0IIb, unless they are implantable or long term invasive devices, in which case they are classified as class\u00a0III.\n7.3.\u00a0\u00a0\u00a0Rule 16\nAll devices intended specifically to be used for disinfecting, cleaning, rinsing or, where appropriate, hydrating contact lenses are classified as class\u00a0IIb.\nAll devices intended specifically to be used for disinfecting or sterilising medical devices are classified as class IIa, unless they are disinfecting solutions or washer-disinfectors intended specifically to be used for disinfecting invasive devices, as the end point of processing, in which case they are classified as class\u00a0IIb.\nThis rule does not apply to devices that are intended to clean devices other than contact lenses by means of physical action only.\n7.4.\u00a0\u00a0\u00a0Rule 17\nDevices specifically intended for recording of diagnostic images generated by X-ray radiation are classified as class\u00a0IIa.\n7.5.\u00a0\u00a0\u00a0Rule 18\nAll devices manufactured utilising tissues or cells of human or animal origin, or their derivatives, which are non-viable or rendered non-viable, are classified as class\u00a0III, unless such devices are manufactured utilising tissues or cells of animal origin, or their derivatives, which are non-viable or rendered non-viable and are devices intended to come into contact with intact skin only.\n7.6.\u00a0\u00a0\u00a0Rule 19\nAll devices incorporating or consisting of nanomaterial are classified as:\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0III if they present a high or medium potential for internal exposure;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIb if they present a low potential for internal exposure; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIa if they present a negligible potential for internal exposure.\n\n\n\n\n7.7.\u00a0\u00a0\u00a0Rule 20\nAll invasive devices with respect to body orifices, other than surgically invasive devices, which are intended to administer medicinal products by inhalation are classified as class\u00a0IIa, unless their mode of action has an essential impact on the efficacy and safety of the administered medicinal product or they are intended to treat life-threatening conditions, in which case they are classified as class\u00a0IIb.\n7.8.\u00a0\u00a0\u00a0Rule 21\nDevices that are composed of substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed by or locally dispersed in the human body are classified as:\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0III if they, or their products of metabolism, are systemically absorbed by the human body in order to achieve the intended purpose;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0III if they achieve their intended purpose in the stomach or lower gastrointestinal tract and they, or their products of metabolism, are systemically absorbed by the human body;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIa if they are applied to the skin or if they are applied in the nasal or oral cavity as far as the pharynx, and achieve their intended purpose on those cavities; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIb in all other cases.\n\n\n\n\n7.9.\u00a0\u00a0\u00a0Rule 22\nActive therapeutic devices with an integrated or incorporated diagnostic function which significantly determines the patient management by the device, such as closed loop systems or automated external defibrillators, are classified as class\u00a0III.\n\n\n\n\n\nANNEX IX\n\nCONFORMITY ASSESSMENT BASED ON A QUALITY MANAGEMENT SYSTEM AND ON ASSESSMENT OF TECHNICAL DOCUMENTATION\n\nCHAPTER I\n\nQUALITY MANAGEMENT SYSTEM\n\n1.\u00a0\u00a0\u00a0The manufacturer shall establish, document and implement a quality management system as described in Article\u00a010(9) and maintain its effectiveness throughout the life cycle of the devices concerned. The manufacturer shall ensure the application of the quality management system as specified in Section\u00a02 and shall be subject to audit, as laid down in Sections\u00a02.3 and 2.4, and to surveillance as specified in Section\u00a03.\n2.\u00a0\u00a0\u00a0Quality management system assessment\n2.1.\u00a0\u00a0\u00a0The manufacturer shall lodge an application for assessment of its quality management system with a notified body. The application shall include:\n\n\n\n\n\n\n\u2014\n\n\nthe name of the manufacturer and address of its registered place of business and any additional manufacturing site covered by the quality management system, and, if the manufacturer's application is lodged by its authorised representative, the name of the authorised representative and the address of the authorised representative's registered place of business,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nall relevant information on the device or group of devices covered by the quality management system,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na written declaration that no application has been lodged with any other notified body for the same device-related quality management system, or information about any previous application for the same device-related quality management system,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na draft of an EU declaration of conformity in accordance with Article\u00a019 and Annex\u00a0IV for the device model covered by the conformity assessment procedure,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation on the manufacturer's quality management system,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na documented description of the procedures in place to fulfil the obligations arising from the quality management system and required under this Regulation and the undertaking by the manufacturer in question to apply those procedures,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na description of the procedures in place to ensure that the quality management system remains adequate and effective, and the undertaking by the manufacturer to apply those procedures,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation on the manufacturer's post-market surveillance system and, where applicable, on the PMCF plan, and the procedures put in place to ensure compliance with the obligations resulting from the provisions on vigilance set out in Articles\u00a087 to\u00a092,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na description of the procedures in place to keep up to date the post-market surveillance system, and, where applicable, the PMCF plan, and the procedures ensuring compliance with the obligations resulting from the provisions on vigilance set out in Articles\u00a087 to 92, as well as the undertaking by the manufacturer to apply those procedures,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndocumentation on the clinical evaluation plan, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na description of the procedures in place to keep up to date the clinical evaluation plan, taking into account the state of the art.\n\n\n\n\n2.2.\u00a0\u00a0\u00a0Implementation of the quality management system shall ensure compliance with this Regulation. All the elements, requirements and provisions adopted by the manufacturer for its quality management system shall be documented in a systematic and orderly manner in the form of a quality manual and written policies and procedures such as quality programmes, quality plans and quality records.\nMoreover, the documentation to be submitted for the assessment of the quality management system shall include an adequate description of, in particular:\n\n\n\n\n\n\n(a)\n\n\nthe manufacturer's quality objectives;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe organisation of the business and in particular:\n\n\n\n\n\n\n\u2014\n\n\nthe organisational structures with the assignment of staff responsibilities in relation to critical procedures, the responsibilities of the managerial staff and their organisational authority,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe methods of monitoring whether the operation of the quality management system is efficient and in particular the ability of that system to achieve the desired design and device quality, including control of devices which fail to conform,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwhere the design, manufacture and/or final verification and testing of the devices, or parts of any of those processes, is carried out by another party, the methods of monitoring the efficient operation of the quality management system and in particular the type and extent of control applied to the other party, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwhere the manufacturer does not have a registered place of business in a Member\u00a0State, the draft mandate for the designation of an authorised representative and a letter of intention from the authorised representative to accept the mandate;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe procedures and techniques for monitoring, verifying, validating and controlling the design of the devices and the corresponding documentation as well as the data and records arising from those procedures and techniques. Those procedures and techniques shall specifically cover:\n\n\n\n\n\n\n\u2014\n\n\nthe strategy for regulatory compliance, including processes for identification of relevant legal requirements, qualification, classification, handling of equivalence, choice of and compliance with conformity assessment procedures,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nidentification of applicable general safety and performance requirements and solutions to fulfil those requirements, taking applicable CS and, where opted for, harmonised standards or other adequate solutions into account,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nrisk management as referred to in Section\u00a03 of Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe clinical evaluation, pursuant to Article\u00a061 and Annex\u00a0XIV, including post-market clinical follow-up,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsolutions for fulfilling the applicable specific requirements regarding design and construction, including appropriate pre-clinical evaluation, in particular the requirements of Chapter II of Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsolutions for fulfilling the applicable specific requirements regarding the information to be supplied with the device, in particular the requirements of Chapter III of Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe device identification procedures drawn up and kept up to date from drawings, specifications or other relevant documents at every stage of manufacture, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmanagement of design or quality management system changes; and\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe verification and quality assurance techniques at the manufacturing stage and in particular the processes and procedures which are to be used, particularly as regards sterilisation and the relevant documents; and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe appropriate tests and trials which are to be carried out before, during and after manufacture, the frequency with which they are to take place, and the test equipment to be used; it shall be possible to trace back adequately the calibration of that test equipment.\n\n\n\n\nIn addition, the manufacturer shall grant the notified body access to the technical documentation referred to in Annexes\u00a0II and III.\n2.3.\u00a0\u00a0\u00a0Audit\nThe notified body shall audit the quality management system to determine whether it meets the requirements referred to in Section\u00a02.2. Where the manufacturer uses a harmonised standard or CS related to a quality management system, the notified body shall assess conformity with those standards or CS. The notified body shall assume that a quality management system which satisfies the relevant harmonised standards or CS conforms to the requirements covered by those standards or CS, unless it duly substantiates not doing so.\nThe audit team of the notified body shall include at least one member with past experience of assessments of the technology concerned in accordance with Sections 4.3. to 4.5. of Annex\u00a0VII. In circumstances where such experience is not immediately obvious or applicable, the notified body shall provide a documented rationale for the composition of that team. The assessment procedure shall include an audit on the manufacturer's premises and, if appropriate, on the premises of the manufacturer's suppliers and/or subcontractors to verify the manufacturing and other relevant processes.\nMoreover, in the case of class IIa and class IIb devices, the quality management system assessment shall be accompanied by the assessment of technical documentation for devices selected on a representative basis in accordance with Sections 4.4 to 4.8. In choosing representative samples, the notified body shall take into account the published guidance developed by the MDCG pursuant to Article\u00a0105 and in particular the novelty of the technology, similarities in design, technology, manufacturing and sterilisation methods, the intended purpose and the results of any previous relevant assessments such as with regard to physical, chemical, biological or clinical properties, that have been carried out in accordance with this Regulation. The notified body in question shall document its rationale for the samples taken.\nIf the quality management system conforms to the relevant provisions of this Regulation, the notified body shall issue an EU quality management system certificate. The notified body shall notify the manufacturer of its decision to issue the certificate. The decision shall contain the conclusions of the audit and a reasoned report.\n2.4.\u00a0\u00a0\u00a0The manufacturer in question shall inform the notified body which approved the quality management system of any plan for substantial changes to the quality management system, or the device-range covered. The notified body shall assess the changes proposed, determine the need for additional audits and verify whether after those changes the quality management system still meets the requirements referred to in Section\u00a02.2. It shall notify the manufacturer of its decision which shall contain the conclusions of the assessment, and where applicable, conclusions of additional audits. The approval of any substantial change to the quality management system or the device-range covered shall take the form of a supplement to the EU quality management system certificate.\n3.\u00a0\u00a0\u00a0Surveillance assessment applicable to class IIa, class IIb and class III devices\n3.1.\u00a0\u00a0\u00a0The aim of surveillance is to ensure that the manufacturer duly fulfils the obligations arising from the approved quality management system.\n3.2.\u00a0\u00a0\u00a0The manufacturer shall give authorisation to the notified body to carry out all the necessary audits, including on-site audits, and supply it with all relevant information, in particular:\n\n\n\n\n\n\n\u2014\n\n\nthe documentation on its quality management system,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndocumentation on any findings and conclusions resulting from the application of the post-market surveillance plan, including the PMCF plan, for a representative sample of devices, and of the provisions on vigilance set out in Articles\u00a087 to 92,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe data stipulated in the part of the quality management system relating to design, such as the results of analyses, calculations, tests and the solutions adopted regarding the risk-management as referred to in Section\u00a04 of Annex\u00a0I, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe data stipulated in the part of the quality management system relating to manufacture, such as quality control reports and test data, calibration data, and records on the qualifications of the personnel concerned.\n\n\n\n\n3.3.\u00a0\u00a0\u00a0Notified bodies shall periodically, at least once every 12 months, carry out appropriate audits and assessments to make sure that the manufacturer in question applies the approved quality management system and the post-market surveillance plan. Those audits and assessments shall include audits on the premises of the manufacturer and, if appropriate, of the manufacturer's suppliers and/or subcontractors. At the time of such on-site audits, the notified body shall, where necessary, carry out or ask for tests in order to check that the quality management system is working properly. It shall provide the manufacturer with a surveillance audit report and, if a test has been carried out, with a test report.\n3.4.\u00a0\u00a0\u00a0The notified body shall randomly perform at least once every five years unannounced audits on the site of the manufacturer and, where appropriate, of the manufacturer's suppliers and/or subcontractors, which may be combined with the periodic surveillance assessment referred to in Section\u00a03.3. or be performed in addition to that surveillance assessment. The notified body shall establish a plan for such unannounced on-site audits but shall not disclose it to the manufacturer.\nWithin the context of such unannounced on-site audits, the notified body shall test an adequate sample of the devices produced or an adequate sample from the manufacturing process to verify that the manufactured device is in conformity with the technical documentation, with the exception of the devices referred to in the second subparagraph\u00a0of Article\u00a052(8). Prior to unannounced on-site audits, the notified body shall specify the relevant sampling criteria and testing procedure.\nInstead of, or in addition to, sampling referred to in the second paragraph, the notified body shall take samples of devices from the market to verify that the manufactured device is in conformity with the technical documentation, with the exception of the devices referred to in the second subparagraph\u00a0of Article\u00a052(8). Prior to the sampling, the notified body in question shall specify the relevant sampling criteria and testing procedure.\nThe notified body shall provide the manufacturer in question with an on-site audit report which shall include, if applicable, the result of the sample test.\n3.5.\u00a0\u00a0\u00a0In the case of class IIa and class IIb devices, the surveillance assessment shall also include an assessment of the technical documentation as referred to in Sections 4.4 to 4.8 for the device or devices concerned on the basis of further representative samples chosen in accordance with the rationale documented by the notified body in accordance with the second paragraph\u00a0of Section\u00a02.3.\nIn the case of class III devices, the surveillance assessment shall also include a test of the approved parts and/or materials that are essential for the integrity of the device, including, where appropriate, a check that the quantities of produced or purchased parts and/or materials correspond to the quantities of finished devices.\n3.6.\u00a0\u00a0\u00a0The notified body shall ensure that the composition of the assessment team is such that there is sufficient experience with the evaluation of the devices, systems and processes concerned, continuous objectivity and neutrality; this shall include a rotation of the members of the assessment team at appropriate intervals. As a general rule, a lead auditor shall neither lead nor attend audits for more than three consecutive years in respect of the same manufacturer.\n3.7.\u00a0\u00a0\u00a0If the notified body finds a divergence between the sample taken from the devices produced or from the market and the specifications laid down in the technical documentation or the approved design, it shall suspend or withdraw the relevant certificate or impose restrictions on it.\nCHAPTER II\n\nASSESSMENT OF THE TECHNICAL DOCUMENTATION\n\n4.\u00a0\u00a0\u00a0Assessment of the technical documentation applicable to class III devices and to the class\u00a0IIb devices referred to in the second subparagraph\u00a0of Article\u00a052(4)\n4.1.\u00a0\u00a0\u00a0In addition to the obligations laid down in Section\u00a02, the manufacturer shall lodge with the notified body an application for assessment of the technical documentation relating to the device which it plans to place on the market or put into service and which is covered by the quality management system referred to in Section\u00a02.\n4.2.\u00a0\u00a0\u00a0The application shall describe the design, manufacture and performance of the device in question. It shall include the technical documentation as referred to in Annexes\u00a0II and III.\n4.3.\u00a0\u00a0\u00a0The notified body shall examine the application by using staff, employed by it, with proven knowledge and experience regarding the technology concerned and its clinical application. The notified body may require the application to be completed by having further tests carried out or requesting further evidence to be provided to allow assessment of conformity with the relevant requirements of the Regulation. The notified body shall carry out adequate physical or laboratory tests in relation to the device or request the manufacturer to carry out such tests.\n4.4.\u00a0\u00a0\u00a0The notified body shall review the clinical evidence presented by the manufacturer in the clinical evaluation report and the related clinical evaluation that was conducted. The notified body shall employ device reviewers with sufficient clinical expertise and, if necessary, use external clinical experts with direct and current experience relating to the device in question or the clinical condition in which it is utilised, for the purposes of that review.\n4.5.\u00a0\u00a0\u00a0The notified body shall, in circumstances in which the clinical evidence is based partly or totally on data from devices which are claimed to be equivalent to the device under assessment, assess the suitability of using such data, taking into account factors such as new indications and innovation. The notified body shall clearly document its conclusions on the claimed equivalence, and on the relevance and adequacy of the data for demonstrating conformity. For any characteristic of the device claimed as innovative by the manufacturer or for new indications, the notified body shall assess to what extent specific claims are supported by specific pre-clinical and clinical data and risk analysis.\n4.6.\u00a0\u00a0\u00a0The notified body shall verify that the clinical evidence and the clinical evaluation are adequate and shall verify the conclusions drawn by the manufacturer on the conformity with the relevant general safety and performance requirements. That verification shall include consideration of the adequacy of the benefit-risk determination, the risk management, the instructions for use, the user training and the manufacturer's post-market surveillance plan, and include a review of the need for, and the adequacy of, the PMCF plan proposed, where applicable.\n4.7.\u00a0\u00a0\u00a0Based on its assessment of the clinical evidence, the notified body shall consider the clinical evaluation and the benefit-risk determination, and whether specific milestones need to be defined to allow the notified body to review updates to the clinical evidence that result from post-market surveillance and PMCF data.\n4.8.\u00a0\u00a0\u00a0The notified body shall clearly document the outcome of its assessment in the clinical evaluation assessment report.\n4.9.\u00a0\u00a0\u00a0The notified body shall provide the manufacturer with a report on the technical documentation assessment, including a clinical evaluation assessment report. If the device conforms to the relevant provisions of this Regulation, the notified body shall issue an EU\u00a0technical documentation assessment certificate. The certificate shall contain the conclusions of the technical documentation assessment, the conditions of the certificate's validity, the data needed for identification of the approved design, and, where appropriate, a description of the intended purpose of the device.\n4.10.\u00a0\u00a0\u00a0Changes to the approved device shall require approval from the notified body which issued the EU technical documentation assessment certificate where such changes could affect the safety and performance of the device or the conditions prescribed for use of the device. Where the manufacturer plans to introduce any of the above-mentioned changes it shall inform the notified body which issued the EU technical documentation assessment certificate thereof. The notified body shall assess the planned changes and decide whether the planned changes require a new conformity assessment in accordance with Article\u00a052 or whether they could be addressed by means of a supplement to the EU technical documentation assessment certificate. In the latter case, the notified body shall assess the changes, notify the manufacturer of its decision and, where the changes are approved, provide it with a supplement to the EU technical documentation assessment certificate.\n5.\u00a0\u00a0\u00a0Specific additional procedures\n5.1.\u00a0\u00a0\u00a0Assessment procedure for certain class III and class IIb devices\n\n\n\n\n\n\n(a)\n\n\nFor class III implantable devices, and for class IIb active devices intended to administer and/or remove a medicinal product as referred to in Section\u00a06.4. of Annex\u00a0VIII (Rule\u00a012), the notified body shall, having verified the quality of clinical data supporting the clinical evaluation report of the manufacturer referred to in Article\u00a061(12), prepare a clinical evaluation assessment report which sets out its conclusions concerning the clinical evidence provided by the manufacturer, in particular concerning the benefit-risk determination, the consistency of that evidence with the intended purpose, including the medical indication or indications and the PMCF plan referred to in Article\u00a010(3) and Part B of Annex\u00a0XIV.\nThe notified body shall transmit its clinical evaluation assessment report, along with the manufacturer's clinical evaluation documentation, referred to in points (c) and (d) of Section\u00a06.1 of Annex\u00a0II, to the Commission.\nThe Commission shall immediately transmit those documents to the relevant expert panel referred to in Article\u00a0106.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nThe notified body may be requested to present its conclusions as referred to in point\u00a0(a) to the expert panel concerned.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nThe expert panel shall decide, under the supervision of the Commission, on the basis of all of the following criteria:\n\n\n\n\n\n\n(i)\n\n\nthe novelty of the device or of the related clinical procedure involved, and the possible major clinical or health impact thereof;\n\n\n\n\n\n\n\n\n\n\n(ii)\n\n\na significantly adverse change in the benefit-risk profile of a specific category or group of devices due to scientifically valid health concerns in respect of components or source material or in respect of the impact on health in the case of failure of the device;\n\n\n\n\n\n\n\n\n\n\n(iii)\n\n\na significantly increased rate of serious incidents reported in accordance with Article\u00a087 in respect of a specific category or group of devices,\n\n\n\n\nwhether to provide a scientific opinion on the clinical evaluation assessment report of the notified body based on the clinical evidence provided by the manufacturer, in particular concerning the benefit-risk determination, the consistency of that evidence with the medical indication or indications and the PMCF plan. That scientific opinion shall be provided within a period of 60 days, starting on the day of receipt of the documents from the Commission as referred to in point\u00a0(a). The reasons for the decision to provide a scientific opinion on the basis of the criteria in points (i), (ii) and (iii) shall be included in the scientific opinion. Where the information submitted is not sufficient for the expert panel to reach a conclusion, this shall be stated in the scientific opinion.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nThe expert panel may decide, under the supervision of the Commission, on the basis of the criteria laid down in point\u00a0(c) not to provide a scientific opinion, in which case it shall inform the notified body as soon as possible and in any event within 21\u00a0days of receipt of the documents as referred to in point\u00a0(a) from the Commission. The expert panel shall within that time limit provide the notified body and the Commission with the reasons for its decision, whereupon the notified body may proceed with the certification procedure of that device.\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nThe expert panel shall within 21 days of receipt of the documents from the Commission notify the Commission, through Eudamed whether it intends to provide a scientific opinion, pursuant to point\u00a0(c), or whether it intends not to provide a scientific opinion, pursuant to point\u00a0(d).\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nWhere no opinion has been delivered within a period of 60 days, the notified body may proceed with the certification procedure of the device in question.\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nThe notified body shall give due consideration to the views expressed in the scientific opinion of the expert panel. Where the expert panel finds that the level of clinical evidence is not sufficient or otherwise gives rise to serious concerns about the benefit-risk determination, the consistency of that evidence with the intended purpose, including the medical indication(s), and with the PMCF plan, the notified body shall, if necessary, advise the manufacturer to restrict the intended purpose of the device to certain groups of patients or certain medical indications and/or to impose a limit on the duration of validity of the certificate, to undertake specific PMCF studies, to adapt the instructions for use or the summary of safety and performance, or to impose other restrictions in its conformity assessment report, as appropriate. The notified body shall provide a full justification where it has not followed the advice of the expert panel in its conformity assessment report and the Commission shall without prejudice to Article\u00a0109 make both the scientific opinion of the expert panel and the written justification provided by the notified body publicly available via Eudamed.\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nThe Commission, after consultation with the Member\u00a0States and relevant scientific experts shall provide guidance for expert panels for consistent interpretation of the criteria in point\u00a0(c) before 26 May 2020.\n\n\n\n\n5.2.\u00a0\u00a0\u00a0Procedure in the case of devices incorporating a medicinal substance\n\n\n\n\n\n\n(a)\n\n\nWhere a device incorporates, as an integral part, a substance which, if used separately, may be considered to be a medicinal product within the meaning of point\u00a02 of Article\u00a01 of Directive\u00a02001/83/EC, including a medicinal product derived from human blood or human plasma and that has an action ancillary to that of the device, the quality, safety and usefulness of the substance shall be verified by analogy with the methods specified in Annex\u00a0I to Directive\u00a02001/83/EC.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nBefore issuing an EU technical documentation assessment certificate, the notified body shall, having verified the usefulness of the substance as part of the device and taking account of the intended purpose of the device, seek a scientific opinion from one of the competent authorities designated by the Member\u00a0States in accordance with Directive\u00a02001/83/EC or from the EMA, either of which to be referred to in this Section\u00a0as \u2018the medicinal products authority consulted\u2019 depending on which has been consulted under this point, on the quality and safety of the substance including the benefit or risk of the incorporation of the substance into the device. Where the device incorporates a human blood or plasma derivative or a substance that, if used separately, may be considered to be a medicinal product falling exclusively within the scope of the Annex to Regulation (EC)\u00a0No\u00a0726/2004, the notified body shall seek the opinion of the EMA.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nWhen issuing its opinion, the medicinal products authority consulted shall take into account the manufacturing process and the data relating to the usefulness of incorporation of the substance into the device as determined by the notified body.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nThe medicinal products authority consulted shall provide its opinion to the notified body within 210 days of receipt of all the necessary documentation.\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nThe scientific opinion of the medicinal products authority consulted, and any possible update of that opinion, shall be included in the documentation of the notified body concerning the device. The notified body shall give due consideration to the views expressed in the scientific opinion when making its decision. The notified body shall not deliver the certificate if the scientific opinion is unfavourable and shall convey its final decision to the medicinal products authority consulted.\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nBefore any change is made with respect to an ancillary substance incorporated in a device, in particular related to its manufacturing process, the manufacturer shall inform the notified body of the changes. That notified body shall seek the opinion of the medicinal products authority consulted, in order to confirm that the quality and safety of the ancillary substance remain unchanged. The medicinal products authority consulted shall take into account the data relating to the usefulness of incorporation of the substance into the device as determined by the notified body, in order to ensure that the changes have no negative impact on the risk or benefit previously established concerning the incorporation of the substance into the device. The medicinal products authority consulted shall provide its opinion within 60 days after receipt of all the necessary documentation regarding the changes. The notified body shall not deliver the supplement to the EU technical documentation assessment certificate if the scientific opinion provided by the medicinal products authority consulted is unfavourable. The notified body shall convey its final decision to the medicinal products authority consulted.\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nWhere the medicinal products authority consulted obtains information on the ancillary substance, which could have an impact on the risk or benefit previously established concerning the incorporation of the substance into the device, it shall advise the notified body as to whether this information has an impact on the risk or benefit previously established concerning the incorporation of the substance into the device. The notified body shall take that advice into account in reconsidering its assessment of the conformity assessment procedure.\n\n\n\n\n5.3.\u00a0\u00a0\u00a0Procedure in the case of devices manufactured utilising, or incorporating, tissues or cells of human or animal origin, or their derivatives, that are non-viable or rendered non-viable\n5.3.1.\u00a0\u00a0\u00a0Tissues or cells of human origin or their derivatives\n\n\n\n\n\n\n(a)\n\n\nFor devices manufactured utilising derivatives of tissues or cells of human origin that are covered by this Regulation in accordance with point\u00a0(g) of Article\u00a01(6) and for devices that incorporate, as an integral part, tissues or cells of human origin, or their derivatives, covered by Directive\u00a02004/23/EC, that have an action ancillary to that of the device, the notified body shall, prior to issuing an EU technical documentation assessment certificate, seek a scientific opinion from one of the competent authorities designated by the Member\u00a0States in accordance with Directive\u00a02004/23/EC (\u2018human tissues and cells competent authority\u2019) on the aspects relating to the donation, procurement and testing of tissues or cells of human origin or their derivatives. The notified body shall submit a summary of the preliminary conformity assessment which provides, among other things, information about the non-viability of the human tissues or cells in question, their donation, procurement and testing and the risk or benefit of the incorporation of the tissues or cells of human origin or their derivatives into the device.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nWithin 120 days of receipt of all the necessary documentation, the human tissues and cells competent authority shall provide to the notified body its opinion.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nThe scientific opinion of the human tissues and cells competent authority, and any possible update, shall be included in the documentation of the notified body concerning the device. The notified body shall give due consideration to the views expressed in the scientific opinion of the human tissues and cells competent authority when making its decision. The notified body shall not deliver the certificate if that scientific opinion is unfavourable. It shall convey its final decision to the human tissues and cells competent authority concerned.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nBefore any change is made with respect to non-viable tissues or cells of human origin or their derivatives incorporated in a device, in particular relating to their donation, testing or procurement, the manufacturer shall inform the notified body of the intended changes. The notified body shall consult the authority that was involved in the initial consultation, in order to confirm that the quality and safety of the tissues or cells of human origin or their derivatives incorporated in the device are maintained. The human tissues and cells competent authority concerned shall take into account the data relating to the usefulness of incorporation of the tissues or cells of human origin or their derivatives into the device as determined by the notified body, in order to ensure that the changes have no negative impact on the established benefit-risk ratio of the addition of the tissues or cells of human origin or their derivatives in the device. It shall provide its opinion within 60\u00a0days of receipt of all the necessary documentation regarding the intended changes. The notified body shall not deliver a supplement to the EU technical documentation assessment certificate if the scientific opinion is unfavourable and shall convey its final decision to the human tissues and cells competent authority concerned.\n\n\n\n\n5.3.2.\u00a0\u00a0\u00a0Tissues or cells of animal origin or their derivatives\nIn the case of devices manufactured utilising animal tissue which is rendered non-viable or utilising non-viable products derived from animal tissue, as referred to in Regulation\u00a0(EU)\u00a0No\u00a0722/2012, the notified body shall apply the relevant requirements laid down in that Regulation.\n5.4.\u00a0\u00a0\u00a0Procedure in the case of devices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body\n\n\n\n\n\n\n(a)\n\n\nThe quality and safety of devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed by, or locally dispersed in, the human body, shall be verified where applicable and only in respect of the requirements not covered by this Regulation, in accordance with the relevant requirements laid down in Annex\u00a0I to Directive\u00a02001/83/EC for the evaluation of absorption, distribution, metabolism, excretion, local tolerance, toxicity, interaction with other devices, medicinal products or other substances and potential for adverse reactions.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nIn addition, for devices, or their products of metabolism, that are systemically absorbed by the human body in order to achieve their intended purpose, the notified body shall seek a scientific opinion from one of the competent authorities designated by the Member\u00a0States in accordance with Directive\u00a02001/83/EC or from the EMA, either of which to be referred to in this Section\u00a0as \u2018the medicinal products authority consulted\u2019 depending on which has been consulted under this point, on the compliance of the device with the relevant requirements laid down in Annex\u00a0I to Directive\u00a02001/83/EC.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nThe opinion of the medicinal products authority consulted shall be drawn up within 150\u00a0days of receipt of all the necessary documentation.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nThe scientific opinion of the medicinal products authority consulted, and any possible update, shall be included in the documentation of the notified body concerning the device. The notified body shall give due consideration to the views expressed in the scientific opinion when making its decision and shall convey its final decision to the medicinal products authority consulted.\n\n\n\n\n6.\u00a0\u00a0\u00a0Batch verification in the case of devices incorporating, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma as referred to in Article\u00a01(8)\nUpon completing the manufacture of each batch of devices that incorporate, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma as referred to in the first subparagraph\u00a0of Article\u00a01(8), the manufacturer shall inform the notified body of the release of the batch of devices and send it the official certificate concerning the release of the batch of human blood or plasma derivative used in the device, issued by a Member\u00a0State laboratory or a laboratory designated for that purpose by a Member\u00a0State in accordance with Article\u00a0114(2) of Directive\u00a02001/83/EC.\nCHAPTER III\n\nADMINISTRATIVE PROVISIONS\n\n7.\u00a0\u00a0\u00a0The manufacturer or, where the manufacturer does not have a registered place of business in a Member\u00a0State, its authorised representative shall, for a period ending no sooner than 10 years, and in the case of implantable devices no sooner than 15 years, after the last device has been placed on the market, keep at the disposal of the competent authorities:\n\n\n\n\n\n\n\u2014\n\n\nthe EU declaration of conformity,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation referred to in the fifth indent of Section\u00a02.1 and in particular the data and records arising from the procedures referred to in point\u00a0(c) of the second paragraph\u00a0of Section\u00a02.2,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation on the changes referred to in Section\u00a02.4,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation referred to in Section\u00a04.2, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe decisions and reports from the notified body as referred to in this Annex.\n\n\n\n\n8.\u00a0\u00a0\u00a0Each Member\u00a0State shall require that the documentation referred to in Section\u00a07 is kept at the disposal of competent authorities for the period indicated in that Section\u00a0in case a manufacturer, or its authorised representative, established within its territory goes bankrupt or ceases its business activity prior to the end of that period.\n\n\n\n\n\nANNEX\u00a0X\n\nCONFORMITY ASSESSMENT BASED ON TYPE-EXAMINATION\n\n1.\u00a0\u00a0\u00a0EU type-examination is the procedure whereby a notified body ascertains and certifies that a device, including its technical documentation and relevant life cycle processes and a corresponding representative sample of the device production envisaged, fulfils the relevant provisions of this Regulation.\n2.\u00a0\u00a0\u00a0Application\nThe manufacturer shall lodge an application for assessment with a notified body. The application shall include:\n\n\n\n\n\n\n\u2014\n\n\nthe name of the manufacturer and address of the registered place of business of the manufacturer and, if the application is lodged by the authorised representative, the name of the authorised representative and the address of its registered place of business,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe technical documentation referred to in Annexes\u00a0II and III. The applicant shall make a representative sample of the device production envisaged (\u2018type\u2019) available to the notified body. The notified body may request other samples as necessary, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na written declaration that no application has been lodged with any other notified body for the same type, or information about any previous application for the same type that was refused by another notified body or was withdrawn by the manufacturer or its authorised representative before that other notified body made its final assessment.\n\n\n\n\n3.\u00a0\u00a0\u00a0Assessment\nThe notified body shall:\n\n\n\n\n\n\n(a)\n\n\nexamine the application by using staff with proven knowledge and experience regarding the technology concerned and its clinical application. The notified body may require the application to be completed by having further tests carried out or requesting further evidence to be provided to allow assessment of conformity with the relevant requirements of this Regulation. The notified body shall carry out adequate physical or laboratory tests in relation to the device or request the manufacturer to carry out such tests;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nexamine and assess the technical documentation for conformity with the requirements of this Regulation that are applicable to the device and verify that the type has been manufactured in conformity with that documentation; it shall also record the items designed in conformity with the applicable standards referred to in Article\u00a08 or with applicable CS, and record the items not designed on the basis of the relevant standards referred to in Article\u00a08 or of the relevant CS;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nreview the clinical evidence presented by the manufacturer in the clinical evaluation report in accordance with Section\u00a04 of Annex\u00a0XIV. The notified body shall employ device reviewers with sufficient clinical expertise and, if necessary, use external clinical experts with direct and current experience relating to the device in question or to the clinical condition in which it is utilised, for the purposes of that review;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nin circumstances in which the clinical evidence is based partly or totally on data from devices which are claimed to be similar or equivalent to the device under assessment, assess the suitability of using such data, taking into account factors such as new indications and innovation. The notified body shall clearly document its conclusions on the claimed equivalence, and on the relevance and adequacy of the data for demonstrating conformity;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nclearly document the outcome of its assessment in a pre-clinical and clinical evaluation assessment report as part of the EU type examination report referred to in point\u00a0(i);\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\ncarry out or arrange for the appropriate assessments and the physical or laboratory tests necessary to verify whether the solutions adopted by the manufacturer meet the general safety and performance requirements laid down in this Regulation, in the event that the standards referred to in Article\u00a08 or the CS have not been applied. Where the device has to be connected to another device or devices in order to operate as intended, proof shall be provided that it conforms to the general safety and performance requirements when connected to any such device or devices having the characteristics specified by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\ncarry out or arrange for the appropriate assessments and the physical or laboratory tests necessary to verify whether, in the event that the manufacturer has chosen to apply the relevant harmonised standards, those standards have actually been applied;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nagree with the applicant on the place where the necessary assessments and tests are to be carried out; and\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\ndraw up an EU type-examination report on the results of the assessments and tests carried out under points (a) to (g).\n\n\n\n\n4.\u00a0\u00a0\u00a0Certificate\nIf the type conforms to this Regulation, the notified body shall issue an EU\u00a0type-examination certificate. The certificate shall contain the name and address of the manufacturer, the conclusions of the type examination assessment, the conditions of the certificate's validity and the data needed for identification of the type approved. The certificate shall be drawn up in accordance with Annex\u00a0XII. The relevant parts of the documentation shall be annexed to the certificate and a copy kept by the notified body.\n5.\u00a0\u00a0\u00a0Changes to the type\n5.1.\u00a0\u00a0\u00a0The applicant shall inform the notified body which issued the EU type-examination certificate of any planned change to the approved type or of its intended purpose and conditions of use.\n5.2.\u00a0\u00a0\u00a0Changes to the approved device including limitations of its intended purpose and conditions of use shall require approval from the notified body which issued the EU\u00a0type-examination certificate where such changes may affect conformity with the general safety and performance requirements or with the conditions prescribed for use of the product. The notified body shall examine the planned changes, notify the manufacturer of its decision and provide him with a supplement to the EU type-examination report. The approval of any change to the approved type shall take the form of a supplement to the EU\u00a0type-examination certificate.\n5.3.\u00a0\u00a0\u00a0Changes to the intended purpose and conditions of use of the approved device, with the exception of limitations of the intended purpose and conditions of use, shall necessitate a new application for a conformity assessment.\n6.\u00a0\u00a0\u00a0Specific additional procedures\nSection\u00a05 of Annex\u00a0IX shall apply with the proviso that any reference to an EU technical documentation assessment certificate shall be understood as a reference to an EU\u00a0type-examination certificate.\n7.\u00a0\u00a0\u00a0Administrative provisions\nThe manufacturer or, where the manufacturer does not have a registered place of business in a Member\u00a0State, its authorised representative shall, for a period ending no sooner than 10 years, and in the case of implantable devices no sooner than 15 years, after the last device has been placed on the market, keep at the disposal of the competent authorities:\n\n\n\n\n\n\n\u2014\n\n\nthe documentation referred to in the second indent of Section\u00a02,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation on the changes referred to in Section\u00a05, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncopies of EU type-examination certificates, scientific opinions and reports and their additions/supplements.\n\n\n\n\nSection\u00a08 of Annex\u00a0IX shall apply.\n\n\n\n\n\nANNEX\u00a0XI\n\nCONFORMITY ASSESSMENT BASED ON PRODUCT CONFORMITY VERIFICATION\n\n1.\u00a0\u00a0\u00a0The objective of the conformity assessment based on product conformity verification is to ensure that devices conform to the type for which an EU type-examination certificate has been issued, and that they meet the provisions of this Regulation which apply to them.\n2.\u00a0\u00a0\u00a0Where an EU type-examination certificate has been issued in accordance with Annex\u00a0X, the manufacturer may either apply the procedure set out in Part A (production quality assurance) or the procedure set out in Part B (product verification) of this Annex.\n3.\u00a0\u00a0\u00a0By way of derogation from Sections 1 and 2 above, the procedures in this Annex\u00a0coupled with the drawing up of technical documentation as set out in Annexes\u00a0II and III may also be applied by manufacturers of class IIa devices.\nPART A\n\nPRODUCTION QUALITY ASSURANCE\n\n4.\u00a0\u00a0\u00a0The manufacturer shall ensure that the quality management system approved for the manufacture of the devices concerned is implemented, shall carry out a final verification, as specified in Section\u00a06, and shall be subject to the surveillance referred to in Section\u00a07.\n5.\u00a0\u00a0\u00a0When the manufacturer fulfils the obligations laid down in Section\u00a04, it shall draw up and keep an EU declaration of conformity in accordance with Article\u00a019 and Annex\u00a0IV for the device covered by the conformity assessment procedure. By issuing an EU declaration of conformity, the manufacturer shall be deemed to ensure and to declare that the device concerned conforms to the type described in the EU type-examination certificate and meets the requirements of this Regulation which apply to the device.\n6.\u00a0\u00a0\u00a0Quality management system\n6.1.\u00a0\u00a0\u00a0The manufacturer shall lodge an application for assessment of its quality management system with a notified body. The application shall include:\n\n\n\n\n\n\n\u2014\n\n\nall elements listed in Section\u00a02.1 of Annex\u00a0IX,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe technical documentation referred to in Annexes\u00a0II and III for the types approved, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na copy of the EU type-examination certificates referred to in Section\u00a04 of Annex\u00a0X; if the EU type-examination certificates have been issued by the same notified body with which the application is lodged, a reference to the technical documentation and its updates and the certificates issued shall also be included in the application.\n\n\n\n\n6.2.\u00a0\u00a0\u00a0Implementation of the quality management system shall be such as to ensure that there is compliance with the type described in the EU type-examination certificate and with the provisions of this Regulation which apply to the devices at each stage. All the elements, requirements and provisions adopted by the manufacturer for its quality management system shall be documented in a systematic and orderly manner in the form of a quality manual and written policies and procedures, such as quality programmes, quality plans and quality records.\nThat documentation shall, in particular, include an adequate description of all elements listed in points (a), (b), (d) and (e) of Section\u00a02.2 of Annex\u00a0IX.\n6.3.\u00a0\u00a0\u00a0The first and second paragraph\u00a0of Section\u00a02.3 of Annex\u00a0IX shall apply.\nIf the quality management system is such that it ensures that the devices conform to the type described in the EU type-examination certificate and that it conforms to the relevant provisions of this Regulation, the notified body shall issue an EU quality assurance certificate. The notified body shall notify the manufacturer of its decision to issue the certificate. That decision shall contain the conclusions of the notified body's audit and a reasoned assessment.\n6.4.\u00a0\u00a0\u00a0Section\u00a02.4 of Annex\u00a0IX shall apply.\n7.\u00a0\u00a0\u00a0Surveillance\nSection\u00a03.1, the first, second and fourth indents of Section\u00a03.2, Sections\u00a03.3, 3.4, 3.6 and 3.7 of Annex\u00a0IX shall apply.\nIn the case of class III devices, surveillance shall also include a check that the quantities of produced or purchased raw material or crucial components approved for the type and correspond to the quantities of finished devices.\n8.\u00a0\u00a0\u00a0Batch verification in the case of devices incorporating, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma referred to in Article\u00a01(8).\nUpon completing the manufacture of each batch of devices that incorporate, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma referred to in the first subparagraph\u00a0of Article\u00a01(8), the manufacturer shall inform the notified body of the release of the batch of devices and send it the official certificate concerning the release of the batch of human blood or plasma derivative used in the device, issued by a Member\u00a0State laboratory or a laboratory designated for that purpose by a Member\u00a0State in accordance with Article\u00a0114(2) of Directive\u00a02001/83/EC.\n9.\u00a0\u00a0\u00a0Administrative provisions\nThe manufacturer or, where the manufacturer does not have a registered place of business in a Member\u00a0State, its authorised representative shall, for a period ending no sooner than 10 years, and in the case of implantable devices no sooner than 15 years, after the last device has been placed on the market, keep at the disposal of the competent authorities:\n\n\n\n\n\n\n\u2014\n\n\nthe EU declaration of conformity,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation referred to in the fifth indent of Section\u00a02.1 of Annex\u00a0IX,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation referred to in the eighth indent of Section\u00a02.1 of Annex\u00a0IX, including the EU type-examination certificate referred to in Annex\u00a0X,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation on the changes referred to in Section\u00a02.4 of Annex\u00a0IX, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe decisions and reports from the notified body as referred to in Sections 2.3, 3.3 and 3.4 of Annex\u00a0IX.\n\n\n\n\nSection\u00a08 of Annex\u00a0IX shall apply.\n10.\u00a0\u00a0\u00a0Application to class IIa devices\n10.1.\u00a0\u00a0\u00a0By way of derogation from Section\u00a05, by virtue of the EU declaration of conformity the manufacturer shall be deemed to ensure and to declare that the class IIa devices in question are manufactured in conformity with the technical documentation referred to in Annexes\u00a0II and III and meet the requirements of this Regulation which apply to them.\n10.2.\u00a0\u00a0\u00a0For class IIa devices the notified body shall assess, as part of the assessment referred to in Section\u00a06.3, whether the technical documentation as referred to in Annexes\u00a0II and III for the devices selected on a representative basis is compliant with this Regulation.\nIn choosing a representative sample or samples of devices, the notified body shall take into account the novelty of the technology, similarities in design, technology, manufacturing and sterilisation methods, the intended use and the results of any previous relevant assessments (e.g. with regard to physical, chemical, biological or clinical properties) that have been carried out in accordance with this Regulation. The notified body shall document its rationale for the sample or samples of devices taken.\n10.3.\u00a0\u00a0\u00a0Where the assessment under Section\u00a010.2. confirms that the class IIa devices in question conform to the technical documentation referred to in Annexes\u00a0II and III and meet the requirements of this Regulation which apply to them, the notified body shall issue a certificate pursuant to this Part of this Annex.\n10.4.\u00a0\u00a0\u00a0Samples additional to those taken for the initial conformity assessment of devices shall be assessed by the notified body as part of the surveillance assessment referred to in Section\u00a07.\n10.5.\u00a0\u00a0\u00a0By way of derogation from Section\u00a06, the manufacturer or its authorised representative shall, for a period ending no sooner than 10 years after the last device has been placed on the market, keep at the disposal of the competent authorities:\n\n\n\n\n\n\n\u2014\n\n\nthe EU declaration of conformity,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe technical documentation referred to in Annexes\u00a0II and III, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe certificate referred to in Section\u00a010.3.\n\n\n\n\nSection\u00a08 of Annex\u00a0IX shall apply.\nPART B\n\nPRODUCT VERIFICATION\n\n11.\u00a0\u00a0\u00a0Product verification shall be understood to be the procedure whereby after examination of every manufactured device, the manufacturer, by issuing an EU declaration of conformity in accordance with Article\u00a019 and Annex\u00a0IV, shall be deemed to ensure and to declare that the devices which have been subject to the procedure set out in Sections 14 and 15 conform to the type described in the EU type-examination certificate and meet the requirements of this Regulation which apply to them.\n12.\u00a0\u00a0\u00a0The manufacturer shall take all the measures necessary to ensure that the manufacturing process produces devices which conform to the type described in the EU type-examination certificate and to the requirements of the Regulation which apply to them. Prior to the start of manufacture, the manufacturer shall prepare documents defining the manufacturing process, in particular as regards sterilisation where necessary, together with all routine, pre-established procedures to be implemented to ensure homogeneous production and, where appropriate, conformity of the devices with the type described in the EU\u00a0type-examination certificate and with the requirements of this Regulation which apply to them.\nIn addition, for devices placed on the market in a sterile condition, and only for those aspects of the manufacturing process designed to secure and maintain sterility, the manufacturer shall apply the provisions of Sections 6 and 7.\n13.\u00a0\u00a0\u00a0The manufacturer shall undertake to institute and keep up to date a post-market surveillance plan, including a PMCF plan, and the procedures ensuring compliance with the obligations of the manufacturer resulting from the provisions on vigilance and post-market surveillance system set out in Chapter VII.\n14.\u00a0\u00a0\u00a0The notified body shall carry out the appropriate examinations and tests in order to verify the conformity of the device with the requirements of the Regulation by examining and testing every product as specified in Section\u00a015.\nThe examinations and tests referred to in the first paragraph\u00a0of this Section\u00a0shall not apply to aspects of the manufacturing process designed to secure sterility.\n15.\u00a0\u00a0\u00a0Verification by examination and testing of every product\n15.1.\u00a0\u00a0\u00a0Every device shall be examined individually and the appropriate physical or laboratory tests as defined in the relevant standard or standards referred to in Article\u00a08, or equivalent tests and assessments, shall be carried out in order to verify, where appropriate, the conformity of the devices with the type described in the EU type-examination certificate and with the requirements of this Regulation which apply to them.\n15.2.\u00a0\u00a0\u00a0The notified body shall affix, or have affixed, its identification number to each approved device and shall draw up an EU product verification certificate relating to the tests and assessments carried out.\n16.\u00a0\u00a0\u00a0Batch verification in the case of devices incorporating, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma referred to in Article\u00a01(8).\nUpon completing the manufacture of each batch of devices that incorporate, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma referred to in the first subparagraph\u00a0of Article\u00a01(8), the manufacturer shall inform the notified body of the release of the batch of devices and send it the official certificate concerning the release of the batch of human blood or plasma derivative used in the device, issued by a Member\u00a0State laboratory or a laboratory designated for that purpose by a Member\u00a0State in accordance with Article\u00a0114(2) of Directive\u00a02001/83/EC.\n17.\u00a0\u00a0\u00a0Administrative provisions\nThe manufacturer or its authorised representative shall, for a period ending no sooner than 10 years, and in the case of implantable devices no sooner than 15 years, after the last device has been placed on the market, keep at the disposal of the competent authorities:\n\n\n\n\n\n\n\u2014\n\n\nthe EU declaration of conformity,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation referred to in Section\u00a012,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe certificate referred to in Section\u00a015.2, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe EU type-examination certificate referred to in Annex\u00a0X.\n\n\n\n\nSection\u00a08 of Annex\u00a0IX shall apply.\n18.\u00a0\u00a0\u00a0Application to class IIa devices\n18.1.\u00a0\u00a0\u00a0By way of derogation from Section\u00a011, by virtue of the EU declaration of conformity the manufacturer shall be deemed to ensure and to declare that the class IIa devices in question are manufactured in conformity with the technical documentation referred to in Annexes\u00a0II and III and meet the requirements of this Regulation which apply to them.\n18.2.\u00a0\u00a0\u00a0The verification conducted by the notified body in accordance with Section\u00a014 is intended to confirm the conformity of the class IIa devices in question with the technical documentation referred to in Annexes\u00a0II and III and with the requirements of this Regulation which apply to them.\n18.3.\u00a0\u00a0\u00a0If the verification referred to in Section\u00a018.2 confirms that the class IIa devices in question conform to the technical documentation referred to in Annexes\u00a0II and III and meet the requirements of this Regulation which apply to them, the notified body shall issue a certificate pursuant to this Part of this Annex.\n18.4.\u00a0\u00a0\u00a0By way of derogation from Section\u00a017, the manufacturer or its authorised representative shall, for a period ending no sooner than 10 years after the last device has been placed on the market, keep at the disposal of the competent authorities:\n\n\n\n\n\n\n\u2014\n\n\nthe EU declaration of conformity,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe technical documentation referred to in Annexes\u00a0II and III, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe certificate referred to in Section\u00a018.3.\n\n\n\n\nSection\u00a08 of Annex\u00a0IX shall apply.\n\n\n\n\n\nANNEX XII\n\nCERTIFICATES ISSUED BY A NOTIFIED BODY\n\nCHAPTER I\n\nGENERAL REQUIREMENTS\n\n\n\n\n\n\n\n\n\n1.\n\n\nCertificates shall be drawn up in one of the official languages of the Union.\n\n\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nEach certificate shall refer to only one conformity assessment procedure.\n\n\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nCertificates shall only be issued to one manufacturer. The name and address of the manufacturer included in the certificate shall be the same as that registered in the electronic system referred to in Article\u00a030.\n\n\n\n\n\n\n\n\n\n\n\n\n4.\n\n\nThe scope of the certificates shall unambiguously identify the device or devices covered:\n\n\n\n\n\n\n(a)\n\n\nEU technical documentation assessment certificates, EU type-examination certificates and EU product verification certificates shall include a clear identification, including the name, model and type, of the device or devices, the intended purpose, as included by the manufacturer in the instructions for use and in relation to which the device has been assessed in the conformity assessment procedure, risk classification and the Basic UDI-DI as referred to in Article\u00a027(6);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nEU quality management system certificates and EU quality assurance certificates shall include the identification of the devices or groups of devices, the risk classification, and, for class IIb devices, the intended purpose.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n5.\n\n\nThe notified body shall be able to demonstrate on request, which (individual) devices are covered by the certificate. The notified body shall set up a system that enables the determination of the devices, including their classification, covered by the certificate.\n\n\n\n\n\n\n\n\n\n\n\n\n6.\n\n\nCertificates shall contain, if applicable, a note that, for the placing on the market of the device or devices it covers, another certificate issued in accordance with this Regulation is required.\n\n\n\n\n\n\n\n\n\n\n\n\n7.\n\n\nEU quality management system certificates and EU quality assurance certificates for class\u00a0I devices for which the involvement of a notified body is required pursuant to Article\u00a052(7) shall include a statement that the audit by the notified body of the quality management system was limited to the aspects required under that paragraph.\n\n\n\n\n\n\n\n\n\n\n\n\n8.\n\n\nWhere a certificate is supplemented, modified or re-issued, the new certificate shall contain a reference to the preceding certificate and its date of issue with identification of the changes.\n\n\n\n\nCHAPTER II\n\nMINIMUM CONTENT OF THE CERTIFICATES\n\n\n\n\n\n\n\n1.\n\n\nname, address and identification number of the notified body;\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nname and address of the manufacturer and, if applicable, of the authorised representative;\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nunique number identifying the certificate;\n\n\n\n\n\n\n\n\n\n\n4.\n\n\nif already issued, the SRN of the manufacturer referred to in to Article\u00a031(2);\n\n\n\n\n\n\n\n\n\n\n5.\n\n\ndate of issue;\n\n\n\n\n\n\n\n\n\n\n6.\n\n\ndate of expiry;\n\n\n\n\n\n\n\n\n\n\n7.\n\n\ndata needed for the unambiguous identification of the device or devices where applicable as specified in Section\u00a04 of Part I;\n\n\n\n\n\n\n\n\n\n\n8.\n\n\nif applicable, reference to any previous certificate as specified in Section\u00a08 of Chapter I;\n\n\n\n\n\n\n\n\n\n\n9.\n\n\nreference to this Regulation and the relevant Annex\u00a0in accordance with which the conformity assessment has been carried out;\n\n\n\n\n\n\n\n\n\n\n10.\n\n\nexaminations and tests performed, e.g. reference to relevant CS, harmonised standards, test reports and audit report(s);\n\n\n\n\n\n\n\n\n\n\n11.\n\n\nif applicable, reference to the relevant parts of the technical documentation or other certificates required for the placing on the market of the device or devices covered;\n\n\n\n\n\n\n\n\n\n\n12.\n\n\nif applicable, information about the surveillance by the notified body;\n\n\n\n\n\n\n\n\n\n\n13.\n\n\nconclusions of the notified body's conformity assessment with regard to the relevant Annex;\n\n\n\n\n\n\n\n\n\n\n14.\n\n\nconditions for or limitations to the validity of the certificate;\n\n\n\n\n\n\n\n\n\n\n15.\n\n\nlegally binding signature of the notified body in accordance with the applicable national law.\n\n\n\n\n\n\n\n\n\nANNEX XIII\n\nPROCEDURE FOR CUSTOM-MADE DEVICES\n\n\n\n\n\n\n\n\n\n1.\n\n\nFor custom-made devices, the manufacturer or its authorised representative shall draw up a statement containing all of the following information:\n\n\n\n\n\n\n\u2014\n\n\nthe name and address of the manufacturer, and of all manufacturing sites,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif applicable, the name and address of the authorised representative,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndata allowing identification of the device in question,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na statement that the device is intended for exclusive use by a particular patient or user, identified by name, an acronym or a numerical code,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe name of the person who made out the prescription and who is authorised by national law by virtue of their professional qualifications to do so, and, where applicable, the name of the health institution concerned,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe specific characteristics of the product as indicated by the prescription,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na statement that the device in question conforms to the general safety and performance requirements set out in Annex\u00a0I and, where applicable, indicating which general safety and performance requirements have not been fully met, together with the grounds,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwhere applicable, an indication that the device contains or incorporates a medicinal substance, including a human blood or plasma derivative, or tissues or cells of human origin, or of animal origin as referred to in Regulation\u00a0(EU)\u00a0No\u00a0722/2012.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nThe manufacturer shall undertake to keep available for the competent national authorities documentation that indicates its manufacturing site or sites and allows an understanding to be formed of the design, manufacture and performance of the device, including the expected performance, so as to allow assessment of conformity with the requirements of this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nThe manufacturer shall take all the measures necessary to ensure that the manufacturing process produces devices which are manufactured in accordance with the documentation referred to in Section\u00a02.\n\n\n\n\n\n\n\n\n\n\n\n\n4.\n\n\nThe statement referred to in the introductory part of Section\u00a01 shall be kept for a period of at least 10 years after the device has been placed on the market. In the case of implantable devices, the period shall be at least 15 years.\nSection\u00a08 of Annex\u00a0IX shall apply.\n\n\n\n\n\n\n\n\n\n\n\n\n5.\n\n\nThe manufacturer shall review and document experience gained in the post-production phase, including from PMCF as referred to in Part B of Annex\u00a0XIV, and implement appropriate means to apply any necessary corrective action, In that context, it shall report in accordance with Article\u00a087(1) to the competent authorities any serious incidents or field safety corrective actions or both as soon as it learns of them.\n\n\n\n\n\n\n\n\n\nANNEX XIV\n\nCLINICAL EVALUATION AND POST-MARKET CLINICAL FOLLOW-UP\n\nPART A\n\nCLINICAL EVALUATION\n\n1.\u00a0\u00a0\u00a0To plan, continuously conduct and document a clinical evaluation, manufacturers shall:\n\n\n\n\n\n\n(a)\n\n\nestablish and update a clinical evaluation plan, which shall include at least:\n\n\n\n\n\n\n\u2014\n\n\nan identification of the general safety and performance requirements that require support from relevant clinical data;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na specification of the intended purpose of the device;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na clear specification of intended target groups with clear indications and contra-indications;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na detailed description of intended clinical benefits to patients with relevant and specified clinical outcome parameters;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na specification of methods to be used for examination of qualitative and quantitative aspects of clinical safety with clear reference to the determination of residual risks and side-effects;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nan indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nan indication how benefit-risk issues relating to specific components such as use of pharmaceutical, non-viable animal or human tissues, are to be addressed; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na clinical development plan indicating progression from exploratory investigations, such as first-in-man studies, feasibility and pilot studies, to confirmatory investigations, such as pivotal clinical investigations, and a PMCF as referred to in Part B of this Annex\u00a0with an indication of milestones and a description of potential acceptance criteria;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nidentify available clinical data relevant to the device and its intended purpose and any gaps in clinical evidence through a systematic scientific literature review;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nappraise all relevant clinical data by evaluating their suitability for establishing the safety and performance of the device;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\ngenerate, through properly designed clinical investigations in accordance with the clinical development plan, any new or additional clinical data necessary to address outstanding issues; and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nanalyse all relevant clinical data in order to reach conclusions about the safety and clinical performance of the device including its clinical benefits.\n\n\n\n\n2.\u00a0\u00a0\u00a0The clinical evaluation shall be thorough and objective, and take into account both favourable and unfavourable data. Its depth and extent shall be proportionate and appropriate to the nature, classification, intended purpose and risks of the device in question, as well as to the manufacturer's claims in respect of the device.\n3.\u00a0\u00a0\u00a0A clinical evaluation may be based on clinical data relating to a device for which equivalence to the device in question can be demonstrated. The following technical, biological and clinical characteristics shall be taken into consideration for the demonstration of equivalence:\n\n\n\n\n\n\n\u2014\n\n\nTechnical: the device is of similar design; is used under similar conditions of use; has similar specifications and properties including physicochemical properties such as intensity of energy, tensile strength, viscosity, surface characteristics, wavelength and software algorithms; uses similar deployment methods, where relevant; has similar principles of operation and critical performance requirements;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nBiological: the device uses the same materials or substances in contact with the same human tissues or body fluids for a similar kind and duration of contact and similar release characteristics of substances, including degradation products and leachables;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nClinical: the device is used for the same clinical condition or purpose, including similar severity and stage of disease, at the same site in the body, in a similar population, including as regards age, anatomy and physiology; has the same kind of user; has similar relevant critical performance in view of the expected clinical effect for a specific intended purpose.\n\n\n\n\nThe characteristics listed in the first paragraph\u00a0shall be similar to the extent that there would be no clinically significant difference in the safety and clinical performance of the device. Considerations of equivalence shall be based on proper scientific justification. It shall be clearly demonstrated that manufacturers have sufficient levels of access to the data relating to devices with which they are claiming equivalence in order to justify their claims of equivalence.\n4.\u00a0\u00a0\u00a0The results of the clinical evaluation and the clinical evidence on which it is based shall be documented in a clinical evaluation report which shall support the assessment of the conformity of the device.\nThe clinical evidence together with non-clinical data generated from non-clinical testing methods and other relevant documentation shall allow the manufacturer to demonstrate conformity with the general safety and performance requirements and shall be part of the technical documentation for the device in question.\nBoth favourable and unfavourable data considered in the clinical evaluation shall be included in the technical documentation.\nPART B\n\nPOST-MARKET CLINICAL FOLLOW-UP\n\n5.\u00a0\u00a0\u00a0PMCF shall be understood to be a continuous process that updates the clinical evaluation referred to in Article\u00a061 and Part A of this Annex\u00a0and shall be addressed in the manufacturer's post-market surveillance plan. When conducting PMCF, the manufacturer shall proactively collect and evaluate clinical data from the use in or on humans of a device which bears the CE marking and is placed on the market or put into service within its intended purpose as referred to in the relevant conformity assessment procedure, with the aim of confirming the safety and performance throughout the expected lifetime of the device, of ensuring the continued acceptability of identified risks and of detecting emerging risks on the basis of factual evidence.\n6.\u00a0\u00a0\u00a0PMCF shall be performed pursuant to a documented method laid down in a PMCF plan.\n6.1.\u00a0\u00a0\u00a0The PMCF plan shall specify the methods and procedures for proactively collecting and evaluating clinical data with the aim of:\n\n\n\n\n\n\n(a)\n\n\nconfirming the safety and performance of the device throughout its expected lifetime,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nidentifying previously unknown side-effects and monitoring the identified side-effects and contraindications,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nidentifying and analysing emergent risks on the basis of factual evidence,\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nensuring the continued acceptability of the benefit-risk ratio referred to in Sections\u00a01 and 9 of Annex\u00a0I, and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nidentifying possible systematic misuse or off-label use of the device, with a view to verifying that the intended purpose is correct.\n\n\n\n\n6.2.\u00a0\u00a0\u00a0The PMCF plan shall include at least:\n\n\n\n\n\n\n(a)\n\n\nthe general methods and procedures of the PMCF to be applied, such as gathering of clinical experience gained, feedback from users, screening of scientific literature and of other sources of clinical data;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe specific methods and procedures of PMCF to be applied, such as evaluation of suitable registers or PMCF studies;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\na rationale for the appropriateness of the methods and procedures referred to in points (a) and (b);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\na reference to the relevant parts of the clinical evaluation report referred to in Section\u00a04 and to the risk management referred to in Section\u00a03 of Annex\u00a0I;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe specific objectives to be addressed by the PMCF;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nan evaluation of the clinical data relating to equivalent or similar devices;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nreference to any relevant CS, harmonised standards when used by the manufacturer, and relevant guidance on PMCF; and\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\na detailed and adequately justified time schedule for PMCF activities (e.g. analysis of PMCF data and reporting) to be undertaken by the manufacturer.\n\n\n\n\n7.\u00a0\u00a0\u00a0The manufacturer shall analyse the findings of the PMCF and document the results in a PMCF evaluation report that shall be part of the clinical evaluation report and the technical documentation.\n8.\u00a0\u00a0\u00a0The conclusions of the PMCF evaluation report shall be taken into account for the clinical evaluation referred to in Article\u00a061 and Part A of this Annex\u00a0and in the risk management referred to in Section\u00a03 of Annex\u00a0I. If, through the PMCF, the need for preventive and/or corrective measures has been identified, the manufacturer shall implement them.\n\n\n\n\n\nANNEX XV\n\nCLINICAL INVESTIGATIONS\n\nCHAPTER I\n\nGENERAL REQUIREMENTS\n\n1.\u00a0\u00a0\u00a0Ethical principles\nEach step in the clinical investigation, from the initial consideration of the need for and justification of the study to the publication of the results, shall be carried out in accordance with recognised ethical principles.\n2.\u00a0\u00a0\u00a0Methods\n2.1.\u00a0\u00a0\u00a0Clinical investigations shall be performed on the basis of an appropriate plan of investigation reflecting the latest scientific and technical knowledge and defined in such a way as to confirm or refute the manufacturer's claims regarding the safety, performance and aspects relating to benefit-risk of devices as referred to in Article\u00a062(1); the clinical investigations shall include an adequate number of observations to guarantee the scientific validity of the conclusions. The rationale for the design and chosen statistical methodology shall be presented as further described in Section\u00a03.6 of Chapter II of this Annex.\n2.2.\u00a0\u00a0\u00a0The procedures used to perform the clinical investigation shall be appropriate to the device under investigation.\n2.3.\u00a0\u00a0\u00a0The research methodologies used to perform the clinical investigation shall be appropriate to the device under investigation.\n2.4.\u00a0\u00a0\u00a0Clinical investigations shall be performed in accordance with the clinical investigation plan by a sufficient number of intended users and in a clinical environment that is representative of the intended normal conditions of use of the device in the target patient population. Clinical investigations shall be in line with the clinical evaluation plan as referred to in Part\u00a0A of Annex\u00a0XIV.\n2.5.\u00a0\u00a0\u00a0All the appropriate technical and functional features of the device, in particular those involving safety and performance, and their expected clinical outcomes shall be appropriately addressed in the investigational design. A list of the technical and functional features of the device and the related expected clinical outcomes shall be provided.\n2.6.\u00a0\u00a0\u00a0The endpoints of the clinical investigation shall address the intended purpose, clinical benefits, performance and safety of the device. The endpoints shall be determined and assessed using scientifically valid methodologies. The primary endpoint shall be appropriate to the device and clinically relevant.\n2.7.\u00a0\u00a0\u00a0Investigators shall have access to the technical and clinical data regarding the device. Personnel involved in the conduct of an investigation shall be adequately instructed and trained in the proper use of the investigational device, and as regards the clinical investigation plan and good clinical practice. This training shall be verified and where necessary arranged by the sponsor and documented appropriately.\n2.8.\u00a0\u00a0\u00a0The clinical investigation report, signed by the investigator, shall contain a critical evaluation of all the data collected during the clinical investigation, and shall include any negative findings.\nCHAPTER II\n\nDOCUMENTATION REGARDING THE APPLICATION FOR CLINICAL INVESTIGATION\n\nFor investigational devices covered by Article\u00a062, the sponsor shall draw up and submit the application in accordance with Article\u00a070 accompanied by the following documents:\n1.\u00a0\u00a0\u00a0Application form\nThe application form shall be duly filled in, containing information regarding:\n\n\n\n\n\n\n1.1.\n\n\nname, address and contact details of the sponsor and, if applicable, name, address and contact details of its contact person or legal representative in accordance with Article\u00a062(2) established in the Union;\n\n\n\n\n\n\n\n\n\n\n1.2.\n\n\nif different from those in Section\u00a01.1, name, address and contact details of the manufacturer of the device intended for clinical investigation and, if applicable, of its authorised representative;\n\n\n\n\n\n\n\n\n\n\n1.3.\n\n\ntitle of the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n1.4.\n\n\nstatus of the clinical investigation application (i.e. first submission, resubmission, significant amendment);\n\n\n\n\n\n\n\n\n\n\n1.5.\n\n\ndetails and/or reference to the clinical evaluation plan;\n\n\n\n\n\n\n\n\n\n\n1.6.\n\n\nIf the application is a resubmission with regard to a device for which an application has been already submitted, the date or dates and reference number or numbers of the earlier application or in the case of significant amendment, reference to the original application. The sponsor shall identify all of the changes from the previous application together with a rationale for those changes, in particular, whether any changes have been made to address conclusions of previous competent authority or ethics committee reviews;\n\n\n\n\n\n\n\n\n\n\n1.7.\n\n\nif the application is submitted in parallel with an application for a clinical trial in accordance with Regulation\u00a0(EU)\u00a0No\u00a0536/2014, reference to the official registration number of the clinical trial;\n\n\n\n\n\n\n\n\n\n\n1.8.\n\n\nidentification of the Member\u00a0States and third countries in which the clinical investigation is to be conducted as part of a multicentre or multinational study at the time of application;\n\n\n\n\n\n\n\n\n\n\n1.9.\n\n\na brief description of the investigational device, its classification and other information necessary for the identification of the device and device type;\n\n\n\n\n\n\n\n\n\n\n1.10.\n\n\ninformation as to whether the device incorporates a medicinal substance, including a human blood or plasma derivative or whether it is manufactured utilising non-viable tissues or cells of human or animal origin, or their derivatives;\n\n\n\n\n\n\n\n\n\n\n1.11.\n\n\nsummary of the clinical investigation plan including the objective or objectives of the clinical investigation, the number and gender of subjects, criteria for subject selection, whether there are subjects under 18 years of age, design of the investigation such as controlled and/or randomised studies, planned dates of commencement and of completion of the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n1.12.\n\n\nif applicable, information regarding a comparator device, its classification and other information necessary for the identification of the comparator device;\n\n\n\n\n\n\n\n\n\n\n1.13.\n\n\nevidence from the sponsor that the clinical investigator and the investigational site are capable of conducting the clinical investigation in accordance with the clinical investigation plan;\n\n\n\n\n\n\n\n\n\n\n1.14.\n\n\ndetails of the anticipated start date and duration of the investigation;\n\n\n\n\n\n\n\n\n\n\n1.15.\n\n\ndetails to identify the notified body, if already involved at the stage of application for a clinical investigation;\n\n\n\n\n\n\n\n\n\n\n1.16.\n\n\nconfirmation that the sponsor is aware that the competent authority may contact the ethics committee that is assessing or has assessed the application; and\n\n\n\n\n\n\n\n\n\n\n1.17.\n\n\nthe statement referred to in Section\u00a04.1.\n\n\n\n\n2.\u00a0\u00a0\u00a0Investigator's Brochure\nThe investigator's brochure (IB) shall contain the clinical and non-clinical information on the investigational device that is relevant for the investigation and available at the time of application. Any updates to the IB or other relevant information that is newly available shall be brought to the attention of the investigators in a timely manner. The IB shall be clearly identified and contain in particular the following information:\n\n\n\n\n\n\n2.1.\n\n\nIdentification and description of the device, including information on the intended purpose, the risk classification and applicable classification rule pursuant to Annex\u00a0VIII, design and manufacturing of the device and reference to previous and similar generations of the device.\n\n\n\n\n\n\n\n\n\n\n2.2.\n\n\nManufacturer's instructions for installation, maintenance, maintaining hygiene standards and for use, including storage and handling requirements, as well as, to the extent that such information is available, information to be placed on the label, and instructions for use to be provided with the device when placed on the market. In addition, information relating to any relevant training required.\n\n\n\n\n\n\n\n\n\n\n2.3.\n\n\nPre-clinical evaluation based on relevant pre-clinical testing and experimental data, in particular regarding in-design calculations, in vitro tests, ex vivo tests, animal tests, mechanical or electrical tests, reliability tests, sterilisation validation, software verification and validation, performance tests, evaluation of biocompatibility and biological safety, as applicable.\n\n\n\n\n\n\n\n\n\n\n2.4.\n\n\nExisting clinical data, in particular:\n\n\n\n\n\n\n\u2014\n\n\nfrom relevant scientific literature available relating to the safety, performance, clinical benefits to patients, design characteristics and intended purpose of the device and/or of equivalent or similar devices;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nother relevant clinical data available relating to the safety, performance, clinical benefits to patients, design characteristics and intended purpose of equivalent or similar devices of the same manufacturer, including length of time on the market and a review of performance, clinical benefit and safety-related issues and any corrective actions taken.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n2.5.\n\n\nSummary of the benefit-risk analysis and the risk management, including information regarding known or foreseeable risks, any undesirable effects, contraindications and warnings.\n\n\n\n\n\n\n\n\n\n\n2.6.\n\n\nIn the case of devices that incorporate a medicinal substance, including a human blood or plasma derivative or devices manufactured utilising non-viable tissues or cells of human or animal origin, or their derivatives, detailed information on the medicinal substance or on the tissues, cells or their derivatives, and on the compliance with the relevant general safety and performance requirements and the specific risk management in relation to the substance or tissues, cells or their derivatives, as well as evidence for the added value of incorporation of such constituents in relation to the clinical benefit and/or safety of the device.\n\n\n\n\n\n\n\n\n\n\n2.7.\n\n\nA list detailing the fulfilment of the relevant general safety and performance requirements set out in Annex\u00a0I, including the standards and CS applied, in full or in part, as well as a description of the solutions for fulfilling the relevant general safety and performance requirements, in so far as those standards and CS have not or have only been partly fulfilled or are lacking.\n\n\n\n\n\n\n\n\n\n\n2.8.\n\n\nA detailed description of the clinical procedures and diagnostic tests used in the course of the clinical investigation and in particular information on any deviation from normal clinical practice.\n\n\n\n\n3.\u00a0\u00a0\u00a0Clinical Investigation Plan\nThe clinical investigation plan (CIP) shall set out the rationale, objectives, design methodology, monitoring, conduct, record-keeping and the method of analysis for the clinical investigation. It shall contain in particular the information as laid down in this Annex. If part of this information is submitted in a separate document, it shall be referenced in the CIP.\n3.1.\u00a0\u00a0\u00a0General\n3.1.1.\u00a0\u00a0\u00a0Single identification number of the clinical investigation, as referred to in Article\u00a070(1).\n3.1.2.\u00a0\u00a0\u00a0Identification of the sponsor \u2014 name, address and contact details of the sponsor and, where applicable, the name, address and contact details of the sponsor's contact person or legal representative in accordance with Article\u00a062(2) established in the Union.\n3.1.3.\u00a0\u00a0\u00a0Information on the principal investigator at each investigational site, the coordinating investigator for the investigation, the address details for each investigational site and the emergency contact details for the principal investigator at each site. The roles, responsibilities and qualifications of the various kinds of investigators shall be specified in the CIP.\n3.1.4.\u00a0\u00a0\u00a0A brief description of how the clinical investigation is financed and a brief description of the agreement between the sponsor and the site.\n3.1.5.\u00a0\u00a0\u00a0Overall synopsis of the clinical investigation, in an official Union language determined by the Member\u00a0State concerned.\n3.2.\u00a0\u00a0\u00a0Identification and description of the device, including its intended purpose, its manufacturer, its traceability, the target population, materials coming into contact with the human body, the medical or surgical procedures involved in its use and the necessary training and experience for its use, background literature review, the current state of the art in clinical care in the relevant field of application and the proposed benefits of the new device.\n3.3.\u00a0\u00a0\u00a0Risks and clinical benefits of the device to be examined, with justification of the corresponding expected clinical outcomes in the clinical investigation plan.\n3.4.\u00a0\u00a0\u00a0Description of the relevance of the clinical investigation in the context of the state of the art of clinical practice.\n3.5.\u00a0\u00a0\u00a0Objectives and hypotheses of the clinical investigation.\n3.6.\u00a0\u00a0\u00a0Design of the clinical investigation with evidence of its scientific robustness and validity.\n3.6.1.\u00a0\u00a0\u00a0General information such as type of investigation with rationale for choosing it, for its endpoints and for its variables as set out in the clinical evaluation plan.\n3.6.2.\u00a0\u00a0\u00a0Information on the investigational device, on any comparator and on any other device or medication to be used in the clinical investigation.\n3.6.3.\u00a0\u00a0\u00a0Information on subjects, selection criteria, size of investigation population, representativeness of investigation population in relation to target population and, if applicable, information on vulnerable subjects involved such as children, pregnant women, immuno-compromised or, elderly subjects.\n3.6.4.\u00a0\u00a0\u00a0Details of measures to be taken to minimise bias, such as randomisation, and management of potential confounding factors.\n3.6.5.\u00a0\u00a0\u00a0Description of the clinical procedures and diagnostic methods relating to the clinical investigation and in particular highlighting any deviation from normal clinical practice.\n3.6.6.\u00a0\u00a0\u00a0Monitoring plan.\n3.7.\u00a0\u00a0\u00a0Statistical considerations, with justification, including a power calculation for the sample size, if applicable.\n3.8.\u00a0\u00a0\u00a0Data management.\n3.9.\u00a0\u00a0\u00a0Information about any amendments to the CIP.\n3.10.\u00a0\u00a0\u00a0Policy regarding follow-up and management of any deviations from the CIP at the investigational site and clear prohibition of use of waivers from the CIP.\n3.11.\u00a0\u00a0\u00a0Accountability regarding the device, in particular control of access to the device, follow-up in relation to the device used in the clinical investigation and the return of unused, expired or malfunctioning devices.\n3.12.\u00a0\u00a0\u00a0Statement of compliance with the recognised ethical principles for medical research involving humans, and the principles of good clinical practice in the field of clinical investigations of devices, as well as with the applicable regulatory requirements.\n3.13.\u00a0\u00a0\u00a0Description of the Informed consent process.\n3.14.\u00a0\u00a0\u00a0Safety reporting, including definitions of adverse events and serious adverse events, device deficiencies, procedures and timelines for reporting.\n3.15.\u00a0\u00a0\u00a0Criteria and procedures for follow-up of subjects following the end, temporary halt or early termination of an investigation, for follow-up of subjects who have withdrawn their consent and procedures for subjects lost to follow-up.\u00a0Such procedures shall for implantable devices, cover as a minimum traceability.\n3.16.\u00a0\u00a0\u00a0A description of the arrangements for taking care of the subjects after their participation in the clinical investigation has ended, where such additional care is necessary because of the subjects' participation in the clinical investigation and where it differs from that normally expected for the medical condition in question.\n3.17.\u00a0\u00a0\u00a0Policy as regards the establishment of the clinical investigation report and publication of results in accordance with the legal requirements and the ethical principles referred to in Section\u00a01 of Chapter I.\n3.18.\u00a0\u00a0\u00a0List of the technical and functional features of the device, with specific mention of those covered by the investigation.\n3.19.\u00a0\u00a0\u00a0Bibliography.\n4.\u00a0\u00a0\u00a0Other information\n4.1.\u00a0\u00a0\u00a0A signed statement by the natural or legal person responsible for the manufacture of the investigational device that the device in question conforms to the general safety and performance requirements apart from the aspects covered by the clinical investigation and that, with regard to those aspects, every precaution has been taken to protect the health and safety of the subject.\n4.2.\u00a0\u00a0\u00a0Where applicable according to national law, copy of the opinion or opinions of the ethics committee or committees concerned. Where according to national law the opinion or opinions of the ethics committee or committees is not required at the time of the submission of the application, a copy of the opinion or opinions shall be submitted as soon as available.\n4.3.\u00a0\u00a0\u00a0Proof of insurance cover or indemnification of subjects in case of injury, pursuant to Article\u00a069 and the corresponding national law.\n4.4.\u00a0\u00a0\u00a0Documents to be used to obtain informed consent, including the patient information sheet and the informed consent document.\n4.5.\u00a0\u00a0\u00a0Description of the arrangements to comply with the applicable rules on the protection and confidentiality of personal data, in particular:\n\n\n\n\n\n\n\u2014\n\n\norganisational and technical arrangements that will be implemented to avoid unauthorised access, disclosure, dissemination, alteration or loss of information and personal data processed;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na description of measures that will be implemented to ensure confidentiality of records and personal data of subjects; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na description of measures that will be implemented in case of a data security breach in order to mitigate the possible adverse effects.\n\n\n\n\n4.6.\u00a0\u00a0\u00a0Full details of the available technical documentation, for example detailed risk analysis/management documentation or specific test reports, shall, upon request, be submitted to the competent authority reviewing an application.\nCHAPTER III\n\nOTHER OBLIGATIONS OF THE SPONSOR\n\n1.\u00a0\u00a0\u00a0The sponsor shall undertake to keep available for the competent national authorities any documentation necessary to provide evidence for the documentation referred to in Chapter\u00a0II of this Annex. If the sponsor is not the natural or legal person responsible for the manufacture of the investigational device, that obligation may be fulfilled by that person on behalf of the sponsor.\n2.\u00a0\u00a0\u00a0The Sponsor shall have an agreement in place to ensure that any serious adverse events or any other event as referred to in Article\u00a080(2) are reported by the investigator or investigators to the sponsor in a timely manner.\n3.\u00a0\u00a0\u00a0The documentation mentioned in this Annex\u00a0shall be kept for a period of at least 10 years after the clinical investigation with the device in question has ended, or, in the event that the device is subsequently placed on the market, at least 10 years after the last device has been placed on the market. In the case of implantable devices, the period shall be at least 15 years.\nEach Member\u00a0State shall require that this documentation is kept at the disposal of the competent authorities for the period referred to in the first subparagraph\u00a0in case the sponsor, or its contact person or legal representative as referred to in Article\u00a062(2) established within its territory, goes bankrupt or ceases its activity prior to the end of this period.\n4.\u00a0\u00a0\u00a0The Sponsor shall appoint a monitor that is independent from the investigational site to ensure that the investigation is conducted in accordance with the CIP, the principles of good clinical practice and this Regulation.\n5.\u00a0\u00a0\u00a0The Sponsor shall complete the follow-up of investigation subjects.\n6.\u00a0\u00a0\u00a0The Sponsor shall provide evidence that the investigation is being conducted in line with good clinical practice, for instance through internal or external inspection.\n7.\u00a0\u00a0\u00a0The Sponsor shall prepare a clinical investigation report which includes at least the following:\n\n\n\n\n\n\n\u2014\n\n\nCover/introductory page or pages indicating the title of the investigation, the investigational device, the single identification number, the CIP number and the details with signatures of the coordinating investigators and the principal investigators from each investigational site.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nDetails of the author and date of the report.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nA summary of the investigation covering the title, purpose of the investigation, description of the investigation, investigational design and methods used, the results of the investigation and conclusion of the investigation. The completion date of the investigation, and in particular details of early termination, temporary halts or suspensions of investigations.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nInvestigational device description, in particular clearly defined intended purpose.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nA summary of the clinical investigation plan covering objectives, design, ethical aspects, monitoring and quality measures, selection criteria, target patient populations, sample size, treatment schedules, follow-up duration, concomitant treatments, statistical plan, including hypothesis, sample size calculation and analysis methods, as well as a justification.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nResults of the clinical investigation covering, with rationale and justification, subject demographics, analysis of results related to chosen endpoints, details of subgroup analysis, as well as compliance with the CIP, and covering follow-up of missing data and of patients withdrawing from the clinical investigation, or lost to follow-up.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nSummary of serious adverse events, adverse device effects, device deficiencies and any relevant corrective actions.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nDiscussion and overall conclusions covering safety and performance results, assessment of risks and clinical benefits, discussion of clinical relevance in accordance with clinical state of the art, any specific precautions for specific patient populations, implications for the investigational device, limitations of the investigation.\n\n\n\n\n\n\n\n\n\nANNEX XVI\n\nLIST OF GROUPS OF PRODUCTS WITHOUT AN INTENDED MEDICAL PURPOSE REFERRED TO IN ARTICLE 1(2)\n\n\n\n\n\n\n\n\n\n1.\n\n\nContact lenses or other items intended to be introduced into or onto the eye.\n\n\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nProducts intended to be totally or partially introduced into the human body through surgically invasive means for the purpose of modifying the anatomy or fixation of body parts with the exception of tattooing products and piercings.\n\n\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nSubstances, combinations of substances, or items intended to be used for facial or other dermal or mucous membrane filling by subcutaneous, submucous or intradermal injection or other introduction, excluding those for tattooing.\n\n\n\n\n\n\n\n\n\n\n\n\n4.\n\n\nEquipment intended to be used to reduce, remove or destroy adipose tissue, such as equipment for liposuction, lipolysis or lipoplasty.\n\n\n\n\n\n\n\n\n\n\n\n\n5.\n\n\nHigh intensity electromagnetic radiation (e.g. infra-red, visible light and ultra-violet) emitting equipment intended for use on the human body, including coherent and non-coherent sources, monochromatic and broad spectrum, such as lasers and intense pulsed light equipment, for skin resurfacing, tattoo or hair removal or other skin treatment.\n\n\n\n\n\n\n\n\n\n\n\n\n6.\n\n\nEquipment intended for brain stimulation that apply electrical currents or magnetic or electromagnetic fields that penetrate the cranium to modify neuronal activity in the brain."}, {"title": "Guidance-on-Article-15-MDR-IVDR-Person-responsible-for-Regulatory-Compliance.pdf.txt", "text": "This document has been endorsed by the Medical Device Coordination Group (MDCG) \nestablished by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of \nrepresentatives of all Member States and it is chaired by a representative of the European \nCommi ssion.  \nThe document is not a European Commission document and it cannot be regarded as \nreflecting the official position of the European Commission. Any views expressed in this \ndocument are not legally binding and only the Court of Justice of the European Union can give \nbinding interpretations of Union law.  \n1 \n MDCG 2019- 7 \nGuidance  on Article 15 of the Medical Device Regulation (MDR) and \nin vitro Diagnostic Device Regulation (IVDR) regarding a \u2018person \nresponsible for regulatory compliance\u2019 (PRRC)  \nManufacturers1 (paragraph 1)  \n\u201cManufacturers shall have available within their organisation at least one person \nresponsible for regulatory compliance who possesses the requisite expertise in the \nfield of medical devices. The requisite expertise shall be demonstrated by either of the \nfollowing qualifications:   \n(a) a diploma, certificate or other evidence of formal qualification, awarded on \ncompletion of a university degree or of a course of study recognised as equivalent by \nthe Member State concerned, in law, medicine, pharmacy, engineering or another \nrelevant scientific discipline, and at least one year of professional experience in \nregulatory affairs or in quality management systems relating to medical devices;  \n(b) four years of professional experience in regulatory affairs or in quality management \nsystems relating to medical devices.  \nWithout prejudice to national provisions regarding professional qualifications, \nmanufacturers of custom -made devices may demonstrate the requisite expertise \nreferred to in the first subparagraph by having at least two years of professional \nexperience within a relevant field of manufacturing. \u201d \nClarification on qualifications  \nIt shall be noted that : \n- For the purpose of fulfilling the requirement laid down in point \u201c a\u201d of Article 15 \n(1), any qualification acquired outside the EU, including any university diplomas \nor certificates, should have been recognised by an EU Member State as \nequivalent to the EU corresponding qualification.  \n                                                           \n1  Enterprises which employ at least  50 persons and whose annual turnover and/or annual balance sheet total \nexceeds EUR 10 million (Commission Recommendation 2003/361/\u0395 C of 6 May 2003) . 2 \n - Professional experience in regulatory a ffairs or in quality management systems \nrelating to medical devices  should be related to the EU requirements in the field .  \nMeaning of \u201cwithin their organisation\u201d  \nThe person responsible for regulatory compliance (PRRC) appointed would need to \nbe an employee of the organisation.  \nOrganisations with more than one legal manufacturer  \nOrganisations with more than one legal manufacturer under the parent company would \nneed to ensure that each legal manufacturer has its own PRRC.2 \nCan the PRRC be located out side the EU?  \nAs to the location of the PRRC, it is important that a close linkage, of a permanent and \ncontinuous nature, is established between the PRRC and the manufacturing activities. \nFor this reason,  for manufacturers located outside the EU, it must be assumed that the \nPRRC should also be located outside the EU. On the other hand, for manufacturers \nlocated in the EU, it must be assumed that the PRRC should also be located in the EU.  \nMicro and small manufacturers3 (paragraph 2)  \n\u201cMicro and small enterpri ses within the meaning of Commission Recommendation \n2003/361/EC shall not be required to have the person responsible for regulatory \ncompliance within their organisation but shall have such person permanently \nand continuously at their disposal .\u201d \nMeaning of \u201cpermanently and continuously at their disposal\u201d  \nThe micro or small enterprise may subcontract the responsibilities of a person \nresponsible for regulatory compliance to a third party, so long as the qualification \ncriteria is met and the manufacturer can de monstrate and document how they can \nmeet their legal obligations. For example, the PRRC may be part of an external \norganisation, with which the manufacturer has established a contract lay ing down \nprovisions so as to ensure the permanent and continuous availability of that party. The \ncontract should mention the relevant person\u2019s qualifications allowing compliance with \npoints a and b of Article 15 (1).  \nCan the PRRC be located outside the EU?  \nFor micro or small enterpr ises located in the EU, it must be assumed that any person \nto be permanent ly and continuously at their  disposal should be also located in the EU . \n                                                           \n2  In the context of Article 15, the obligation for having available within the organisation at least one PRRC refers \nto the individual legal manufacturer.  \n3  Enterprises which employ fewer than  50 persons and whose annual turnover and/or annual balance sheet \ntotal does not exceed EUR 10 million (Commission Recommendation 2003/361/\u0395C of 6 May 2003) . 3 \n Authorised representatives (paragraph 6)  \n\u201cAuthorised representatives shall have permanently and continuously at their \ndisposal  at least one person responsible for regulatory compliance who possesses \nthe requisite expertise regarding the regulatory requirements for medical devices in the \nUnion. The requisite expertise shall be demonstrated by either of the followi ng \nqualifications:  \n(a) a diploma, certificate or other evidence of formal qualification, awarded on \ncompletion of a university degree or of a course of study recognised as equivalent by \nthe Member State concerned, in law, medicine, pharmacy, engineering or another \nrelevant scientific discipline, and at least one year of professional experience in \nregulatory affairs or in quality management systems relating to medical devices;  \n(b) four years of professional experience in regulatory affairs or in quality management \nsystems relating to medical devices. \u201d \nMeaning of \u201cpermanently and continuously at their disposal\u201d  \nThe authorised representative may subcontract the responsibilities of a person \nresponsible for regulatory compliance to a third party, so long as the qualification \ncriteria is met and the authorised representative can demonstrate and document how \nthey can meet their legal obligations. For example, the PRRC may be part of an \nexternal organisation with which the authorised representative has established e a \ncontract laying down provisions so as to ensure the permanent and continuous \navailability of that party.  The contract should mention the relevant person\u2019s \nqualifications allowing compliance with points a and b of Article 15 (1).  \nCan the PRRC be located outside the EU?  \nTaking into account that the Authorised Representative is located in the EU, it must be \nassumed that any person to be permanently and continuously at its disposal should be \nalso located in the EU . \nRoles and responsibilities of the person r esponsible for regulatory compliance \nwithin a manufacturer (paragraph 3)  \nFor the purpose of this position paper, the roles and responsibilities of a PRRC have \nbeen cross -referred to the roles and responsibilities of a manufacturer, as stated in \nArticle 10 of the MDR and IVDR. This paper does not interpret the roles and \nresponsibilities of a PRRC. We recommend that any guidance on post -market \nsurveillance, vigilance, clinical investigations and performance studies, created at a \nEuropean level, should cross -refer to Article 15, paragraph 3 to provide guidance on \nwhat a PRRC of a manufacturer would be expected to do in these areas.  \n  4 \n \u201cThe person responsible for regulatory compliance shall at least be responsible for \nensuring that:  \n(a) the conformity of the dev ices is appropriately checked, in accordance with the \nquality management system under which the devices are manufactured, before a \ndevice is released; \u201d  \nManufacturers \u201cof devices, other than investigational [performance study] devices, \nshall establish, document, implement, maintain, keep up to date and continually \nimprove a quality management system that shall ensure compliance with this \nRegulation in the most effective manner and in a manner that is proportionate to the \nrisk class and the type of device\u201d (Article 10(9) of the MDR and Article 10(8) of the \nIVDR).  \n\u201c(b) the technical documentation and the EU declaration of conformity are drawn up \nand kept up- to-date; \u201d \nManufacturers \u201c[of devices other than custom -made devices] shall draw up and keep \nup to date technical documentation for those devices\u201d (Article 10(4) of the MDR and \nIVDR) and \u201cshall draw up an EU declaration of conformity\u201d (Article 10(6) of the MDR \nand Article 10(5) of the IVDR).  \n\u201c(c) the post -market surveillance obligations are complied with in accordance with \nArticle 10(10) [Article 10(9) of the IVDR]; \u201d \nManufacturers \u201cof devices shall implement and keep up to date the post -market \nsurveillance system\u201d (Article 10(10) of the MDR and Article 10(9) of the IVDR).  \n\u201c(d) the reporting obligations ref erred to in Articles 87 to 91 [Article 82 and 86 of the \nIVDR] are fulfilled; \u201d \nManufacturers \u201cshall have a system for recording and reporting of incidents and field \nsafety corrective actions as described in Articles 87 and 88\u201d (Article 10(13) of the MDR \nand Article 10(12) of the IVDR).  \n\u201c(e) in the case of investigational devices, the statement referred to in Section 4.1 of \nChapter II of Annex XV [Section 4.1 of Annex XIV of the IVDR] is issued. \u201d \nManufacturers shall ensure that \u201ca signed statement by the natural or legal person \nresponsible for the manufacture of the investigational device [for performance study] \nthat the device in question conforms to the general safety and performance \nrequirements apart from the aspects covered by the clinical investigati on [performance \nstudy] and that, with regard to those aspects, every precaution has been taken to \nprotect the health and safety of the subject.\u201d  \n  5 \n Roles and responsibilities of the person responsible for regulatory compliance \nwithin an authorised represent ative (paragraph 3)  \nThe PRRC of an AR should be responsible for ensuring that the tasks of an AR  as \nspecified in the given mandate, in accordance with Article 11(3), are fulfilled. . \nCan one individual be the PRRC for a manufacturer and its authorised representative?  \nThe person responsible for regulatory compliance for an authorised representative and \nfor an 'outside EU' manufacturer cannot be the same person. There is a clear desire \nwithin the Regulations for the authorised representative to be adding an additional level \nof scrutiny and ensure that the supervision and control of the manufacture of devices, \nand the relevant post -market surveillance and vigilance activities  are adequately \neffected. If the two roles were conducted by the same person, the additional level of \nscrutiny would be undermined.  \nFor the same reason, the PRRC of a micro or small enterprise and the PRRC of the \nauthorised representative of that same enterprise shall not belong to the same external \norganisation."}, {"title": "md_mfr_stepbystep.pdf.txt", "text": "Implementation Model for\nMedical Devices  \nRegulation  \nStep by Step Guide\nMEDICAL DEVICES  CHANGE OF LEGISLATION\n1STEP  INTENTION / ACTION\nPre-assessmentBrief management to ensure a clear understanding of the importance and  \nbusiness implications of the MDR\nConsider organisational challenges: management awareness,  \nstaffing capability and availability, budget implications\nGAP analysis and actions  \nresulting from thisAssess impact on products, internal resources, organisation and budget\nCheck new classification rules (MDR Classes I, IIa, IIb and III) and confirm conformity \nassessment routes for existing and future products\nCheck the new definition of MD, particularly with respect to its expanded scope. \nThis also applies to products covered in Annex XVI\nReview the changes needed to existing technical documentation (Technical Files)\nReview and upgrade quality management system (QMS) (point 3 below)\nCheck the adequacy of available clinical evidence and risk  \nmanagement and identify any gaps (Article 61)\nReview product labelling (Annex I Chapter III)\nEnsure post-market surveillance (PMS) arrangements are adequate (Chapter VII \nSection 1)\nPrepare a post-market clinical follow-up plan (PMCF, Annex XIV Part B)\nGet ready for the new vigilance requirements (Chapter VII Section 2)\nEnsure the respect of traceability obligations (Chapter III) \nQuality Management  \nSystem (QMS)Review adequacy of QMS to meet standards and processes for medical devices \nunder the new Regulation\nBuild new regulatory requirements into the QMS\nIdentify/hire the person responsible for regulatory compliance within your  \norganisation (Article 15) and be sure it is adequately qualified and trained1\n2\n3What you need to know!\nInternal market, \nIndustry,  \nEntrepreneurship  \nand SMEs2Legal entitiesClarify how the company is affected: legal entities, obligation of economic  \noperators, organisational structures and resources\nConsider organisational challenges: management awareness, staffing capability \nand availability, budget implications\nEnsure product liability insurance is adequate\nPortfolioDo a cost/benefit analysis for your product portfolio; bear in mind costs for the \npossible upgrade of risk class of MDs and for the new procedures for conformity \nassessment as well as the costs for post-market surveillance and gaps in the \ntechnical documentation, and plan your transition to the MDR accordingly\nReview supply chain provisions, and clarify roles and responsibilities of business \npartners (authorised representatives, importers, distributors)\nMaster  \nimplementation planBuild a roadmap for implementation, including definition of sub-projects,  \nresource requirements and a steering group, and ensure overall responsibility for \nMDR implementation has been established\nGive special consideration to certificate expiry dates, bearing in mind the  \ntransitional period, transitional provisions and availability of your Notified Bodies\nNotified BodiesContact the selected Notified Bodies and determine their capacity and  \navailability to service the implementation plan\nRegulatory trainingEmpower and train staff through MDR implementation and transition workshops\nExecute master  \nimplementation planImplement the various sub-projects (clinical evaluation, technical documentation, \nrelation with other economic operators, Unique Device Identification, labelling,  \nregistration, post-market surveillance, vigilance, and reporting IT systems)\nEnsure a cross-functional project management team is in place to cover all \naspects of implementation\nEnsure overall and individual responsibilities for MDR implementation have been \nestablished\nReview efficiency and  \neffectivenessImplement regular meetings on project status and progress, discrepancy and \ngap analyses, risks, next steps and requirements\nHold regular progress reviews against the MDR implementation plan and include \nthese in the management review process\nNotified Body submissionDiscuss submission dates to avoid delays in the approval process\nOngoing monitoringActively monitor the still-developing European regulatory environment and \nguidelines expected in the coming months (check DG GROW web pages on  \nmedical devices and subscribe to the newsletter)\nEstablish a procedure for dealing with unannounced inspections from Notified Bodies\nRegularly review the MDR implementation plan, identifying and addressing key \nareas of risk4\n5\n6\n7\n8\n9\n10\n11\n12\n\u00a9 European Union, [2018]  Reuse is authorised provided the source is acknowledged.\nThe reuse policy of European Commission documents is regulated by Decision 2011/833/EU (OJ L 330, 14.12.2011, p. 39).\nET-03-18-103-EN-N\nISBN: 978-92-79-89702-3    DOI: 10.2873/66341"}, {"title": "MDCG 2019-8 v2 Implant guidance Card.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document                                               MDCG 2019-8 v2    \n \n \n \n       \n   MDCG 2019-8 v2  \nGuidance document \nImplant Card relating to the application  \n       of Article 18 Regulation (EU) 2017/745  \n       of the European Pa rliament and of the Council  \n       of 5 April 2017 on medical devices           \n \n             March 2020 \n \n \n  \n \nThis document has been endorsed b y the Medical Device Coordinat ion Group (MDCG) established by \nArticle 103 of Regulation (EU) 2017/745. The MDCG is composed o f representatives of all Member \nStates and it is chaired by a representative of the European Co mmission. \nThe document is not a European Commission document and it canno t be regarded as reflecting the \nofficial position of the European Commission. Any views express ed in this document are not legally \nbinding and only the Court of Justice of the European Union can  give binding interpretations of Union \nlaw. \n \n \n  Medical Devices: Guidance document \nImplant Card relating to the app lication of Article 18 Regulati on (EU) 2017/745 of the \nEuropean Parliament and of the Council of 5 April 2017 on medic al devices \n \n  List of Content \n \n1. Scope ............................................................................................................... 4  \n2. Purposes of the Implant Card ..................................................................... 4  \n3. Legal consideration on Implant Card design ........................................... 4  \n4. Information to be provided by the manufacturer on the Implant Card \nand information to be added by the health institution ........................... 5  \n5. Use of symbols .............................................................................................. 6  \n6. Language requirements on specific fields ................................................ 7  \n7. Benefits of an informativ e instruction leaflet ........................................... 7  \n8. Implant Card for implantable systems ...................................................... 7  \nAnnex I examples of principle designs of Implant Cards and leaflets ....... 8  \n \n  1. Scope \nThis document provides guidance for Memb er States, concerned industry and other \nstakeholders on a blueprint of an implant card (IC) required by the MDR (Regulation (EU) \n2017/745). It describes the intended use, cont ent and information to be provided by the \nmanufacturer together on the IC and a definition of fields to be completed by the implanting \nhealthcare institutions or healthcare provider s according to national law in Member States. \nWhereas the intended purpose and most of the da ta elements of the IC are already defined in \nArticle 18 of the MDR, this document contains the description of other data elements which must be completed by the healthcare institution or healthcare provider and which must be considered by the individual Member State wh en implementing Article 18 MDR as required\n1. \n2. Purposes of the Implant Card \nThe aim of introducing an IC has been to achieve three main objectives: \n1. Enable the patient to identify the impl anted devices and to get access to other \ninformation related to the implanted device (e.g. via EUDAMED, and other websites). \n2. Enable patients to identify themselves as persons requiring special care in relevant \nsituations e.g. security checks. \n3. Enabling e.g. emergency clinical staff or fi rst responder to be informed about special \ncare/needs for relevant patients in case of emergency situations. \n3. Legal consideration on Implant Card design \nArticle 18 MDR describes the requirements rega rding the IC which shall be provided by the \nmanufacturer together with the device. Wherea s Article 18 para 1a) describes the information \nwhich shall be provided by the manufacturer on the IC, Article 18 pa r a  2  l a y s  d o w n  t h e  \nobligation of Member States to require health in stitutions to provide the IC to the concerned \npatient. In accordance with Article 18, 1a) the manufact urer should provide th e following information \non the IC (preferably on the card itself or, alternatively, as stickers to be placed by the clinician): \n\u0081 Device name; \n\u0081 Serial number, lot number; \n\u0081 Unique device identification (UDI); \n\u0081 Name, address and the website of manufacturer; \n\u0081 Device type.\n2  \nArticle 18, 2 lays down that Member States shall require health institutions (or healthcare \nproviders) inter alia to make available the IC to the relevant patient. The IC should bear their \n                                                      \n1 This guidance doesn\u2019t include the patient information described in Ar ticle 18 para 1 (b-d) which might \nbe provided by the manufacturer by any means that allow rapid access to that information and that \nshall be stated in the language(s) determined by the concerned Member State.  \n2 In Article 18 1a) of the MDR, the term \u201cdevice model\u201d  is used. However, this term which is not defined \nin the MDR, is part of the UDI-DI related info r m a t i o n  t o  b e  p r o v i d e d  t o  E U D A M E D .  T o  a v o i d  \nduplication and in the context of the intended purpos e of the IC (to be used in situations requiring \nspecial care or in emergency situations), it is cons idered that reference to device model in the MDR for \nthe purpose of the IC shall be read as reference to device type, like \u201cpacemaker\u201d, \u201chip implant\u201d, etc. \nWhen the European Medical device nomenclature is made available, a \u201cstandardised\u201d set of terms of \nthis nomenclature should be recommended for use in relation to the field \u201cdevice type\u201d.  identity . For this purpose, the IC provided togeth er with the device should contain blank \nfields which shall be filled out by the health institution or healthcare provider, respectively. \nSince the establishment of (and the logistics behind) many different national IC designs is very \nexpensive and of no additional benefit, Member States should ensure that, in the context of \nnational implementation of Article 18 of the MD R, only the following information is required \nto be provided by the health institution or healthcare provider on the IC (together with the information provided by the manufacturer). Accordingly, a European or international \nblueprint for an IC which supports the purposes  described in Article 18, 2 should contain the \nfollowing blank fields: \n1. Name of the patient or patient ID; \n2. Name and address of the health institution or healthcare provider who performed the \nimplantation; \n3. Date of implantation. \nIn order to be fit for the purposes described in Article 18, the outer dimensions of the IC should \nbe the same as those of credit cards, ATM cards or ID cards (85.60 mm \u00d7 53.98 mm /3 3 \u20448 \u00d7 \n2 1\u20448  inches) and with a radius of 2.88\u20133.48 mm\n3. \n4. Information to be provided by the  manufacturer on the Implant \nCard and information to be adde d by the health institution \nThe manufacturer shall provide the following necessary information: \n1. Device name; \n2. Device type; \n3. Serial number or, where app licable, lot or batch number; \n4. Unique device identification (UDI); the UDI as AIDC4 format and the UDI-DI as HRI5 \n5. Name and address of the manufacturer of the medical device; \n6. Website of the manufacturer of the medical device. \nThe text provided on the IC and on the instru ction for completing the IC by the healthcare \ninstitution or healthcare provider must be legible and at least 2 millimetres high. \u2018Text\u2019 includes any: number, letter,  symbol, or  letter or number in a symbol.   \nIn addition, the manufacturer shou ld design the IC in a way that the following blank fields to \nbe filled out by the implanting healthcare institution or healthcare provider are available: \n1. Name of the patient or patient ID; \n2. Name and address of the healthcare inst itution which performed the implantation; \n3. Date of implantation. \n  \n                                                      \n3 Dimensions to conform to the standard ISO/IEC 7810 ID-1.  \n4 AIDC - Automatic identification and data capture format (e.g. linear or 2D-Barcodes)  \n5 HRI - Human readable interpretation   5. Use of symbols \nTo avoid national versions of the IC , the use of symbols is advisable.  \nThe following list contains symbols which have either been validated by users and have been \nsubmitted and accepted for inclusion in an upco ming international standard or already exist \nin the ISO database (Online Browsing Platform). The explanation of symbols on the IC should \nbe provided in a leaflet (see section  7) or  on the back of the IC, if space allows. \nArticle 18(1) lays down that the information provided in the IC shall be stated in the \nlanguage(s) determined by the concerned Member State. \nList of symbols recommended for use on the IC6: \n \n \n  \n Patient Name or patient ID\n \n \n \n \n Date of implantation  \n \n \n \n  Name and Address of the implanting healthcare \ninstitution/provide\nr  \n \n \n \n Name and Address of the manufacturer  \n Information website for patients  \n Device Name7 \n \n Serial Number  \n \n \n Lot Number/Batch Code  \n \n                                                      \n6 The symbols for patient name or patient ID, name and ad dress of the implanting healthcare institution/provider, \ndate of implantation, name and address of the manufacturer, serial number, lot number/batch code are already available and published in existing ISO standards. The symbols for device name, patient information website and \nUDI have been validated by users according to the ISO 15223-2 process. Note that the symbols listed here to indicate \nthe following terms: \u2018Device Name\u2019, \u2018Patient Name or Pati ent ID\u2019, \u2018Date of Implantation\u2019, \u2018Name and address of the \nimplanting healthcare institution/provider\u2019 on the implant card, are used in the ISO context to indicate \u2018Medical Device\u2019, \u2018Patient Identification\u2019, \u2018Date\u2019, \u2018Health Care Center or Doctor\u2019.   \n7 Please note that in the ISO context, the \u2018MD\u2019 symbol is used to identify that the product in question is a medical \ndevice. On the implant card, this symbol is used to indicate the device name.  \n \n UDI as AIDC format  \nUDI-DI information in a HRI format should  be introduced by the wording \u201cUDI-DI\u201d. \n6. Language requirements on specific fields \nDespite the nearly complete list of symbols for fields on the IC, there is currently no symbol \navailable for the required field \u201cDevice Type\u201d. \nThe lack of a symbol and the purpose of this field makes it necessary that the information on \nthe device type must be provided in the language accepted/required by the concerned \nMember State. \nThere are several possibilities available to provid e this information in the necessary languages, \ne.g. the information is already printed on the IC in the different languages or stickers are \nprovided with the IC and the healthcare professional selects the right one etc. \n7. Benefits of an informati ve instruction leaflet8 \nAs mentioned above (section 5), there is a need to provide, together with the IC, instructions \non how to complete the IC and to explain the us ed symbols. This information shall be stated \nin the language(s) determined by the concerned Member State. For this reason, the use of a leaflet, containing the relevant information, to be provided together with the IC and the \nimplantable device, is the recommended solution.  \nAs part of the risk management, the manufacturer has to investigate, by means of an \nergonomic analysis or ergonomic usability test procedure, if the provided instructions are \nsufficient to enable the health professional to complete the IC correctly. The instructions must reflect the solution chosen by the manufacturer (e .g. pre-printed IC, blank IC with sticker(s) to \nbe added, mixture of both). Special considerat ions might be needed when providing a system \nIC or an IC for a separate implantable compon ent, when there is not yet a common practice \n(standard) established.  \n8. Implant Card for implantable systems \nIf an implantable device contains implantable components which might be replaced by other \n(or the same) components, for example in case of a later revision, the manufacturers should \nconsider the use of a System IC. In Annex I to this guide an example is provided. \nW a y s  c o u l d  b e  e x p l o r e d  b y  r e l e v a n t  s t a k e h o l d e r s  t o  d e v e l o p  c o m m o n  r u l e s  o n  h o w  t h e  \nnecessary information to be placed on the Sy stem IC is delivered with the replaceable \ncomponent and how health professionals could en sure t hat  the  System  I C is  appropriately  \nupdated, when necessary. \n  \n                                                      \n8 This leaflet should not be confused with any possible vector of information referred to in points \u201cb\u201d, \u201cc\u201d and \u201cd\u201d \nof Article 18(1) of the MDR.  UDI Annex I examples of principle designs of Implant Cards and leaf lets \n \nGENERAL NOTE: All examples contained in this  Annex are to be intended as illustrative \nexamples only.9  \nThe basic shape of the IC shall be designed in  compliance with ISO/IEC 7810 ID-1 (credit card \nform). \nThe following pictures provide exam ples for individual device ICs.  \nExample 1: \n \nFront \u2013 Not to scale (handwritten text on pre-printed content) \n \n \n \n \n \n \n \n \n \nBack \u2013 Not to scale (blank \u2013 serial printed content in \nproduction) \n \n \n \n \n  \n                                                      \n9 Please note that this includes translations (into languages other than English) shown in Examples \nthroughout Annex 1, which are machine translated and not intended to be read as official translations \ninto EU languages. International Implant Card \nhttps://www.genericmed.com/patientimplantinfo John Smith\n27/05/2021\nABC Healthcare Center\n123 Medical Parkway, Cork, Ireland\nDr. H.C. Professional\nPM-5503  Pacer Advanced \nUDI-DI: (01)01865494261654  \nSN79856214  \nGenericmed \n500 Genericmed Place, Minneapolis, MN 55123 USA \nwww.genericmed.com \n \n \n \n    Example 2: \nBack \u2013 Not to scale (blank \u2013 batch/lot printed content in \nproduction) \n \n \n \n \n \n \n \n \n \n \n \n  PM-5503  Pacer Advanced \nUDI-DI: (01)03584124658462  \nGenericmed \n500 Genericmed Place, Minneapolis, MN 55123 USA \nwww.genericmed.com AO.582122\nExample 3 (suggested design of a foldable System IC): \nTo be able to represent medical device syst ems in one IC, the IC shall be available in \ncollapsible form.  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n     ABC Healthcare CenterInternational Implant Card \nwww.genericmed.com/patientimplantinfo John Smith \n27/05/2021 \n123 Medical Parkway\nDr. H.C. Professional\nGenericmed  \n500 Genericmed Place,  \nMinneapolis, MN 55123 USA \nwww.genericmed.com  \nCork, Ireland PM-5503 \nPacer Advanced Pacemaker \nUDI-DI: (01)85412654285216 \nSN65695452 \nGenericmed  \n500 Genericmed Place,  \nMinneapolis, MN 55123 USA \nwww.genericmed.com  PL-55-4 \nPacer Lead Pro Pacemaker Lead \nUDI-DI: (01)89654213882154 \nSN86223214 \n \nExamples of IC Leaflet  \nFront 1 (no stickers \u2013 preferred option) \n \nInstruction for completion (to be provided in the language(s) determined by the concerned member State(s)) \n1. Name of the patient or patient ID. To be f illed by the healthcare institution/provider. \n2. Date of implantation. To be filled by  the healthcare institution/provider. \n3. Name and address of the healthcare institutio n/provider. To be filled by the healthcare \ninstitution/provider. \n \n   \n \n \n  \nPM-5503  \nPacer Advanced  \n(01)8541265428\n5216  \nSN65695452 \nGenericmed  \n500 Genericmed Place,  \nMinneapolis, MN 55123 www.genericmed.com/patientimplantinfo \n \n \nFront 2 (sticker only for device type information) \n \nInstruction for completion (to be provided in the language(s) determined by the concerned member State(s)) \n1. Name of the patient or patient ID. To be f illed by the healthcare institution/provider. \n2. Date of implantation. To be filled by  the healthcare institution/provider. \n3. Name and address of the healthcare instit ution. To be filled by the healthcare \ninstitution/provider. \n5. Add sticker with device type in required language. \n  \n \n \n \n \n \n  \n   \n \n \n  \n \nStickers (to be detached and placed on the righ t place at the IC according to the numbers)  \n \n  \nPM-5503  \nPacer Advanced  \n(01)85412654285216 \nGenericmed  \n500 Genericmed Place,  \nMinneapolis, MN 55123 SN65695452 www.genericmed.com/patientimplantinfo \n5 \n \nFront 3 (stickers)  \n \nInstruction for completion (to be provided in the language(s) determined by the concerned member State(s)) \n1. Name of the patient or patient ID. To be f illed by the healthcare institution/provider. \n2. Date of implantation. To be filled by  the healthcare institution/provider. \n3. Name and address of the healthcare institutio n/provider. To be filled by the healthcare \ninstitution/provider. \n4. Manufacturer\u2019s information website.  \n5. Device type in required language.  \n6. Device name.  \n7. UDI-DI Code (HRI). \n8. UDI code (AIDC format). \n9. Serial number. \n10. Name and address of the \nmanufacturer of the implanted \nmedical device.  \n \nNOTE: Fields 4-10 might be filled \nwith stickers (though this is not the \npreferred solution) \n  \n \n \n  \n \n \nStickers (to be detached and plac ed on the right place at the IC  according to the numbers)  \n5, 6 \n \n9 \n \n    8           \n \n 7 2 081019001 002 4  \n10 \n \n4 \n \nBack  \n Explanation/ transl ation of symbols \n Patient Name or patient ID, \u0418\u043c\u0435 \u043d\u0430 \u043f\u0430\u0446\u0438\u0435\u043d\u0442\u0430 , Jm\u00e9no pacienta, Patientens navn, \nPatientenname, \u038c\u03bd\u03bf\u03bc\u03b1 \u03b1\u03c3\u03b8\u03b5\u03bd\u03bf\u03cd\u03c2 , Nombre del paciente, Patsiendi nimi, Potilaan nimi, \nNom du patient, Ime i prezime bolesnika, Imi \u0119 i nazwisko pacjenta, A beteg neve, \nNome del paziente, Paciento vardas ir pavard \u0117, Pacienta v \u0101rds, uzv\u0101rds, Naam pati\u00ebnt  \nPasientens navn, A beteg neve, Nome do doente, Nume pacient, Meno pacienta, Ime bolnika, Patientens namn \n Name and Address of the implanting healthcare institution/provide r , \u00e9tablissement \nsanitaire, centro de salud, struttura sanitaria, Gesundheitseinrichtung, \ngezondheidszorginstelling, plac\u00f3wka s\u0142u \u017cby zdrowia, \u0437\u0434\u0440\u0430\u0432\u043d\u043e  \u0437\u0430\u0432\u0435\u0434\u0435\u043d\u0438\u0435, vesel\u012bbas \napr\u016bpes iest\u0101de, \u03b5\u03b3\u03ba\u03b1\u03c4\u03ac\u03c3\u03c4\u03b1\u03c3\u03b7 \u03b3\u03b9\u03b1 \u03c4\u03b7\u03bd \u03c5\u03b3\u03b5\u03af\u03b1  \n Date of Implantation , \u0414\u0430\u0442\u0430  \u043d\u0430 \u0438\u043c\u043f\u043b\u0430\u043d\u0442\u0438\u0440\u0430\u043d\u0435, Datum implantace, Implanteringsdato, \nImplantationsdatum, \u0397\u03bc\u03b5\u03c1\u03bf\u03bc\u03b7\u03bd\u03af\u03b1  \u03b5\u03bc\u03c6\u03cd\u03c4\u03b5\u03c5\u03c3\u03b7\u03c2,  \nFecha de implantaci\u00f3n, Implanteerimiskuup\u00e4ev, Implantointip\u00e4iv\u00e4m\u00e4\u00e4r\u00e4, Date d\u2019implantation, Datum implantacije, Be\u00fcltet\u00e9s d\u00e1tuma, Data dell'impianto, Implantavimo data, Implant \u0113\u0161anas datums, \nImplantatiedatum, Data wszczepienia , Data do implante, Data implant \u0103rii, D\u00e1tum \nimplant\u00e1cie, Datum vsaditve \n Device Name, Nazwa urz \u0105dzenia medy \ncznego, N\u00e1zev zdravotnick\u00fdch prost \u0159edk\u016f, Medicinsk enhed, Name des \nMedizinprodukts, Nombre del dispositivo m\u00e9dico, Nom du dispositif m\u00e9dical, Orvosi eszk\u00f6z neve, Namn p\u00e5 medicinsk enhet, Ime medicinske naprave Nome do dispositivo m\u00e9dico \n \u03ba\u03b1\u03c4\u03b1\u03c3\u03ba\u03b5\u03c5\u03b1\u03c3\u03c4\u03ae\u03c2, Producent, Fabrikant, Produttore, Fabricante, Fa bricant, manufacturer, \nHersteller  \n Information website for patients , Webov\u00e1 str\u00e1nka s informacemi pro pacienta, \nInformationswebsite for patienten, Webseite mit Informationen f\u00fcr Patienten, Sitio web \ncon informaci\u00f3n para el paciente, Site d'in formations pour le patient, Inform\u00e1ci\u00f3s \nhonlap betegek sz\u00e1m\u00e1ra, Sito web con le informazioni per i pazienti, Website met informatie voor pati\u00ebnten, Strona internetowa z informacjami dla pacjenta \n \n Translation of serial number in required languages. \n \n Translation of LOT number in required languages. \n Explanation of unique device identi fier (UDI) in required languages. \n \n \nPlace to attach the  \nImplant card"}, {"title": "md_guidance-manufacturers_en.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document    MDCG  2019 -15 rev1   \n \n \n \n \n \n \n \n \n \nMDCG  2019 -15 rev.1  \n        GUIDANCE NOTES FOR MANUFACTURERS  \n        OF CLASS I MEDICAL DEVICES              \n \n             December   2019  \n July 2020 rev.1  \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) established by \nArticle 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member \nStates and it is chaired by a representative of the European Commission.  \nThe document is not a European Commission document and it cannot be regarded as reflecting the \nofficial position of the European Commission. Any views expressed in this doc ument are not legally \nbinding and only the Court of Justice of the European Union can give binding interpretations of Union \nlaw. \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n2 \n  \nMDCG 2019 -15 revision 1 changes  \nMDR postponement dates: from 2020 to 2021  \n \n \n \n \n \nGUIDANCE NOTES FOR MANUFACTURERS  \nOF CLASS I  MEDICAL DEVICES  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n3 \n Contents  \nList of acronyms  ................................ ................................ ................................ ................................ .... 4 \nForeword  ................................ ................................ ................................ ................................ ................  5 \nIntroduction  ................................ ................................ ................................ ................................ ...........  5 \nDefinitions  ................................ ................................ ................................ ................................ ..............  8 \nPlacing on the market of Class I medical devices: The necessary steps  ................................ .........  11 \n0) Integrate MDR  in the Quality Management System (QMS).  ................................ ..................  11 \n1) Confirm product as a medical device  ................................ ................................ ........................  11 \n2) Confirm product as a Class I medical device  ................................ ................................ ............  11 \n3) Procedures before placing on the market  ................................ ................................ ..................  12 \na) Meet the general safety and performance requirements  ................................ .......................  12 \nb) Conduct clinical evaluation  ................................ ................................ ................................ ... 12 \nc) Prepare technical documentation  ................................ ................................ ..........................  14 \nd) Request Notified Body involvement  ................................ ................................ .....................  16 \ne) Prepare Instructions for Use and Labelling  ................................ ................................ ...........  16 \n4) Check compliance with general obligations for manufacturers  ................................ ................  17 \n5) Draw -up the EU Declaration of Conformity  ................................ ................................ .............  18 \n6) Affix the CE marking  ................................ ................................ ................................ ................  18 \n7) Registration of devices and manufacturers in Eudamed  ................................ ...........................  19 \n8) Post Market Surveillance (PMS)  ................................ ................................ ...............................  20 \na) Review experience gained from Post -Market Surveillance  ................................ ..................  20 \nb) Vigilance  ................................ ................................ ................................ ...............................  20 \nc) Non conforming products  ................................ ................................ ................................ ..... 22 \n \n \n \n \n \n \n \n \n \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n4 \n List of acronyms  \nMDD \u2013 Medical Devices Directive  \nMDR \u2013 Medical Devices Regulation  \nFSCA \u2013 Field Safety Corrective Action  \nFSN - Field Safety Notice  \nUDI - Unique Device Identifier  \nSRN - Single Registration Number  \nNB - Notified Body  \nISO - International Organization for Standardization  \nIEC - International Electrotechnical Commission  \nCA \u2013 Competent Authority  \nPPE \u2013 Personal Protective Equipment  \nQMS - Quality Management System  \nIm \u2013 Class I devices with measuring function  \nIs \u2013 Class I sterile devices  \nIr \u2013 Class I reusable surgical instruments  \nDI \u2013 Device Identifier  \nEudamed - European database on medical devices  \nMD - Medical Device   \nCS - Common Specification   \nPMS \u2013 Post Market Surveillance  \nIFU \u2013 Instructions for use   \nPMCF - Post Market Clinical Follow -up   Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n5 \n Foreword  \nThese guidance notes do not aim to be a definitive interpretation of Regulation (EU) 2017/745 of the \nEuropean Parliament and of the Council of 5 April 2017 on medical devices (MDR) and are intended for  \nguidance purposes only.  \n \nIntroduction  \nThe purpose of this document is to provide guidance to manufacturers of Class I medical devices (other \nthan custom made devices) who place on the Union market medical devices (from now on referred to as \ndevices) under their name or trade mark, to help them meet the provi sions of the MDR.  This guidance \nshould also be applicable for situations when an importer, distributor or any other legal person assumes \nthe obligations incumbent on manufacturers, as per Article 16 (1), while not  covering the exception \nindicated by Artic le 16 (2).  \nThe MDR has changed the scope of the medical device legislation and it now extends its application to \nall economic operators in the supply chain (manufacturer, authorised representative, importer and \ndistributor) as well as a broadened range of products such as those specifically intended for the cleaning, \ndisinfection or sterilization of devices (Article 2 (1)) and products without an intended medical purpose \n(such as certain aesthetic products, as indicated in Annex XVI of the MDR). In addition , more emphasis \nis placed on a life -cycle approach to safety, backed up by clinical data and new requirements such as \ntransparency and traceability1. \nBefore placing a device on the market, the manufacturer will affix the CE mark in accordance with \nAnnex V and draw up the EU declaration of conformity, including all the information required by \nAnnex IV. Prior to that, the manufacturer will demonstrate conformity with the MDR and compliance \nwith the applicable general safety and performance requirements laid o ut in Annex I.  \nIn order to accomplish the abovementioned tasks, the manufacturer will carry out the following:   \n\uf02d Put in place a quality management system and a system for risk management according to Article \n10(2) and 10(9).  \n\uf02d Conduct a clinical evaluation i n accordance with Article 61, as established in Article 10(3) and \nAnnex XV.   \n\uf02d Conduct a conformity assessment according to Article 52(7). In specific cases ( sterile devices, \ndevices with measuring function, reusable surgical instruments ) defined in the referred Article, \nthe manufacturer will request the involvement of a Notified Body (NB).    \n\uf02d Draw up and keep up -to-date technical documentation related to devices as set out in Annexes II \nand III, in accordance with Article 10(4).  \n\uf02d Draw up an EU declaration of conformity in accordance with Article 19.  \n\uf02d Submit the required information to the electronic system for registration of economic operators \n(Eudamed) and comply with the registration obligation. The manufacturer will use the Single \nRegis tration Number (SRN) when applying to a NB for conformity assessment, if applicable and \nfor further accessing Eudamed2 in order to fulfil its obligations related to registration of the \ndevices.  \n\uf02d Register the device in Eudamed assigning the Basic UDI -DI to t he device, as defined in Part C of \nAnnex VI, and provide this to the UDI database together with the other core data elements \nreferred in Part B of Annex VI related to that device.  \n\uf02d Assign to the device and, if applicable, to all higher levels of packaging,  a UDI which will allow \nidentification and traceability.  \n                                                      \n1  More information can be found at  https://ec.europa.eu/health/md_sector/overview   \n2  Regarding all references to Eudamed in this document, please be advised that for the purposes of this guidance, obligations s trictly related to \nEudamed will only apply when it is fully functional and any u pdates will be published on the EU Commission webpage.    Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n6 \n \uf02d Ensure that the device is accompanied by the information needed to identify it and its \nmanufacturer, and any safety and performance information relevant to the user, or any other \nperson, as appropria te (Article 10(11)). This information, set out according to Section 23 of \nAnnex I, must be provided in an official Union language(s) determined by the Member State in \nwhich the device is made available to the user or patient. The particulars on the label w ill be \nindelible, easily legible and clearly comprehensible to the intended user or patient.   \n\uf02d Implement a post -market surveillance system in accordance with Article 83 (Article 10(10)) \nproportional to the risk class and appropriate for the type of device,  this includes additional \naspects to be taken into account in case of devices placed on the market in sterile condition, with \na measuring function or that are reusable surgical instruments. This system will be an integral \npart of the manufacturer's quality  management system based on a post -market surveillance plan \n(Article 84) , which will be part of the technical documentation specified in Annex III.  \n\uf02d Implement a system for recording and reporting incidents and field safety corrective actions as \ndescribed in  Articles 87 and 88 (Article 10(13)).  \n\uf02d Put measures in place to provide sufficient financial coverage in respect of their potential liability \nunder Directive 85/374/EEC3, without prejudice to more protective measures under national law. \nThese measures will be proportional to the risk class, type of device and the size of the enterprise \n(Article 10(16)).  \nFurther detail on the aforementioned list of obligations is provided in the chapter \u201cPlacing Class I \nmedical devices on the market \u201d.  \nFor devices placed on the market in a sterile condition, with a measuring function or which are reusable \nsurgical instruments, the manufacturer will apply the procedures set out in Chapters I and III of Annex \nIX, or in Part A of Annex XI which require a NB assessment, limited t o critical aspects such as those \nconcerning sterile condition, metrological requirements and the reuse of the device, as relevant, \naccording with Article 52 (7 a, b and c).  \n                                                      \n3  Council Directive 85/374/EEC of 25 July 1985 on the approximation of the laws, regulations and administrative provisions of t he Member \nStates concerning liability for defective products  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n7 \n  \nFigure 1. Illustration of the conformity procedures for  the assessment of Class I devices with and \nwithout NB involvement.  \nFor big and medium size enterprises, the manufacturer will have available within their organization at \nleast one person responsible for regulatory compliance4, as established by Article 15. Micro and small \nenterprises5 are required to have such person permanently and continuously at their disposal.  \nA manufacturer with a registered place of business outside the Union will designate a sole authorised \nrepresentative, at least per each gener ic device group, according to a written mandate. Such a mandate \nwill establish the tasks to be performed by the authorised representative. To enable the fulfilment of \nthese tasks, the manufacturer ensures that the authorised representative has the necessar y documentation \npermanently available and up -to date. The mandate will require the authorised representative to perform \nat least the tasks described in Article 11(3),  however the manufacturer cannot delegate its obligations \nlaid down in Article 10(1), (2),  (3), (4), (6), (7), (9), (10), (11) and (12). In case of the  change of \nauthorised representative, Article 12 establishes the minimum content of agreement to be addressed \nbetween the manufacturer, where practicable the outgoing authorised representative, a nd the incoming \nauthorised representative.  \nUpon request, the manufacturer will provide all the information and documentation necessary to \ndemonstrate conformity of the device to competent authorities and cooperate with them on any \ncorrective action. If th e manufacturer does not cooperate or does not provide the requested information \nor documentation, the competent authority (CA) can adopt restrictive measures.  \nThe manufacturer should periodically verify whether implementing and delegated acts, common \nspeci fications, technical standards and guidelines might be available on the European Commission \nwebsite6. Such documents might for example cover specific parts of legislation (e.g. classification of \n                                                      \n4  See the  relevant MDCG guidance on Article 15 of MDR and IVDR regarding a \"person responsible for regulatory compliance\" (PRRC)  \n5  See Commission Recommendation 2003/361/EC  \n6  https://ec.europa.eu/health/md_sector/overview     \nClass I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n8 \n medical devices, clinical evaluation) or specific requirement s regarding certain medical device \ntechnologies (e.g. software, 3D printing ) that can also be applicable for Class I devices.  \nDuring the transitional period, manufacturers might be tempted to refer to guidance documents \ndeveloped under the Directive 93/42/ EC. However, the old guidance documents, unless otherwise \nupdated in line with the MDR, may have only some limited indicative value under the MDR. For the \npurpose of the MDR, only the text of the Regulation is valid in law and sets out requirements not \nreflected in the old guidance. Hence, the MDR alone can be relied upon as a  legal basis . \nDefinitions  \nFor the complete list of definitions refer to Article 2 of the MDR. This is an excerpt of some definitions.  \nAccessory for a medical device - means an article  which, whilst not being itself a medical device, is \nintended by its manufacturer to be used together with one or several particular medical device(s) to \nspecifically enable the medical device(s) to be used in accordance with its/their intended  purpose(s)  or \nto specifically and directly assist the medical functionality of the medical device(s) in terms of its/their \nintended purpose(s) (Article 2(2)) . \nAuthorised representative - means any natural or legal person established within the Union who has \nreceived  and accepted a written mandate from a manufacturer, located outside the Union, to act on the \nmanufacturer's behalf in relation to specified tasks with regard to the latter's obligations under the MDR \n(Arti cle 2(32)). The designation of an authorised repre sentative will be in compliance with Article 11 \nand effective at least for all devices o f the same generic device group  (Article 11(2)) . \nAdverse event - means any untoward medical occurrence, unintended disease or injury or any untoward \nclinical signs, inc luding an abnormal laboratory finding, in subjects, users or other persons, in the \ncontext of a clinical investigation, whether or not related to the investigational device  (Article 2(57)) . \nBenefit -risk determination  - means the analysis of all assessments of benefit and risk of possible \nrelevance for the use of the device for the intended purpose, when used in accordance with the intended \npurpose given by the manufacturer (Article 2(24)) . \nClass I medical devices with  measuring function - are considered Class I medical devices which measure \nphysiological parameters or anatomical parameter  or energy, respectively, or volume of medicinal \nproducts, body liquids or other substances administered to or removed from the body and display or \nindicate its value in a unit of measurement (example: urine bags, non -active thermometers,  measuring \nspoons).   \nNote: According to section 15.2 of Annex I, measurements made by devices with a measuring function \nwill be expressed in legal un its7. \nCE marking of conformity or CE marking - means a marking by which a manufacturer indicates that a \ndevice is in conformity with the applicable requirements set out in the MDR and other applicable \nUnion harmonisation legislation providing for its affix ing (Article 2(43)) . \nNote: CE marking will be made in accordance with Annex V.  \nClinical evaluation - means a systematic and planned process to continuously generate, collect, analyse \nand assess the clinical data pertaining to a device in order to verify th e safety and performance, \nincluding clinical benefits, of the device when used as intended by the manufacturer. (Article 2(44)).  \nClinical data - means information concerning safety or performance that is generated from the use of a \ndevice and is sourced fr om the following:  \n\uf0b7 clinical investigation(s) of the device concerned,  \n                                                      \n7  In conformance to the provisions of Council Directive  80/181/EEC   Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n9 \n \uf0b7 clinical investigation(s) or other studies reported in scientific literature, of a device for which \nequivalence to the device in question can be demonstrated,  \n\uf0b7 reports published in peer re viewed scientific literature on other clinical experience of either the \ndevice in question or a device for which equivalence to the device in question can be \ndemonstrated,  \n\uf0b7 clinically relevant information coming from post -market surveillance, in particular the post -\nmarket clinical follow -up. (Article 2(48))  \nConformity Assessment \u2013 The process demonstrating whether the requirements of the MDR relating to a \ndevice have been fulfilled. (Article 2(40)). This process depends on the medical device classification, \naccording to the procedures described in the MDR, in particular Article 52 (7) applicable for class I \ndevices.  \nDistributor  - means any natural or legal person in the supply chain, other than the manufacturer or the \nimporter that makes a device available on  the market, up until the point of putting into service (Article \n2(34)) . \nEconomic operator  - means a manufacturer, an authorised representative, an importer, a distributor or \nthe person referre d to in Article 22(1) and 22(3)  (Article 2(35)) . \nField safety corrective action  - means corrective action taken by a manufacturer for technical or \nmedical reasons to prevent or reduce the risk of a serious incident in relation to a device made available \non the market (Article 2(68)) . \nField safety notice - means a com munication sent by a manufacturer to users or customers in relation to \na field safety corrective action  (Article 2(69)) . \nHarmonised standard - means a European standard as defined in point (1)(c) of Article 2 of Regulation \n(EU) N\u00b0 1025/20128, (as referred on the Article 2(70)) \u2013 means a European standard adopted on the basis \nof a request made by the Commission for the application of Union harmonisation legislation.  \nImporter  - means any natural or legal person established within the Union that places a devic e from a \nthird country on the Union market  (Article 2(33)).  \nIntended purpose/intended use - means the use for which a device is intended according to the data \nsupplied by the manufacturer on the label, in the instructions for use or in promotional or sales  materials \nor statements and as specified by the manufacturer in the clinical evaluation (Article 2(12)).  \nInstructions for use  - means the information provided by the manufacturer to inform the user of a device's \nintended purpose and proper use, and of any  precautions to be taken (Article 2(14)).  \nLabel  - means the written, printed or graphic information appearing either on the device itself, or on the \npackaging of each unit or on the packaging of multiple devices (Article 2(13)).  \nMedical device  - means any instrument, apparatus, appliance, software, implant, reagent, material or \nother article intended by the manufacturer to be used, alone or in combination, for human beings for one \nor more of the following specific medical purposes:  \n\u2012 diagnosis, prevention, m onitoring, prediction, prognosis, treatment or alleviation of disease,  \n\u2012 diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability,  \n\u2012 investigation, replacement or modification of the anatomy or of a physiological or path ological \nprocess or state,  \n\u2012 providing information by means of in vitro examination of specimens derived from the human \nbody, including organ, blood and tissue donations,  \n  \n                                                      \n8  Regulation  (EU) No 1025/2012 of the European Parliament and of the Council , of 25 October 2012 , on European standardization  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n10 \n and which does not achieve its principal intended action by pharmacological, immuno logical or \nmetabolic means, in or on the human body, but which may be assisted in its function by such means. \nThe following products shall also be deemed to be medical devices:  \n\u2012 devices for the control or support of conception;  \n\u2012 products specifically intended for the cleaning, disinfection or sterilisation of devices as referred to \nin Article 1(4) and of those referred to in the first paragraph of this point. (Article 2(1))  \nManufacturer -  means a natural or legal person who manufactures or fully refur bishes a device or has a \ndevice designed, manufactured or fully refurbished, and markets that device under its name or \ntrademark ; (Article 2(30)).  \nNotified Body - means a conformity assessment body designated in accordance with the MDR (Article \n2(42)).  \nPlacing on the market  - means the first making available of a device, other than an investigational device, \non the Union market (Article 2(28)).  \nPost-market surveillance - means all activities carried out by manufacturers in cooperation with other \neconomic op erators to institute and keep up to date a systematic procedure to proactively collect and \nreview experience gained from devices they place on the market, make available on the market or put into \nservice for the purpose of identifying any need to immediate ly apply any necessary corrective or \npreventive actions (Article 2(60)).  \nRisk - means the combination of the probability of occurrence of harm and the severity of that harm \n(Article 2(23)).  \nSerious incident  - means any incident that directly or indirectly led, might have led or might lead to any of \nthe following:  \n(a) the death of a patient, user or other person,  \n(b) the temporary or permanent serious deterioration of a patient's, user's or other person's state \nof health,  \n(c) a serious public health threat; ((Article 2( 65)) \nSerious public health threat -  means an event which could result in imminent risk of death, serious \ndeterioration in a person's state of health, or serious illness, that may require prompt remedial action, and \nthat may cause significant morbidity or mortality in humans, or that is unusual or unexpected for the \ngiven place and time (Article 2(66)) . \nUnique Device Identifier (UDI) - means a series of numeric or alphanumeric characters that is created \nthrough internationally accepted device identification  and coding standards and that allows unambiguous \nidentification of specific devices on the market (Article 2(15)).  \nUser - means any healthcare professional or lay person who uses a device  (Article 2(37)).  \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n11 \n Placing Class I medical devices on the market:  \nThe necessary steps  \nManufacturers that intend to place Class I medical devices on the market must guarantee compliance \nwith all the requirements below. Please note that some of the described requirements are inter -dependent \nand can be performed in a differe nt order than the one presented.  \nFor Class I devices already placed on the market in accordance with the MDD, the manufacturer will \nconduct a gap analysis in order to guarantee that all the necessary requirements outlined below are fully \ncompleted at the d ate of the application of MDR.  \n0) Integrate MDR in the Quality Management System (QMS).  \nThe applicable provisions of the MDR will be integrated into the QMS of the manufacturer. This will \nallow the correct assessment/decision to be made and  the proper documented evidence to be created, \nensuring compliance with the following requirements.  \n1) Confirm product as a medical device  \nConfirm that the product qualifies as a medical device as defined in Article 2(1) in accordance with its \nintended purpose and principal mode of action. If the manufacturer assigns several different intended \npurposes to their product, not all of which fall under the scope of the MDR, such a product qualifies as a \nmedical device only with respect to those intended medical purposes which are covered by Article 2(1). \nThis is applicable, for instance, for the case of examination gloves that are intended by the manufacturer \nto be used to protect the patient (medical purpose - MD) and also to protect the healthcare professional \n(protecti on purpose \u2013 PPE9). In that case the relevant requirements of both legislations will be applicable.  \nIn the case of accessories to medical devices, despite not being medical devices per se, they are covered \nby MDR provisions and fall under the term \u201cdevice\u201d  in the meaning of the MDR. However, accessories \nto devices covered by the MDR by virtue of its Annex XVI are not covered by the MDR.  \nFor borderline  products where such a determination could be difficult, please consult primarily the \ninformation10 available  on the European Commission website. Your CA may be able to provide \nguidance on where to find published information and regulatory requirements.  \n2) Confirm product as a Class I medical device  \nConsult Annex VIII of the MDR to confirm that the product is correc tly classified as Class I. It should be \nnoted that some Class I devices according to MDD will be reclassified under the MDR considering the \nnew classification rules of that annex, this is the case for most software (rule 11) and devices that are \ncomposed o f substances or of combination of substances (rule 21) . \nFor devices that were reclassified from Class I to higher risk classes by application of the MDR, the \npresent guideline cannot be applied.   \nThe application of the classification rules will be governe d by the intended purpose of the device and \n                                                      \n9  Directive 89/686/EEC is repealed with effect from 21 April 2018 by Regulation (EU) 2016/425  \n10  Guidelines available on  https://ec.europa.eu/health/md_sector/new_regulations/guidance_en   Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n12 \n their inherent risks linked to the duration of use, part of the body, whether it is active or not, whether it is \ninvasive or non -invasive.  \nIf more than one rule according to Annex VIII applies to the intended pur poses of the device, the highest \nclassification applies to the device, i.e. it must be classified on the basis of the most critical specified \nuse. \nFor classification issues, please primarily consult the information11 available on the European \nCommission web site. Your CA may be able to provide guidance on where to find published information \nand regulatory requirements.  \n3) Procedures before placing on the market  \na) Meet the general safety and performance requirements  \nThe devices will meet the general safety and per formance requirements  set out in Annex I of the MDR \nwhich apply to them, taking into account the purposes intended by their manufacturers.  \nParticular attention will be given to devices that are also machinery, within the meaning of Article 2(2), \npoint (a) , Machinery Directive 2006/42/EC12, where the relevant requirements of that directive will also \nbe covered given their specificity (according to Article 1(12)).  \nThe manufacturer will establish and implement a risk management system, which will allow for the  \nidentification and analysis of the hazards associated with each device, estimation and evaluation of the \nassociated risks, elimination or control of residual risks and evaluation of the adopted measures based on \nthe information collected from the post -market surveillance system.  \nThe risk management will be understood as a continuous iterative process throughout the entire lifecycle \nof a device, requiring regular systematic updating. To carry out this process the manufacturer can find \nsolutions in common sp ecifications, or in harmonised standards, published in the Official Journal of the \nEuropean Union, or in other referential materials. Where a harmonised standard exists but the \nmanufacturer is following other referential, the application of that referentia l should guarantee at least \nthe same level of safety and performance. Conformity with the relevant harmonized standards will \nprovide presumption of conformity with the requirements of the MDR covered by those standards or \nparts thereof.  Where common speci fications are available the manufacturer is obliged to follow them \nunless they can duly justify that they have adopted a solution at least with the same level of safety and \nperformance.  \nThe risk management, clinical evaluation processes and PMS will be inter-dependent and will be \nperiodically updated.  \nb) Conduct clinical evaluation  \nAll devices, regardless of risk classification, require a clinical evaluation as part of the technical \ndocumentation requirements of the MD R13. \nThe manufacturer will specify and justify the level of clinical evidence necessary to demonstrate \n                                                      \n11  Guidelines available on  https://ec.europa.eu/health/md_sector/new_regulations/guidance_en%20   \n12  Directive 2006/42/EC  of  the  European  Parliament  and  of  the  Council  of  17  May 2006  on  machinery, and amending \nDirective  95/16/EC (OJ  L 157, 9.6.2006,  p. 24) \n13  For further, see Annex II of the MDR  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n13 \n conformity with the relevant general safety and performance requirements described in Annex I. That \nlevel of clinical evidence will be appropriate in view of the characteristics of the device and its intended \npurpose. In order to do that, manufacturers will plan, conduct and document a clinical evaluation in \naccordance with Article 61 and Part A of Annex XIV.  \nGuidance on the process of conducting clinical eval uation is also available on the Commission website.14  \nConformity to Annex I requirements can only be assumed when the following items are aligned with each \nother:  \n\uf0b7 Risk management;  \n\uf0b7 The information materials supplied by the manufacturer, including:  \no labelling ,  \no instructions for use (where required),   \no available promotional materials,  \no any accompanying documents foreseen by the manufacturer;  \n\uf0b7 The clinical evaluation (the device description used for the clinical evaluation, other contents of the \nclinical evaluati on report);  \n\uf0b7 The available clinical data (such as results of clinical investigations, publications, Post Market \nSurveillance studies, clinical registries, etc.).  \nThe MDR reinforces the need to consider the following aspects when carrying out a clinical eval uation:  \n\u2022 Consideration of available alternative treatment options  is required as part of clinical \nevaluation for the MDR15. Whilst the existence of better alternative treatment options does not \ninfluence the compliance of the device with the MDR, the manufacturer needs to be able to \njustify the clinical benefit of using their device if alternatives are available.  \n\u2022 The incorpo ration of clinical data  obtained throughout the life cycle of the device from the \nmanufacturers post -market clinical follow -up plan and post -market surveillance plan to update \nthe clinic al evaluation and documentation16. \n\u2022 The acceptability of the benefit -risk ratio  must be based upon sufficient clinical data and  \nwill be continuously monitored and reassessed from clinical data collected through the post -\nmark et surveillance phase. The post -market surveillance plan should incorporate suitable \nindicators and thr eshold values to be used in this reassessment 17. \nIf available clinical data are not sufficient to demonstrate compliance with the MDR, further clinical \ndata will be obtained or generated by clinical investigations.  \nFor devices which are currently certifie d with respect to the Directive 93/42/EC, and for which the \navailable clinical data are not sufficient to demonstrate compliance with MDR, additional clinical data \nmay be obtained by post -market clinical follow -up studies of the device. Sometimes, even dat a from the \ngeneral post -market follow -up might suffice to close the gap18. \nNote : if a clinical investigation is required, then the Member State requires advance notification of the \nproposal and the provisions of Article 62 and Annex XV will be applicable.  \n                                                      \n14  https://ec.europa.eu/health/md_sector/new_regulations/guidance_en       \n15  MDR, Article 61(3)(c)  \n16  MDR, Article 61(11)  \n17  MDR, Article 61(1) and Annex III 1.1b  \n18  An MDCG guidance is intended to be published  on this matter including \u2018sufficient clinical da ta\u2019 in 2020 and will be availabl e at the EU \nCommission webpage  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n14 \n In duly justified and substantiated cases, some Class I devices manufacturers may exceptionally \ndemonstrate that the conformity with general safety and performance requirements based on clinical data \nis not deemed appropriate. Such a justification by the m anufacturer must be based upon an evaluation of \nevidence in accordance with Article 61(10).  \nThe clinical evaluation, risk management processes and PMS will be inter -dependent and will be \nperiodically updated.  \nc) Prepare technical documentation  \nThe manufactur er will draw up and keep up to date the technical documentation that demonstrates the \nconformity of their devices with the technical requirements of the MDR. This technical documentation \nmust be prepared according to Annex II and III and prior to drawing u p the EU declaration of \nconformity.  \nThe technical documentation  and, if applicable, its summary, will be drawn up and presented by the \nmanufacturer in a clear, organised, readily searchable and unambiguous manner.  \nThe manufacturer must make the technical d ocumentation available to the CA, the authorised \nrepresentative (when applicable) and NB (when applicable).  \nThe technical documentation will be prepared following review of the general safety and performance \nrequirements  and relevant technical provisions o f the MDR and, if applicable, of the Machinery \nDirective19 and will cover all the relevant aspects from Annex II and III, such as:  \n- Rationale for the  qualification as a medical device and  the risk class  attributed.  \n- Description and specification  - A general d escription of the device, including its intended \npurpose and intended users/patient population and, if applicable, accessories and variants of the \nproduct (for example trade names, model numbers, references, sizes). In addition , the Basic \nUDI-DI as per Par t C of Annex VI will be provided.  \n- Technical Specifications of the device - Specifications including details of raw materials, \ndrawings of components and/or master patterns and any quality control  procedures.  \n- Information to be supplied by the manufacturer - Labels on the device and packaging, such  as \nsingle  unit packaging,  sales  packaging,  transport packaging  in case of specific  management  \nconditions and instruction for use (if applicable),  in the languages determined by  the Member  \nStates  where  the device is envisaged to be sold.  \n- Reference to previous generations of the device and to similar devices  - Provide an overview of \nprevious generation(s) of the device and similar devices available on the market as ap plicable  \n- Design and manufacturing information \u2013 Information that allows the understanding of the \ndesign and manufacturing of a device, including the results of qualifications tests and design \ncalculations relevant to the intended use of the product, includ ing connections to other devices \nin order for it to operate as intended. If the manufacturer can provide information showing that \na safe design has been established for a number of years and that product has been performing \nas intended during that time suc h information is likely to be sufficient to cover this  \n                                                      \n19  According to Article 1 (12)  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n15 \n requirement. The identification of all sites, suppliers and sub -contractors, where design and \nmanufacturing activities are performed will also be included.  \n- General safety and performance requirements \u2013 information for the demonstration of \nconformity with the general safety and performance requirements, set out in Annex I. In order \nto do this, the manufacturer will refer to all the methods and solutions used for conformity \ndemonstration with each safety and performance requirement, including harmonised standards \nand/or common specifications (CS). The same applies for the requirements contained in the \nMachinery Directive.  \n- Demonstration of conformity  with the requirements set out in Annex I should typically be \npresented in the form of a checklist. This should list all requirements referred to in Annex I and \nspecify:  \n(1) the applicability of each requirement to the device,  \n(2) the solution adopted by the man ufacturer to comply with each applicable requirement,  \n(3) the reference to any possible CS or harmonized standards applied in full or in part and  \n(4) the reference to where to find evidence of the solution adopted in the technical \ndocumentation.  \nManufacturers wil l list the relevant harmonised standards (concerning for example sterilisation, \nlabelling and information to be supplied with the device, biocompatibility, specific groups of \nproducts) which have been applied in full or in part. If harmonised standards hav e not been \napplied in full, additional data will be required and provided detailing remaining solutions \nadopted to meet the concerned requirements.  \nInformation on standards harmonised under the MDR will be made available in the Official \nJournal of the Euro pean Union.  \nChanges on the harmonised standards used to demonstrate the conformity of device will be \nadequately taken into account in a timely manner.  \nPlease note that no standard harmonized under the Directive 93/42/EC, has ever covered all the \nrequirements of the Annex I to that Directive. Hence,  it is not likely that any one standard \nharmonized under the MDR will cover all the requirements of the Anne x I to the MDR. The \nscope of coverage is indicated in the so -called Annex Z to the European \u201cEN\u201d standard. The \nscope of coverage is never to be found in the ISO or IEC standard text.  \n- Benefit -risk analysis (sections 1 and 8 of Annex I) and Risk management ( section 3 of Annex I).  \n- Pre-clinical and Clinical evaluation data \u2013 Information to be provided on the results from pre -\nclinical and clinical evaluation.  \n- The post -market surveillance system  - The technical documentation on post -market surveillance \nto be dr awn up by the manufacturer in accordance with Articles 83 to 85 will be presented in a \nclear, organized, readily searchable and unambiguous manner. It shall address and cover the \nelements of point 1.1 of Annex III. The plan will cover  the post -market clini cal follow up plan as \nreferred to in part B of Annex XIV or a justification as to why it is not applicable. The PMS \nreport of article 85 shall be part of the technical documentation on post -market surveillance.  \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n16 \n - Records  - Manufacturers will keep the techn ical documentation, the EU declaration of \nconformity and, if applicable, a copy of any relevant certificate, including any amendments and \nsupplements, issued in accordance with Article 56, available for the competent authorities for a \nperiod of at least 10  years after the last device covered by the EU declaration of conformity has \nbeen placed on the market (Article 10(8)).  \nAvailability of documentation  \u2013 In case of request by the CA, the manufacturer will provide the required \ntechnical documentation in an official Union language determined by the Member State concerned \n(Article 10(14)).  \nd)  Request Notified Body involvement  \nIn the case of devices placed on the market in sterile condition, having a measuring function or being \nreusable surgical instruments, the manufacturer will apply the procedures set out in Chapters I and III of \nAnnex IX, or in Part A of Annex XI of MDR. This requires the involvement of a NB. In all other cases \nthe intervention of a NB is not required for Class I devices. If involvement of  the NB is needed it is \nlimited:  \n- In the case of devices placed on the market in sterile condition, to the aspects of manufacture \nconcerned with securing and maintaining sterile  conditions;  \n- In the case of devices with a measuring function, to the aspects of man ufacture concerned with \nthe conformity of the devices with the metrological  requirements;  \n- In the case of reusable surgical instruments20,  to the aspects relating to the reuse of the device, in \nparticular cleaning, disinfection, sterilization, maintenance a nd functional testing and the related \ninstructions for use.  \nManufacturers can choose any NB designated according to the MDR for the relevant codes and \ncorresponding types of devices as established by Regulation (EU) 2017/2185 (code MDS 1005 for \n\u201cDevices in  sterile condition\u201d, code MDS 1006 for \u201cReusable surgical instruments\u201d and code MDS 1010 \nfor \u201cDevices with a measuring function\u201d) . The list of designated NBs is available in the NANDO \ndatabase at the following link: http://ec.europa.eu/growth/tools -databases/nando/  \nPlease note that notification under the Directive 93/42/EC, become s void after the application of the MDR \non the 26 May 202 1.  Hence, it is necessary to consult the NANDO database for the MDR.  \ne) Prepare Instructions for Use and Labelling  \nEach device must be accompanied by any safety and performance information needed to use it safely \nand to identify the device as well as the manufacturer and/or the authorised representative, taking \naccount of the training and knowledge of the potential users. This information comprises the label, \ndevice packaging and the data in the instructions for use. By way of derogation to the general principles, \nno instructions for use are required for Class I de vices if they can be used properly and safely without \nsuch instruction. An exception is most likely posed for Class Ir devices as reprocessing (cleaning and \nsterilization) will require an instruction.  \nThe requirements regarding the information to be suppl ied with the device will be found in Annex I, \nChapter III (23). In the labelling and instructions for use as well as in promotional materials of the \ndevice, the manufacturer may not (Article 7):  \n                                                      \n20  Please also note that involvement of a Notified Body in the case of reusable surgical instruments is a new requirement under the MDR, which \ndid not exist under the MDD. Manufacturers of such products are advised to take this into consideration for their pl ans to meet the provisions \nof the MDR before its application on the 26 May 202 1. Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n17 \n - Ascribe functions and properties to the device which the devi ce does not have;  \n- Create a false impression regarding treatment or diagnosis, functions or properties which the \ndevice does not have;  \n- Fail to inform the user or the patient of a likely risk associated with the use of the device in line \nwith its intended purpose;  \n- Suggest uses for the device other than those stated to form part of the intended purpose for \nwhich the conformity assessment was carried out.  \nNational language requirements must be taken into account in relation to the labelling and instructions \nfor use. Versions of labelling  and IFU ( in each of the relevant national languages) will be included in the \ntechnical documentation.  \nNote : According to Article 16(2), a distributor or importer may provide a translation of the information \nprovided according to Section 23 of Annex I. The manufacturer will be informed about the intended \ntranslation and receive a copy 28 days prior to the date of making the device available in the respective \ncountry. It is advisable to perform a review of the translation, as a w rong or misleading translation can \ncause harm to patients or others, leading to possible liability of the manufacturer.  \nWhere appropriate, the information supplied by the manufacturer will take the form of internationally \nrecognised symbols. Any symbol or identification colour used will conform to harmonised standards or \ncommon specifications (CS). In areas for which no harmonised standards or CS exist, the symbols and \ncolours will be described in the documentation supplied with the device.  \nThe label should  have the indication that the product is a \u201cmedical device\u201d.  \n4) Check compliance with general obligations for manufacturers  \nBefore placing a device on the market, the manufacturer will make sure to comply with the general \nobligations for manufacturers as est ablished in Article 10.  \nSpecial attention will be given to the establishment of an appropriate QMS that will ensure compliance \nwith the MDR in the most effective manner, for example by means of an internal audit. The QMS will \nbe documented, implemented, m aintained, kept up to date and continually improved and will cover at \nleast the following aspects:  \na) a strategy for regulatory compliance;  \nb) identification of applicable general safety and performance requirements and exploration of \noptions to address those requirements;  \nc) responsibility of the management;  \nd) resource management, including selection and control of suppliers and sub -contractors;  \ne) risk management;  \nf) clinical evaluation, including post market clinical follow -up (PMCF);  \ng) product realisation, including planning, design, development, production and service provision;  \nh) verification of the UDI assignments;  \ni) setting -up, implementation and ma intenance of a post -market surveillance system;  \nj) handling communication with competent authorities, notified bodies, other economic operators, \ncustomers and/or other stakeholders;  \nk) processes for reporting of serious incidents and field safety corrective ac tions in the context of \nvigilance;  \nl) management of corrective and preventive actions and verification of their effectiveness;  \nm) processes for monitoring and measurement of output, data analysis and product improvement.  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n18 \n The QMS will be established at least in  parallel, if not prior to chapter 3 a) and 3 b) as described in this \nguidance note.  \nNatural or legal persons may claim compensation for damage caused by a defective device in \naccordance with applicable Union and national law. Therefore, manufacturers sha ll, in a manner that is \nproportionate to the risk class, type of device and size of the enterprise, have measures in place to \nprovide sufficient financial coverage in respect of their potential liability under Directive 85/374/EEC, \nwithout prejudice to mor e protective measures under national law.  \n5)  Draw -up the EU Declaration of Conformity  \nThe EU declaration of conformity, referred to in Article 19, is the procedure whereby the manufacturer, \nwho fulfils the obligations imposed by Article 52(7), declares that the devices concerned fulfil the \nrequirements of the MDR which apply to them. The declaration of conformity will contain as a \nminimum all information referred to in Annex IV and will be available to the CA.  \nThe manufacturer will continuously update the EU declaration of conformity and will translate it into an \nofficial union language or languages required by Member States in which the device is made available.  \nIf, in addition to the MDR, a device is covered by other Union legislation which also requires an EU \ndeclaration of conformity, the manufacturers will elaborate a single EU declaration of conformity where \nall the Union legislation applied to the product are referred to.  \nBy drawing up the EU declaration of conformity the manufacturer assumes the respon sibility for the \nregulatory compliance of the device with all Union legislation applicable to it.  \nBefore affixing a CE mark, for class Ir, Im and Is devices, the manufacturer will have an EC certificate \nissued by NB according to the Annex IX, Chapter I and III, or to Annex XI, Part A.  \n6)  Affix the CE marking  \nAll Class I medical devices placed on the mar ket will bear the CE marking of conformity, which will be \naffixed in a visible, legible and indelible form on the device or on its sterile packaging. Where such \naffixing is not possible or not warranted on account of the nature of the device, the CE markin g shall be \naffixed to the packaging. The CE marking shall also appear  on the instructions for use, as well as on any \nsales packaging.  \nIn the case of Class I medical devices placed on the market in a sterile condition and/or devices with \nmeasuring function  and/or reusable surgical instruments, the CE marking will be accompanied by the \nidentification number of the relevant NB.  \nIt is prohibited to affix marks which are likely to mislead third parties with regard to the meaning of the \nCE marking. Other additio nal marks may be affixed to the device, to the packaging or the instructions \nfor use, but must not impair the visibility or legibility of the CE marking.  \nThe CE marking format will be in compliance with Annex V. Where the device is very small the \nminimum d imensions of the CE mark may be waived.  \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n19 \n 7) Registration of devices and manufacturers in Eudamed  \nBefore placing a device on the market, the manufacturer of a Class I medical device will register the \ndevice in Eudamed.  \nIn order to register the device, the manufacturer will submit to the electronic system referred to in \nArticle 30 the information referred to in Section 1 of Part A of Annex VI, provided that they have not \nalready been registered in accordance with Article 31. In cases where the conformity ass essment \nprocedure requires the involvement of a NB pursuant to Article 52, the information referred to in \nSection 1 of Part A of Annex VI will be provided to that electronic system before applying to the NB.  \nAfter having verified the data about the manufac turer, the CA will validate it in Eudamed and the \nmanufacturer will obtain a SRN from said electronic system.  \nThe manufacturer will use the SRN when applying to a NB for conformity assessment and for accessing \nEudamed in order to fulfil its obligations und er Article 29.  \nNote: Authorised representatives and importers are also required to register to get an SRN in order to \naccess Eudamed and provide data, as appropriate  \nThe registration of a device in Eudamed by the manufacturer includes:  \n\uf0b7 Assignment of a UDI -DI (with a Basic UDI -DI) as defined in Part C of Annex VI to the device \n(in accordance with the rules of the issuing entity referred to in Article 27(2) and introduction of \nthe UDI -DI (with a Basic UDI -DI) to the UDI database together with the other core d ata elements \nreferred to in Part B of Annex VI related to that device.  \n\uf0b7 Entering, or if already provided, verifying in Eudamed the information referred to in Section 2 of \nPart A of Annex VI, with the exception of Section 2.2 thereof, and thereafter keeping the \ninformation updated.  \nIf the manufacturer has its devices designed or manufactured by another legal or natural person, the \ninformation on the identity of that person will be part of the information (Section 2.13 of Part A of \nAnnex VI) to be submitted to  Eudamed before the registration of the device.  \nNote 1  \u2013 The Unique Device Identification system will allow the identification and facilitate the \ntraceability of devices (as referred on Article 27). [Special attention will be given to point 11 of Article \n27]. \nNote 2  \u2013 The Basic UDI -DI as defined in Part C of Annex VI is the primary identifier of a device model. \nIt is the main key for records in the UDI database and is referenced in relevant certificates and EU \ndeclarations of conformity21. \nNote 3 \u2013 For Class I devices placed on the market according to MDD, afte r the date of application of \nMDR manufacturers will have in consideration the guidance documents applicable to legacy devices \ntimelines22 and registration in Eudamed23. \n                                                      \n21  For more information on the Basic UDI -DI, please refer to https://ec.europa.eu/docsroom/documents/28667   \n22  See at EU Commission webpage the relevant guidance on timelines for registration of device data elements in EUDAMED23  See at EU \nCommission webpage the relevant guidance on the registration of legacy devices in EUDAMED  \n23  See at EU Commission webpage the relevant guidance on the registration of legacy devices in EUDAMED  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n20 \n   Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n21 \n All devices including legacy devices of the manufacturer portfolio which are placed on the market or put \ninto service will have to be registered in Eudamed.  However, until Eudamed is fully functional the \nmanufacturer of a Class I medical device, or, where the manufacturer has no place of business in the EU, \nits authorised representative must  inform the CA of the country in which they have their registered place \nof business and provide a description of the device that is sufficient to identify it. The manufacturer or \nits authorised representative will contact their relevant CA for the required  procedures and forms \nrequired for such notifications. A fee might be applicable.  \n8) Post Market Surveillance (PMS)  \nAfter placing the Class I device on the market, the manufacturer will follow the next PMS steps:  \na) Review experience gained from Post -Market Sur veillance  \nThe manufacturer will put in place the required post market surveillance (PMS) system and actively \nkeep this PMS up to date in accordance with Article 83 of MDR. This includes actively and regularly \ncollecting the user experience from devices on the market, reviewing these and ensuring timely \nimplementation of any necessary corrective action, taking account of the nature and risks in relation to \nthe product.  In addition, there should be an evaluation of whether the intended benefits are achieved a nd \nwhether the benefit -risk profile stays positive.  The manufacturer will involve the distributors of the \ndevice and where applicable, the authorised representative and importers of the device in this system, in \norder to obtain the relevant  information from the market.  \nThis system will be part of the QMS, and be supported by the manufacturer\u2019s PMS plan, which must \naddress a range of information (Annex III), such as information from the vigilance context, information \nfrom trending and trend reporting, inf ormation and data on any undesirable side -effects, information \nfrom reports, complaints and incidents, provided by users and economic operators, related to the device. \nMoreover, the manufacturer will gather and assess the relevant information such as techn ical literature, \ndatabases, registers review and public information for the device itself as well as for similar devices \nalready present on the market.  \nA PMS report will be prepared according to Article 85, summarizing the results and conclusions of the \nanalysis of all of the data from the market. This report will be updated when necessary, for example  the \nintended benefits are not achieved or there is a change in the benefit -risk balance. The report can be \nrequested by the CA at any time.  \nData gathered from PMS system must be used to actively update the clinical evaluation, benefit -risk \ndetermination, improve risk management, as well as other technical documentation on a regular basis.  \nb) Vigilance   \nThe manufacturer is responsible for reporting all serious incidents and field safety corrective actions \n(FSCA) to the relevant CAs, according to Article 87 (1) of the MDR. After serious incident notification, \nthe manufacturer is obliged to make investigations, according to Article 89, which will include a risk \nassessment of the incident. If needed, a FSCA will be implemented in order to reduce the risk associated \nwith the use of the device.  \nThe manufacturer will involve the distributors of the device and, where applicable, the authorised \nrepresentative and import ers in the system, in order to obtain the information needed from the market, \nespecially for FSCA and issued field safety notices (FSN) to ensure that required actions are followed \nand completed in a timely manner.  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n22 \n When Eudamed is available, serious incide nts and FSCAs will be submitted via this electronic system \nonly.  \nManufacturers will report any serious incident immediately after they have established the causal \nrelationship between that incident and their device or that such a causal relationship is re asonably \npossible.  \nThe timeframe to report serious incidents must not exceed the following upper limits:  \n\uf0b7 In the event of a serious public health threat, a report will be submitted not later than 2 days \nafter becoming aware of the threat. (Article 87 (4))  \n\uf0b7 In the event of death or an unanticipated deterioration in a person\u2019s state of health a report will \nbe submitted not later than 10 days after becoming aware of the serious incident. (Article 87 \n(5)) \n\uf0b7 In all other cases not later than 15 days after becoming aware of the serious incident (Article 87 \n(3)) \nWhere necessary to ensure timely reporting of serious incidents, the manufacturer may submit an initial \nreport that is incomplete followed up by a complete report. If, after becoming aware of a potentially \nreportable incident, the manufacturer is uncertain about whether the incident is reportable, it shall \nnevertheless submit a report. Serious incidents will be reported only to the competent authority of the \ncountry in which the serious incident occurred via Eu damed.  \nThe manufacturer will provide a final report to that competent authority via Eudamed setting out its \nfindings from the investigation. The report will set out conclusions and - where relevant - indicate \ncorrective actions to be taken.  \nWhen the compet ent authority notifies a manufacturer of a suspected serious incident, communicated to \nthe competent authority by a healthcare professional, patient or user, the manufacturer is obliged to:  \n\uf0b7 submit a report of this serious incident to the notifying competen t authority via Eudamed within \nthe timeframes described above;  \n\uf0b7 submit an explanatory statement, to the competent authority, if the manufacturer believes the \nsuspected serious incident does not fulfil the reporting criteria.  \nIn case the competent authority disagrees with the explanatory statement provided by the manufacturer a \nreport of the serious incident may be required to be provided to the competent authority that does not \nagree via Eudamed by the manufacturer.  \nIf a FSCA is undertaken, manufacturers wil l without unnecessary delay report the field safety corrective \naction via Eudamed in advance of the carrying out of the FSCA unless urgency demands the \nmanufacturer to undertake the actions immediately.  \nManufacturers will ensure that the information relate d to the FSCA is brought without delay to the \nattention of users of the device in question by means of a FSN. Except in cases of urgency, the content \nof the draft FSN will be submitted to the evaluating competent authority or to the coordinating \ncompetent authority to allow it to make comments. Unless duly justified by the situation of the \nindividual Member State, the content of the field safety notice will be consistent in all Member States. \nManufacturers will also report the FSN(s) to Eudamed.  \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n23 \n The FSN w ill allow the correct identification of the manufacturer ( by including the, if issued, SRN), the \ndevice or devices affected (by including the relevant UDIs) and the FSN will explain, in a clear manner, \nwithout understating the level of risk, the reasons fo r the FSCA. This includes a clear reference to the \ndevice deficiency and the associated risks for patients, users or other persons and will clearly indicate all \naction to be taken by the users.  \nManufacturers will report by the means of a trend report to Eudamed any statistically significant \nincrease in the frequency or severity of incidents that are not serious incidents or that are expected \nundesirable side -effects, when it could have a significant impact on the benefit -risk analysis and which \nhave led o r may lead to risks to the health or safety of patients, users or other persons that are \nunacceptable when weighed against the intended benefits.  \nManufacturers will, if they exist, follow national provisions in the field of vigilance specifically in but \nnot limited to the case of field safety corrective actions:  \n\uf0b7 The allowed languages used to communicate with users by means of the Field Safety Notice.  \nManufacturers are asked to check if templates exist (on European Commission website) on any of the \nreporta ble forms and make sure that all the necessary information according to these templates is \nprovided. This will be only applicable until Eudamed is available.  \nManufacturers should keep concerned economic operators informed of reported serious incidents and \nFSCA activities.  \nc) Non-conforming  products  \nIf a manufacturer has reasons to believe that a device which they have placed on the market or put into \nservice is not in conformity with the MDR they will immediately take the necessary corrective action to \nbring t hat device into conformity, to withdraw it or to recall it, as appropriate. The manufacturer will \ninform the distributors of the device in question and, if applicable, the authorised representative and \nimporters. If the device presents a serious risk, the manufacturer will immediately inform the competent \nauthorities of the Member States in which the manufacturer made the device available and, where \napplicable, the notified body that issued a certificate for the device, in particular, of the non -compliance \nand of any corrective action taken."}, {"title": "mdcg_2019_3_rev1_cecp_en.pdf.txt", "text": "Medical Devices       \nMedical Device  Coordination Group Document   MDCG  201 9-3 Rev.1   \nPage 1 of 4 \n  \n \n \n \n \nMDCG  2019 -3 Rev. 1 \n Interpretation of Article 54(2)b     \n          \n \n \n April 2020  \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commission document and it cannot be regar ded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  \n \n  Medical Devices       \nMedical Device  Coordination Group Document   MDCG  201 9-3 Rev.1   \nPage 2 of 4 \n  \nMDCG 2019 -3 Rev. 1 changes  \nAddendum on procedural aspects  New \n \n \nInterpretation of Article 54(2)b  \nArticle 54(2) of the MDR lays down three criteria that exempt devices from the pre -\nmarket clinical evaluation consultation procedure with the involvement of expert \npanels. In particular that article states that:  \n\u201cThe procedure referred to in paragraph 1 shall not be required for the devices \nreferred to therein:  \n(a)  in the case of renewal of a certificate issued under this Regulation;  \n(b)  where the device has been designed by modifying a device already marketed by \nthe same manufacturer for the same intended purpose, provided that the \nmanufacturer has demonstrated to the satisfaction of the notified body that the \nmodifications do not ad versely affect the benefit -risk ratio of the device; or  \n(c) where the principles of the clinical evaluation of the device type or category have \nbeen addressed in a CS referred to in Article 9 and the notified body confirms that the \nclinical evaluation of the manufacturer for this device is in compliance with the \nrelevant CS for clinical evaluation of that kind of device\u201d.  \nInterpretation of point (b) of Article 54(2) is unclear, notably in relation to the \napplication of the word \u201cmarketed\u201d.  In fact, while in point \u201ca\u201d the co -legislator \nexplicitly indicates that the certificates referred to are those issued under the new \nRegulation, in point \u201cb\u201d there is no indication of whether a \u201cdevice already marketed\u201d \nrefers to devices already marketed under the Directi ves or the Regulations.  \nThis has raised questions from the public and from Member States.  \nAs we are about to launch the procedures for the establishment of expert panels, \nclarification of this issue is extremely urgent, notably due to its impact on the fu ture \nworkload of panels and hence on relevant budget and workload estimations.  \nThe following considerations seem to indicate that the expression \u201cdevice already \nmarketed\u201d cannot be intended to refer to a device already marketed uniquely under \nthe new Regu lation : \n\uf0b7 If the co -legislators had decided to restrict the application of point \u201cb\u201d to devices \nmarketed uniquely under the MDR, they would have explicitly stated so, as they \ndid for point \u201ca\u201d;  \n\uf0b7 Article 54, together with other Articles (such as Article 61(6) and Article 120(3)), \nwas written at the end of the negotiation process with a view to smoothen the  Medical Devices       \nMedical Device  Coordination Group Document   MDCG  201 9-3 Rev.1   \nPage 3 of 4 \n  \n \nimplementation of the new Regulation. Therefore the interpretation of the \nexemption should be understood in line with the spirit and intention of the co -\nlegislators.  \n \nIt has to be noted that, in respect to devices that have been marketed already under \nthe relevant Directives, the word \u201cmodification\u201d shall be meant as limited only to those \nmodifications needed in order to comply with the new legal requiremen ts introduced \nby the MDR1 2. \n \n \nAddendum - Procedural aspects  \n \nTogether with the application to be lodged under the applicable conformity \nassessment procedure, the manufacturer will provide the notified body with:  \n\uf0b7 a statement that it has marketed the device  in question for the same intended \npurpose under the relevant Directive,  \n\uf0b7 copy of the last issued certificate(s) together with the certificate history, and  \n\uf0b7 a description of the modifications introduced to comply with the MDR  \nAs part of its technical documen tation assessment according to the MDR, the notified \nbody will verify that the \u201cmodifications\u201d, as referred to in the main document, do not \nadversely affect the benefit -risk ratio. In particular, the notified body will verify:  \n\uf0b7 that the device in question h ad a valid certificate under the Directives,  \n\uf0b7 in case the certificate has been withdrawn, suspended3 or expired, if there is \nan impact on compliance with the general safety and performance \nrequirements, and  \n\uf0b7 that there is no pending assessment of changes fo r the device or outstanding \nnon-compliance.   \nIn addition, the notified body will verify the description of modifications provided and \nassess if these modifications are limited only to those needed in order to comply with \nthe new legal requirements introdu ced by the MDR. Limitations of the intended \npurpose of the device should not trigger the consultation procedure in accordance to \nArt. 54.  \n                                                            \n1  These devices will anyhow be subject to all applicable new MDR requirements, including those ones related \nto the clinical evaluation, and will need to be assessed by notified bodies against these new (and higher) \nrequirements. This aspect together with the increased notified bodies\u2019 oversight foreseen under MDR should \nguarantee a high standard of safety for these products.  \n2  From a practical perspective, u nder the scenario where those products had to be subject to clinical evaluation \nconsultation procedure with the involvement of expert panels, as a result of the application of criteria set in \nAnnex IX 5c, in most if not all of the cases, the panel would de cide not to give an opinion. Therefore , a very \nsignificant additional workload and financial burden would be created for an extremely limited added value.  \n3    Certificates for which the rationale for withdrawal or suspension is linked to lack of complian ce with essential   \nrequirements may adversely affect the benefit -risk ratio of the device and will require a clinical evaluation \nconsultation procedure.  Medical Devices       \nMedical Device  Coordination Group Document   MDCG  201 9-3 Rev.1   \nPage 4 of 4 \n  \n \nIn case that any of the abovementioned conditions are not fulfilled the notified body \nwill follow the consultation procedure in accordance to Art. 54.  \nThe assessment of the above conditions will be documented by the notified body in \naccordance with Section 4.6 of Annex VII in the clinical evaluation assessment report \nthat will be made available to competent authorities  in accordance with Art. 54 (1) \nand (3).  \n \n \nClarifications in respect to the applicability of Art. 54(2)b with regard to devices \nalready marketed under the MDR are to be provided in a separate guidance."}, {"title": "mdcg_2019_11_guidance_qualification_classification_software.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document   MDCG  2019-11    \n \n \n \n  \n \n \nMDCG  2019-11  \n        Guidance on Qualification and Classification  \n        of Software in Regulation (EU) 2017/745 \u2013 MDR  \n        and Regulation (EU) 2017/746 \u2013 IVDR    \n           \n \n           October   2019 \n \n \n  \n    \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member States and it is chaired by a representative of the European Commission. The document is not a European Commission document and it cannot be regarded as reflecting the official position of the European Commission. Any views expressed in this document are not legally binding and only the Court of Justice of the European Union can give binding interpretations of Union law.  \n \n   \nPage 1 of 28 \n   \nGuidance on Qualification and \nClassification of Software in \nRegulation (EU) 2017/745 \u2013 MDR and \nRegulation (EU) 2017/746 \u2013 IVDR \n \n Guidance on \nQualification and \nClassification of \nSoftware  \nOctober 201 9  \nPage 2 of 28 \n  \n \n \nTable of Contents \n \n 1.\n Scope and purpose of this document 3  \n2. Definitions and abbreviations 3  \n3. Qualification 6  \n3.1. Introduction to qualification criteria 6  \n3.2. Medical Device Software (MDSW)  7  \n3.3. \u2018Software  driving or influencing the use of a medical device\u2019 8  \n3.4. Qualification criteria of MDSW as an in vitro  diagnostic medical device 10  \n4. Classification of MDSW per MDR 2017/745 12  \n4.1. Implementing Rules 12  \n4.2. Classification Rules 12  \n5. Classification and implemen ting rules per IVDR 2017/746 15  \n5.1. Implementing Rules: 15  \n5.2. Classification Rules: 15  \n6. Considerations on placing on the market  and conformity asse ssment of MDSW 16  \n6.1. Option 1: as a medical device in its own right 16  \n6.2. Option 2: as an integral component/part of a device 17  \n7. Modules 17  \n8. Consideration of changes to an MDSW 18  \n9. Annex I: Illustrative examples of qualifica tion of software used in the healthcare \nenvironment 18  \n10. Annex II - Qualification examples of Medical Device Software (MDSW) according to \nFigures 1 and 2 24  \n11. Annex III - Usability of the IMDRF risk classification framework in the context of the \nMDR  26 \n12. Annex IV \u2013 Classification examples 27  \n \n \n  \nPage 3 of 28 \n 1. Scope and purpose of this document \nThis document, which primarily targets medical software manufacturers, defines the criteria for the \nqualification of software falling within the scope of the new medical devices regulations1 and provides \nguidance on the application of classification criteria for software under Regulation (EU) 2017/745 \u2013 \nMDR and Regulation (EU) 2017/746 \u2013 IVDR.2 The guidance also provides information related to \nplacing on the market. The classification criteria (classification rules) are set out in Annex VIII of the \nMedical Devices Regulation (EU) 2017/745 (MDR) and Annex VIII of the In vitro Diagnostic Medical Devices Regulation (EU) 2017/746 (IVDR).  \nThe criteria specified in this document shall also apply to applications (commonly referred to as apps), \nmay they be operating on a mobile phone, in the cloud or on other platforms. \n2. Definitions and abbreviations \nIntended purpose : \nAccording to Regulation (EU) 2017/745 \u2013 MDR, \u201cIntended purpose\u201d means the use for which a \ndevice is intended according to the data supplied by the manufacturer on the label, in the instructions \nfor use or in promotional or sales materials or statements and as specified by the manufacturer in the \nclinical evaluation;3 \nAccording to Regulation (EU) 2017/746 \u2013 IVDR, \u201cIntended purpose\u201d means the use for which a \ndevice is intended according to the data supplied by the manufacturer on the label, in the instructions for use or in promotional or sales materials or statements or as specified by the manufacturer in the \nperformance evaluation;\n4 \nAccessory: \nAccording to Regulation (EU) 2017/745 \u2013 MDR, \u201cAcc essory for a medical device\u201d means an article \nwhich, whilst not being itself a medical device, is intended by its manufacturer to be used together \nwith one or several particular medical device(s) to specifically enable the medical device(s) to be used in accordance with its/their intended purpose(s) or to specifically and directly assist the medical \nfunctionality of the medical device(s) in terms of its/their intended purpose(s);\n5 \nAccording to Regulation (EU) 2017/746 \u2013 IVDR, \u201cAccessory for an in vitro diagnostic medical \ndevice\u201d means an article which, whilst not being itself an in vitro diagnostic medical device, is \nintended by its manufacturer to be used together with one or several particular in vitro diagnostic \nmedical device(s) to specifically enable the in vitro diagnostic medical device(s) to be used in \naccordance with its/their intended purpose(s) or to specifically and directly assist the medical \nfunctionality of the in vitro diagnostic medical device(s) in terms of its/their intended purpose(s);6  \nNote:  Software accessory may be driving or influencing the use of a medical device.  \nNote:  Manufacturers must describe in the technical documentation accessories of a medical device or \nan in vitro diagnostic medical device which are intended to be used in combination with it; and in case \n                                                 \n1 The use of \u201cThe Medical Devices Regulations\u201d from here on out refers to both Regulation (EU) 2017/745 \u2013 MDR and \nRegulation (EU) 2017/746 \u2013 IVDR. \n2 It shall be noted that the term \u201cstandalone software\u201d which was used in the text of the medical device directives, is no \nlonger used in the context of the Medical Device Regulation. The rationale of the change is that software should be qualified and classified depending on its intended purpose uniquely, regardless of its location. \n3 Article 2(12) of Regulation (EU) 2017/745 \u2013 MDR  \n4 Article 2(12) of Regulation (EU) 2017/746 \u2013 IVDR  \n5 Article 2(2) of Regulation (EU) 2017/745 \u2013 MDR \n6 Article 2(4) of Regulation (EU) 2017/746 \u2013 IVDR   \nPage 4 of 28 \n of medical devices they must include in the instructions for use information allowing the selection of \nthe corresponding software and accessories.7 \n \nPlacing on the market: \nAccording to Regulation (EU) 2017/745 \u2013 MDR, \u201cPlacing on the market\u201d means the first making available of a device, other than an investigational device, on the Union market;\n8 \n \nAccording to Regulation (EU) 2017/746 \u2013 IVDR, \u201cPlacing on the market\u201d means the first making \navailable of a device, other than a device for performance study, on the Union market;9 \nPutting into service: \nAccording to Regulation (EU) 2017/745 \u2013 MDR, \u201cPut ting into service\u201d means the stage at which a \ndevice, other than an investigational device, has been made available to the final user as being ready \nfor use on the Union market for the first time for its intended purpose;10 \n \nAccording to Regulation (EU) 2017/746 \u2013 IVDR, \u201cPutti ng into service\u201d means the stage at which a \ndevice, other than a device for performance study, has been made available to the final user as being ready for use on the Union market for the first time for its intended purpose;\n11 \nMedical device : \n\u201cmedical device\u201d means any instrument, apparatus, appliance, software , implant, reagent, material or \nother article intended by the manufacturer to be used, alone or in combination, for human beings for \none or more of the following specific medical purposes: \n- diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease,  \n- diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability, \n- investigation, replacement or modification of the anatomy or of a physiological or \npathological process or state,  \n- providing information by means of in vitro examination of specimens derived from the human \nbody, including organ, blood and tissue donations,  \nand which does not achieve its principal intended action by pharmacological, immunological or \nmetabolic means, in or on the human body, but which may be assisted in its function by such means.  \nThe following products shall also be deemed to be medical devices:  \n- devices for the control or support of conception;  \n- products specifically intended for the cleaning, disinfection or sterilisation of devices as \nreferred to in Article 1(4) and of those referred to in the first paragraph of this point.12 \nActive medical device:  \n\u201cactive device\u201d means any device, the operation of which depends on a source of energy other than \nthat generated by the human body for that purpose, or by gravity, and which acts by changing the \ndensity of or converting that energy. Devices intended to transmit energy, substances or other elements \nbetween an active device and the patient, without any significant change, shall not be deemed to be active devices. Software shall also be deemed to be an active device;\n13 \n \n                                                 \n7 Article 32.2(c), Annex I, Chapter III Section 23.4(f), Annex II Section 1.1(h) of Regulation (EU) 2017/745 \u2013 MDRArticle \n29.2(c) and  Annex II Section 1.1(m) of Regulation (EU) 2017/746 \u2013 IVDR  \n8 Article 2(28) of Regulation (EU) 2017/745 \u2013 MDR \n9 Article 2(21) of Regulation (EU) 2017/746 \u2013 IVDR \n10 Article 2(29) of Regulation (EU) 2017/745 \u2013 MDR \n11 Article 2(22) of Regulation (EU) 2017/746 \u2013 IVDR \n12 Article 2(1) of Regulation (EU) 2017/745 \u2013 MDR \n13 Article 2(4) of Regulation (EU) 2017/745 \u2013 MDR   \nPage 5 of 28 \n In vitro  diagnostic medical device: \n\u201cIn vitro diagnostic medical device\u201d means any medical device which is a reagent, reagent product, \ncalibrator, control material, kit, instru ment, apparatus, piece of equipment, software  or system, \nwhether used alone or in combination, intended by the manufacturer to be used in vitro for the \nexamination of specimens, including blood and tissue donations, derived from the human body, solely \nor principally for the purpose of providing information on one or more of the following:  \n- concerning a physiological or pathological process or state;  \n- concerning congenital physical or mental impairments;  \n- concerning the predisposition to a medical condition or a disease;  \n- to determine the safety and compatibility with potential recipients;  \n- to predict treatment response or reactions;  \n- to define or monitoring therapeutic measures.  \nSpecimen receptacles shall also be deemed to be in vitro diagnostic medical devices;14 \n \nSoftware: \nFor the purpose of this guidance, \u201csoftware\u201d is defined as a set of instructions that processes input data \nand creates output data. \nInput data : \nAny data provided to software in order to obtain ou tput data after computation of this data can be \nconsidered as input data. Input data examples (non-exhaustive): \n- Data given through the use of a human data-input device such as a keyboard, mouse, stylus, or \ntouch screen; \n- Data given through speech recognition; \n- Digital document: formatted for general purpose such as Word file or pdf file or jpeg image, \nformatted for medical purpose such as DICOM file or ECG records or Electronic Health \nRecord, unformatted document. Note that digital documents have to be differentiated from \nsoftware able to read such documents; \n- Data received from/transmitted by devices. \nOutput data : \nAny data produced by a software can be considered  as an output data. Output data examples (non-\nexhaustive): \n- Screen display data (such as layout with number, characters, picture, graphics, etc.); \n- Print data (such as layout with number, characters, picture, graphics, etc.); \n- Audio data; \n- Digital document (formatted for a general purpose such as Word file or pdf file or jpeg image, \nor formatted for medical purpose such as DICOM file or ECG records or Electronic Health \nRecord, unformatted document). \n- Haptic buzzing as an alternative to audio sound \nSoftware driving or influencing the use of a device  \nSoftware which is intended to drive or influence the use of a (hardware) medical device and does not  \nhave or perform a medical purpose on its own , nor does it create information on its own  for one or \nmore of the medical purposes described in the definition of a medical device or an in vitro  diagnostic \nmedical device. This software can, but is not limited to:  \n(a) operate, modify the state of, or control the device either through an interface (e.g., software, \nhardware) or via the operator of this device \n(b)  or supply output related to the (hardware) functioning of that device \nNote:  Software driving or influencing the use of a (hardware) medical device may be qualified as an \naccessory for a (hardware) medical device.  \n                                                 \n14 Article 2(2) of Regulation (EU) 2017/746 \u2013 IVDR   \nPage 6 of 28 \n Medical Device Software (MDSW) \nMedical device software is software that is intended to be used, alone or in combination, for a purpose \nas specified in the definition of a \u201cmedical device\u201d in the medical devices regulation15 or in vitro  \ndiagnostic medical devices regulation.16 \n3. Qualification \n3.1. Introduction to qualification criteria \nThe purpose of this section is to clarify what software is in itself subject to the medical devices \nregulations.  \nSoftware must have a medical purpose on its own to be qualified as a medical device software \n(MDSW). It should be noted that the intended purpose as described by the manufacturer of the \nsoftware is relevant for the qualification and classification of any device. \nIn order to be qualified as medical device software, the product must first fulfil the definition of \nsoftware according to this guidance and the definiti on of a medical device according to Article 2(1) of \nRegulation (EU) 2017/745 \u2013 MDR. To be qualified as an in vitro  diagnostic medical device software, \nthe product must additionally fulfil the definition of an in vitro  diagnostic medical device according to \nArticle 2(2) of Regulati on (EU) 2017/746 \u2013 IVDR.  \nWhere a given product does not fall under the definition of a medical device, or is excluded by the \nscope of the Medical Devices Regulations, other Community and/or national legislation may be \napplicable. Software that does not meet th e definition of a medical device or an in vitro diagnostic \nmedical device (i.e. software that is not MDSW) but is intended by the manufacturer to be an \naccessory for a medical device, or an in vitro  diagnostic medical device, falls respectively under the \nscope of the Regulation (EU) 2017/745 \u2013 MDR or Regulation (EU) 2017/746 \u2013 IVDR. \nSoftware can directly control a (hardware)  medical device (e.g. radiotherapy treatment software), can \nprovide immediate decision-triggering information (e .g. blood glucose meter software), or can provide \nsupport for healthcare professionals (e.g. ECG interpretation software).  \nIt is important to clarify that not all software used within healthcare is qualified as a medical device. \nFor example, \u201cSimple search\u201d, which refers to the retrieval of records by matching record metadata \nagainst record search criteria or to the retrieval of information does not qualify as medical device \nsoftware (e.g. library functions).  \nHowever, software which is intended to process, an alyse, create or modify medical information may \nbe qualified as a medical device software if the creation or modification of that information is \ngoverned by a medical intended purpose. For example, the software which alters the representation of \ndata for a medical purpose would qualify as a medical device software. (e.g. \u201csearching image for \nfindings that support a clinical hypothesis as to th e diagnosis or evolution of therapy\u201d or \u201csoftware \nwhich locally amplifies the contrast of the finding on an image display so that it serves as a decision \nsupport or suggests an action to be taken by the user\u201d). However, altering the representation of data for \nembellishment/cosmetic or compatibility purposes does not readily qualify the software as medical \ndevice software.  \nSoftware intended for non-medical purposes (excludi ng MDR Annex XVI devices), such as invoicing \nor staff planning, does not qualify as a medical device software. These software do not fall under the \nMedical Devices Regulations. \n                                                 \n15 Article 2(1) of Regulation (EU) 2017/745 \u2013 MDR \n16 Article 2(2) of Regulation (EU) 2017/746 \u2013 IVDR   \nPage 7 of 28 \n A task such as e-mailing, web or voice messaging, data parsing, word processing, and back-up is by \nitself not considered as having a medical purpose. \nAdditionally, software may run on different operating systems or in virtual environments. These \noperating systems or virtual environments do not impact the qualification criteria. \nIt must be highlighted that the risk of harm to patients, users of the software, or any other person, \nrelated to the use of the software within healthcare, including a possible malfunction is not a criterion \non whether the software qualifies as a medical device.  \n3.2. Medical Device Software (MDSW)   \nMedical device software is software that is intended to be used, alone or in combination , for a \npurpose as specified in the definition of a \u201cmedical device\u201d in the MDR or IVDR, regardless of \nwhether the software is independent or driving or influencing the use of a device. \nNote 1:  MDSW may be independent , by having its own intended medical purpose and thus meeting \nthe definition of a medical device or in vitro  diagnostic medical device on its own (i.e. alone ) \nMDSW that uses maternal parameters such as ag e, concentration of serum markers and information \nobtained through foetal ultrasound examination for evaluating the risk of trisomy 21. \nMDSW that receives measurements from transrectal  ultrasound findings, age, and in vitro diagnostic \ninstruments and calculates a patient\u2019s risk of developing prostate cancer. \nMass Spectrometry MDSW intended to analyse LC-MS/MS data to be used for microorganism \nidentification and detection of antibiotic resistance. \nMDSW smartwatch app, which is intended to send alarm notifications to the user and/or health \npractitioner  when it recognises irregular heartbeats for the purpose of detecting cardiac arrhythmia. \nNote 2:  If the software drives or influences a (hardware) medical device and also has a medical \npurpose, then it is qualified as a MDSW \nMelanoma image analysis software intended to drive a near-infrared laser light scanner. \nMDSW intended to measure and transmit blood glucose levels, calculate insulin dose required and \ndrive the insulin pump to administer the calculated dosage (closed loop insulin delivery system). \nNote 3:  Software may be qualified as MDSW regardless of its location (e.g. operating in the cloud, on \na computer, on a mobile phone, or as an additional functionality on a hardware medical device). \nMDSW that is intended to operate a point of care test from a remote location.  \nNote 4:  MDSW may be intended to be used by healthcare professionals or laypersons (e.g. patients or \nother users).17, 18 \nMDSW that provides insulin dose recommendations to  a patient regardless of the method of delivery \nof the prescribed dose, whether via an insulin pump, insulin pen or insulin syringe. \n                                                 \n17 Where MDSW is intended to be used by a lay person, the manufacturer shall apply safety and performance requirements \noutlined in MDR Annex I. 22 and 23.4 (w); or IVDR Annex I. 9.4 and 20.4.2. \n18 MDSW which can be considered as an IVD for self-testing shall be considered as a device intended to be used by \nlaypersons.   \nPage 8 of 28 \n Manufacturers must ensure that all regulatory requirements for placing on the market and conformity \nassessment have been fulfilled. As set out in Article 7 of MDR and IVDR, this also entails that any claims, relating to the intended medical purpose of their MDSW are supported by clinical evidence. If \nthis is not the case, the software would not meet the requirements of the regulations and therefore may \nnot be CE marked as a medical device, nor present said claims.  \n3.3. \u2018Software  driving or influencing the use of a medical device\u2019  \nIs software intended to drive or influence the use of a (hardware)  medical device and does not  have or \nperform a medical purpose on its own , nor does it create information on its own  for one or more of the \nmedical purposes described in the definition of a medical device or an in vitro  diagnostic medical \ndevice. This software can, but is not limited to:  \na) operate, modify the state of, or control the device either through an interface (e.g., software, \nhardware) or via the operator of this device \nb)  or supply output related to the (hardware) functioning of that device \nNote:  Software that is driving or influencing the use of a medical device is covered by the medical \ndevices regulations either as a part/component of a device or as an accessory for a medical device. \n(refer to Figure 2, box 2).  \nSoftware that is intended to be used to operate a clinical chemistry analyser. \nSoftware with built-in electronic controls for IVD quality control procedures. These quality control \nprocedures are intended to provide users with assurance that the device is performing within \nspecifications. \nDecision steps for qualification of software as MDSW (Figure 1) \nDecision step 1 : if the product is software according to Section 2 (Definitions and Abbreviations) of \nthis guidance, then it may be a medical device software, proceed to decision step 2; if the product is \nnot software according to the definition of this guidance, then it is not covered by this guidance but \nmay still be covered by the Medical Devices Regulations. \nDecision step 2 : if the product is an MDR Annex XVI device, or is an accessory for a medical \ndevice19, or is software driving or influencing the use of a medical device, then it must be considered \nas part of that device in its regulatory process or independently if it is an accessory. If it is not, proceed \nto decision step 3. \nDecision step 3 : if the software does perform an action on data, or performs an action beyond storage, \narchival, communication20, simple search, lossless compression (i.e. using a compression procedure \nthat allows the exact reconstruction of the original data) then it may be a medical device software \n(Refer to section 3.1 for more guidance on these software functions) proceed to step 4. \n \nDecision step 4 : is the action for the benefit of individual patients?  \nExamples of software which are not considered as being for the benefit of individual patients are those \nwhich are intended only to aggregate population data, provide generic diagnostic or treatment \npathways (not directed to individual patients), scientific literature, medical atlases, models and \ntemplates as well as software intended only for epidemiological studies or registers. \n \nDecision step 5:  Is the software medical device software (MDSW) according to the definition of this \nguidance? \n                                                 \n19 According to Article 2(2) of the Medical Devices Regulation or In Vitro  Diagnostic Medical Devices Regulation. \n20 Communication: The flow of information from one point, known as the source, to another, the receiver; Source: IEEE \n610.10-1994.   \nPage 9 of 28 \n  \n  \n \nPage 10 of 28 \n 3.4. Qualification criteria of MDSW as an in vitro  diagnostic medical \ndevice \nMedical Device Software (MDSW) fulfilling the definition of an in vitro  diagnostic medical device \nfalls under the in vitro diagnostic medical devices Regulation (EU) 2017/746.  Provided that MDSW is \nintended specifically by its manufacturer to be used together with an in vitro diagnostic  medical device \nto enable it to be used in accordance with its in tended purpose, this MDSW falls under the scope of the \nin vitro  diagnostic medical devices regulation and shall be treated as an In Vitro  Diagnostic MDSW \n(IVD MDSW) in its own right.  \nIn cases when software is driving or influencing the use of a (hardware) device, the software should be \nconsidered as falling under the respective regulation of the driven or influenced (hardware) device.  \nSoftware that analyses and interprets the optical density delivered by an ELISA reader, line or spot \npattern of a blot.  Such software takes raw data outputs and use clinical algorithms for diagnostic \nand/or prognostic purposes, in which case it qualifies as IVD MDSW. \n \n \nDecision steps for qualification of MDSW as either a medical device or an in vitro  \ndiagnostic medical device (Figure 2) \nDecision Step 1: Does the  Medical Device Software (MDSW) provide information within the scope \nof the in vitro  diagnostic medical device definition? \nMDSW which provides information according to Re gulation (EU) 2017/746 \u2013 IVDR Article 2(2) (a) \nto (f) should qualify as In Vitro  Diagnostic Medical Device Software (IVD MDSW) \n(a) concerning a physiological or pathological process or state (by investigation of this process or \nstate); or \n(b) concerning congenital physical or mental impairments  \n(c) concerning the predisposition to a medical condition or a disease;  \n(d) to determine the safety and compatibility with potential recipients;  \n(e) to predict treatment response or reactions;  \n(f) to define or monitoring therapeutic measures. \nA MDSW which falls under the definition set out in EU Article 2 (1) of Regulation (EU) 2017/745 \u2013 \nMDR should qualify as Medical Device Software (MD MDSW). In specific, the following \nconsiderations should apply on the prov ision of information by software on: \n(g) diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease \n(h) diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability, \n(i) investigation, replacement or modification of the anatomy or of a physiological or \npathological process or state, \n(j) control or support of conception; \n(k) products specifically intended for the cleaning, disinfection or sterilization of devices as \nreferred to in Article 1(4) and Annex XVI products.  \nDecision Step 2 : Does the MDSW create information based on data obtained by in vitro  diagnostic \nmedical devices only?  \nIf the information provided is based on data obtained solely from  in vitro  diagnostic medical devices, \nthen the software is an in vitro  diagnostic medical device and is therefore an IVD MDSW. \nIf the data analysed is obtained from a combination of both in vitro  diagnostic medical devices and \nmedical devices, proceed to step 3.     \nPage 11 of 28 \n Decision Step 3 : Is the intended purpose substantially driven by data sources coming from in vitro  \ndiagnostic medical devices? If yes, then the appli cable legislation is Regulation (EU) 2017/746. If the \nintended purpose is substantially driven by data sources coming from medical devices, then the \napplicable legislation is Regulation (EU) 2017/745.  \n \nIn the condition where the intended purpose of the MDSW output data fulfils both the medical device \nand in vitro  diagnostic medical device definitions set out in the MDR and IVDR (refer to Decision \nStep 2), a weighting of the data sources based on the significance of the information21 in relation to \nfulfilling the intended purpose should be conducted to aid the manufacturer in determining which regulation to apply. \n \nAnnex II of this guidance offers some prescrip tive examples of how such a weighting may be \nperformed. \n \n \n \n                                                 \n21 A qualitative approach is intended to drive the weighting of data. The weighing aims to assess the contribution of each data \ntowards achieving the result.  \n \nPage 12 of 28 \n 4. Classification of MDSW per MDR 2017/745 \n4.1. Implementing Rules \nAll implementing rules in Annex VIII of Regulation (EU) 2017/745 shall be considered.  \nSpecial considerations on Implementing Rule 3.3 and 3.5:  \nThe first sentence of implementing rule 3.3  of Annex VIII clarifies the regime applicable to software \ndriving or influencing the use of a device:   \n\u2018Software, which drives or influences the use of a device, shall fall within the same class as the device\u2019  \nThe second sentence of implementing rule 3.3  of Annex VIII clarifies that the regime applicable to \nIndependent MDSW:  \n \u2018If software is independent of any other device, it shall be classified in its own right\u2019 \nThis rule should also be considered at least as an orientation for finding the correct (minimum) \nclassification of software which is placed on the market in combination with a (hardware) medical \ndevice. Therefore, Medical Device Software that both achieves its own intended purpose and also \ndrives or influences the use of a (hardware) device for a medical purpose is classified on its own, \nbased on the intended purpose achieved. In such a case, however, the risk class shall not be lower than \nthe risk class of the hardware medical device.  \nImplementing rule 3.5  of Annex VIII is relevant for all devices and states that  \n\u2018If several rules, or if, within the same rule, seve ral sub-rules, apply to the same device based on the \ndevice\u2019s intended purpose, the strictest rule and sub-rule resulting in higher classification will apply\u2019  \nMelanoma image analysis software intended to be used with a near-infrared laser light scanner , \nwhich is considered class IIa per Rule 10. The software \u201cdrives or influences the use of\u201d the near-\ninfrared laser light scanner as it is intended to take control of the scanner by letting it execute \nproprietary multi-exposure programs for the detection of melanoma. As such, implementing rule 3.3  \napplies. However, Rule 11 would also apply based on the intended medical purpose of the software \ne.g. cancer diagnosis. The MDSW would be classified as class III based on Rule 11 (see section \nClassification Rules) and per implementing rule 3.5  of Annex VIII. \n4.2. Classification Rules \nRules 9, 10 and 12 mainly categorise the risks related to the exchange of energy/substances between \nthe body and diagnostic or therapeutic active devices, taking into account the different healthcare \nsituations (condition of patients).  \nMDSW, in the majority of cases, does not (directly) relate to such risks. It relates to the consequences \nof indirect harm from failure to provide correct information.  \nTherefore, in line with Recital 5 of the Medical Device Regulation and international guidance from the \nIMDRF (International Medical Device Regulators Forum)22, Rule 11 was introduced into the MDR \nand is intended to address the risks related to the information provided by an active device, such as \nMDSW. Rule 11, in particular, describes and categorises the significance of the information provided \nby the active device to the healthcare decision (patient management) in combination with the healthcare situation (patient condition). \nAs software is defined as an active device, for the classification of active (hardware) devices, which \nalso includes MDSW providing information for patient management, Rules 9, 10, 11, 12, 13, 15 and \n                                                 \n22 IMDRF is a voluntary group of medical device regulators from around the world who have come together to build on the \nstrong foundational work of the Global Harmonization Task Force on Medical Devices (GHTF) and aims to accelerate international medical device regulatory harmonization and convergence.  \nPage 13 of 28 \n 22 of Annex VIII MDR 2017/ 745 should be considered. In line with implementation rule 3.5, the \nstrictest rule or sub-rule should hence apply. \nMDSW should be classified in the same way, rega rdless of the software's location or the type of \ninterconnection between the software and a (hardware) device.  \n4.2.1.  Rule 11 \u2013 Software for decisions with diagnosis or therapeutic purposes or \nsoftware intended to monitor  physiological processes  \nRule 11 states:  \nSoftware intended to provide information which is used to take decisions with diagnosis or \ntherapeutic purposes is classified as class IIa, except if such decisions have an impact that \nmay cause: \ndeath or an irreversible deterioration of a person's state of health, in which case it is in class \nIII; or \na serious deterioration of a person's state of health or a surgical intervention, in which case it \nis classified as class IIb.  \nSoftware intended to monitor physiological processes is classified as class IIa, except if it is \nintended for monitoring of vital physiological parameters, where the nature of variations of \nthose parameters is such that it could result in immediate danger to the patient, in which case \nit is classified as class IIb.  \nAll other software is classified as class I. \nThe text of Rule 11 can be divided into what are essentially three sub-rules that are applied depending \non the intended use/purpose of the MDSW: \n11a: (3 first paragraphs of Rule 11) intended to provide information which is used to take \ndecisions with diagnostic or therapeutic purposes; \n11b: (Paragraph 4 of Rule 11) intended to monitor physiological processes or parameters; \n11c: (Paragraph 5 of Rule 11) all other uses.  \nSub-rule 11a): \nThe wording \u201cintended to provide information which is used to take decisions with diagnosis or \ntherapeutic purposes\u201d describes, in very general terms, the \u201cmode of action\u201d which is characteristic of \nall MDSW.  Therefore, this sub-rule is generall y applicable to all MDSW (excluding those MDSW \nthat have no medical purpose). \nSub-rule 11a), states that MDSW (which is intende d to provide information which is used to take \ndecisions with diagnosis or therapeutic purposes) is classified as class IIa. \nThere are two exceptions from sub-rule 11a) that ar e mainly intended to apply a risk classification \nbased on the significance of the provided information and the potential impact of an (incorrect) \ndecision made using information from the MDSW.23 Accordingly, MDSW that is intended to provide \ninformation which is used to take decisions with diagnosis and therapeutic purposes, is at a higher risk \nclass where such decisions, if based on incorrect information from the MDSW, are reasonably likely to have an impact that may cause: \ni. death or an irreversible deterioration of a person's state of health, in which case it is in class III; \nii. serious deterioration of a person's state of health or surgical intervention, in which case it is \nclassified as class IIb. \n                                                 \n23 Compare IMDRF/SaMD WG/N12FINAL:2014 which states that there are two major factors that provide adequate \ndescription of the intended use of software: A. - Significance of  the information provided by the software to the healthcare \ndecision and B. - State of the healthcare situation or patient condition.   \nPage 14 of 28 \n The MDR contains several references to \u201cserious deterioration of a person\u2019s state of health\u201d and \n\u201csurgical intervention\u201d, notably in the vigilance or clinical investigation context. Further horizontal guidance could be provided in the future and will be available at: \nhttps://ec.europa.eu/growth/sectors/medical-devices/new-regulations/guidance_en    \nRule 11 was also introduced to mirror the regulatory guidance developed at international level and \nnotably in the context of the International Medi cal Device Regulators Forum (IMDRF). The IMDRF \nframework for risk categorisation of software as a medical device (SaMD) (\u201cIMDRF Risk \nFramework\u201d) categorises the risk of software based on the combination of the significance of the \ninformation provided by the software to the healthcare decision and the healthcare situation or patient condition. IMDRF also developed a table for assisting operators in identifying the appropriate risk \ncategory for their own product. \nSuch a table could provide operators placing MDSW on the EU market with some useful indications \non the risk class applicable to their products as a result of the application of Rule 11 of the MDR. For \nthis purpose, a table is provided in Annex III to this document which lists the IMDRF risk categories and the possible corresponding MDR risk classes accor ding to Rule 11 of the MDR. It must be noted \nthat this table does not take into account MDSW which is Class I.   \nSub-rule 11b): \nMDSW that is intended to monitor physiological processes will, under most circumstances, provide \n\u201cinformation which is used to take decisions with diagnosis or therapeutic purposes and hence fall under sub-rule 11a. Sub-rule 11b) should therefore be considered as a specific rule for MDSW \nintended only for monitoring purposes. Sub-rule 11b) was introduced to ensure that MDSW which has \nthe same intended purpose as (hardware) devices which would fall under rule 10, third indent, are in \nthe same risk class.  \nHowever, this sub rule applies to MDSW intended to be used for monitoring any/all physiological \nprocesses and not just vital physiological processes (equivalent to rule 10, third indent).  \nVital physiological processes and parameters include, for example, respiration, heart rate, cerebral \nfunctions, blood gases, blood pressure and body temperature. \nSub-rule 11c): \nSub-rule 11c) implies that all other MDSW is classified as class I. \n4.2.2.  Rule 12 \u2013 Active devices intended to administer and/or remove \nsubstances \nAs software devices cannot physically administer and/or remove substances, please refer to the \nimplementation rule 3.3 of Annex VIII for MDSW covered by this rule.  \n4.2.3.  Rule 13 \u2013 All other active devices \nTaking into consideration all implementing and classification rules applicable to active devices, if no \nother rule applies, all other active devices are class I. 24 \n4.2.4.  Rule 15 - Devices used  for contraception \nRule 15 applies to devices used for contraception or prevention of the transmission of sexually \ntransmitted diseases. Software used for contraception will be classified as class IIb. \n                                                 \n24 Specific implementation or classification rules for active Annex XVI devices (which might also include software) are \nexpected to be provided together with the relevant Common Specifications for those devices.   \nPage 15 of 28 \n 4.2.5.  Rule 22 \u2013 Closed loop systems \nActive therapeutic devices with an integrated or incorporated diagnostic function which significantly \ndetermines the patient management by the device, such as closed loop systems or automated external \ndefibrillators, are classified as class III.  \nSee also implementing rule 3.3 fo r MDSW covered by this rule. \nFurther horizontal Guidance on the application of MD classification and implementing rules can be \nfound at https://ec.europa.eu/growth/sectors/medical-devices/new-regulations/guidance_en . This is \nexpected to provide useful orientation in relation to the application of non-software specific \nclassification rules.   \n5. Classification and implementing rules per IVDR 2017/746 \n5.1. Implementing Rules: \nAll implementing rules in Annex VIII of Regulation (EU) 2017/746 shall be considered.  \nSpecial considerations on Implementing Rule 1.4 and 1.9:  \nImplementing rule 1.4  is only applicable for software which drives or influences the use of an in vitro  \ndiagnostic medical device. This rule should also be considered at least as an orientation for finding the \nright (minimum) classification of software which is placed on the market in combination with a \n(hardware) medical device.  \nAccording to the second sentence of implementing rule 1.4 , if the software is independent of any other \ndevice, it shall be classified in its own right.  \nExamples for applying this implementing rule under the in vitro  diagnostic medical devices regulation:  \n\u0081 Software that is exclusively intended to drive or influence the use of an instrument intended by \nthe manufacturer specifically to be used for in vitro diagnostic procedures is classified in the \nsame class as the instrument. \n\u0081 A software that is intended to operate (driving) a C-reactive protein (CRP) measuring \nanalyser from a remote location is classified in the same class as the analyser i.e. if the \nanalyser is a classified as class A then the software operating the analyser falls into Class A. \n\u0081 MDSW that integrates genotype of multiple genes to predict risk a disease or medical \ncondition developing or recurring; this is an independent IVD MDSW and is classified on its \nown.  \nImplementing rule 1.9  states that if several classification rules apply to the same device based on the \ndevices\u2019 intended purpose, the rule resulting in higher classification will apply. To classify In Vitro \nDiagnostic Medical Device Software (IVD MDSW) which is independent of any other device, see the \nMDCG Guidance on Classification of IVDs when available at \nhttps://ec.europa.eu/growth/sectors/medical-devices/new-regulations/guidance_en . \n5.2. Classification Rules:  \nIn determining the proper classification of MDSW  under the IVDR, the manufacturer shall consider \nall classification and implementing rules of Annex VIII of the IVD Regulation (EU) 2017/746. \nAs spelled out by Implementing Rule 1.1 of Annex VIII of Regulation (EU) 2017/746, the application \nof the classification rules shall be governed by the intended purpose of the MDSW.   \nPage 16 of 28 \n Guidance on the application of the IVD classification and implementing rules can be found at \nhttps://ec.europa.eu/growth/sectors/medical-devices/new-regulations/guidance_en25 \nExamples for the classification of MDSW under the IVDR: \n\u0081 Software intended to be installed on a fully automated enzyme-linked immunosorbent assay \n(ELISA) analyser, and intended to determine the Human HbA1c concentration in serum from \nthe results obtained with a Human HbA1c ELISA, intended to screen for and diagnose \ndiabetes and monitor diabetic patients, should be in class C per Rule 3(k). \n\u0081 Software within a PAP stain automated cervical cytology screening system, intended to \nclassify the PAP cervical smear as either normal or suspicious, should be in class C per Rule \n3(h). \n\u0081 Software for the interpretatio n of automated readings of line immunoassay for the \nconfirmation and determination of antibodie s to HIV-1, HIV-1 group O and HIV-2 in human \nserum and plasma, should be in class D per Rule 1. \n\u0081 Software that uses maternal parameters such as age, concentration of serum markers and \ninformation obtained through foetal ultrasound ex amination for evaluating the risk of trisomy \n21, should be in class C per Rule 3(l). \nClassification examples in Annex IV are provided for guidance purposes and aim to illustrate how \na particular rule may be applied to a device. The indicated classification in the example is not a confirmation of the final classification of the device, as other rules must also be considered.  \n6. Considerations on placing on the market and conformity \nassessment of MDSW \nThe type of interconnection between the MDSW and the device (e.g. embedded systems, wires, Wi-Fi, \nBluetooth) does not affect the qualification of the software as a device under the MDR and IVDR (e.g. \nwhether the software is incorporated in a device or is at a different location). However, MDSW can be \nplaced on the market in two different ways: as a medical device or in-vitro  diagnostic medical device \nin its own right or as an integral component or part of a hardware device. \n6.1.  Option 1: as a medical d evice in its own right \nMDSW may be placed on the market or put into service in its own right. \n\u0081 MDSW intended to be installed on a fully aut omated enzyme-linked immunosorbent assay \n(ELISA) analyser, and intended to determine the Human HbA1c concentration in serum from \nthe results obtained with a Human HbA1c ELISA. \n\u0081 MDSW app that provides a 10-year risk of cardiovascular disease from data input by a lay \nuser. \n\u0081 MDSW app that calculates anticoagulant dosage fo r patients in oral anticoagulant therapy, \nfrom INR test results input by IVD instrume nts and other manually entered patient data. \n\u0081 MDSW app that analyses digital images of stained HEp-2 cell substrates from a microscope, \nfor detecting antinuclear antibody (ANA) patterns to guide confirmatory testing useful in elucidating a specific clinical diagnosis or prognosis. \nConformity assessment:  \n                                                 \n25 Please note that at the time of the adoption of this document, the referenced Guidance on the application of IVDR \nclassification and implementing rules was under finalisation.   \nPage 17 of 28 \n MDSW placed on the market as a device or put into service in its own right shall undergo an \nappropriate regulatory process that shall take into consideration the qualification, classification and intended purpose of the MDSW. \n6.2. Option 2: as an integral component/part of a device \nMDSW may be placed on the market or put into service as an integral component/part of a device.  \n\u0081 MDSW contained within a blood gas analyser that enables a user to run tests on the \ninstrument. \n\u0081 MDSW that is part of a handheld hardware device intended for near-patient testing (POCT: \npoint of care testing) for the determinat ion of the blood glucose concentration. \n\u0081 A fully automated enzyme-linked immunosorb ent assay (ELISA) analyser, composed of \nhardware and MDSW, intended to determine the Human HbA1c concentration in serum from \nthe results obtained with a Human HbA1c ELISA. \n\u0081 MDSW that is part of a pulse oximeter intended to digitally filter the noise from low perfusion \nperformance and motion artefacts, to calculate the ratio of red light/infrared light and to use a \nlookup table based on Beer-Lambert law to convert the ratio into the oxygen saturation in a person\u2019s blood (SpO2). \nConformity assessment: \nMDSW that is placed on the market or put into se rvice solely as an integral component/part of a \n(hardware) device may not have to undergo its own regulatory process.\n26 In this case, the MDSW shall \nbe assessed through the regulatory process applied to the device as a whole, as it is placed on the \nmarket. \nApplying the classification rules to these hardware devices, which is de-facto  a combination of the \nhardware device and the MDSW, requires careful consideration of the intended purpose of the \nMDSW. This must also be analysed when later changes to the MDSW are done. \nNote:  MDSW could be independent under both scenarios described in 6.1 and 6.2, despite the \npresentation in which it is placed on the market. \n7. Modules \nSome medical device software may be segregated into a number of applications where each of these \napplications is correlated with a module. Some of  these modules have a medical purpose, some not. \nSuch modules may be intended to cover many needs, e.g.: \n\u0081 Collect and maintain administrative patient data; \n\u0081 Keep on file the medical history of the patient; \n\u0081 Invoicing and other accounting functions; \n\u0081 Provide a link to the social security system for reimbursement; \n\u0081 Provide a link to drug prescription systems (with possible link to drug dispensing outlets); \n\u0081 Provide expert system assistance for medical decision making (e.g. radiotherapy dose \nplanner). \n                                                 \n26 Note: MDSW that is intended specifically to replace a part or com ponent of a device and that significantly changes the \nperformance or safety characteristics or the intended purpose of the device shall be considered to be a device and shall meet the requirements laid down in this Regulation (see Article 23.2 (2)).\n  \nPage 18 of 28 \n This raises the issue as to whether the whole product can be CE marked when not all applications have \na medical purpose.   \nComputer programmes used in healthcare can have applications which consist of both medical device \nand non-medical device modules. \n \nThe modules which are subject to the Medical Devices Regulations (figure 1 and 2) must comply with \nthe requirements of the medical device regulations and must carry the CE marking. The non-medical \ndevice modules are not subject to the requirements for medical devices. It is the obligation of the manufacturer to identify the boundaries and the interfaces of the different modules.  \n \nThe boundaries of the modules which are subject to the medical device regulations should be clearly \nidentified by the manufacturer based on the intended use. \nIf the modules which are subject to the medical device regulations are intended for use in combination \nwith other modules of the whole software stru cture, other devices or equipment, the whole \ncombination, including the connection system, must be safe and must not impair the specified \nperformances of the modules which are subject to the medical device regulations.\n27 \n8. Consideration of changes to an MDSW \nManufacturers shall evaluate the potential impact of any changes to the function, intended use, \nessential design, and manufacturing characteristics on the software\u2019s qualification as MDSW and its \nclassification (including the classification of the combination of the MDSW with another medical \ndevice). \nIt is to be noted that a change to or the addition of functionality to a software may lead it to be \nqualified as MDSW, or a revision of the classificati on of the MDSW. Similarly, a module that is added \nto a software might be qualified as a MDSW on its own. \nWhen determining the risk class of a combinati on of a modified MDSW and a medical device, the \nintended purpose and functionality of that (new) combination must be considered. \nNote:  For all MDSW, the manufacturer shall ensure safety and performance throughout the lifecycle \nof the software, through a continuous process of clinical and/or performance evaluation and risk management.  \n \n \n \n9. Annex I: Illustrative examples of qualification of software \nused in the healthcare environment \nSoftware for a medical purpose is rapidly evolving. Thus, the list of examples provided below is not \nexhaustive. The examples have been drafted in light of today\u2019s state of the art, in order to give the reader a better understanding of the application of the principles set out in the guideline. \nThe Manual on borderline and classification in the Community regulatory framework for medical \ndevices contains many examples related to qualification of software and apps, under the current \n                                                 \n27 i.e. general safety and performance requirements 14.1 of EU MDR 2017/745 and 13.1 of EU IVDR 2017/746   \nPage 19 of 28 \n Directives28.  The Manual is currently under revision for adaptation to MDRs. In light of the \ntechnological progress, further examples will be regularly published in both the Manual and in this guidance.  \n \na) Hospital Information Systems \nHospital Information Systems mean, in this context, systems that support the process of patient \nmanagement. Typically they are intended for patient admission, for scheduling patient appointments, \nfor insurance and billing purposes. \nThese Hospital Information Systems are not qualified as medical devices. However, they may be used \nwith additional modules, as described hereafter. These modules might be qualified in their own right as medical devices. \n \nb) Decision Support Software \nIn general, these are computer based tools which combine general medical information databases and \nalgorithms with patient-specific data. They are intended to provide healthcare professionals and/or \nusers with recommendations for diagnosis, prognosis, monitoring and treatment of individual patients. \n \nBased on Figure 1, they are qualified as medical devices.  \n\u0081 Radiotherapy treatment planning systems\n29 are intended to calculate the dosage of ionizing \nirradiation to be applied to a specific patient . They are considered to control, monitor or \ndirectly influence the source of ionizing radiation and are qualified as medical devices. \n \n\u0081 Drug planning systems (e.g. chemotherapy) are intended to calculate the drug dosage to be \nadministered to a specific patient and therefore are qualified as medical devices. \n \n\u0081 Computer Aided Detection systems are intended to provide information that may suggest or \nexclude medical conditions are qualified as medical devices (MDSW). For example, such \nsystems would be able to automatically analyse x-ray images or interpret ECGs. \n \nc) Information Systems \nInformation Systems that are intended only to transfer, store, convert, format, archive data are not \nqualified as medical devices in themselves. However, they may be used with additional modules which maybe qualified in their own right as medical devices (MDSW). \nc.1.) Electronic Patient Record Systems \nElectronic patient record systems are intended to store and transfer electronic patient records. They \narchive all kinds of documents and data related to a specific patient. The electronic patient records \nshould not be qualified as a medical device, i.e. an electronic patient record that simply replaces a patient\u2019s paper file does not meet the definition of a medical device. The modules used with electronic \npatient record system modules that might be qualified in their own right as medical devices (MDSW) \nare for example: \n\u0081 An image viewer with functionality for diagnosis based on digital images; \n\u0081 A medication module \n                                                 \n28 http://ec.europa.eu/DocsRoom/documents/12867/a ttachments/1/translations/en/renditions/native   \n29 See EN 62083 \u201cRequirements for the safety and radiotherapy treatment planning systems\u201d   \nPage 20 of 28 \n c.1.1.) Clinical Information Systems \u2013 CIS / Patient Data Manag ement Systems \u2013 PDMS \nA CIS/PDMS is a software-based system primarily intended to store and transfer patient information \ngenerated in association with the patient\u2019s intensive care treatment (e.g. intensive care units).  \nUsually the system contains information such as patient identification, vital intensive care parameters and other documented clinical observations.  \nThese CIS/PDMS are not qualified as medical devices. \nModules that are intended to provide additional information that contributes to diagnosis, therapy and \nfollow-up (e.g. generate alarms) are qualified as medical devices. \nc.1.2.) Pre-hospital Electrocardiograph (ECG) System \nA system for managing pre-hospital ECG is a software-based system intended for ambulance services \nto store and transfer information from patients to a doctor at remote location. Usually the system \ncontains information about patient identification, vital parameters and other documented clinical \nobservations. These Pre-hospital Electrocardiograph (ECG) Systems are not qualified as medical \ndevices.  \nModules that create and provide new patient treatment information to the paramedics or to the doctor \nat a remote location to start the patient\u2019s treatment while the patient is being transported are qualified \nas medical devices.   \n \nc.1.3.) Picture Archive Communication System (PACS) \nThe Manual on Borderline and Classification in th e Community Regulatory Framework for Medical \nDevices addresses the qualification of PACS.\n30 The transposition of this Directive Guidance to the \nRegulations is currently underway and will be published at \nhttps://ec.europa.eu/growth/sectors/medical-devices/new-regulations/guidance_en  \nd) Communication Systems \nThe healthcare sector uses communication systems (e.g. email systems, mobile telecommunication \nsystems, video communication systems, paging, etc.) to transfer electronic information. Different \ntypes of messages are sent such as prescription, referrals, images, patient records, etc. \nMost of the communication systems handle types of messages other than medical information. This communication system is intended for general purpos es, and is used for transferring both medical and \nnon-medical information. \nCommunication systems are normally based on software for general purposes, and do not fall within \nthe definition of a medical device. \nCommunication system modules might be used with other modules that might be qualified in their own right as medical devices (MDSW). \n \nA software module generating alarms based on th e monitoring and analysis of patient specific \nphysiological parameters is qualified as a medical device (MDSW). \n \nd.1) Telemedicine systems \nTelemedicine Systems are intended to allow monitoring and/or delivery of healthcare to patients at \nlocations remote from where the healthcare professional is located. \n                                                 \n30 https://ec.europa.eu/docsroom/documents/35582/attachments/1/translations/en/renditions/native   \nPage 21 of 28 \n d.1.1.) Telesurgery \nTelesurgery is intended to conduct a surgical procedure from a remote location. Virtual reality \ntechnology may be used to support a remote surgeon to control a surgical robot performing the \nsurgical procedure. Telesurgery systems should be qualified as medical devices according to Figure 2 of this document.  \nRemote control software used in combination with telesurgery robots is a software that drives or \ninfluences the use of a medical device. Communication modules themselves are not medical devices. \nOther modules that are intended to influence the su rgery procedure are qualified as medical devices \n(MDSW). \ne) Web systems for monitoring of data \nA web system for the monitoring of clinical data typically interacts with a medical device (e.g. \nimplanted devices or homecare devices), and uses a transmitter to send the information over the \ninternet, a landline telephone or a mobile network. \nThe information is collected and stored on a web server usually run by an external party who is \ngenerally the manufacturer of the system. The information can be reached by authorized health \nprofessionals or the patient through an internet connection. \n\u0081 Monitoring of performance of medical devices: \nModules that are intended to monitor the medical performance of medical devices fall under \nthe medical device regulations. \nThis includes the clinical performance and failures that could affect medical performance of the device. One example of such a product is a web system for monitoring of active implants \nsuch as pacemakers or Intra Cardiac Defibrillators (ICDs). \n \n\u0081 Monitoring of non-medical performance of medical devices \nModules that are intended to perform administrative monitoring of non-medical performance \nof medical devices do not necessarily fall under the scope of the medical devices regulations. \nSoftware for the monitoring of medical devices in hospital systems for the purpose of \nmaintenance and repair.  \nf) In vitro  diagnostic medical device software \n \nf.1.) Laboratory Information Systems (LIS) and Work Area Managers (WAM) \nLaboratory Information System (LIS) and Work Area Managers (WAM) mean, in this context, \nsystems that support the process from patient sample to patient result. Typically, they have pre-\nanalytical functions for ordering, sorting and distribution of test samples. The main task is the management and validation of incoming information obtained from in vitro  \ndiagnostic medical device analysers connected to the system, such as calibration, quality control, \nproduct expiry and feedback (e.g. retesting of samples needed) through interconnections with various \nanalytical instruments (technical and clinical validation). \nFinally the post-analytical process allows communication of laboratory results, statistics and optional reporting to external databases. \nThe software normally supports the following functions: \n\u0081 Ordering of laboratory tests, samples with labels and sorting; \n\u0081 Technical and clinical validation, connection to analytic instruments; \n\u0081 Laboratory results and reports on paper, fax or electronic records that can be directly returned \nto e.g. the ordering clinic\u2019s patient record; \n\u0081 Analytical instruments can be interfaced with Hospital Information Systems (HIS), Electronic \nPatient Record Systems, Infectious control databases, etc.  \nPage 22 of 28 \n Note : software intended to modify the representation of available in vitro  diagnostic medical device \nresults is not considered an in vitro  diagnostic medical device, e.g. basic operations of arithmetic (e.g. \nmean, conversion of units) and/or plotting of results in function of time, and/or a comparison of the \nresult to the limits of acceptance set by the user. \nThe results are available, readable and understandable without the intervention of the software. \nLaboratory Information Systems (LIS) and Work Area Managers (WAM) are not qualified as \nmedical devices in themselves.  However, they may be used with additional modules. These modules \nmight be qualified in their own right as medical devices. \nA module whose intended purpose is to assess the criticality of tests required and to perform \nautomatic reprioritisation of the order based on patient data is qualified as a MDSW.  \nf.2.) Expert system \nMDSW which is intended to provide information within the scope of the in vitro diagnostic medical \ndevices definition by capturing and analysing together one or multiple results obtained for one patient \nby means of in vitro  examination of body samples (possibly combined with information from medical \ndevices and non-medical devices). \n\u0081 MDSW that integrates genotype of multiple genes to predict risk a disease or medical \ncondition developing or recurring; \n\u0081 MDSW that uses an algorithm to characterise viral resistances to various drugs, based on a \nnucleotide sequence generated by genotyping assays. This software serves to generate new information (virus resistance profile) from avai lable information on the genotype of the virus; \n\u0081 MDSW intended to be used in microbiology for the identification of clinical isolates and/or the \ndetection of antimicrobial resistances. \nRefer to Figure 2 of this guidance if data is obtained from both in vitro  diagnostic medical devices and \nmedical devices.  \nf.3.) Interpretation of raw data \nIn the case where MDSW is necessary to render raw data, readable for the user, obtained from an in \nvitro  diagnostic medical device by means of in vitro  examination of body samples, this MDSW is to \nbe considered driving or influencing the use of the in vitro  diagnostic medical device when it is \nspecifically intended to be used together with this in vitro  diagnostic medical device to enable it to be \nused in accordance with its intended purpose. \n \nMDSW intended for the analysis and interpretatio n of enzyme-linked immunosorbent assay (ELISA) \nreader optical density results, line patterns or spot patterns of a blot. \n \nf.4.) Home care monitoring, wired or mobile \nSoftware intended for archiving patient result s or for transferring results obtained from in vitro  \ndiagnostic medical devices from the home environment to the healthcare provider is not an in vitro  \ndiagnostic medical device. The results are available, readable and understandable by the user without \nthe intervention of the software. \n \nf.5.) Image Management System (IMS) \nAn IMS is a software-based system primarily intended to be networked with digital pathology \nsystems, e.g., whole slide scanners, scanning microscopes, as well as LIS. It does not contain controls \nfor the direct operation of the digital pathology syst ems, and is intended to access, display, annotate, \nmanage, store, archive and share collections of digitised patient images. IMS may be configured to  \nPage 23 of 28 \n provide limited or extensive capabilities to further visualise or analyse patient images acquired from \nnetworked digital pathology systems. \n \nAn IMS only used for viewing, archiving and transmitting images are not considered medical devices \nin themselves. However, these IMS may be used with additional modules that might be qualified in \ntheir own right as medical devices (MDSW). \n \nIMS that incorporate functions to support post-processing of images for diagnostics purposes, e.g., \nimage processing functions which alter image data or complex quantitative functions to aid in diagnosis, are qualified as MDSW. \n   \nPage 24 of 28 \n 10. Annex II - Qualification examples of Medical Device \nSoftware (MDSW) according to Figures 1 and 2 \nFigure 1 - Example 1: \nA software module which runs on an in vitro  diagnostic medical device instrument and tracks how the \nlaboratory is performing in real-time on key operational metrics such as test volumes, turnaround \ntimes, pending tests, and quality control. Its intent is to improve a laboratory\u2019s operations by providing \nreal-time monitoring of performance metrics that can drive change management and continuous improvement initiatives within the lab. The software is configurable so that customers can choose the \nmetrics on which they would like to focus. \n \nQualification: Step 1 is concluded with a \u201cyes\u201d as the software is a product which uses a set of \ninstructions (or algorithm) to process input data and create output data.  Step 2 determines that the software is not an MDR Annex XVI device, nor is it an accessory for a medical device, nor a software \ndriving or influencing the use of a medical device. Step 3 is answered \u201cyes\u201d since the software is \ndoing more than storage, archival, communication or simple search of information. Step 4 is answered \n\u201cno\u201d as the software does not perform this action for the benefit of individual patients.  The conclusion \nis that the software does not fall under the Medical Devices Regulations.  This is appropriate since the software is intended to be a Laboratory Information Systems (LIS), which is not considered a medical \ndevice. \n \nFigure 2 - Example 2:  \nMDSW intended to generate a risk score in order to trigger care processes to help reduce ICU \ntransfers, readmissions, adverse events and length of stay. The risk score by default includes \nrespiratory rate, heart rate, blood pressure and Sp O2, but a user can configure it to include other \nparameters, including in vitro  diagnostic medical device results. \n \nQualification:  In decision Step 1, the MDSW can be understood  to meet criteria (a), (f) and (h), it is \ntherefore answered \u201cyes\u201d. Step 2 is answered with a \u201cNo\u201d as an in vitr o diagnostic medical device \nresult may be included in the in the calculation. Step 3 directs the significance of the medical device \nderived information as driving the intended purpose, re sulting in the qualification of the software as an \nMD MDSW (as the data received from the in vitro  diagnostic medical device is not deemed decisive \nfor the overall calculation result (output) achieved by the MDSW) \n \nFigure 2 - Example 3: \nA MDSW algorithm intended to provide information on the statistical predisposition for Down \nsyndrome (Trisomy 21) and Edwards syndrome (Trisomy 18) in the first and second trimesters of \npregnancy. 31 The MDSW analyses input data from various in vitro  diagnostic medical device assays32 \nas well as, ultrasound measurements of the nasal bone or neck fold.  The MDSW  provides \nclinicians/obstetricians with a risk factor score for a foetus\u2019s likelihood of having genetic mutations in \nthe first or second trimester of pregnancy.  The risk score suggests whether or not additional diagnostic testing is needed to confirm the genetic mutations of Trisomy 21, Trisomy 18.\n33 \n \nQualification: Step 1 can be answered \u201cyes\u201d as the software bears a medical purpose and fulfils the \ndefinition of MDSW. The MDSW meets criteria (c) as it provides information according to the in vitro  \n                                                 \n31 The software can also detect neural tube defects (NTD) in the second trimester as well as the risk for Patau\u2019s syndrome \n(Trisomy 13). \n32 AFP (LKAP, L2KAP), Unconjugated Estriol (LKUE3, L2KUE3), hCG (LKCG, L2KCG), free \u03b2-hCG (LKFB, L2KFB), \nPAPP A (LKPC, L2KPC) \n33 or neural tube defects and Trisomy 13   \nPage 25 of 28 \n diagnostic medical devices definition. Decision step 2 is answered \u201cno\u201d as an imaging measurement is \nincluded in the calculation. Step 3 is answered \u201cyes\u201d as the intended purpose is substantially driven by in vitro  diagnostic medical device data resulting in the qualification of the software as an IVD MDSW \n(as the data received from the in vitro  diagnostic medical devices (markers) are deemed decisive for \nthe overall calculation result (output) achieved by the MDSW). \n \nFigure 2- Example 4:  \nA bioinformatics MDSW intended to analyse digi tal Next Generation Sequencing (NGS) raw data \ncoming from sequenced patient\u2019s cancer genomes. It allows the detection and visualisation of somatic genome alterations (such as substitutions, small insertions and deletions (indels), copy number \nalterations, and genomic rearrangements) across a selected number of genes. Additionally, it is also \ncapable of determining genomic signatures* (such as microsatellite instability [MSI] and/or tumour \nmutational burden [TMB]). The types of somatic genome alterations and genomic signatures detected \ndepend on the test chosen.  The MDSW assists the user in identifying and visualising genomic alterations and is intended to identify somatic genome alterations to support diagnosis and treatment \ndecisions.   \n \nQualification: Decision step 1 is concluded with a \u201cyes\u201d as the MDSW is intended for analysing \ncongenital data to provide information on the predisposition to a medical condition or disease, thus meeting criteria (b) and (c) laid out in the decision step. As the MDSW processes data coming only \nfrom in vitro  diagnostic medical devices into the calculation, then the software is qualified as an IVD \nMDSW according to Step 2.  \n \n \n   \nPage 26 of 28 \n 11. Annex III - Usability of the IMDRF risk classification \nframework in the context of the MDR 34 \nThe table below, which is intended for illustrative purposes only, may provide operators placing \nMDSW on the EU market with some useful indicative orientation on the risk class applicable to their \nproducts as a result of the application of Rule 11 a of the MDR.  \nNote:  MDR 2017/745 Sub-rule 11(a), point i., referr ing above to MDR class III, aligns with IMDRF \nrisk category IV . Sub-rule 11(a), point ii.,, referring above to MDR class IIb, aligns with IMDRF risk \ncategory III  products mentioned in section 7.2 of the mentioned IMDRF document. The IMDRF risk \ncategory II and IMDRF risk category I products are classified as MDR class IIa as per Rule 11. \nThis table does not take into account MDSW which is Class I.   \n \n  Significance of Information provided by the \nMDSW to a healthcare situation related to \ndiagnosis/therapy  State of Healthcare  \nsituation or patient condition   High \nTreat or  \ndiagnose  \n~ IMDRF 5.1.1  Medium  \nDrives clinical \nmanagement  \n~ IMDRF 5.1.2  Low \nInforms clinical \nmanagement  \n(everything else)  \nCritical situation \nor patient \ncondition  \n~ IMDRF 5.2.1  Class III \nCategory IV.i Class IIb \nCategory III.i Class IIa \nCategory II.i \nSerious situation \nor patient \ncondition  \n~ IMDRF 5.2.2 Class IIb \nCategory III.ii Class IIa \nCategory II.ii Class IIa \nCategory I.ii \nNon-serious \nsituation or \npatient condition  \n(everything else) Class IIa \nCategory II.iii Class IIa \nCategory I.iii Class IIa \nCategory I.i \nTable 1: Classification Guidance on Rule 11 \n \n \n \n                                                 \n34 Annex III and IV are not relevant for IVD MDSW. See sec tion 4.2 in order to classify IVD MDSW. MDCG Guidance on \nClassification of IVDs should also be considered.   \nPage 27 of 28 \n 12. Annex IV \u2013 Classification examples  \nThe examples are provided for guidance purposes only, to illustrate how a particular rule may be \napplied to a device. The indicated classification in  the example is not a confirmation of the final \nclassification of the device, as other rules might also be considered.  \nMoreover, the proposed classification reflects the specific intended purpose, or the healthcare context \nor situation, in which the device is used as described in the example itself. Any change to the intended \npurpose or the healthcare context/situation in which that same device is used might result in a different risk class. \n\u0081 MDSW intended to  perform diagnosis by means of image analysis for making treatment \ndecisions in patients with acute stroke should be classified as class III  under Rule 11(a)  \n- IMDRF Risk Category IV.i as the healthcare situation (stroke) is critical and the \nsignificance of the information is \u201ctreat or diagnose\u201d.   \n\u0081 Cognitive therapy MDSW that includes a diagnostic function which is intended to  feed back \nto the software to determine follow-up therapy , e.g. software adapts treatment of depression \nbased on diagnostic feedback, should be in class III per Rule 22 . When a specialist \ndetermines the necessary cognitive therapy base d on the outcome provided by the MDSW, the \nMDSW would be classified as class IIa per Rule 11(a).  \n- IMDRF Risk Category II.ii as the healthcare situation is serious and the significance \nof the information is to \u201cdrive clinical management\u201d. \n\u0081 Medical devices including MDSW intended to be used for continuous surveillance of vital \nphysiological processes in anaesthesia, intensive care or emergency care should be classified as class IIb per (Rule 11(b)) . \n\u0081 Medical devices, including MDSW intended to monitor physiological processes that are not \nconsidered to be vital, and devices intended to be used to obtain readings of vital physiological signals in routine check-ups incl uding monitoring at home should be classified \nas class IIa (Rule 11(b)).  \n\u0081 A mobile app intended to analyse a user\u2019s he artbeat, detect abnormalities and inform a \nphysician accordingly should be classified as class IIb per Rule 11(a) , if the information \nprovided by the software is intended to guide the physician in the diagnosis.  \n- IMDRF Risk Category III.i as the information drives clinical management. \n\u0081 Diagnostic MDSW intended for scoring depression based on inputted data on a patient\u2019s \nsymptoms (e.g. mood, anxiety) should be classified as class IIb under Rule 11(a) ,  \n- (IMDRF  Risk Category III.ii)  as the healthcare situation (depression) is serious and \nthe significance of the information is \u201cdiagnosis\u201d). \n\u0081 Ambulatory respiratory ventilation systems MD SW intended for long-term use (e.g. at home) \nthat alert the user/operator to any disconnection or deviation to the programmed respiratory \nvolume should be classified as class IIb per Rule 9 .  \n\u0081 Active devices, such as electronic thermometers and stethoscopes, which include MDSW \nintended for direct diagnosis may be classified as class IIa per Rule 10 , third indent since \nbody temperature and heart rate are considered decisive information for diagnosis \n(implementing rule 3.7), where the nature of the variations of these parameters would not \nresult in immediate danger to the patient.  \n\u0081 MDSW intended to rank therapeutic suggestions for a health care professional based on \npatient history, imaging test results, and patient characteristics, for example, MDSW that lists and ranks all available chemotherapy options for BRCA-positive individuals, should be \nclassified as class IIa per Rule 11(a)    \nPage 28 of 28 \n - IMDRF Risk Category II.i as it informs clinical management for cancer, a critical \ndisease. \n\u0081 MDSW app intended to support conception by calculating the user\u2019s fertility status based on a \nvalidated statistical algorithm. The user inputs health data including basal body temperature (BBT) and menstruation days to track and predict ovulation. The fertility status of the current \nday is reflected by one of three indicator lights: red (fertile), green (infertile) or yellow \n(learning phase/cycle fluctuation). This MDSW app should be classified as class I per Rule \n11c."}, {"title": "md_mfr_factsheet.pdf.txt", "text": "Factsheet for  \nManufacturers  \nof Medical Devices\nWhat you need to know!MEDICAL DEVICES  CHANGE OF LEGISLATION\nThis Factsheet is aimed at manufacturers of medical devices. \nFor a general overview of the impact of the In-Vitro   Medical \nDevices Regulation (IVDR) on manufacturers see the Factsheet \nfor manufacturers of in-vitro diagnostic medical devices. Refer -\nences to  Annexes and Articles in this factsheet refer to the MDR \n(2017/745/EU).\nThe new Medical Devices Regulation \n(2017/745/EU) (MDR) and the In-vitro \nDiagnostic Medical Devices Regulation \n(2017/746/EU) (IVDR) bring EU legislation \ninto line with technical advances, chang -\nes in medical  science, and progress in law \nmaking.\nThe new Regulations will create a robust, \ntransparent, and sustainable regulatory \nframework, recognised internationally, that \nimproves clinical safety and creates fair \n market access for manufacturers.\nIn contrast to Directives, Regulations do \nnot need to be transposed into national \nlaw. The MDR and the IVDR will therefore \nreduce the risks of discrepancies in inter -\npretation across the EU market.\nTransitional periods are planned to smooth \nthe application of the new Regulations. \nHowever, you should bear in mind that con -\nsultants, in-house professionals, and Notified \nBodies will all get busier as the deadline \ndraws closer. \nAct now to be ready on time!       Medical Devices Regulation  \n   (MDR) background\nThe MDR will replace the existing Medical Devices Directive (93/42/EEC) \n(MDD) and the Active Implantable Medical Devices Directive (90/385/EEC) \n(AIMDD). The MDR was published in May 2017, marking the start of a \nthree-year period of transition from the MDD and the AIMDD.\nDuring the transitional period the MDR will come into force gradually, start -\ning with the provisions related to the designation of Notified Bodies and \nthe ability of manufacturers to apply for new certificates under the MDR.\nThe transitional period will end on 26 May 2020, the \u201cDate of Application\u201d \n(DoA) of the Regulation. From that date the MDR will apply fully.\n1\nInternal market, \nIndustry,  \nEntrepreneurship  \nand SMEs\nRef. Ares(2018)3873669 - 20/07/20182To avoid market disruption and allow a smooth transition from \nthe Directives to the Regulation, several transitional provisions \nare in place (Article 120). Some devices with certificates issued \nunder the Directives (AIMDD/MDD certificates) may continue to \nbe placed on the market until 27 May 20241, and made avail -\nable until 27 May 20252 .\nDuring the transition phase, products certified under the Direc -\ntives and products certified under the Regulation will coexist on \nthe market. Both will have equal status under the law, and no \ndiscrimination in public tenders may take place.\n   What has changed?  \nIn terms of their impacts on manufacturers and products, the \nDirectives and the MDR largely share the same basic regulatory \nrequirements. No existing requirements have been removed, but \nthe MDR adds new requirements.\nCompared to the current Directives, the MDR places more em -\nphasis on a life-cycle approach to safety, backed up by clinical \ndata.\nThe MDR brings more stringent requirements for the designation \nof Notified Bodies, with increased control and monitoring by the \nnational competent authorities and the Commission.\nThe MDR reclassifies certain devices and has a wider scope. \nFor instance, the MDR explicitly covers all devices for cleaning, \nsterilising or disinfecting other medical devices (Article 2.1); re -\nprocessed single-use medical devices (Article 17)3; and certain \ndevices with no intended medical purpose (Annex XVI).\nThe MDR also covers internet sales of medical devices and med -\nical devices used for diagnostic or therapeutic services offered \nat a distance (Article 6).\nThe MDR introduces a clinical evaluation consultation procedure \nfor some Class IIb devices and for implantable Class III devices \nby an independent expert panel (Article 54).\nA new Unique Device Identification system (Article 27) will \nsignificantly enhance the traceability and the effectiveness of \npost-market safety-related activities.\nThe MDR will also provide increased transparency, with infor -\nmation on devices and studies being made public. The new Eu -\nropean Database for Medical Devices \u2013 Eudamed \u2013 will play a \ncentral role in making data available and increasing both the \nquantity and quality of data (Article 33).\n1  For definition see Article 2 paragraph 282\n2  For definition see Article 2 paragraph 27\n3  Reprocessing and further use of single-use devices may only take place where permitted by national law and only in accordance with this Article.  \n4  EEA: European Economic Area   What does this mean  \n   in practice?\nScope (Article 1)\nThe scope of the MDR has broadened, so as a manufacturer you \nmust check your product portfolios to find out whether more of \nyour devices fall within the scope of the Regulation compared \nto the Directives. Pay attention to products listed in Annex XVI, \nwhich will be covered by the Regulation once the respective Im -\nplementing Regulation setting out common specifications has \nbeen adopted. The list of products excluded from the scope can \nbe found in paragraph 6. Some products that combined a medi -\ncal device and an in-vitro diagnostic device or a medicinal prod -\nuct follow specific rules (see paragraphs 7, 8, 9).\nIt is now explicit that devices and services sold online fall under \nthe scope of this Regulation (Article 6).\nDefinitions (Article 2)\nThe definition of a medical device has been slightly modified \nand there are more definitions of terms in the Regulation than in \nthe Directives, in order to ensure a common understanding at EU \nlevel. Examples include: Unique Device Identifier (Definition 15), \nclinical data (Definition 48), clinical evidence (Definition 51), and \nserious incident (Definition 65).\nObligations of manufacturers\nThe obligations of the different actors and their relations are \nnow clearly stated in the Regulation.\nAccording to Article 10, manufacturers shall have systems \nfor risk management (paragraph 2) and quality management \n(paragraph 9); conduct clinical evaluations (paragraph 3); com -\npile technical documentation (paragraph 4); and apply a confor -\nmity assessment procedure (paragraph 6). Manufacturers are \nalso responsible for their devices once they are on the market \n(paragraphs 12, 13, 14). They must have systems in place to \ncover their financial responsibility for harm caused by defective \ndevices (paragraph 16).\nEvery manufacturer shall have a named person responsible for \nregulatory compliance (Article 15).\nManufacturers of some implantable devices will have to provide \nan implant card for the patient (Article 18).\nOnce they have completed all these obligations, manufacturers \nshall draw up a declaration of conformity (Article 19) and apply \nCE marking to their devices (Article 20).\nManufacturers outside the EU/EEA shall have a contract with an \nauthorised representative inside the EU/EEA4 (Article 11).3The obligations of authorised representatives (Article 11), \n importers (Article 13) and distributors (Article 14) are also \n clearly described.\nRisk classes of devices\nAs a manufacturer you must check your portfolio of products \nto determine whether some of your devices will be reclassified \nor will need to be scrutinised by a Notified Body. Determining \nthe risk class of a medical device is essential in specifying the \nsteps required for CE marking (Article 51), especially in terms \nof the choice of conformity assessment procedure and clinical \nrequirements.\nThe MDR sets out 22 rules for determining risk classes (Annex \nVIII), compared to 18 rules under the Directive. You should pay \nspecial attention to rules regarding: invasive devices, surgically \ninvasive devices and implantable devices (Section 5: Rules 5 to \n8); active devices (Section 6: Rules 9 to 13, for example, soft -\nware now falls under Rule 11); devices utilising tissues and cells \n(Rule 18); devices incorporating nanomaterials (Rule 19); and \ndevices composed of substances (Rule 21).\nNotified Bodies (Chapter IV)\nNotified Bodies have to be designated under the new Regula -\ntion. They will be required to meet more stringent criteria, par -\nticularly in terms of clinical competence. Notified Bodies can \napply to be designated from 26 November 2017. The process \nof designation, which might take 12 months or more, involves \nassessors from different national and European authorities. This \nmeans that the first Notified Bodies designated under the new \nRegulation might be available by the end of 2018.\nThe database of Notified Bodies (NANDO) can be found here.\nhttp://ec.europa.eu/growth/tools-databases/nando/\nAs a manufacturer you must verify whether your Notified Body \nwill be designated under the new Regulation and whether the \nscope of its designation will cover all your products. You must \nalso start working with your Notified Body to plan the timing \nof certification for your product portfolio, taking into account \nthe availability of your Notified Body, the need for additional \ndata on devices and the transitional provisions in the new \nRegulation.\nDevice identification\nA system of unique device identifiers (UDIs) will enhance the \nidentification  (Article 27)  and traceability (Article 25) of MDs. \nThis is a completely new feature of the Regulation.\nEach MD \u2013 and as applicable, each package \u2013 will have a UDI \ncomposed of two parts: a device identifier (UDI-DI) specific to a \ndevice, and a production identifier (UDI-PI) to identify the unit \nproducing the device.Manufacturers are responsible for entering the necessary data \non the European database (Eudamed), which includes the UDI \ndatabase, and for keeping it up to date.\nConformity assessment (Chapter V Section 2)\nThe assessment of the conformity of a device for CE marking \nvaries according to the risk class and specific features of certain \ndevices (Article 52). The intervention of a Notified Body is need -\ned for all Class IIa, IIb and III devices, as well as some specific \nClass I devices (see paragraphs 7a5, b6, and c7). The different \nroutes of assessment according to the class of the device are \ndescribed in Article 52 and the Annexes IX, X, XI. In some cases \nmanufacturers have some choice regarding the conformity as -\nsessment route.\nFor certain Class III and Class IIb devices there is a new clinical \nevaluation consultation procedure to be carried out by an inde -\npendent expert panel, based on the clinical evaluation assess -\nment report of the Notified Body (Article 54).\nAnnex I specifies the general safety and performance require -\nments, while Annexes II and III specify the makeup of the tech -\nnical documentation.\nThe scope of the Quality Management System (Article 10 para -\ngraph 9) now includes clinical evaluation and post-marketing \nclinical follow-up (PMCF). A clinical evaluation plan must pre -\ncede the clinical evaluation itself (Annex XIV, Part A).\nCommon specifications defining additional requirements may be \nput in place for certain devices (Article 9).\nClinical requirements (Chapter VI)\nThe new Regulation reinforces the requirements for clinical \nevaluation (Article 61), introducing some of the biggest changes \ncompared to the previous regime.\nAs under the Directives, it includes the collection of clinical data \nalready available in the literature as well as the setting up of \nany necessary clinical investigations. The concept of equiva -\nlence with other devices for which clinical data already exists \ncan still be used, but only in a limited number of situations, and \nthe new rules are tighter (Article 61 paragraphs 4, 5, 6).\nArticle 62 and Annex XV set out the new and more precise re -\nquirements for clinical investigations. With only certain excep -\ntions, implantable and Class III medical devices must now go \nthrough clinical investigations.\nFor all Class III devices, and for Class IIb devices intended to \nadminister a medicinal product (or remove it from the body), \nthe manufacturer has the option to consult a group of European \nexperts to obtain an upstream review of its intended clinical de -\nvelopment strategy (Article 61 paragraph 2).\n5 \u201cDevices placed on the market in sterile condition, to the aspects relating to establishing, securing and maintaining sterile conditions\u201d.\n6 \u201cDevices with a measuring function, to the aspects relating to the conformity of the devices with the metrological requirements\u201d.\n7 \u201cReusable surgical instruments, to the aspects relating to the reuse of the device, in particular cleaning, disinfection, sterilization,  \n maintenance and functional testing and the related instructions for use\u201d.4Summary of safety and clinical performance  \n(Article 32)\nFor Class III and implantable devices, manufacturers shall draw \nup a summary of their safety and clinical performance in a form \nthat intended users (and patients, if relevant) can understand. \nThis summary will form part of the technical documentation \nsent to the Notified Body\n   Timing your transition  \n                  to the new Regulation\nAs a manufacturer, the timing of your transition to the MDR is \nup to you.\nFrom 26 May 2020, all new certificates will have to be delivered \naccording to the Regulation. The certificates delivered under the \nDirectives can be valid until their date of validity for a maximum \nof four years (27 May 20248 at the latest). However, in the latter \ncase, the requirements of the new Regulation relating to post-mar -\nket surveillance, market surveillance, vigilance, and the registration \nof economic operators and devices shall apply from the Date of \nApplication (Article 120 paragraph 3).\nClass I devices (other than those that have a valid certificate \nunder the Directive) will have to conform to the new Regulation \nfrom 26 May 2020.\nClass I (except sterile devices, devices with a measuring func -\ntion and reusable surgical instruments) and Class IIa might be \neasiest to start with. Classes IIb and III will be more challenging \nbecause of the more stringent requirements for clinical data.\nAs a manufacturer, you can start now by making sure that:\n1. all your products are classified appropriately;\n2. all product documentation and evidence of compliance will \nbe available in a timely fashion and conforms with the \nMDR; and\n3. you have the necessary systems in place to handle clinical \nevaluation, quality management, post-market surveillance, \nand liability for defective devices.\nMore information\nFor more information on any of the above topics, please refer to \nthe Medical Devices section  on the DG GROW website.\nhttps://ec.europa.eu/growth/sectors/medical-devices_en         Frequently asked  \n   questions\nBelow you can find an extract from the FAQs of the Competent \nAuthorities for Medical Devices. For a complete list, see: \nhttp://www.camd-europe.eu/sites/default/files/media/docu -\nments/FAQ_MDR_180117_V1.0.pdf .\nWhen does the Medical Devices Regulation (MDR) \napply?\nThe MDR (EU) 2017/745 will apply from 26 May 2020 \u2013 the \n\u201cDate of Application\u201d (DoA).\nSome provisions of the MDR will come into force earlier (e.g. \nregarding Notified Bodies and the Medical Device Coordination \nGroup). Some will apply later (e.g. regarding UDI labelling).\nWhen do the existing Directive cease to apply?\nIn general, Directives 90/385/EEC and 93/42/EEC will be  \nrepealed on 26 May 2020 (the DoA). However, there are some \nexceptions, such as:\n\u2022 for the continued marketing of devices that comply with the \nDirectives (see below); and\n\u2022 to serve as a backup in case Eudamed is not fully functional \nby the DoA.\nWhat is the applicable legislation up to 26 May 2020?\nUntil the Date of Application, the laws and regulations adopted \nby Member States in accordance with the Directives will contin -\nue to apply. However, there are some exceptions.\nIs it possible to place devices on the market that \nare compliant with the MDR prior to the DoA?\nYes, you may certainly place MDR-compliant devices on the \nmarket before the end of the transitional period. This applies \nto devices in all risk classes, and includes, for example, cus -\ntom-made devices, systems and procedure packs.\nHowever, devices subject to the \u201cclinical evaluation consultation \nprocedure\u201d, which covers certain devices in Classes IIb and III, \nmay not be placed on the market before the Medical Device \nCoordination Group (MDCG) and the expert panels have been \nestablished.\nDepending on the risk class of the device, conformity assess -\nment may involve an appropriate Notified Body. This require -\nment may create further delays before such devices can be \nmarketed due to the delays in the availability of appropriate \nNotified Bodies for all technologies.\n8 There are some exceptions described in Article 120 paragraph 25As a manufacturer, which obligations of the Regulation \ndo I need to fulfil in order to place compliant devices \non the market before the DoA?\nYou should meet as many obligations as possible, bearing in \nmind that the complete MDR infrastructure, including Eudamed, \nis unlikely to be complete before the Date of Application.\nBoth the device and the manufacturer must comply with the \nMDR. You should assess the conformity of your device \u2013 a pro -\ncess that may require the involvement of a Notified Body. Other \nimportant points include:\n\u2022 Clinical evaluation\n\u2022 Risk management\n\u2022 Quality Management System (QMS)\n\u2022 Post-market surveillance\n\u2022 Technical documentation and other reports\n\u2022 Liability for defective devices.\nUntil Eudamed is fully operational, some parts of the Directives \nwill have to substitute for the corresponding requirements of \nthe Regulation. These include the registration of devices and \neconomic operators.\nA person responsible for regulatory compliance needs to be \navailable but not necessarily registered until Eudamed is \n operational.\nDo certificates issued by Notified Bodies  \nunder the existing Directives remain valid  \nafter the DoA?\nYes, AIMDD/MDD certificates will generally remain valid un -\ntil their indicated expiry dates. This applies to all the certifi -\ncates commonly issued by Notified Bodies, including the EC \nDesign- Examination Certificates, Certificates of Conformity, EC \nType  Examination Certificates, the EC Certificate Full Quality \n Assurance System, and the EC Certificate Production Quality \n Assurance.However, all certificates issued after 25 May 2017 will be void \nat the latest by 27 May 2024. After this date there will be no \nmore valid AIMDD/MDD certificates.\nIs it possible to have valid MDR and AIMDD/MDD \ncertificates in parallel until 27 May 2024?\nYes.\nCan manufacturers still place on the market/put \ninto service Directive-compliant devices after the \nend of the transition period?\nYes, under certain conditions there will be an option to con -\ntinue placing on the market/putting into service devices that \ncomply with the Directives until their existing certificates ex -\npire. This may avoid the immediate need for a new certificate \nunder the MDR.\nTo use this option, all the existing certificates will have to be val -\nid (including, for example, the QMS), the purpose and nature of \nthe device must not change, and you must follow the new MDR \nrules for registration, surveillance and vigilance.\nWhat is the \u201csell-off\u201d provision about? \nThe \u201csell-off\u201d provision is intended to limit the time during which \ndevices that are compliant with the Directives and have already \nbeen placed on the market may be made available. \nAny devices that are still within the supply chain and that have \nnot reached their final user as being ready for use, for example \na hospital, on 27 May 2025 are no longer marketable and must \nbe withdrawn. \nOnce a Directive-compliant device has been made available to \nthe final user by the deadline, the further making available of \nthis device is not subject to/covered by the Regulation.\n\u00a9 European Union, [2018]  Reuse is authorised provided the source is acknowledged.\nThe reuse policy of European Commission documents is regulated by Decision 2011/833/EU (OJ L 330, 14.12.2011, p. 39).\nISBN: 978-92-79-89634-7    DOI: 10.2873/614436\nET-03-18-102-EN-N"}, {"title": "cnd_general_principles_en.pdf.txt", "text": "Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 1 of 13 \n The CND Nomenclature  \n\u2018Classificazione Nazionale Dispositivi medici\u2019  \n \n \nTable of Contents  \n1. Background and General Principles  ................................ ................................ ................................ ...... 2 \n2. The CND structure  ................................ ................................ ................................ ................................ .. 4 \nAnatomic Categories \u2013 by anatomical area of use:  ................................ ................................ ...................  6 \nFunctional Categories \u2013 by intended use or clinical method:  ................................ ................................ .... 6 \nSpecial Categories \u2013 by other criteria:  ................................ ................................ ................................ .......  6 \nGroups: the second hierarchical level  ................................ ................................ ................................ ........  7 \nType: the third hierarchical level (expands into several levels of detail (1\u00b0, 2\u00b0, 3\u00b0, 4\u00b0 and 5\u00b0))  ...........  7 \n3. External links  ................................ ................................ ................................ ................................ ...........  8 \n \n \nThe purpose of this document is to provide information regarding the basic principles and the \nstructure of the Italian  \u201cClassificazione Nazionale Dispositivi medici\u201d (CND) . In March 2019, an d \naccording to the criteri a set out by the Medical Device  Coordination Group1 (MDCG) , the CND \nwas selected as the basis for the future European M edical Device Nomenclature  (EMDN ). The \nEMDN  will support the functi oning of EUDAMED  as stated by the MDCG and in accordance with \nArticles 23 of Regulation (EU) 2017/745 \u2013 MDR and Regulation (EU) 2017/746.  \n \n \n  \n                                                           \n1 (MDCG 2018 -2) \u2013 Future EU medical device nomenclature: Description of requirements  Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 2 of 13 \n 1. Background and General Principles2 \nIn 2005, the Italian Ministry of Health set out that the  CND would be the  official Italian medical \ndevice  classification and  nomenclature. Since then, t he CND has been  implemented not only in  Italy, \nbut also  in Portugal and Greece.  \nAbout 15.000 manufacturers3 from various countries have used the CND for the registration of \nmedical devices and in vitro  diagnostic medical devices in the Italian database. The distribution of \nmanufacturers of medical devices and in vitro  diagnostic  medical  devices per countr y is reported \nbelow in Figure 1. \n \n \n   Fig. 1 Distribution of manufacturers of medical devices per countr y \n \nThe CND nomenclature  is one of the tools used in the  governance of the medical device sector  and \nis characteri sed by its refined and hierarchical structure . It aims to support the improvement of \npatient safety and the quality of health systems by enabling information to be communicated in a \nstandard ised manner . \n \nUpdates and maintenance of CND:  \n                                                           \n2 The principles and rules presented thereafter are the ones historically established/followed when building the CND nomenclature u p \nto the last update in 2018. This is without prejudice to the new rules that will govern the EMDN  which will be  established by th e \nMDCG.  \n3 Source NSIS: data updated on 10 August 2019  31,6%  \n15,2%  \n10,2%  9,8%  \n3,9%  3,6%  2,7%  2,5%  2,0%  18,5%  \n0,0%5,0%10,0%15,0%20,0%25,0%30,0%35,0%Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 3 of 13 \n The construction of the CND , its subsequent updates and maintenance have been  based  on three  \nfundamental principles.  \nA) Participative approach:  \nFor the update and maintenance of a qualitative nomenclature, highly differentiated and \nqualified expertise is required. As the  medical device sector is acknowledged  for its \nheterogeneity and complex ity, a broad participation of all stakeholders (economic operators and \nhealthcare professional from NHS - at all levels of its organisation ) is essential.   \n \nB) Qualified validation of proposals :  \nNomenclature and Classification proposals are technically validated based on  assessment s of \nactual need . Factors taken into  consideration are: \n\uf0b7 other existing nomenclature and classification systems available at international level  \n\uf0b7 consumption and expense information  \n\uf0b7 assessment with sector experts from the different disciplines  \n \nC)  Formal adoption and free public availability:  \nThe CND system , which represents the basis of the whole information system on medical \ndevices is formally approved and thus constitutes an offici al reference, freely available to all \nstakeholders.  \n \nMore information on previous  updates of the CND up to 2018 can be found in Annex I of this \ndocument.  \n \nThe following pr oducts are currently not included in the CND : \n\uf0b7 Medicinal products  \n\uf0b7 Cosmetics products  \n\uf0b7 Human blood and its derivatives;  \n\uf0b7 Organs, tissues and cells of human origin, products including human tissues and cells and \nproducts derived therefrom.  \n\uf0b7 Organs, tissues and cells of animal origin except medical devices manufactured using \nanimal devitalized tissues o r devitalized products derived from animal tissue.  \n\uf0b7 Individual Protection Devices  Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 4 of 13 \n 2. he CND structure   \nThe CND is characterised by its alphanumeric  structure that  is established  in a multi -level \nhierarchical tree . It clusters medical devices in  three main levels:  \n\uf0b7 Category:  the first hierarchical level  \n\uf0b7 Group:  the second hierarchical level  \n\uf0b7 Type:  the third hierarchical level  (which  if necessary, expands into several levels of detail \n(1\u00b0, 2\u00b0, 3\u00b0, 4\u00b0 e 5\u00b0))  \n \n \n \nEach medical device is classified by an alphanumeric code consisting of a letter referring to the \n\u201cCategory\u201d, a couple of numbers referring to the \u201cGroup\u201d and a series of other couples of numbers \nreferring to the \u201cType\u201d (whose amount depends on the level o f detail) up to a maximum of 7 levels . \n \n \nEach level isidentified by:\n\u2022an alphanumeric code (max 13 digits )\nA ## ## ## ## ## ##\nLevel 1: \nC ategoriesLevel 2: \nGroupsLevel from 3 to 7:\nTypesMedical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 5 of 13 \n Categories:  the first hierarchical level  \nThe first hierarchical level of the CND is defined  as a \u201cCategory\u201d.  There are 22 categories, each \nidentif ied by a letter of the alphabet:  \n \nEach \u201cCategory \u201d includes devices regulated under Directive 93/42/EEC, 90/385/EEC or 98/79/EC \nor following a dedicated prescription from reimbursement rules in Italy. These \u201ccategories\u201d are used \nfor the same specific apparatus, anatomical district or organ or as a replace ment of them \n(anatomical categories), or devices characterised by similar use, intended use or clinical m ethod \n(functional categories).  \nConsidering these criteria and the ramified tree structure with different detail level, the following \nAnatomic (8), Fun ctional (9) and Special (5) Categories have been defined:  \n \nMedical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 6 of 13 \n Anatomic Categories \u2013 by anatomic al area of use:  \n\u2022 B \u2013 HEMATOLOGY AND HEMOTRANSFUSION DEVICES  \n\u2022 C \u2013 CARDIOCIRCULATORY DEVICES  \n\u2022 F \u2013 DYALISIS DEVICES  \n\u2022 G \u2013 GASTROINTESTINAL DEVICES  \n\u2022 N \u2013 DEVICES FOR NERVOUS AND MEDULLAR SYSTEMS  \n\u2022 Q \u2013 DENTAL, OPHTALMOLOGIC AND ENT DEVICES  \n\u2022 R \u2013 RESPIRATORY SISTEM AND ANAESTHESIA DEVICES  \n\u2022 U \u2013UROGENITAL APPARATUS  DEVICES  \n \nFunctional Categories \u2013 by intended use or clinical method:   \n\u2022 A \u2013  DEVICES FOR ADMINISTRATION, COLLECTING AND PICKING  \n\u2022 D \u2013 DISINFECTANTS, ANTISEPTICS AND P ROTEOLYTICS FOR MEDICAL \nDEVICES  (regulated by Italian Legislative Decree No. 46/97  and European Directive \n93/42/EEC ) \n\u2022 H \u2013 SUTURE DEVICES  \n\u2022 K \u2013 ENDOTHERAPY AND ELECTROSURGICAL DEVICES  \n\u2022 L \u2013 REUSABLE SURGICAL INSTRUMENT S \n\u2022 M \u2013 DEVICES FOR GENERIC AND SPECIALISTIC MEDICATION  \n\u2022 S \u2013 STERILIZATION DEVICES  \n\u2022 T \u2013 PROTECTION DEVICES AND INCONTINENCE AIDS ( regulated by Italian \nLegislative Decree No. 46/97  and European Directive 93/42/EEC ) \n\u2022 V \u2013 MEDICAL DEVICES - VARIOUS  \n \nSpecial Categories \u2013 by other criteria : \n\u2022 J \u2013 ACTIVE -IMPLANTABLE DEVICES : MDs  regulated by Directive 385/90 EEC   \n\u2022 P \u2013 IMPLANTABLE PROSTHETIC DEVICES AND OSTEOSYNTHESIS DEVICES : \nnon-active implantable MDs  \n\u2022 Y \u2013 SUPPORTS OR TECHNICAL AIDS FOR DISABLED PERSONS  \n\u2022 W \u2013 IN VITRO DIAGNOSTIC DEVICES MDs regulated by Directive 98/79  EEC  \n\u2022 Z \u2013 MEDICAL EQUIPMENT AND RELATED ACCESSORIES AND MATERIALS  \n Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 7 of 13 \n Groups : the second hierarchical level  \nThe second  hierarchical level s are  called \u201cGroup s\u201d. There are 146 anatomical/functional Medical \nDevices Gr oups  4, which  represent the various differentiations that distinguish devices contained in \nthe Categories. They are identified by two -digit nu mbers from 01 to 99 for each Category.  \nNumber \u201c90\u201d identifies the gr oups of devices having various characteristics that are not related to \nexisting gro ups. Number \u201c99\u201d  \u201cAltri \u2013 Others\u201d is reserved to medical d evices that are not included \nin already existing Groups and will be categori sed in later updates.  \nType: the third hierarchical level (expands into several levels of detail (1\u00b0, 2\u00b0, 3\u00b0, \n4\u00b0 and 5\u00b0)) \nThe \u201cType\u201d represents the third hierarchical level . If necessary, it expands into several level s of \ndetail (1\u00b0, 2\u00b0, 3\u00b0, 4\u00b0 and 5\u00b0). The group of every type includes medical devices characteri sed by a \nhigh affinity of use, intended use or s imilar clinical method. In case of doubt, the peculiar \ncharacteristics of the medical device under examination should be considered for a proper \ncollocation or search proces s (i.e. the anatomic -functional characteristics and/or the intended use \ndeclared by the manufacture r). \nAs explained, the term \u201cot hers\u201d marked with the code \u201c99 \u201don the first detail level is suitable for \ndevices not included i n existing types. The \u201c99\u201d  types will be submitted for later updates. Th e code \nreserved to the generic term \u201cothers\u201d must be used by users only if it is not possible to classify the \nmedical device in existing typologies .  This type is subject  to continuous checks and monitoring.  \nRegarding accessories, e very accessory follows the CND classification code of the medical device \nthat it is associated with , according to the intended use  given by the manufacturer . If an accessory \ncan be used with multiple medical devices belonging to several group s, it must be placed  in the \nprevalent type.  \n \n  \n                                                           \n4 Updated as of the Italian Ministerial Decree of 13 March 2018.  Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 8 of 13 \n 3. External links  \n \nFor more information, please  consult the Italian Ministry website at: \nhttp://www.salute.gov.it/portale/temi/p2_6.jsp?lingua=italiano&id=328&area=dispositivi -\nmedici&menu=classificazione  \n      \nThe fo llowing documents  may also be of use : \n\uf0b7 National Classification of Medical Devices (CND) - as modified by Ministerial Decree \n13.03.2018 ( PDF format)  \n\uf0b7 National Classification of Medical Devices (CND) - as modified by Ministerial Decree \n13.03.2018 (XLSX format)  \n\uf0b7 English translation of National Classification of Medical Devices Codes (as modified by \nMinister ial Decree 13.03.2018 -pdf, format).  \n\uf0b7 English translation of National Classification of Medical Devices Codes (as modified by \nMinisterial Decree 13.03.2018 -XLSX format).  \n\uf0b7 Search code and description of the CND  \n\uf0b7 Search in alphabetical order  \n \n  Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 9 of 13 \n Annex I \u2013 CND updates up to 2018  \nThe periodical updating process of the CND was schematically subdivided into four main phases:  \n \n\uf0b7 Phase 1:  \nCollection of proposals  This phase is open to all stakeholders who submit proposals for \nthe definition of new classifications or for the revision of existing \nones.  \n\uf0b7 Phase 2:  \nPreliminary technical \nevaluation and elaboration \nof the proposal.  The MoH MD Technical Team (MDTT) analyses th e collected \nproposals, the existing systems and the contents of the medical \ndevices database to identify elements useful for classification.  \n\uf0b7 Phase 3:  \n \u201cWidespread validation\u201d \nof the proposal.  The proposal is formally evaluated in three steps:  \nA) the regional levels of the NHS involving clinical professionals \nin technical sessions  \nB) Technical Health Committee - medical devices section of the \nMinistry of Health  \nC) State - Regions Conference   \n\uf0b7 Phase 4:  \nFormal adoption of the \nproposal  Finally, the proposal is approved by formal MoH act and \npublished on the Italian Official journal as well as the website of \nthe Italian MoH  \n \n \nMost of the inputs adopted for updating purposes are listed below:  \n\uf0b7 The analysis of the terminal typologies \"90\" and \"99\":  \nImplemented and consolidated, it originates from the analysis of information within the Italian \ndatabank and consider s data from  all the medical device s registered and classified in the CND \nterminal types with code \" 90\" ( - various) and \"99\" ( - other) of specific categories or groups \nidentified. In fact, the classification system had already foreseen ab origine that medical devices \nthat are not placed in a specific \u201ctypology\u201d are classified in the generic typologies in dicated \nwith the codes 90 and 99.  \n\uf0b7 Manufacturer requests:  \nWhen a manufacturer is unable to classify a medical device in an appropriate way inside the \nCND terminal level, a specific request for the introduction of a new CND class is required, with \na communic ation to the MoH of a rationale and the technical characteristics and / or intended \nuse that differentiate the device from the specific terminal classes already represented in the \nCND.  \n\uf0b7 The analysis of CND coming from vigilance system:  Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 10 of 13 \n Market surveillance and the vigilance system are part of the institutional activities of the MOH. \nThe lack of classificatory level can emerge in order to identify products that need particular \nattention for public health.   Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 11 of 13 \n \uf0b7 The analysis of consumption by the NHS:  \nThe revision of the CND made through the processing of the consumption data of the \nMonitoring Database is based on identification of medical devices with great economic \nrelevance or price variability.  \n\uf0b7 The analysis coming from HTA Report s: \nHealth Technology Assessment documents are periodically published by the Ministry of Health. \nThese reports are considered when evaluating  the revision of the CND.  \nThe following principles were considered in the revision of the CND:  \n\uf0b7 the number of levels in the CND structure can be inc reased up to a maximum of seven, by \ncoherently applying the homogeneity of the classification rules and of the coding system \ndefined for the first CND structure.  \n\uf0b7 for the definition of a new CND branch the number of manufacturers manufacturing the medical \ndevices that will be placed in the new typology of the CND should be more than 1;  \n\uf0b7 significant characteristics of medical devices detected by NHS professionals should be \nevaluated  \n\uf0b7 the proposal of relocation of medical devices placed in class 90 or 99 should  be consistent.  \n\uf0b7 for the definition of a new CND branch significant differences of price between similar medical \ndevices could be considered if necessary:  \n\uf0b7 for the definition of a new CND branch an assessments related to the use of medical devices is \nconside red (quantity and number of users in NHS);  \n \nFor each update proposal of the CND, the information associated to the devices registered in the \nItalian database were analysed and, if necessary, the information detect ed by the \u201cConsumption \nMonitoring Database\u201d were processed.  \n \n \n \n \n  Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 12 of 13 \n Annex II \u2013 CND VERSIONS  \nArt. No. 57 of the Italian Law n\u00b0 289 of the 27 December 2002 stated the  requirement of the  \nestablishment of a Commission on Medical Devices (CUD) as a technical advisory board to the \nMinistry of H ealth. The CUD has the task of defining and updating the repertoire of medical \ndevices and classifying all medical devices in specific classes and sub -classes.  \nThe CUD d efined the first version of the Classificazione Nazionale dei Dispositivi Medici (CND) \non July 2005 (Italian Ministerial Decree of 22 Sept .2005). In Vitro  Diagnostic Medical Devices \n(regulated by European Directive No. 98/79 EEC and Italian Legislative De cree No. 332/2000) \nwere not  included in the first version of the Classification , although they belong to a class of \nMedical Devices.  \nThe Italian Financial Law of 2006 (Law No. 266 of the year 2005, art. 1, par. 409) established that \nthe CND has to be appr oved by a decree of the Minister of Health in agreement with the State -\nRegions Conference.  \nThe CUD considered it appropriate to review and update the CND with the inclusion of in vitro  \ndiagnostic medical devices before proceeding with the State -Regions Con ference . Therefore,  on 20 \nFebruary 2007 , and after a revision of the classification, the Health Minister decreed  the approval of \nthe Classificazione Nazionale dei Dispositivi Medici (CND) drawn up by the CUD. The \nclassification refers to the medical device s regulated by Italian legislative decrees N\u00b0. 507/92, N\u00b0. \n46/97, N\u00b0. 332/2000 and subsequent amendments.  \nIn 28 March2013, the Italian D.P.R. n.44, replaced the Commission on Medical Devices (CUD) \nwith the Technical Committee section F on medical devices.  \nThe Classification represented the first step towards the establishment of the Italian Repertoire of \nthe Medical Devices.  \nAccording to the art. N\u00b0 2 of The Italian Financial Law No. 266, the Technical Committee section F  \n(previously CUD) , review the CND a nd make  the necessary changes and updates. Every update is \napproved by a Ministerial Decree:  \n \n1. Decree of the Italian Ministry of Health (13 Mar 2008) regarding Modification and update of \nClassificazione Nazionale dei Dispositivi Medici (CND) published in th e Official Gazette - GU \nNo. 125 of 29/05/2008. Links:  \nhttp://www.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_2_file.pdf   Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 13 of 13 \n www.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_3_file.xls   \n2. Decree of the Italian Ministry of Health (12 Feb 2010) regarding Modification and update  of \nClassificazione Nazionale dei Dispositivi Medici (CND) published in the Official Gazette - GU \nNo.119 of 24/05/2010. Links:  \nhttp://www.salute.gov.it/imgs/C_1 7_pagineAree_328_listaFile_itemName_5_file.pdf   \nwww.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_7_file.xls   \n3. Decree of the Italian Ministry of Heal th (7 Oct 2011) regarding Modification and update of \nClassificazione Nazionale dei Dispositivi Medici (CND) published in the Official Gazette - GU \nNo.259 of 7/11/2011.Links:  \nhttp://www.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_9_file.pdf   \nwww.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_10 _file.xls   \n4. Decree of the Italian Ministry of Health (29 July 2013) regarding Modification and update of \nClassificazione Nazionale dei Dispositivi Medici (CND) published in the Official Gazette - GU \nNo. 258 of 04/11/2013). Links:  \nhttp://www.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_16_file.pdf   \nwww.sa lute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_17_file.xlsx   \n5.  Decree of the Italian Ministry of Health (8 J une 2016 ) regarding Modification and update of the \nClassificazione Nazionale dei Dispositivi Medici (CND )  published in the Official Gazette G.U. \nSerie Generale, n. 242 del 15/10/2016).  \n6. Decree of the Italian Ministry of Health (13 march 2018) regarding Mod ification and update of \nthe Classificazione Nazionale dei Dispositivi Medici (CND ) published in the Official Gazette \nG.U. Serie Generale, No. 116 del 21/05/2018). Links:  \nhttp://www.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_15_file.pdf   \nwww.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_18_file.xlsx"}, {"title": "mdcg_2019_2_gui_udi_dev_en.pdf.txt", "text": "Medical Devices       \nMedical Devices Coordination Group Document   MDCG  201 9-2   \nPage 1 of 3 \n  \n \n \n \n \nMDCG  201 9-2    \n Guidance on application of UDI rules to  \n device -part of products referred to in Article \n 1(8), 1(9) and 1(10) of Regulation 745/2017  \n                 \n \n \n February 2019  \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commission document and it cannot be regarded \nas reflecting the official position of the European  Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  Medical Devices       \nMedical Devices Coordination Group Document   MDCG  201 9-2   \nPage 2 of 3 \n  \n1. Scope  \nArticle 1(8),1(9), 1(10) of the Medical Device Regulation (EU) 2017/745 (MDR) set \nthe basic criteria to determine whether and to what extent the relevant legislation on \nmedical devices, medicinal products, human tissue and cells apply to certain \nproducts c ontaining a medical device part. In particular,  \n\u201c8. Any device which, when placed on the market or put into service, incorporates, as \nan integral part, a substance which, if used separately, would be considered to be a \nmedicinal product as defined in poin t 2 of Article 1 of Directive 2001/83/EC, including \na medicinal product derived from human blood or human plasma as defined in point \n10 of Article 1 of that Directive, and that has an action ancillary to that of the device, \nshall be assessed and authorised  in accordance with this Regulation.  \nHowever, if the action of that substance is principal and not ancillary to that of the \ndevice, the integral product shall be governed by Directive 2001/83/EC or Regulation \n(EC) No 726/2004 of the European Parliament an d of the Council, as applicable. In \nthat case, the relevant general safety and performance requirements set out in Annex \nI to this Regulation shall apply as far as the safety and performance of the device part \nare concerned.  \n9. Any device which is intende d to administer a medicinal product as defined in point \n2 of Article 1 of Directive 2001/83/EC shall be governed by this Regulation, without \nprejudice to the provisions of that Directive and of Regulation (EC) No 726/2004 with \nregard to the medicinal produ ct.  \nHowever, if the device intended to administer a medicinal product and the medicinal \nproduct are placed on the market in such a way that they form a single integral \nproduct which is intended exclusively for use in the given combination and which is \nnot reusable, that single integral product shall be governed by Directive 2001/83/EC \nor Regulation (EC) No 726/2004, as applicable. In that case, the relevant general \nsafety and performance requirements set out in Annex I to this Regulation shall apply \nas far  as the safety and performance of the device part of the single integral product \nare concerned.\u201d  \n10. Any device which, when placed on the market or put into service, incorporates, as \nan integral part, non -viable tissues or cells of human origin or their de rivatives that \nhave an action ancillary to that of the device shall be assessed and authorised in \naccordance with this Regulation. In that case, the provisions for donation, \nprocurement and testing laid down in Directive 2004/23/EC shall apply.  \nHowever, if the action of those tissues or cells or their derivatives is principal and not \nancillary to that of the device and the product is not governed by Regulation (EC) No \n1394/2007, the product shall be governed by Directive 2004/23/EC. In that case,  the \nrelevant general safety and performance requirements set out in Annex I to this \nRegulation shall apply as far as the safety and performance of the device part are \nconcerned\u201d.  \n Medical Devices       \nMedical Devices Coordination Group Document   MDCG  201 9-2   \nPage 3 of 3 \n  \n2. Application to UDI rules to the device part of products referred to in \npoint 1 that are governed by the medical device Regulations  \nEXAMPLES:  \n- Catheters coated with heparin or an antibiotic  \n- Soft tissue fillers incorporating local anaesthetics  \n- Implantable infusion pump  \n- Spacer devices for use with metered dose inhalers  \n- Bone void  filler with an antibiotic  \n- Bone void filler with animal growth factors, where the action of the growth \nfactors is demonstrated to be ancillary to that of the physical filler  \nIf a product referred to in point 1 is assessed and authorised in accordance with  the \nMedical device regulations, the device part will be subject to all UDI -related \nobligations.  \n3. Application to UDI rules to the device part of combination products that \ndo not fall under the medical device Regulations  \nEXAMPLES:  \n- Non-reusable autoinjectors  containing a medicinal product as integral part  \n- Nebulizers precharged with a specific medicinal product  \n- Patches for transdermal drug delivery  \n- Wound dressings impregnated with an antibiotic, where the primary intended \npurpose is to administer the antibioti c to the wound  \n- Bone void filler with animal growth factors, where the action of the growth \nfactors cannot be demonstrated to be ancillary to that of the physical filler  \nIn general terms, if a product referred to in point 1 is governed by the medicinal \nproduct or tissue and cell legislation, the device part is required to comply only with \nthe relevant general safety and performance requirements set out in Annex I to the \nRegulation on medical devices. This cannot be interpreted as meaning that the \nrelevant o bligations related to UDI, as laid down in Chapter III and Annex VI of the \nRegulation on medical devices, apply to the medical device part or the package of \nthe relevant combination. For this reason, the medical device part is not mandatorily \nrequired to c omply with any UDI -related obligation. This also means that a UDI is not \nneeded on the package that combines the medicinal product and the medical device1 2. \n                                                           \n1  However,  if the medical device part bears a UDI on its label, that should not be deemed as being in contrast with the \napplicable medical device legislation  \n2  For products such as prefilled syringes which are made on the b asis of a UDI direct part marked (MDR compliant) \nsyringe it shall be noted that, while UDI rules do not apply to the device part of the integral product, the direct mark \nUDI on the syringe shall not be removed unless that mark compromises the safety and pe rformance of the integral \nproduct."}, {"title": "mdcg_2018_4_udi_core_spp_en.pdf.txt", "text": "Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -4   \nPage 1 of 3 \n  \n \n \n \n \nMDCG  2018 -4 \nAnnex: UDI database  \nDefinitions/Descriptions and formats  \n of the UDI core elements for systems  \n or procedure packs  \n               \n October  2018  \n \n \n  \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission . \nThe document is not a European Commission document and it cannot be regarded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  \n \n  Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -4   \nPage 2 of 3 \n  \nIn accordance with Article 29(2) and Annex VI, Part B of the MDR, in the case of \nsystems and procedure packs, the system or procedure pack producer shall \nprovide to the UDI database the UDI -DI and all of the following information1: \n \n1. quantity per package configuration (meaning the quantity of systems or \nprocedure packs in a package, whenever applicable)  \n2. the Basic UDI -DI as referred to in Article 29 (MDR) and any additional UDI -\nDIs, \n2a. Indication of s pecific medical purpose of the system or procedure pack  \n3. the manner in which the system or procedure pack is controlled (expiry date \nor manufacturing date, lot number, serial number),  \n5. name and address of the system or procedure pack producer (as indic ated \non the label),  \n6. the SRN of the system or procedure pack producer  \n8. The medical device nomenclature code as provided for in Article 26 (MDR)2 \n9. risk class (to be intended as the highest risk class of the device components \nof the system or procedure  pack),  \n10. if applicable, name or trade name,  \n11.A. name or, if applicable, system or procedure pack model associated with \nthe BASIC UDI -DI in the statement drawn in accordance with Article 22.1 of \nthe MDR  \n11.B. reference or catalogue number, or product n umber found on the system \nor procedure pack label or accompanying packaging to identify a system or \nprocedure pack  \n13. additional product description,  \n14. if applicable, storage and/or handling conditions of the system or \nprocedure pack (as indicated on th e label or in the instructions for use),  \n15. if applicable, additional trade names of the system/procedure pack,  \n18. labelled sterile (y/n) (meaning that the system or procedure pack in its \nentirety is labelled as sterile),  \n19. need  for sterilisation before use (y/n)  \n22. URL for additional information, such as electronic instructions for use \n(optional),  \n23. if applicable, critical warnings or contra -indications  \n \n                                                            \n1 Please note that format and definition of all UDI data elements are  provided at \nhttps://ec.europa.eu/docsroom/documents/28669   \n2 Applicability of this data element to systems and procedure packs is to be determined at the time of \ndesignation of the future EU nomenclature for medical devices (foreseen end of 2018/beginning 2019).  Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -4   \nPage 3 of 3 \n  \n24. status of the system or procedure pack (on the market, no longer placed \non the market, recalled, field safety corrective action initiated).  \n \nWhenever a label is referred to, the label of the entire system/procedure pack shall \nbe meant, in accordance with Article 22(5) of Regulation 745/2017.  \n \n \n,"}, {"title": "faq_udi_en.pdf.txt", "text": "Introduction to the new \nUDI system and the \nobligations of operators\nThe existing regulatory framework on medical \ndevices dates back to the 1990s and consists of \nthree Directives. Two new Regulations (Regulation \n(EU) 745/2017 on medical devices and Regulation \n(EU) 746/2017 on  In Vitro  diagnostic medical devices) \nwere adopted in April 2017 and entered into force on \n25 May 2017. The general application dates of the \ntwo Regulations are 26 May 2021 for medical devices \nand 26 May 2022 for In Vitro  diagnostic medical \ndevices, though different timelines apply for certain \nspecific provisions. \nThese Regulations introduce an EU identification sys -\ntem for medical devices based on a Unique Device \nIdentifier (UDI).\n1The UDI system will facilitate easier traceability of medical \ndevices, significantly enhance the effectiveness of the post-mar -\nket safety-related activities for devices and allow for better \nmonitoring by competent authorities. It will also help to reduce \nmedical errors and to fight against falsified devices. The use of \nthe UDI system finally should also improve purchasing and waste \ndisposal policies and stock-management by health institutions \nand other economic operators.\n1  IMDRF/UDI WG/N7FINAL:2013  UDI Guidance Unique Device Identification (UDI) of Medical Device s\n2  IMDRF/UDI WG/N48 FINAL: 2019 Unique Device Identification system (UDI system) Application Guide - DOCX (12.5Mb)The new system will be applied to all medical devices except \ncustom-made and performance study/investigational devices and \nis substantially based on internationally recognised principles, \nnotably by using definitions that are compatible with those used \nby major trade partners.1,2MEDICAL DEVICES  CHANGE OF LEGISLATION\nWhat you need to know! \nUnique Device  \nIdentification (UDI) System  \nunder the EU medical devices Regulations \n2017/745 and 2017/746European \nCommission\nHealth and Food \nSafety 2Article 27 of Regulation (EU) 2017/745 (\u2018MDR\u2019) and Article 24 of \nRegulation (EU) 2017/746 (\u2018IVDR\u2019) lay down that the UDI system \nshall consist of:\na. the production of a UDI that comprises a UDI device identifier \n(\u2018UDI-DI\u2019) specific to a manufacturer and a device, providing \naccess to the information, and a UDI production identifier \n(\u2018UDI-PI\u2019) that identifies the unit of device production and \nif applicable the packaged devices, as specified in Part C \nof Annex VI;\nb. the placing of the UDI carrier on the label of the device or \non its packaging or in case of reusable devices on the device \nitself (direct marking);\nc. the storage of the UDI by economic operators, health insti -\ntutions and healthcare professionals, in accordance with the \nconditions laid down in paragraphs 8 and 9, respectively, of \nthe Articles;\nd. the establishment of an electronic database for Unique \nDevice Identification (the \u2018UDI database\u2019), which is part of \nthe Eudamed database, in accordance with Article 28 of MDR \nand Article 25 of IVDR.\nIn accordance with the new rules, any manufacturer shall thus \nassign a unique UDI to a device and to all higher levels of packag -\ning before placing that device on the market except custom-made \nmedical devices and performance study/investigational devices. \nThe UDI carrier shall be placed on the label of the device and on all \nhigher levels of packaging and in case of reusable devices on the \ndevice itself (direct marking). The manufacturer shall also ensure \nthat the information \u2013 related to the device in question - referred \nto in Part B and Part A, Section 2, of Annex VI of the relevant \nRegulation, is correctly submitted to the European Database on \nMedical Devices (Eudamed) as required by Article 27(3) of MDR \nand Article 24(3) of IVDR. The manufacturer shall also maintain \nunique UDIs for its devices.\nNOTE: Timelines related to those obligations are indicated under \nquestion 6 of this document.\nWithin the EU, the manufacturer shall assign to their devices, \ntogether with a UDI, also a Basic UDI-DI, which is not yet required \nby other jurisdictions. The Basic UDI-DI is the main key in Eudamed \nand relevant documentation (e.g. certificates, declaration of \nconformity, technical documentation and summary of safety \nand clinical performance) and will also be the access key for \ndevice-related information entered in the database.\nUDI issuing entities designated by the European Commission \noperate a system for the assignment of UDI in the EU.3\n3  Issuing entities have been designated on 6 June 2019 via the Commission Implementing Decision (EU) 2019/939 .Frequently Asked  \nQuestions and Answers\n1. What is the UDI?\nThe UDI is a series of numeric or alphanumeric characters that \nis created through a globally accepted device identification and \ncoding standard. It allows the unambiguous identification of a \nspecific medical device on the market. The UDI is comprised of the \nUDI-DI and UDI-PI. The unique identifier may include information \non the lot or serial number and be able to be applied anywhere \nin the world.\nThe production of a UDI comprises the following:\n\u2022 A UDI device identifier (\u2018UDI-DI\u2019) specific to a device, providing \naccess to the information laid down in Part B of Annex VI.\n\u2022 A UDI production identifier (\u2018UDI-PI\u2019) that identifies the unit \nof device production and if applicable the packaged devices, \nas specified in Part C of Annex VI.\n2. What is the Basic UDI-DI?\nThe Basic UDI-DI is the main access key for device-related \ninformation in the Eudamed database and it is referenced in \nrelevant documentation [e.g. certificates (including certificate of \nfree sale), EU declaration of conformity, technical documentation \nand summary of safety and (clinical) performance)].\nIt is intended to identify and connect devices with the same \nintended purpose, risk class and essential design and manufac -\nturing characteristics.\nIt is independent/separate from the packaging/labelling of the \ndevice and it does not appear on any trade item.\nAny Basic UDI-DI shall identify the devices (group) covered by \nthat Basic UDI-DI in a unique manner.\nMDCG 2018-1 v3  guidance provides additional information on \nBasic UDI-DI.\n3. Which products are subject to the UDI system?\nThe UDI system should apply to all devices, except custom-made \nand performance study/investigational devices.34.  Who is responsible for placing the UDI carrier \non the device itself, on the label and on the \npackage of a device?\nThe manufacturer is responsible for complying with all UDI related \nrequirements. This includes the assignment of the UDI (and Basic \nUDI-DI), the UDI (and Basic UDI-DI) registration in the Eudamed \ndatabase and the placement of the UDI carrier on the label of \nthe device or on its packaging or, in case of reusable devices, on \nthe device itself (direct marking).\n4.1 What happens in the case of Article 16 of the MDR and \nIVDR? Which obligations do economic operators have \nregarding UDI when assuming obligation incumbent \non manufacturers per Article 16 of the MDR and IVDR?\nAny distributor, importer or other natural or legal person that \nassumes the obligations incumbent on manufacturers in accord -\nance with Article 16(1), assumes all the relevant responsibilities \nrelated to UDI, including UDI labelling. \nThe distributor or importer carrying out the operations described \nin Article 16(2) (providing translation or repackaging of devices) \nshall ensure that: \n\u2022 the activities are performed by means and under conditions \nthat in no way compromise the readability of the UDI carrier \nand its information identifying the actual device. \n\u2022 the specific procedures are part of the distributor\u2019s or import -\ner\u2019s quality management system.\nA dedicated guideline with additional information on this aspect \nis available at the MDCG 2018-6 guidance document .\n5.  What is the procedure for systems and procedure \npacks to undergo a UDI registration?\nSystems and procedure packs shall undergo a UDI registration, \nas described in Article 29(2) of MDR.\nBefore placing on the market a system or procedure pack pursuant \nto Article 22(1) and (3), that is not a custom-made device, the \nsystem or procedure pack producer shall assign to the system or \nprocedure pack, in compliance with the rules of the issuing entity, \na Basic UDI-DI and shall provide it to the Eudamed database \ntogether with the other relevant core data elements listed in the \nMDCG 2018-4 guidance document .6.  What is the mandatory deadline for a device \nto comply with the UDI requirements?\nThe obligation for UDI assignment applies as from the date \nof application of the two new Regulations, i.e. 26 May 2021 for \nmedical devices and 26 May 2022 for In Vitro  diagnostic medical \ndevices.\nThe obligation for submission of UDI data in the EUDAMED \ndatabase  applies from 26 November 2022 for medical devices \nand 26 November 2023 for in vitro  diagnostic medical devices \n(provided that EUDAMED is fully functional before the date of \napplication of the respective Regulation; otherwise, this obligation \napplies 24 months after EUDAMED has become fully functional)\nHowever, manufacturers will be in a position to voluntarily comply \nwith registration obligations as from 26 May 2021 for medical \ndevices and 26 May 2022 for  In Vitro  diagnostic medical devices.\nIt shall be noted that, provided that Eudamed is fully functional, \nat any time after 26 May 2021 for medical devices and 26 May \n2022 for In Vitro  diagnostic medical devices, the full registration \nof devices (Article 29 of MDR and Article 26 of IVDR) remains a \npre-condition for the possible registration of their relevant serious \nincident in Eudamed.\nThe MDCG 2019-4  guidance document provides more information \non this subject.\nThe obligation for placing the UDI carrier applies according \nto the following timelines:\nDevice as per\nRegulation (EU) 2017/745  (MDR)Implantable  \ndevices and \nClass III devicesClass IIa and\nClass IIb \ndevicesClass I  \ndevices\nPlacing UDI-carriers  \non the labels of devices\nMDR Article 123(3)(f), Article 27(4)26 May  \n202126 May  \n202326 May  \n2025\nDirect marking of the  \nreusable devices\nMDR Article 123(3)(g), Article 27(4)26 May  \n202326 May  \n202526 May  \n2027\nDevice as per\nRegulation (EU) 2017/746 (IVDR)Class D \nIVDsClass C and B \nIVDsClass A \nIVDs\nPlacing UDI-carriers on the  \nlabels of devices\nIVDR Article 113(3)(e), Article 24(4)26 May \n202326 May  \n202526 May \n2027\nNOTE: Devices which are compliant with the Regulations may be placed on \nthe market ahead of the general application date of 26 May 2021 (MDR) and \n26 May 2022 (IVDR). For more information on this aspect, please consult  \nFAQ - MDR Transitional Provisions  and FAQ - IVDR Transitional Provisions .47.  Are devices, which are compliant with the \nMedical Device Directives (MDD and AIMDD) \nand placed on the market after the applica -\ntion date of the Regulations (legacy devices), \ncontinue to be subject to UDI requirements?\nIn order to facilitate the transition to the new system, the new \nRegulations give manufacturers the possibility to place products \non the market after the general application dates of the new \nRegulations (and until 26 May 2024 at the latest) by virtue of \nvalid Directive certificates.4\nThese legacy devices are not subject to UDI obligations but they \nshould be registered in the Eudamed database. Timelines for \nregistration as described under question 6 also apply to these \nproducts. More information on the operational aspects of the \nregistration of legacy devices is available at the MDCG 2019-5 \nguidance document .\n8.  What is the role of the UDI issuing entities? \nWho designates them?\nThe issuing entities operate a system for the assignment of UDIs.\nFollowing a call for applications launched at the end of 2018, the \nCommission has designated the following entities:\na. GS1 AISBL\nb. Health Industry Business Communications Council (HIBCC)\nc. International Council for Commonality in Blood Banking \nAutomation (ICCBBA)\nd. Informationsstelle f\u00fcr Arzneispezialit\u00e4ten (IFA) GmbH\nFor more information, please refer to the relevant implementing \nact designating the entities: Commission Implementing Decision \n(EU) 2019/939  of 6 June 2019 designating issuing entities \ndesignated to operate a system for the assignment of Unique \nDevice Identifiers (UDIs) in the field of medical devices. \n4 For additional information on the general conditions for legacy devices to be placed on the market after the general application dates of the new  \n Regulations, see the MDR and IVDR transitional FAQs  published by the CAMD Transitional Task-force  9.  How should a UDI appear on the label or  \npackage of a device?\nThe UDI Carrier [Automated Identification for Data Capture (AIDC) \nand human readable interpretation (HRI) representation of the \nUDI] shall be on the label or on the device itself and on all higher \nlevels of device packaging.\nIn the event of significant space constraints on the unit of use \npackaging, the UDI carrier may be placed on the next higher \npackaging level.\nHigher levels of packaging shall have their own unique UDI. \nPlease note that shipping containers shall be exempted from \nthe requirement.\nThe UDI must appear in a plain-text version/human readable \ninformation (HRI) and in a form that uses AIDC technology. AIDC \nmeans any technology that conveys the unique device identifier \nor the device identifier of a device in a form that can be entered \ninto an electronic patient record or another computer system via \nan automated process. The HRI consists of legible characters that \ncan easily be read by people.\nIf there are significant constraints limiting the use of both AIDC \nand HRI on the label, only the AIDC format shall be required to \nappear on the label.\nFor devices intended to be used outside healthcare facilities, such \nas devices for home care, the HRI shall, however, appear on the \nlabel even if this results in there being no space for the AIDC.\nFor other specific requirements related to the UDI carrier, please \nconsult Section 4 of Annex VI Part C of the two Regulations.\nFor single-use devices of classes I and IIa medical devices and \nclass A and class B IVD medical devices packaged and labelled \nindividually, the UDI carrier shall not be required to appear on \nthe packaging but it shall appear on a higher level of packaging, \ne.g. a carton containing several (individually packaged) devices. \nHowever, when the healthcare provider is not expected to have \naccess, in cases such as in home healthcare settings, to the \nhigher level of device packaging, the UDI shall be placed on the \npackaging (of the individual device).\nFor devices exclusively intended for retail point of sale, the UDI-\nPIs in AIDC shall not be required to appear on the point of sale \npackaging. \nIf the UDI carrier is readily readable or, in the case of AIDC, \nscannable, through the device\u2019s packaging, the placing of the UDI \ncarrier on the packaging shall not be required.510.  Are there any requirements for the PI  \n(Production Identifier) information?\nIf a lot number, serial number, software identification or expiry \ndate appears on the label, it shall be part of the UDI-PI. If there \nis also a manufacturing date on the label, it does not need to be \nincluded in the UDI-PI. If there is only a manufacturing date on \nthe label, this shall be used as the UDI-PI.\nThe different types of UDI-PIs include serial number, lot number, \nsoftware identification and manufacturing date and/or expiry date. \nThe UDI-PI characteristics such as the lot or serial number shall \nbe defined by the manufacturer. However:\n\u2022 For active implantable devices, the UDI-PI shall include at \nleast the serial number; for other implantable devices, the \nserial number or lot number. \n\u2022 A configurable device UDI-PI shall be assigned to each indi -\nvidual configurable device.\nIt is important to note that no UDI-PI information can be included \nin the UDI database.\n11.  What changes in the medical device would \nrequire a new UDI-DI?\nA new UDI-DI shall be required whenever there is a change that \ncould lead to misidentification of the device and/or ambiguity \nin its traceability. In particular, a new UDI-DI shall be required in \nthe case of any change of the following elements: name or trade \nname, device version or model, labelled as single use, packaged \nsterile, need for sterilisation before use, quantity of devices \nprovided in a package, critical warnings or contra-indications and \nCMR/Endocrine disruptors.\nA UDI-DI shall be associated with one and only one Basic UDI-DI.\nAdditional information on this aspect is available at  MDCG \n2018-1 v3 guidance document .12.  What are the obligations of economic operators \nand health institutions in relation to UDI?\nAccording to the two medical devices Regulations, manufacturers \nshall be responsible for the UDI assignment and placement of the \nUDI carrier, the initial submission and updates of the identifying \ninformation and other device data elements in the Eudamed \ndatabase. Manufacturers shall update the relevant database \nrecord within 30 days of a change being made to an element, \nwhich does not require a new UDI-DI.\nDistributors and importers shall verify that, where applicable, a \nUDI has been assigned by the manufacturer.\nAll economic operators and health institutions shall store and \nkeep preferably by electronic means the UDI of the devices, which \nthey have supplied or with which they have been supplied if \nthose devices belong to class III implantable devices. Please note \nthat the Commission may decide to adopt implementing acts to \nexpand the scope of devices for which economic operators shall \nstore and keep the UDI.\n13.  Is the software subject to UDI rules?\nThe UDI shall be assigned at the system level of the software.\nOnly software that is commercially available on its own and \nsoftware that constitutes a device in itself shall be subject to \nthat requirement.\nThe software identification shall be considered the manufacturing \ncontrol mechanism and shall be displayed in the UDI-PI.\nUDI requirements for software are laid down in Annex VI Part C \nof the two medical device Regulations.\nA dedicated guideline with additional information on this aspect \nis available at MDCG 2018-5 guidance document .614.  Direct marking of reusable devices. Are there \nexemptions?\nDevices that are reusable shall bear a UDI carrier on the device \nitself.\nThe UDI carrier for reusable devices that require disinfection, ster -\nilisation or refurbishing between patient uses shall be permanent \nand readable after each process performed to make the device \nready for the subsequent use throughout the intended lifetime \nof the device.\nThe UDI carrier shall be readable during normal use and throughout \nthe intended lifetime of the (reusable) device.\nThe requirements shall not apply to the device in case of the \nfollowing circumstances:\n\u2022 any type of direct marking would interfere with the safety \nor performance of the device;\n\u2022 the device cannot be directly marked because it is not tech -\nnologically feasible.\n15.  Is there an adjudication process for ad-hoc \nexemptions foreseen for medical devices?\nAn adjudication process to allow for ad-hoc exemptions is not \nenvisaged in the EU. All devices are therefore subject in principle \nto UDI requirements, with the only exceptions explicitly stated in \nthe Regulation.However, the UDI Expert Group will analyse requests for adap -\ntation of UDI requirements to certain specific device types and \nrecommend the Medical Device Coordination Group (MDCG) to \nissue dedicated guidelines, where necessary.\n16.  What are the UDI and device data sets to be \nprovided in Eudamed?\nDedicated guidelines containing information on this aspect \nare available at https://ec.europa.eu/health/md_sector/\nnew_regulations/guidance .\nGuidance\nFurther information on EUDAMED is available at  https://ec.europa.\neu/health/md_eudamed/overview_en .\nNOTE: The Commission intends to expand this document on a regular \nbasis based on the assessment of most frequently asked questions and/\nor of other specific needs.\nET-02-18-963-EN-N\nFunded under the Third EU Health Programme\nISBN:XXXXX    DOI: XXXXX01/08/2020\n\u00a9 European Union, [2018] Reuse is authorised provided the source is acknowledged.\nThe reuse policy of European Commission documents is regulated by Decision 2011/833/EU (OJ L 330, 14.12.2011, p. 39).https://ec.europa.eu/health/\nmd_sector/overview_en"}, {"title": "mdcg_2019_1_budi_rules_ie_en.pdf.txt", "text": "Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2019 -1   \nPage 1 of 2 \n  \n \n \n \n \nMDCG  201 9-1    \n MDCG guiding principles for issuing entities \n rules on Basic UDI -DI \n                \n \n \n January 2019  \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commissio n document and it cannot be regarded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law. \n Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2019 -1   \nPage 2 of 2 \n  \n \nIn order to ensure, to the maximum possible extent, the quality of the code value \nentered in Eudamed, the Basic UDI -DI requirements on format should be as close as \npossible to the ones for the UDI -DI. In particular,  \n\uf0b7 the Basic UDI -DI code value sha ll have maximum 25 characters, so that it \ndoes not differ too significantly from the maximum length of the UDI -DI as \nestablished by the issuing entities;  \n\uf0b7 a check digit/character must be part of the Basic UDI -DI, based on an \nalgorithm defined by the issuin g entity. This algorithm shall be provided by the \nissuing entities to the Commission and to the manufacturers."}, {"title": "MDCG 2018-1 v3 Guidance on basic UDI-DI and changes to UDI-DI.pdf.txt", "text": "1 \n Medical Device       \nMedical Device Coordination Group Document    MDCG 2018-1 v3   \n \n \n \n \n       \n   MDCG 2018-1 v3  \nGuidance on BASIC UDI-DI  \n      and changes to UDI-DI            \n \n             March 2020 \n \n  \n \nThis document has been endorsed b y the Medical Device Coordinat ion Group (MDCG) established by \nArticle 103 of Regulation (EU) 2017/745. The MDCG is composed o f representatives of all Member \nStates and it is chaired by a representative of the European Co mmission. \nThe document is not a European Commission document and it canno t be regarded as reflecting the \nofficial position of the European Commission. Any views express ed in this document are not legally \nbinding and only the Court of Justice of the European Union can  give binding interpretations of Union \nlaw.   \n2 \n Guidance on BASIC UDI-DI and changes to UDI-DI \nIntroduction \nThe new Medical Device Regulations (EU) 2017/745 and (EU) 2017/746 introduce a \nUnique Device Identification (UDI) system for medical devices.  \nMain provisions related to the establishment of the UDI system are contained in \nChapter III and Annex VI of the two medical device Regulations.  \nThe main features of the UDI system and relevant obligations for operators will be \nprovided in a dedicated Q/A paper to be published by the Commission in spring 2018.  \nThis guidance is intended to provide a clarification on the notion of Basic UDI-DI, its \nuse in relevant documentation and the factors triggering UDI-DI changes.   \n----------------------------- \nThe Basic UDI-DI \nThe Basic UDI-DI is the main key in the database and relevant documentation (e.g. \ncertificates, declaration of conformity, technical documentation and summary of safety and clinical performance) to connect devices with same intended purpose, risk class and essential design and manufacturing characteristics.  \nIt is independent/separate from the packaging/labelling of the device and it does not \nappear on any trade item.  \nAny Basic UDI-DI shall identify the devices (group) covered by that Basic UDI-DI in a \nunique manner. \nLink with between Basic UDI -DIs and certificates or declaration of conformity \nIn accordance with Annex XII of the medical device Regulations, the scope of the \ncertificates shall unambiguously identify the device or devices covered. The scope of EU technical documentation assessment certificates, EU type-examination certificates and EU product verification certificates shall include, together with the Basic UDI-DI, a clear identification, including the name, model and type, of the device or devices, the intended purpose, as included by the manufacturer in the instructions for use and in relation to which the device has been assessed in the conformity assessment procedure and the risk classification. \nEach of the abovementioned certificates shall identify and cover all devices \nassociated with the same Basic UDI-DI, that is referred to in that certificate.  \nThe association between different Basic UDI-DIs, where applicable, shall be \nidentified through the technical dossiers.  \nIn accordance with Annex IV of the two Regulations, the declaration of conformity \nshall contain the Basic UDI-DI and the product and trade name, product code,  \n3 \n catalogue number or  other unambig uous reference allowi ng identif ication and \ntraceability of the device covered by the EU declaration of conformity. \nChanges of UDI-DI \nA new UDI\u2014DI shall be required whenever there is a change that could lead to \nmisidentification of the device and/or ambiguity in its traceability. In particular, a new UDI-DI shall be required in the case of any change of the following elements: name or trade name, device version or model, labelled as single use, packaged sterile, need for sterilization before use, quantity of  devices provided in a package, critical \nwarnings or contra-indications (e.g. containing latex or DEHP), CMR/Endocrine disruptors\n1 2. \n A UDI-DI shall be associated with one and only one Basic UDI-DI.  \n \n  \nRegarding changes to the specific data elements listed below\n3, the following \nconsiderations should be noted: \n1. Is the Device Directly Marked (Yes/No) \nThe database design will force the creation of a new UDI-DI only if there is a change \nfrom Yes to No and not vice versa for this data element.  \n \n2. Manner in which production of the device Is controlled (expiry date or \nmanufacturing date, lot number, serial number, software identification)  - Type of UDI-PI  \nAs long as there is no change to the la bel, a change to this data element will not \nrequire the allocation of a new UDI-DI. \n                                                           \n1  It should be noted that a new regulatory decision classifying  an existing product as CMR/Endocrine \ndisruptor might not result in a new UDI-DI for products already  containing that substance. The decision on \nwhether to assign a new UDI-DI should be based on the conformit y assessment of the product with regard \nto the impact of the information provided and the significance of the change. \n2  Specific attention shall be paid to the fact that changes of colour or language might also require a new UDI-\nDI when those changes might lead to misidentification of produc t or change the product \nsafety/performance. For example:  \nA- Change of colour coding of e.g. connectors, latex-free surgi cal gloves, blood tubes  \nB- Two identical self-testing de vices, that exist in parallel a nd cannot be substitute d due to local labelling \nrequirements (IVD Article 10(10) of Regulation 746/2017), requi res different UDI-DIs \nSpecifications of EU designated issuing entity should be used a s a reference source to identify other \npossible examples.  \n3 Please refer to Guidance UDIWG 2018-1 on \"UDI database. Defini tions, descriptions and formats of the UDI \ncore elements\u2019  available at https://ec.europa.eu/docsroom/documents/28669   \n4 \n  \nWARNING: This guidance does not address requirements for reprocessed devices, \nsystems or procedure packs, software, Annex  XVI, nor for cases of parallel trade or \nown brand labelling. Specific requirement s for those products are addressed in \nspecific guidance."}, {"title": "mdcg_2018_5_software_en.pdf.txt", "text": "Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -5   \nPage 1 of 3 \n  \n \n \n \n \nMDCG  2018 -5 \nUDI Assignment to Medical Device Software  \n  \n \n            \n October  2018  \n \n \n  \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commission document and it cannot be regar ded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  \n \n  Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -5   \nPage 2 of 3 \n  \nSpecific consideration on UDI rules for software  \nUDI Assignment to Medical Device Software  \n \n- Scope of UDI requirements for software  \nIn accordance with Annex VI, Part C of the Medical Device Regulation (EU) 2017/745 \n(MDR) and the In -Vitro Diagnostic Medical Device Regulation (EU)  2017/746 (IVDR), \nonly software which is commercially available on its own as well as software which \nconstitutes a device in itself shall be subject to UDI requirements.   \n \n- Basic UDI -DI \nIn line with the general Guidance on Basic UDI -DI and changes to UDI -DI1, the Basic \nUDI-DI connects software with same intended purpose, risk class and essential \ndesign and manufacturing characteristics.  \n \n- Changes to UDI -DI \nin accordance with Annex VI Part C, Section 6.5 of the MDR and Section 6.2 of the \nIVDR, a new UDI -DI is required whenever there is a modification that changes the \noriginal performance, the safety of the software or the interpretation of data . Such \nmodifications include new or modified algorithms, database structures, operating \nplatforms, architecture, user i nterfaces and new channels for interoperability . Such \nchanges would be considered \u201csignificant.\u201d  \nThe Guidance on Basic UDI -DI and changes to UDI -DI2, defines standard rules on \ntriggers that entail the creation of a new UDI -DI. It lays down that a new UDI \u2014DI \nshall be required whenever there is a change that could lead to misidentification of a \ndevice and/or ambiguity in its traceability. In particular, a new UDI -DI shall be \nrequired in the case of any change of the following device related elements: name or \ntrade name, device version or model, labelled as single use, packaged sterile, need \nfor sterilization before use, quantity of devices provided in a package, critical \nwarnings or contra -indications (e.g. containing latex or DEHP3), CMR4/Endocrine \ndisruptors , colour, language. Not all those data elements are however applicable to \nsoftware.  \n                                                            \n1 The Guidance is available at https://ec.europa.eu/docsroom/documents/28667   \n2 The Guidance is available at https://ec.europa.eu/docsroom/documents/28667   \n3 DEHP stands for Bis(2 -ethylhexyl) phthalate  \n4 CMR stands for carcinogenic, mutagenic, or toxic for reproduction  Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -5   \nPage 3 of 3 \n  \nIt can therefore be concluded that, in the specific case of software,  \n- Any change of the Basic UDI -DI5 \n- Any changes which impact the original performance, safety, or the \ninterpretation of data6 \n- A change to the name or trade name, version or model number, critical \nwarnings or contra -indications, user interface language  \nwould require a new UDI -DI.   \nThis is to guarantee the traceability and correct identification of the med ical device \nsoftware.  \n \n- Minor software revisions  \nIn accordance with Annex VI, Part C, point 6.5.4 of the MDR and Annex VI, Part C, \npoint 6.2.4 of the IVDR, minor software revisions require a new UDI -PI and not a new \nUDI-DI. Minor software revisions are generally associated with bug fixes, usability \nenhancements that are not for safety purposes, security patches or operating \nefficiency. Minor software revisions shall be identified by a defined manufacturer -\nspecific form of identification.  \n- Evaluation of ch anges to software by the manufacturers  \nAs part of their maintenance and post -market surveillance activities, manufacturers \nshould evaluate the possible impact of any changes to the function of software on the \nsoftware\u2019s qualification as medical device soft ware, its classification, its intended \npurpose and essential design and manufacturing characteristics, as that could trigger \na new Basic UDI -DI.   \nLikewise, any changes shall be assessed in defining the need of a new UDI -DI. \nUDI Placement Criteria  \nUDI plac ement criteria for software are laid down in Annex VI, Part C, point 6.5.4 of \nthe MDR and Annex VI, Part C, point 6.2.4 of the IVDR.  Additional considerations on \nthis aspect will be provided in future guidance.  \n                                                            \n5 This is a general rule. As indicated in the Guidance on Basic UDI -DI and changes to UDI -DI (available at \nhttps://ec.europa.eu/docsroom/documents/28667 ), \"a UDI-DI shall be associated with one an d only one Basic \nUDI-DI\u201d.  \n  \n6 Annex VI, Part C, point 6.5.2 of the MDR and Annex VI, Part C, point 6 .2.2 of the IVDR"}, {"title": "mdcg_2018_7_languages_en.pdf.txt", "text": "Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -7   \nPage 1 of 3 \n  \n \n \n \nMDCG  2018 -7 \nProvisional considerations regarding language \n issues associated with the UDI database  \n (Annex VI, Part A Section 2 and Part B of the \n Medical Device Regulation (EU) 2017/745 (MDR) \n and the In -Vitro Diagnostic Medical Device \n Regulation (EU) 2017/746 (IVDR ))            \n  \nOctober  2018  \n \n \n  \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commission document and it cannot be regarded \nas reflecti ng the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  \n \n  Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -7   \nPage 2 of 3 \n  \nGeneral principles  \nIn consideration of the following:  \n- In accordance with Article 28(3) MDR and Article 25(3) IVDR, the core data \nelements to be provided to the UDI database shall be accessible to the public,  \n- Annex VI Part C of the MDR and IVDR on the UDI System requires explicitly in its \nsection 5.10 that the user interface of the UDI database shall be available in all \nofficial languages of the Union and that  the use of free - text fields shall, however, be \nminimized in order to reduce translations,   \n-  one of the main declared purposes of th e European database on medical devices \n(Eudamed) as per Recitals 43 -46 and Article 33(1a) of the MDR and Recitals 40 -43 \nof the IVDR is to enable the public (including the healthcare professionals) to be \nadequately informed about devices placed on the marke t, \nit is essential that the information in the UDI database is publicly available and easily \nunderstandable by any European citizen.   \n \nUse of free -text and translation  \nAmong the UDI core data elements of Part B of Annex VI of the MDR and IVDR, only \nthree data elements (\"Additional product description\", \"Storage and handling \nconditions\" and \"Critical warnings or contra -indications\") are expected to have a free -\ntext format, while a fourth data element (nomenclature term) is associated with a text \nallowing to  understand the meaning of the associated code (description).  \nAs to the nomenclature, ideally, all the terms/description associated with the \nnomenclature codes should be translated in the different Union official languages. \nHowever, it could be also consi dered having terms available only in English, \nparticularly taking into account that the nomenclature will have a code. Appropriate \nbudget and legal verifications will be made on this matter, in the context of the \ndesignation procedure for the new nomenclat ure.   \nAmong the three data elements that use free -text, one is an optional field: \"Additional \nproduct description\". It should be provided in English as well as in the languages of \nthose countries where the device is made available. A data field will be av ailable for \neach relevant language.  \nFor the data elements \"Storage and handling conditions\" and \"Critical warnings or \ncontra -indications\", relevant information (as per Annex I Section 23.2 of the MDR and \nAnnex I Section 20.2 of the IVDR: (k) \"any special s torage and/or handling \nconditions\" and (m) \"warning or precautions to be taken\") should be provided in  Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -7   \nPage 3 of 3 \n  \nEnglish as well as in the languages of those countries where the device is made \navailable. It shall be noted that, as laid down in the provisional guid ance related to \nformats and definitions of UDI data elements, only storage/handling conditions and \ncritical warnings or contra -indications, that are required to be on the label, shall be \ntransmitted to the UDI database. With respect to those two data eleme nts, the \npossibility to use (in EUDAMED) \u2013 as an alternative option - symbols and/or list of \nreference that can categorise and provide enough information understandable by \nanyone is currently being explored.  \n \nIndication of hazardous substances (only appli cable for MDR)  \nFor CMR substances, the Commission intends to explore the feasibility for \nEUDAMED to provide the list of official CMR1 substances (from CLP Regulation2) \navailable in the ECHA3 database. The CAS number4, EC number and/or official \nchemical nam e could be used to identify those substances.  \nWith regard to endocrine disruptor substances, pending verification that an official \ndatabase managed by the Commission containing these substances is available, a \nsolution is currently being explored.  \nInform ation to be provided is known by the economic operator in charge of the \nsubmission as it shall be displayed on the device label (Annex I Section 23.2 (f) of the \nMDR).  \n \n                                                            \n1 CMR stands for carcinogenic, mutagenic, or toxic for reproduction  \n2 Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (the 'CLP \nRegulation')  \n3 The European Chemicals Agency  \n4 A CAS Registry Number, also referred to as CASRN or CAS Number, is a unique numerical identifier assigned by \nthe Chemical Abstracts Service (CAS) to every chemical substance described in the open scientific literature"}, {"title": "mdcg_2018_6_art16_en.pdf.txt", "text": "Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -6   \nPage 1 of 2 \n  \n \n \n \nMDCG  2018 -6 \nClarifications of UDI related responsibilities in \n relation to Article 16 of the Medical Device \n Regulation (EU) 2017/745 and the  \n In-Vitro Diagnostic Medical Device  \n Regulation (EU) 2017/746  \n            \n October  2018  \n \n \n  \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commission document and it cannot be regarded \nas reflecting the official position of the European  Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  \n \n  Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -6   \nPage 2 of 2 \n  \nRelevant obligations arising from Article 16(1)  \nAny distributor, importer or other natural or legal person that assumes the obligations \nincumbent on manufacturers in accordance with Article 16(1), assumes all the \nrelevant responsibilities related to UDI, including UDI labelling.  \nThis means that those e conomic operators must also apply for registration as \nManufacturers, receive a Single Registration Number (SRN), apply for the \nappropriate conformity assessment procedure and feed and provide UDI -product \nregistration.  \nHowever, in accordance with the provis ion of Article 16(1)a, when a distributor or \nimporter enters into an agreement with a manufacturer whereby the manufacturer is \nidentified as such on the label, the manufacturer is responsible for meeting the \nrequirements placed on manufacturers in this Reg ulation, including the relevant UDI \nobligations.  \n \nRelevant obligations arising from Article 16(2) to 16(4)  \nThe distributor or importer carrying out the operations in Article 16(2) shall ensure \nthat: \n-  the activities mentioned in points  (a) and  (b) of par agraph  2 are performed by \nmeans and under conditions that in no way compromise the readability of the UDI \ncarrier and its information identifying the actual device.  \n- the specific procedures are part of the distributor's or importer\u2019s quality \nmanagement sy stem."}, {"title": "mdcg_2018_2_nomenclature_en.pdf.txt", "text": "This document has been endorsed by the Medical Device Coordination Group (MDCG) \nestablished by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of \nrepresentatives of all Member States and it is chaired by a representative of the European \nCommi ssion.  \n \nThe document is not a European Commission document and it cannot be regarded as \nreflecting the official position of the European Commission. Any views expressed in this \ndocument are not legally binding and only the Court of Justice of the European  Union can \ngive binding interpretations of Union law.  \n \n1 \n  \nMDCG 2018 -2 \nFuture EU medical device nomenclature   \nDescription of requirements                                                                                                                                                                                                                                             \n \nIntroduction  \n \nAccording to Article 26 of the Regulation 745/2017 on medical devices and Article 23 \nof Regulation 746/2017  on in-vitro diagnostic medical device , the Commission is \nrequired to make available a medical device nomenclature to support the functioning \nof the future  EUDAMED . \n \nThis document intends to provide a detailed description of requirements and criteria \nthat the future nomenclature is expected to fulfil. This is expected to serve as a \nreference basis throughout the decision process and will also ensure th at all legal \nand technical issues associated with the future EU medical device nomenclature are \nproperly mapped.  \n \n \n1. Description of legal requirements  \n \nIt arises from the text of the new Regulations (namely Article 26 of Regulation \n745/2017 and Article 23 of Regulation 746/2017) that t he future EU medical device \nnomenclature  will have to comply with certain defined requirements . \n \nFirst of all, t he future nomenclature shall be available free of charge to \nmanufacturers and other natural o r legal persons required by the  Regulation to use \nthat nomenclature, this meaning that no manufacturer or natural/legal person should \nbe subject to fee or suffer from any discrimination, compared to other operators, in \nrelation to the use of the nomenclature under the new Medical Device Regulations.  \n \nIt shall be therefore ensured that relevant names and codes are accessible (in full) in \nEUDAMED to all operators that are requested to provide the relevant UDI \nsubmissions.  \n \nProvisions in Chapter III and Annex VI of the new Regulations, and in particular  the \ncombination of Article 28( 3) of the Regulation 745/2017 on medical devices and \npoint 8 of part B of Annex VI , provide that moreover names and codes are publicly \navailabl e in the UDI database (in EUDAMED ).  \n \nBy virtue of Article 26, t he Commission shall a lso endeavour to ensure that the  \nnomenclature is available to other stakeholders free of charg e, where reasonably This document has been endorsed by the Medical Device Coordination Group (MDCG) \nestablished by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of \nrepresentatives of all Member States and it is chaired by a representative of the European \nCommi ssion.  \n \nThe document is not a European Commission document and it cannot be regarded as \nreflecting the official position of the European Commission. Any views expressed in this \ndocument are not legally binding and only the Court of Justice of the European  Union can \ngive binding interpretations of Union law.  \n \n2 \n practicable. The public availability of terms and codes in EUDAMED is in itself an \nideal vehicle to provide sufficient access of all stakeholders .   \n \nFinally the nomenclature shall be internationally recognised at the time of the date of \napplication of the Regulations. In this context, global harmonisation principles and \norientations followed and adopted by  the International Medical Device Regulators \nForum  (IMDRF)  and the World Health Organisation , are taken into particular \naccount .  \n \nWithout prejudice to the fulfilment of requirements d escribed in previous paragraphs, \nthe European Commission and the Competent Authorities  from EU Member States  \nshall benefit from the full access to the most up to date nomenclature system  and its \nhierarchies  free of charge . They shall not be charged  for any service received from \nthe nomenclature provider, which is necessary for them to exert their supervisory \nrole over the nomenclature and the fulfilment of their obligations under the new \nRegulations.   \n \n2. Description of other relevant criteria  \n \nIn order for the system to leverage further the potential of the future EU \nnomenclature, some other essential requirements that the nomenclature shall fulfil  \nhave been identified .  \n \nWhile those requirements are not explicitly mentioned in the texts of the two  \nRegulation s, they are  essential to guarantee the good functioning of the future \nEUDAMED  and to the fulfilment of some of the regulatory objectives set in the new \nRegulation s, namely facilitating effective market surveillance  operations  and \nfacilitating  device traceability throughout the supply chain.  \n \nPolicies/rules for update, removal  and creation of names  and descriptions  in the \nnomenclature are to be sound and must reflect regulators \u2019 and the wider healthcare \neconomy needs . An EU regulatory team on no menclature  composed of regulators , to \nbe established possibly  as an MDCG sub -group , will review, determine (preferably \nwithin a global perspective) and validate those rules prior to designation decision and \nwill continue to hold an advisory role on these matters . On a  periodic basis, in \naccordance with a pre -defined procedure, and in consultation with the nomenclature \nprovider, that group shall also provide feedback and advice on the governance  of \nterms and descriptions, based, inter alia, on the requests received from economic \noperators and other stakeholders.  \n \nIn the context of activities mentioned in the previous paragraph, it shall be aimed to \nensure that the terminology structure used for it should not be unnecessarily  granular  \nand should not contain names that are only used by only a few  economic operators This document has been endorsed by the Medical Device Coordination Group (MDCG) \nestablished by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of \nrepresentatives of all Member States and it is chaired by a representative of the European \nCommi ssion.  \n \nThe document is not a European Commission document and it cannot be regarded as \nreflecting the official position of the European Commission. Any views expressed in this \ndocument are not legally binding and only the Court of Justice of the European  Union can \ngive binding interpretations of Union law.  \n \n3 \n or stakeholders , unless it is proven to be advantageous to regulators or the wider \nhealthcare economy.  \n \nThe structure and design of the future nomenclature should facilitate the \nestablishment of lin ks with the codes defining N otified Bodies  competence \n(designation scope) , the scope of medical device s QMS  (Quality Management \nSystem)/QA (Quality Assurance)  certificates , and product portfolio s in the mandate  \nof Authorised Representatives .   \n \nThe nomenclature should have hierarch ies by which terms and codes could be \nmeaningfully grouped  into categories and subcategories   \n \nThe future nomenclature system shall adequately support the functioning of the \nEUDAMED database and the functioning of the new Regulations as a whole. In this \ncontext, EUDAMED shall make available the most updated names/codes related \ninformation, to the be nefit of operators and general public. Therefore, the \nnomenclature provider will need to have procedures and services in place that shall \nallow E UDAMED  to be kept up -to-date at any time.  When setting the procedure, in \nparticular the frequency, related to the periodic review of nomenclature terms and \ndescriptions , this shall be taken into account.  \n \nFor enforcement purposes , in relation to its obligations vis -\u00e0-vis the Commission and \nthe EU economic operators, the nomenclature provider  shall have a legal entity in \neither one of the EEA countries  or Switzerland  or Turkey1 with an exception being \nforeseen for international organisations in which the EU is one of the members .   \n \nSystem/processes shall be in place to periodically  review the terminology structure \nand content to incorporate learning from ongoing experience with real -world use of \ndevice nomenclature (ex. EUDAMED, GUDID, registries)  as well as from \ntechnological  innovation . \n \nAvailability of names and descriptions in all the official EU langu ages is recognised \nas of being of high importance.  \n \nAll copyright s associated with the nomenclature shall be secured.  \n                                                       \n1 Indication of these countries is based on current situation with the applicable directives on medical devices \nas a result of the combination of the legal text of those Directives and relevant currently applicable \ninternational agreements . this list of countries might be subject to change in the context of the new m edical \ndevice framework."}, {"title": "12 MDCG 2020-12 Guidance on transitional provisions for consultations of authorities on devices.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-12  \n \nPage 1 of 6 \n  \n \n \n \nMDCG 2020-12 \n  \n         Guidance on transition al provisions for \n       consultations of authorities on devices \n       incorporating a substance which may be \n       considered a medicinal product and which  \n       has action ancillary to that of the device,  \n       as well as on devices manufactured using  \n       TSE suscep tible animal tissues   \n             \n \n           June 2020 \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member States and it is chaired by a representative of the European Commission.The document is not a European Commission document and it cannot be regarded as reflecting the official position of the European Commission. Any views expressed in this document are not legally binding and only the Court of Justice of the European Union can give binding interpretations of Union law. \n  Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-12  \n \nPage 2 of 6 \n  \nGuidance on transitional provisions for consultations of author ities on \ndevices incorporating a substa nce which may be considered a \nmedicinal product and which has action ancillary to that of the  device, \nas well as on devices manufacture d using TSE susceptible animal  \ntissues \n \nI. Consultations for a substance which may be considered a medicin al product \nand which has action ancillary to that of the device (including  human blood \nderivatives) \n \nConsultation procedure under the MDD and AIMDD \nAccording to Annex I section 7.4 of Directive 93/42/EEC on medical devices (the MDD), and Annex \nI section 10 of Directive 90/385/EEC on active im plantable medical devices (the AIMDD), for \ndevices containing a substance which, if used separately, would be considered to be a medicinal \nproduct and which is liable to act upon the body with an action ancillary to that of the device, the \nnotified body is required, having verified the usefulness of the substance as part of the medical device \nand taking account of the intended purpose of the device, to seek a scientific opinion from one of the competent authorities designated by the Member St ates or the European Medicines Agency (EMA) on \nthe quality and safety of the  substance in the medical device, including the clinical benefit/risk profile \nof the incorporation of the substance into the device. Similarly, where changes are made to that \nsubstance, particularly relating to its manufacturing process, the notified body is required to consult \nwith the same authority in order to confirm that the quality and safety of that substance are maintained \nand to ensure that the changes have no negative impact on the established benefit/risk profile of the \naddition of the substance in the medical device. This consultation on changes is referred to as supplementary consultation in this guidance document.  \n \nThere is an equivalent consultation requirement for medical devices containing a human blood \nderivative with ancillary action. In this case the notified body is required to consult the EMA only. \n \nTransitioning from MDD and AIMDD to MDR \n \nRegulation (EU) 2017/745 on medical devices (the MDR)  establishes a similar requirement in Article \n52 (9) (Annex IX section 5.2 and Annex X Section 6): fo r devices incorporating, as an integral part, a \nsubstance which, if used separately, may be considered to be a medicinal product\n1 and which has an \naction ancillary to that of the device (hereafter referred to in this document as the ancillary substance), \nthe notified body is required, having verified the usefulness of the substance as part of the medical \ndevice and taking account of the intended purpose of the device, to consult a medicinal products \nauthority designated by a Member State or the EMA2 on the quality and safety of the substance, \nincluding the benefit or risk of the incorporation of the substance into the device. The notified body is \n                                                           \n1 including a medicinal product derived from human blood or human plasma \n2 only the EMA in the case of medicinal products derived from human blood or human plasma, or those falling \nexclusively within the scope of Regulation (EC) 726/2004  Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-12  \n \nPage 3 of 6 \n required to do so both for the initial conformity assessment of the device (this consultation is referred \nto as initial in this guidance document) and for an y subsequent changes to the ancillary substance, in \nparticular in relation to its manufacturing process (the consultation on changes is referred to as a \nsupplementary consultation, by analogy to the M DD/AIMDD). A competent auth ority designated by a \nMember State in accordance with Directive 2001/83/EC or the EMA (hereafter referred as medicinal products authority in this document) consulted has 210 days since the receipt of all the necessary \ndocumentation to provide its opinion in the case of an initial consultation, or 60 days for a \nsupplementary consultation. Unlike the MDD and AIMDD, the MDR also states that the notified \nbody may not deliver the certificate if the opinion is unfavourable (Annex IX 5.2 (e) and (f)).  \n This document provides guidance on fulfilling th is requirement for the first time under the MDR for \ndevices which already underwent a consultation with a medicinal products authority according to \nAnnex I 7.4 of the MDD or Annex I 10 of the AIMDD. \n \nConsultation for ancillary substances under the MDR for devices which have undergone the \nconsultation under the MDD or AIMDD \n \nIn order for the notified body to issue the first certificate for a given device under the MDR, a full \nconformity assessment covering all requirements has to be carried out even if the device has been \ncertified under the MDD (Q&A IV.1 MDCG 2019-6). For devices containing ancillary substances, this includes the consultation of the medicinal products authority as per Article 52 (9) of the MDR.  \n \nFor some devices, there may be no change to the device, the ancillary substance and its manufacturing \nprocess since the last consultation of the me dicinal products authority  under the MDD/AIMDD. \nNevertheless, there may be changes in the documentation of the device due to the new requirements \nof the MDR, for example in clinical evaluation, which have a bearing on the quality, safety or \nusefulness of the ancillary substance. There may also be changes in the assessment of the device and its documentation by the notified body under the MDR. Lastly, the medicinal products authority may \nhave new information on the substance, leading to a modified or different opinion.   \n \nFor the first consultation under the MDR, the notified body is required to submit the full \ndocumentation package to the medicinal products authority as described in dedicated guidance. The notified body is free to approach any medicinal products authority at its discretion, not necessarily the \none consulted under the MDD/AIMDD. This should in clude the last opinion of the medicinal products \nauthority under the MDD/AIMDD (whether initial or supplementary), as well as a consolidated list of \nchanges, if any, in the following:  \n\u0081 the ancillary substance, \n\u0081 its manufacturing process,   \n\u0081 the way the substance is incorporated into the device, \n\u0081 design, manufacturing of the device which could influence the quality, safety or usefulness of \nthe ancillary substance, and/or \n\u0081 the parts of the technical documentation related to the above aspects.  \nIf there were no changes to some or any of the above, the package may be accompanied by a \ndeclaration by the notified body to this effect, stating the elements that have remained identical. If \nthere have also been no changes to the assessment of this documentation by the notified body, this \nmay be included in the declaration. Should there be only administrative changes to the above (e.g. \nchanges of names or addresses, changes in document layout, etc.), these should be clearly detailed in the declaration.  \n \nThe medicinal products authority may consider the depth of its review given the extent of the changes \nsince the previous consultation under the MDD/AIMDD. It is at the discretion of the medicinal Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-12  \n \nPage 4 of 6 \n products authority to issue its opinion in less than 210 days. If many elements concerning the \nsubstance remain identical, the medicinal products authority is highly recommended to expedite its \nreview.   \n \nThe medicinal products authority may contact the authority consulted on this device under the MDD/AIMDD, who may, at its discretion, confirm the opinion provided in the previous consultation \nand/or share any additional information. The final opinion for the consultation under the MDR and its \nissuance according to the stipulated timeline remains the responsibility of the medicinal products \nauthority to which the notified body submitted the request under the MDR.  \n  \nNote on \u201cliability to act upon the body\u201d  \n \nIt should be noted that Annex I 7.4 of the MDD refers to devices in which the substance is liable to \nact upon the body . In the MDR (Article 52(9), referring to Article 1(8), and Section 5.2 of Annex \nIX), this is no longer the case. Therefore, for al l those devices where the \"liability to act upon the \nbody\" was used by the manufacturer as a justification not to follow the consultation, the consultation \nmust take place under the MDR.  In those cases where there are doubts on the applicability of the \nconsultation, independently of any considerations concerning the classification of the device, the \nnotified body should seek the scientific opinion as described in Annex IX Section 5.2 (b) of the MDR.    \nRelevant text from MDD and MDR  \nMDD \u2013 Annex I Section 7.4 [emphasis added] \nWhere a device incorporates, as an integral part, a substance which, if used separately, may be \nconsidered to be a medicinal product as defined in Article 1 of Directive 2001/83/EC and which is \nliable to act upon the body  with action ancillary to that of the device, the quality, safety and \nusefulness of the substance must be verified by an alogy with the methods specified in Annex I to \nDirective 2001/83/EC. \n \nFor the substances referred to in the first paragraph, t he notified body shall, having verified the \nusefulness of the substance  as part of the medical device and taking account of the intended purpose \nof the device, seek a scientific opinion from one of the competent authorities designated by the \nMember States or the European Medicines Agency (EMEA)  acting particularly through its \ncommittee in accordance with Regulation (EC) No 726/2004 (1) on the quality and safety of the \nsubstance including the clinical benefit/risk profile of the incorporation of the substance into the \ndevice . When issuing its opinion, the competent authority or the EMEA shall take into account the \nmanufacturing process and the data related to the usefulness  of incorporation of the substance into \nthe device as determined by the notified body. \n \nWhere a device incorporates, as an integral part, a human blood derivative, the notified body shall, \nhaving verified the usefulness of the substance  as part of the medical device and taking into account \nthe intended purpose of the device, seek a scientific opinion from the EMEA , acting particularly \nthrough its committee, on the quality and safety of the substance including the clinical benefit/risk \nprofile of the incorporation of the human blood derivative into the device . When issuing its opinion, \nthe EMEA shall take into account the manufacturing process and the data related to the usefulness of \nincorporation of the substance into the device as determined by the notified body. \nWhere changes are made to an ancillary substance incorporated in a device, in particular related to \nits manufacturing process, the notified body shall be informed of the changes and shall consult the \nrelevant medicines competent authority (i.e. the one involved in the initial consultation), in order to confirm that the quality and safety of the ancillary substance are maintained. The competent authority Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-12  \n \nPage 5 of 6 \n shall take into account the data related to the usef ulness of incorporation of the substance into the \ndevice as determined by the notified body, in order to ensure that the changes have no negative \nimpact on the established benefit/risk profile of the addition of the substance in the medical device. \n \n \nMDR \u2013 Annex IX 5.2 b \n \n(a) Where a device incorporates, as an integral part, a substance which, if used separately, may be \nconsidered to be a medicinal product within the meaning of point 2 of Article 1 of Directive \n2001/83/EC, including a medicinal product derive d from human blood or human plasma and \nthat has an action ancillary to that of the device, the quality, safety and usefulness of the \nsubstance shall be verified by analogy with the methods specified in Annex I to Directive \n2001/83/EC. \n \n(b) Before issuing an EU technical documentation assessment certificate, the notified body shall, \nhaving verified the usefulness of the substance  as part of the device and taking account of the \nintended purpose of the device, seek a scientific opinion from one of the competent authorities \ndesignated by the Member States in accor dance with Directive 2001/83/EC or from the EMA , \neither of which to be referred to in this Section as \u2018the medicinal products authority consulted\u2019 \ndepending on which has been consulted under this point, on the quality and safety of the \nsubstance including the benefit or risk of the incorporation of the substance into the device . \nWhere the device incorporates a human blood or plasma derivative or a substance that, if used \nseparately, may be considered to be a medicinal product falling exclusively within the scope of \nthe Annex to Regulation (EC) No 726/2004, the notified body shall seek the opinion of the EMA.  \n \n(c) When issuing its opinion, the medicinal products authority consulted shall take into account the \nmanufacturing process and the data relating to the usefulness  of incorporation of the substance \ninto the device as determined by the notified body. \n \nII. Consultations for medical device s containing TSE susceptible an imal tissue \nunder the MDR, where such a consultation took place under the M DD or \nAIMDD \n \nArticle 5(4) of Regulation (EU) 722/2012 requires that for all medical devices, including active \nimplantable medical devices, manufactured utilising tissues of animal origin which are susceptible to \ntransmissible spongiform encephalopathy (TSE), the notified body must, through their competent \nauthority, carry out a consultation of the other competent authorities and the Commission. \nUnder the MDR, this requirement rema ins unchanged (Annex IX Section 5.3.2). \nIn order to fulfil the requirements of the MDR, during the first certification under the MDR, the \nnotified body is required to submit the full summary evaluation report as stated in Regulation (EU) \n722/2012 to the competent authorities. If there have been no changes to the documentation required \nfrom the manufacturer as per Regulation (EU) 722/2012, the summary evaluation report may be \naccompanied by a declaration by the notified body to this effect, stating the elements that have remained identical. If there have also been no changes to the assessment of this documentation by the \nnotified body, this may also be included in th e declaration. Should there be only administrative \nchanges to the above (e.g. changes of names or addresses, changes in document layout, etc.), these \nshould be clearly detailed in the declaration.  Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-12  \n \nPage 6 of 6 \n  \nAs stated in Article 5(5) of Regulation (EU) 722/2012, the competent authorities and the Commission \nmay agree on shortening the time periods for the consultation. If many elements of the summary evaluation report remain identical, it is highly recommended to expedite the review. \nRelevant text from Regulation (EU) 722/2012 \nArticle 5 (4) and (5) 4. Before issuing an EC design-examination certificate or an EC type-examination certificate, the \nnotified bodies shall, through their competent authority, hereinafter \u2018coordinating competent \nauthority\u2019, inform the competent authorities of th e other Member States and the Commission of their \nassessment carried out pursuant to paragraph 2 by means of a summary evaluation report in \naccordance with Annex II to this Regulation.  \n5. The competent authorities of the Member States may submit comments on the summary evaluation \nreport referred to in paragraph 4 within the following deadlines:  \n(a) in relation to medical devices using starting materials for which a TSE certificate of suitability as \nreferred to in paragraph 3 has been submitted, within four weeks from the date on which the notified \nbody informed the coordinating competent authority pursuant to paragraph 4;  \n(b) in relation to medical devices using starting materials for which a TSE certificate of suitability has \nnot been submitted, within 12 weeks from the date on which the notified body informed the \ncoordinating competent authority pursuant to paragraph 4.  \nThe competent authorities of the Member States  and the Commission may agree on shortening the \ntime periods set out in points (a) and (b)."}, {"title": "mdcg_2018_8_crf_transfer_en.pdf.txt", "text": "Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -8   \nPage 1 of 2 \n  \n \n \n \n \nMDCG  2018 -8 \nGuidance on c ontent of the certificates,    \n voluntary certificate transfers  \n                 \n \n \n November 2018  \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical  Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commissi on document and it cannot be regarded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union  law. \n Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -8   \nPage 2 of 2 \n  \n \nIn the meeting of 30 November 2018, MDCG endorsed the below positions. These \npositions will be part of a more comprehensive guideline related to notified bodies, \ncurrently under development.  \n \nContent of the certificate under MDR / IVDR Annex XII, Chapter II, section 10  \nCertificates do not need to include reference to relevant common specifications or \nharmonised standards as long as such information on all examinations and tests \nperformed is traceable and available from e.g. report(s) which are ment ioned in the \ncertificate.  \n \nVoluntary certificate transfer under MDR Article 58 / IVDR Article 53  \nWhile MDR Article 58(1) / IVDR Article 53(1) sets out the requirements for a transfer \nagreement, it does not specify the conformity assessment activities to be  performed \nby the incoming NB. The incoming NB may decide not to carry out full conformity \nassessment activities according to Article 52 MDR / Article 48 IVDR, as long as it \ndoes have sufficient information in respect to the conformity activities performed  by \nthe outgoing NB.  \nFor quality management system certificates, the incoming NB needs to perform \nappropriate on -site audit(s) and assessments to ensure that the manufacturer in \nquestion applies the approved QMS and the post -market surveillance plan prior to \nthe issue of any certificate. In respect to the assessment of technical documentations \non a sampling basis, the oncoming NB shall review the previous assessment results \ntogether with a sample of a  technical documentation and draw up or amend a \nsampling plan. For product certificates (Annex IX Chapter II/Annex X), new \ncertificates without a  comprehensive (initial) review may be issued as long as the \ndocumentation received does not identify ongoing existing or other concerns.  \nThe incoming NB assumes full responsibility for the new certificates issued following \nthe transfer."}, {"title": "mdcg_2019_14_MDR_codes.pdf.txt", "text": "1 \n Medical Device       \nMedical Device Coordination Group Document   MDCG  2019-14    \n \n  \n \n \n \nMDCG  2019-14  \n        Explanatory note on MDR codes   \n           \n \n           December   2019 \n \n \n  \n    \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission. \nThe document is not a European Commission document and it cannot be regarded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European Union can give binding interpretations of Union law.  \n   \n2 \n Explanatory note on MDR codes \n \n1 Introduction \nCommission Implementing Regulation 2017/2185 establishes the codes for the designation of notified \nbodies in medical devices under Regulation (EU) 2017/745 and in vitro  diagnostic medical devices \nunder Regulation (EU) 2017/746.  These codes are primarily used by designating authorities to define \nthe notified body scope of designation but they are also used by the notified body to:  \n1) describe the individual qualification of the NBs staff members 2) describe the qualification required for assessing a device  \nThese codes may be very broad and, furthermore, unequivocal authorisation of personnel to codes \nand the assignment of codes to a device is not always straightforward. However, the notified body\u2019s system needs to ensure, in all cases, that the authorisation of personnel and team allocation for the conformity assessment of a device ensures adequate knowledge and expertise.  \n \n2 Scope \nThe lists of codes and corresponding types of devices established by the above mentioned \nRegulation takes into account various device types which can be characterised by design and intended purpose, manufacturing processes and technologies used, such as sterilisation and the use of nanomaterials.  \nThese lists of codes should be used in a way that provides for a multi-dimensional application to all \ntypology of devices. This will ensure that notified bodies as well as the staff assigned to conformity assessment are fully competent for the devices they are required to assess. \nThis guidance is intended to explain the different level of codes and how they should be used, \nincluding the use of conditions with a view to ensure a harmonised use of the codes especially for the allocation of resources to conformity assessment activities.  \n \n \n3 \n 3 Assignment of codes to devices within the conformity \nassessment procedure \nWhen a manufacturer lodges an application with a notified body, the type of devices and technologies \nsubject to conformity assessment activities are to be indicated. Usually, at the application review stage (as defined in section 4.3 of Annex VII MDR), notified bodies will verify the assignment of codes provided by the manufacturer or will assign these codes to the devices themselves. This verification is carried out in order to ensure that the notified body is able to assess the application based on its designation, and that it has available resources to carry out the relevant conformity assessment \nactivities (feasibility evaluation). The final assignment is made by the NB.  \nAfter this application review, and signing of the contract, the notified body will allocate appropriately \nqualified and authorised personnel to carry out audit activities or product reviews.  \nThe following table presents an overview of the different types of codes and a summary of the main \ncharacteristics of each of them for the assignment to specific devices and the allocation of resources. \nType Code Assignment of codes to the \ndevice Relevance for allocation of \nconformity assessment team \nMDA / MDN Codes reflect design and \nintended  purpose of \ndevice Exactly 1 code per device. \n \nThe codes should be selected \naccording to their hierarchical order in Regulation 2017/2185. If more than 1 MDA/ MDN code is applicable, the one that is highest in the list should be selected.  Allocation of personnel involved in \nthe review of technical \ndocumentation (e.g. product \nreviewers) or in audits concerning product related aspects. \nMDS Horizontal codes that \nreflect the specific \ncharacteristics of the device  0 to several per device \n \nAssign all codes applicable to the \ndevice.  Select once an MDN/MDA code has been assigned.  Allocation of personnel involved in \nthe review of technical \ndocumentation (e.g. product \nreviewers of sterilisation validation).   \nMay also be applicable to staff \nperforming audits concerning  \ncertain special processes (e.g. \nsterilization).* \nMDT  \nHorizontal codes that describe technologies or processes  1 to several per device \n Assign the codes which describe the main production technologies or processes.  \n \nSelect once an MDN/MDA code has been assigned. Allocation of personnel involved in \naudits (e.g. site auditors involved in the auditing of metal processing). \n* Note: Assessment of these codes could be performed by Product reviewers or Site auditors depending on their competence  \n \n3.1 MDN / MDA-codes \nMDA / MDN-codes reflect the design and intended purpose of the device and hence are mostly \nrelevant for the allocation of personnel involved in the review of technical documentation.  In some \nspecific cases, the NB may assign product reviewers to assess product performance and safety aspects during an audit. This means that if there are product related issues to be audited and the auditors do not possess the required qualification, product reviewers who are qualified for the device in question should be part of the audit team.  \nThe NB needs to ensure that the personnel allocated to the project are competent to assess for the \ndevices and technologies under assessment . Special attention should be paid in situations such as \nthe one described in example 4 of this section.   \n4 \n The MDA / MDN codes may either specify a field of medical application (e.g. MDA 0309 Active non-\nimplantable ophthalmologic devices) or the physical or technological principle of the device (e.g. MDA \n0302 Active non-implantable devices utilising non-ionizing radiation or MDA 0315 Software). \nTherefore, there are cases where more than one specific code might apply to a device (e.g. surgical \nlaser for refractive surgery of the eye ). Also, where there is a broad intended purpose, several codes \nmay apply. \nHaving these issues in mind, when drafting the Regulation 2017/2185, the codes were put in order \nsuch that the MDA/MDN codes that require very specific technological knowledge and experience are highest in the code lists. Therefore, in cases where more than one MDA/MDN code apply, the code highest in the list is to be selected. This approach ensures consistent assignment of codes (and therefore consistent assignment of suitably qualified staff) to devices. \nExample 1: A surgical laser for refractive surgery of the eye is assigned to MDA 0302 Active \nnon-implantable devices utilising non-ionizing radiation and not to MDA 0309 Active non-\nimplantable ophthalmologic devices because, even though both codes are specific for the device, since MDA 0302 is higher in the list. \nExample 2: A screw for orthopaedic surgery is assigned to MDN 1102 Non-active osteo- and \northopaedic implants and not to 1104 Non-active soft tissue and other implants, because MDN 1102 is higher in the list. \nDevices may be composed of different \u201ccomponents\u201d which, if they were products on their own, would \nbelong to different MDA/MDN codes\n(1). In such cases, the intended purpose or the main physical or \ntechnological principle of the device should be considered (Example 3).  Nonetheless, the notified body needs to ensure that the assigned staff is qualified to assess all components of the device.  \nExample 3: A medical devices is composed of a suture anchor (a bone screw attached to a \nsurgical suture to reattach ruptured tendons) as well as a single use deployment instrument \nand a single use bone drill. The components are provided sterile in a blister, are covered by the same technical documentation and are not available individually (e.g. are not medical devices on their own). This product is assigned to MDN 1102 Non-active osteo- and orthopaedic implants and not to MDN 1208 Non-active non-implantable instruments because the implanted component of the device is associated with the intended purpose rather than the deployment instrument and the drill.  \nNote that, given the complexity and the diversity of medical devices, in exceptional cases deviations \nfrom the guidance given above may be necessary when assigning codes to devices in order to ensure \nsuitably qualified staff in the conformity assessment. In such cases, a brief rationale shall be documented (see Example 4).  \nExample 4: A heater-cooler unit (HCU) for cardiac surgery is a device through which blood \ncirculates, and which changes the circulating blood\u2019s temperature in order to achieve hypo- or hyperthermia. Both the codes MDA 0303 Active non-implantable devices utilising hyperthermia/hypothermia and MDA 0306 Active non-implantable devices for extra-corporal circulation, administration or removal of substances and haemapheresis are specific to the \ndevice. Since MDA 0303 Active non-implantable devices utilising hyperthermia/hypothermia is \na code that describes physical or technological characteristics higher in the list, according to the rule explained above MDA 0303 should be chosen. Nonetheless, the notified body assigns the device to the code MDA 0306 Active non-implantable devices for extra-corporal circulation, administration or removal of substances and haemapheresis and documents that \nthe risks associated with the HCU are such that the staff having experience in this code is \nmore suitable to assess the device.  \nIt is important to note that Stand-alone software (i.e. software that is not part of a physical medical \ndevice) should be assigned to MDA 0315 since assessment of software requires very specific knowledge (see annex VII 3.2.2 5\nth indent MDR) and also that  non-implantable cardiovascular \n                                            \n1 This description does NOT refer to procedure packs or systems according to MDR Article 2 (10) and (11) since those are \ncombinations of individual CE-marked products that have been subjected to separate conformity assessments.  \n5 \n catheters, guidewires, introducers, filters and related tools shall fall under MDN 1203 (instead of MDN \n1201 or MDN 1202). \n \n3.2 MDS codes \nMDS codes are horizontal codes that are applicable to devices with specific characteristics. All codes \nthat are applicable need to be assigned to a device in order to ensure that the review team possesses \nthe full set of qualifications necessary for the conformity assessment. The MDS-codes are mainly relevant for the allocation of personnel involved in the review of technical documentation. This is because, generally, the auditing aspects linked to MDS codes have their corresponding MDT code for \nthe relevant technology (e.g. MDS 1001 Devices incorporating medicinal substances  vs MDT 2007  \nDevices which require knowledge regarding the production of pha rmaceuticals ). However, MDS \ncodes may also be applicable to staff performing audits concerning  certain special processes (for \nexample MDS 1005 for staff auditing ethylene oxide sterilization processes). \nExample 1: A partially resorbable, sterile surgical implant that contains an antibiotic to prevent \npost-surgical infection will need to be assigned to the following MDS codes:  \n1) MDS 1005 - Devices in sterile condition: because it is provided sterile,  \n2) MDS 1008 - Devices utilising [...] being wholly or mainly absorbed or locally dispersed \nin the human body [\u2026]:  because it is absorbed, and  \n3) MDS 1001 - Devices incorporating medicinal substances: because it contains an \nantibiotic. \nExample 2: An infusion pump should be assigned to MDS 1009 - Devices incorporating \nsoftware/utilising software/controlled by software [\u2026] because the infusion pump is controlled \nby software. \n3.3 MDT codes \nMDT codes relate to the technologies and processes that are used in the manufacturing and making available of the devices. MDT codes are relevant for the allocation of site auditors. \nAssignment of MDT codes should be done taking into consideration production of the device itself as \nwell as for critical upstream production steps. This means that, even  though many codes could be \napplicable when taking into consideration the processes involved in the entire supply chain of a medical device, these should not be considered for the use of MDT codes (e.g. for an electronic \nmedical thermometer, at one point, metal processing, plastic processing, non-metal mineral processing, chemical processing, manufacture in clean rooms, manufacturing using electronic components, labelling and packaging are necessary to assemble the device from raw materials).  \nExample 1: An electronic medical thermometer for layman\u2019s use should be assigned to the \nfollowing MDT codes:  \n1) MDT 2010 Devices manufactured using electronic components including \ncommunication devices because the product is assembled from electronic \ncomponents and  \n2) MDT 2011 Devices which require packaging, including labelling because the device is \npacked and labelled. \nExample 2: A sterile animal derived bone graft substitute is manufactured using several steps. \nIn the first step, the raw animal bone undergoes a sequence of chemical treatments to remove organic components. In a second step, the remaining mineral bone component is subjected to a heat treatment, then ground and sieved to obtain particles of defined sizes. The material is packed, labelled and sterilized. Therefore the following MDT codes should be assigned:  \n6 \n 1) MDT 2008 Devices manufactured in clean rooms and associated controlled \nenvironments, because the manufacturing of the implant after the heat treatment is conducted in clean rooms,  \n2) MDT 2009 Devices manufactured using processing of materials of human, animal, or \nmicrobial origin because the implant is made from animal bone \n3) MDT 2011 Devices which require packaging, including labelling because the implant \nis packed and labelled. \nNote: MDT 2006 Devices manufactured using chemical processing and MDT 2003 \nDevices manufactured using non-metal mineral processing (e.g. glass, ceramics) \nwere not applied since the chemical treatment and (bone) mineral processing are already considered within the scope of processing of animal materials.  \nExample 3: A calcium phosphate bone cement is provided as a sterile powder composed of a \nmixture of calcium salts and a vial with sterile saline.  The following MDT codes should be assigned: \n1) MDT 2008 Devices manufactured in clean rooms and associated controlled \nenvironments, because the manufacturing of the implant is in a controlled environment,  \n2) MDT 2006 Devices manufactured using chemical processing, because the main risks \nin manufacturing are related to the testing and mixing of the components, \n3) MDT 2011 Devices which require packaging, including labelling because the implant \nis packed and labelled. \nExample 4: A manufacturer of cross-linked hyaluronic acid implants has no in-house \nmanufacturing. The finished, labelled implant is bought from a supplier. The implant raw \nmaterial (hyaluronic acid) is produced by fermentation using bacteria. The following MDT \ncodes should be assigned: \n1) MDT 2008 Devices manufactured in clean rooms and associated controlled \nenvironments, because the manufacturing of the implant is in a controlled environment,  \n2) MDT 2005 Devices manufactured using bi otechnology, because the main risks in \nmanufacturing are related to the production and cross-linking of the hyaluronic acid. \n3) MDT 2011 Devices which require packaging, including labelling because the implant \nis packed and labelled. \nNote that, despite the fact that the manufacturer itself does not physically manufacture the \ndevice, the MDT codes concerning the manufacturing steps are assigned to the device since they are relevant when auditing suppliers / subcontractors. \n4 Competence description: conditions (including limitations) \nConditions should be established by the notified body for individual codes in cases where the qualification of the staff authorised to a certain code is not sufficient to cover the entire spectrum of the devices within this code.  The designating authority could also apply conditions to the notified \nbody's designation where the notified body does not have sufficient competence to cover a given \ncode or could seek designation for conformity assessment of only certain devices within a code. \nConditions, including limitations, should be formulated in an unambiguous way (see example 1). \nFurthermore, since the technical codes basically mirror the competence system of the notified body, the conditions and limitations should concern device characteristics (see example 2). \nExample 1: \u201cMDN 1101 Non-active cardiovascular, vascular and neurovascular implants. \nCondition: heart valves\u201d. This condition is unsuitable since it is not clear whether the notified body is restricted to assessment of heart valves or whether those products are excluded from  \n7 \n the scope of designation. Therefore, the condition should be \u201cexcluding heart valves\u201d or \n\u201cincluding only heart valves\u201d. \nExample 2: \u201cMDN 1102 Non-active osteo- and orthopaedic implants. Condition: excluding \nclass III devices\u201d. The scope of designation is intimately linked to the qualification of the staff \nthat the notified body needs to have available. Conditions serve to exclude the devices for \nwhich the notified body does not have competent staff and/or suitable procedures; therefore, they need to be expressed in a way that they relate to knowledge and experience of staff and/or procedures. The condition \u201cexcluding class III devices\u201d does not allow this and therefore it is unsuitable. In this case, the designating authority has to determine, based on the qualification of the notified body\u2019s staff, which devices are included in the scope. This \nmight result, for example, in the following condition: \u201cincluding only orthopaedic plates and \nscrews; excluding implants that are applied in or on the spine\u201d. \nFurther examples of conditions are illustrated in the final column of the table below. Considerations of \nthe conditions should be based on the demonstrated competence of the applicant body\n. \n   \n8 \n  \n5 Specific clarifications linked to individual codes  \nThe devices included in the third and fourth columns are only a few examples of the devices covered in the relevant code. The t hird \ncolumn is not intended to provide an exhaustive list of devices included in each code. \n \nMDA \nCODE Active implantable devices Devices covered and Specific \nConsiderations1 Examples of \nconditions \nMDA 0101 Active implantable devices for stimulation / inhibition / monitoring Implanted defibrillator \nSpinal cord stimulator \nImplantable cardiac pacemakers \nImplantable bladder stimulators Excluding brain stimulation \nMDA 0102 \n Active implantable devices delivering drugs or other substances Implanted drug delivery pump \n  \nMDA 0103  Active implantable devices supporting or replacing organ functions Artificial heart \nCochlear implants \n \n  \nMDA 0104 \n Active implantable devices utilising radiation and other active implantable \ndevices Prostate radioactive seed implant \n \n  \n  \n                                            \n1 The assessment also should consider Section 5.1 of Annex IX applies as well as Validation of SSCP acc. Article 32 .   \n9 \n MDA \nCODE Active non-implantable devices for imaging, monitoring and / or \ndiagnosis Devices covered and Specific \nConsiderations Examples of conditions \nMDA 0201 \n Active non-implantable imaging devices utilising ionizing radiation X-ray computer tomography equipment  \nGamma cameras \nFluoroscopy equipment \nPET scanner Restricted to X-ray and gamma \ncameras \nMDA 0202  Active non-implantable imaging devices utilising non-ionizing radiation MRI computer tomograph \n  \nMDA 0203 \n Active non-implantable devices for monitoring of vital physiological \nparameters Blood pressure monitor \nMedical thermometer \nPulse oximeter \nApnoea monitors  \nIntensive care patient monitoring system \nSpirometers \nElectrocardiographs \nElectroencephalographs \n  \nMDA 0204 \n Other active non-implantable devices for monitoring and / or diagnosis Ocular tonometer \nAudiometers \nRetinal cameras  \n   \n10 \n MDA \nCODE Active non-implantable therapeutic devices and general active \nnon-implantable devices Devices covered and Specific \nConsiderations Examples of conditions \nMDA 0301 \n Active non-implantable devices utilising ionizing radiation \n Radioactive sources for cancer after \nloading therapy \nTherapeutic cyclotrons and linear \naccelerators   \nMDA 0302 \n Active non-implantable devices utilising non-ionizing radiation Surgical laser for refractive surgery of the \neye \nLaser for pain treatment \n \n Including only microwave and \nmagnetotherapy medical devices \nMDA 0303  Active non-implantable devices utilising hyperthermia / hypothermia Medical heating blanket \n \nWarming and cooling blankets \nBlood warmers \nParaffin bath  \nMDA 0304  Active non-implantable devices for shock-wave therapy (lithotripsy) Extracorporeal shock wave lithotripsy \ndevice \n \n  \nMDA 0305  Active non-implantable devices for stimulation or inhibition \n Automated external defibrillator \nDevice for the transcranial magnetic brain \nstimulation \nDevice for transcutaneous electrical nerve \nstimulation (TENS) \nMuscle stimulators \nElectrical acupuncture \nExternal bone growth stimulators \n  \n   \n11 \n MDA \n0306 \n Active non-implantable devices for extra- corporal circulation, administration or \nremoval of substances and haemapheresis Haemodialysis machine and equipment \nCardiopulmonary bypass pump \nInfusion pumps \nFeeding pumps \nJet injectors for vaccination \nBlood pumps for heart-lung machines \nAnaesthesia machines  \nMDA \n0307 \n Active non-implantable respiratory devices \n Medical ventilator \nHyperbaric chambers \nNebulisers  \nMDA \n0308 \n Active non-implantable devices for wound and skin care \n Water jet for wound debridement \n  \nMDA \n0309 \n Active non-implantable ophthalmologic devices \n Aspiration pump for opthalmological use \n(removal of crystalline residue)  \nMDA \n0310 \n Active non-implantable devices for ear, nose and throat  \n Hearing aids \n \nMDA \n0311 \n Active non-implantable dental devices \n Powered dental surgical unit and hand \npieces \nSurgical suction device for dental use \nUltrasonic scalers  \nChairs with equipment \n  \nMDA \n0312 \n Other active non-implantable surgical devices \n RF electrosurgical generator \nElectrosurgical instrument Cauterization \ndevices. \nPowered surgical drills and saws    \n12 \n MDA \n0313 \n Active non-implantable prostheses, devices for rehabilitation and devices for \npatient positioning and transport  Hospital beds \nPatient hoists \nElectric Wheelchairs \nActive limb prostheses \nExoskeletons  \nMDA \n0314 \n Active non-implantable devices for processing and preservation of human cells, \ntissues or organs including in vitro fertilisation (IVF) and assisted reproductive \ntechnologies (ART) IVF cryopreservation systems \nblood bank refrigerator  \nMDA \n0315 \n Software  \n Radiotherapy planning system. \n \nMDA \n0316 \n Medical gas supply systems and parts thereof \n Medical gas supply system in a hospital \nGas manifold and line pressure regulator \nfor medical regulators \nMedical gas supply pipeline systems   \nMDA \n0317 \n Active non-implantable devices for cleaning, disinfection and sterilisation Sterilizers like autoclaves etc \nWasher disinfector for medical devices.  \nMDA \n0318 \n Other active non-implantable devices \n  \n \n   \n13 \n MDN \nCODE Non-active implants and long term surgically invasive devices Devices covered and Specific \nConsiderations Examples of conditions \nMDN \n1101 \n Non-active cardiovascular, vascular and neurovascular implants Cardiac vascular stent \nPeripheral vascular stent \nArtificial heart valve \nCardiac Valve Prostheses, Vascular and \nneurovascular grafts, shunts, vascular \nstents, cardiovascular patches \nSutures for cardiovascular surgery \nFor biological heart valves MDS 1003 \nshould be applied. For drug eluting stents - \nMDS 1001 should be appliedIncluding only cardiac stents \nMDN \n1102 \n Non-active osteo- and orthopaedic implants \n Artificial spinal disc \nSpinal cage \nBone graft substitute for orthopaedic \nindications \nProsthetic joint replacements (i.e knee, hip \nimplants) \nBone cement \nHyaluronic acid implant for intra-articular \nuse \nOrthopaedic nails, screws,plates \nBone graft substitute for maxillofacial \nindications \nsutures, suture anchors, staples for \northopedic surgery \nspacers, ligament reconstruction products \n \nFor antibiotic bone cements- MDS 1001 \nshould be applied \nFor absorbable substances MDS 1008 \nshould be applied   \n14 \n MDN \n1103 \n Non-active dental implants and dental materials \n Dental implant  \nDental fillers \nRoot canal filler \nAbutments   \n   \n15 \n MDN \n1104 \n Non-active soft tissue and other implants \n Hyaluronic acid dermal fillers \nIntraocular lenses \nIntrauterine dispositive- IUD \nBreast implant \nHernia mesh \nUrethral stent implants \nSutures (not falling within the above codes) \nEyelid implants \n \nBariatric surgery devices: Intragastric \nBalloons, Gastric Bands, Anti-Reflux \nimplants. \nLung Volume Reduction devices: Coils, \nValves, Sealants. Biliary and Pancreatic \nstents \n \nFor contraceptive intrauterine devices \ncontaining copper or silver \u2013 MDS 1001 \nshould be applied \n Excluding breast implants \nMDN \nCODE Non-active non-implantable devices Devices covered  and specific \nconditions Examples of conditions \nMDN \n1201 \n Non-active non-implantable devices for anaesthesia, emergency and intensive \ncare Device for pleural drainage \nMasks, tubes for the administration of \ngases. \nEndotracheal tube \nTracheostomy tubes Endotracheal tube \nintroducers   \n16 \n MDN \n1202 \n Non-active non-implantable devices for administration, channelling and removal \nof substances, including devices for dialysis Intravenous line \nHypodermic needle \nSyringe tubing, bags for injection or \ntransfusion \nDialysis filter \nDialysis solution \nEpidural catheters, Urinary Catheter \nAmnioscopic needles  \n \nMDN \n1203 \n Non-active non-implantable guide catheters, balloon catheters, guidewires, \nintroducers, filters, and related tools Vascular filter catheter \nEmbolectomy catheter  \nCardiovascular guidewires and catheters \nNeurovascular catheters \ncentral venous catheter.  \nMDN \n1204 \n Non-active non-implantable devices for wound and skin care \n Wound dressing \nCotton wool \nGauze dressings \nBandages \nSutures for dermal wound closure (of less \nthan 30 days) \nSurgical gloves \nFor dressings incorporating an \nantimicrobial agent -  MDS 1001 should be \napplied \nMDN \n1205 \n Non-active non-implantable orthopaedic and rehabilitation devices Orthoses \nCrutches \nWheelchairs   \n17 \n MDN \n1206 \n Non-active non-implantable ophthalmologic devices \n Contact lenses \nEye drops \nInstrument for ophthalmologic surgery \nSolutions for contact lenses.  \nMDN \n1207 \n Non-active non-implantable diagnostic devices  Thermal expansion thermometer  \nMDN \n1208 \n Non-active non-implantable instruments \n Instruments for general use in surgery: \nForceps, clamps, scalpels, dental \ninstruments \n  \nMDN \n1209 \n Non-active non-implantable dental materials \n Etching solution for dental use \nBraces \nDental cements (when not considered long \nterm surgically invasive) \nDental impression materials  \nMDN \n1210 \n Non-active non-implantable devices used for contraception or prevention of the \ntransmission of sexually transmitted diseases Condom \nContraceptive diaphragms  \nMDN \n1211 \n Non-active non-implantable devices for disinfecting, cleaning and rinsing Solutions for disinfecting medical devices  \nContact lens care, catheter lock solutions \n  \nMDN \n1212 \n Non-active non-implantable devices for processing and preservation of human \ncells, tissue or organs including in vitro fertilisation (IVF) and assisted \nreproductive technologies (ART) Freezing solution for egg cells \nEmbryo transfer catheters \nArtificial insemination probes \nMedia, substances or mixture of \nsubstances intended for washing, \nseparating, sperm immobilizing, \ncryoprotecting solutions. \n   \n18 \n MDN \n1213 \n Non-active non-implantable devices composed of substances to be introduced \ninto the human body via a body orifice or the dermal route   \nMDN \n1214 \n General non-active non-implantable devices used in health care and other non-\nactive non-implantable devices Ultrasound gels   \n   \n19 \n MDS \nCODE Devices with specific characteristics Devices covered  and specific \nconditions Examples of conditions \nMDS \n1001 \n Devices incorporating medicinal substances \n Devices incorporating medicinal products \nincluding herbal substances and human \nblood derivatives are included in this code.   \nMDS \n1002 \n Devices manufactured utilising tissues or cells of human origin, or their \nderivatives Section 5.3.1 of Annex IX applies   \nMDS \n1003 \n Devices manufactured utilising tissues or cells of animal origin, or their \nderivatives Section 5.3.2 of Annex IX applies \nDevices manufactured utilising tissues or \ncells of animal origin, or their derivatives, \nwhich are non- viable or rendered non-\nviable, unless such devices are intended to \ncome into contact with intact skin only   \nMDS \n1004 \n Devices which are also machinery as defined in point (a) of the second \nparagraph of Article 2 of Directive 2006/42/EC of the European Parliament and \nof the Council1   \nMDS \n1005 \n Devices in sterile condition  Including aseptic processing, \nethylene oxide gas sterilisation \n(EOG), low temperature steam, \nformaldehyde sterilisation, moist \nheat sterilisation, radiation (gamma, \nx-ray, electron beam), sterilisation \nwith hydrogen peroxide, sterilisation \nwith liquid chemical sterilising \nagents, thermic sterilisation with dry \nheat \n                                            \n1 Directive 2006/42/EC of the European Parliament and of the Council of 17 May 2006 on machinery, and amending Directive 95/16/E C (recast) (OJ L 157 \n9.6.2006, p. 24).  \n20 \n MDS \n1006 \n Reusable surgical instruments \n Reusable surgical instruments according to \nart. 52 (7) c) MDR   \nMDS \n1007 \n Devices incorporating or consisting of nanomaterial  \n   \nMDS \nCODE Devices with specific characteristics Devices covered  and specific \nconditions Examples of conditions \nMDS \n1008 \n Devices utilising biologically active coatings and / or materials or being wholly or \nmainly absorbed or locally dispersed in the human body or are intended to \nundergo a chemical change in the body Section 5.4 of Annex IX applies for devices  \nintended to be introduced into the human \nbody via a body orifice or applied to the \nskin and devices  at are systemically \nabsorbed by the human body in order to \nachieve their intended purpose   \nMDS \n1009 \n Devices incorporating software / utilising software / controlled by software, \nincluding devices intended for controlling, monitoring or directly influencing the \nperformance of active or active implantable devices   \nMDS \n1010 \n Devices with a measuring function \n    \nMDS \n1011 \n Devices in systems or procedure packs \n   \nMDS \n1012 \n Products without an intended medical purpose listed in Annex XVI to Regulation \n(EU) 2017/745    \n21 \n MDS \n1013 \n Class III custom-made implantable devices  \n   \nMDS \n1014 \n Devices incorporating as an integral part an in vitro  diagnostic device \n   \n   \n22 \n MDT \nCODE Devices for which specific technologies or processes are used Examples of device manufacturing technologies \nMDT \n2001 Devices manufactured using metal processing \n 3 d printing, Casting, Welding \n3d printing (metal), turning (metal), anodization, passivation, polishing, surface \nmodification, laser tube cutting, honing \nMDT \n2002 Devices manufactured using plastic processing \n Injection molding, Extrusion, Bonding \npolymer compounding, 3d printing (plastics), thermoforming, blow moulding, turning \n(plastics) \n \nMDT \n2003 Devices manufactured using non-metal mineral processing (e.g. glass, \nceramics) Ceramic sintering, ceramic compounding,  \n \nMDT \n2004 Devices manufactured using non-metal non-mineral processing (e.g. textiles, \nrubber, leather, paper) Weaving, knitting  \nMDT \n2005 Devices manufactured using biotechnology \n Fermentation using cell cultures, enzymatic production processes, purification and \nmodification of biomolecules  \nMDT \n2006 Devices manufactured using chemical processing  \n Compounding, buffering  \nMDT \n2007 Devices which require knowledge regarding the production of pharmaceuticals production, handling and incorporation into a device of substances which, if used \nseparately, can be considered to be a medicinal product  \nMDT \n2008 Devices manufactured in clean rooms and associated controlled environments  \nMDT \n2009 Devices manufactured using processing of materials of human, animal, or \nmicrobial origin Handling, dissection, storage, processing, inactivation and sterilization of human \nand animal tissues   \n \nMDT \n2010 Devices manufactured using electronic components including communication \ndevices  \nMDT \n2011 Devices which require packaging, including labelling \n   \n23 \n MDT \n2012 Devices which require installation, refurbishment \n Installation of devices at the point of use by or under the manufacturer\u2019s \nresponsibility  \nMDT \n2013 Devices which have undergone reprocessing"}, {"title": "QA requirements for notified bodies V2 01102019.pdf.txt", "text": "Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 1 of 14 \n  \n \n \n \n  \nMDCG  2019-6 v2  \nQuestions and answers: \nRequirements relating to notified bodies \n \n \n Version 2 - October 2019 \n \n \n This document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission. \nThe document is not a European Commission document and it cannot be regarded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  \n \n  Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 2 of 14 \n  \nIntroduction This document presents questions and answers on requirements relating to notified \nbodies under Regulation (EU) 2017/745 on medical devices (MDR) and Regulation \n(EU) 2017/746 on in vitro  diagnostic medical devices (IVDR). The issues covered by \nthis document have been identified in the context of joint assessments, and the \ndocument may be updated from time to time as new issues are identified. \nI. ORGANISATIONAL AND GENERAL REQUIREMENTS \nI.1. Are CABs obliged to follow guidance endorsed by the Medical \nDevices Coordination Group (MDCG)? \nGuidance documents are by definition not compulsory. However, all guidance \ndocuments endorsed by the MDCG reflect the interpretation of the EU law jointly agreed by the authorities which are in charge of interpreting and applying the EU law. Hence notified bodies should be encour aged to apply these guidance documents \n(also taking into consideration Section 1.6.2 of Annex VII to the MDR/IVDR\n1). \nFurthermore, it is to be noticed that the European Court of Justice often refers to guidance documents when developing its rulings. Hence Notified Bodies have an interest, also in terms of liabilit y risk, to follow that guidance.  \nI.2. What is the meaning of \u201clegal  personality\u201d under Section 1.1.1 of \nAnnex VII\n2? \nThe CAB needs to have legal personality, meaning that it has to exist as a legal \nentity. To that end, it must be registered as legal entity, also called \"legal person\". The wording of the MDR/IVDR does not exclude that only a part of a legal entity undertakes conformity assessment activities in the field of medical devices. In this case, where the CAB is part of a wider legal entity, the documentation provided should be clear as to where the CAB sits within that legal entity. In case the entire legal entity is the CAB, the documentation to be provided refers to the legal entity as such. It is always this legal entity as such which is designated (and not its organisational part). \nI.3. What is the meaning of \u201corgan isation\u201d as described in 1.1.2 of \nAnnex VII? \nThe term of \"organisation\" as described in 1.1.2 refers to the whole organisation (e.g. \ncorporate group) to which the CAB belongs including the CAB's legal entity. The concept of \"organisation\" should be based not only on ownership rights (e.g. shares), but also functional/hierarchical links, such as voting/management/other control rights. One typical example of organisation is a holding company owning different companies (i.e. separate legal entities), one of them being or containing the CAB.  \n                                                           \n1 1.6.2. The notified body shall take into consideration guidance and best practice documents.  \n2 Unless specified otherwise, a reference to Annex VII means a reference to both Annex VII of the MDR and Annex VII of the \nIVDR.  Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 3 of 14 \n I.4. Does the term \u201corganisational structure\u201d as per 1.1.5 refer only to \nhierarchical relationships? \nIf a notified body is part of a larger organisation, both hierarchical (i.e. mother and \ndaughter companies of the CAB) and horizontal relationships (e.g. sister companies where there is a common mother company) between the notified body and other entities belonging to that organisation are covered by the term \"organisational structure\".  \nThe organisational structur e of the CAB will vary depending on the complexity of the \nlegal entity and the organisation to which it belongs. For instance, in the case of holding companies, the CAB could provide a matricial organisational chart with dual reporting relationships (i.e. functional and managerial). In this case, hierarchical and reporting lines should be clear and should match the information provided in job descriptions for the activities related to the MDR/ IVDR certification. \nI.5. Is a 3-year competitor clause for consultants covered in the MDR / \nIVDR requirements? \nThe MDR/IVDR does no longer define the timelines for clearance of consultants that \nwere defined in Section 1.3b of Annex I to the Implementing Regulation (EU) 920/2013, except in case that the person worked for the same company or the group (Section 1.2.4 of Annex VII). However, the requirements under the Implementing Regulation (EU) 920/2013 on the management of impartiality for consultants are included in sections 1.2.2, and 1.2.3 (c), (d) and (e) of Annex VII. Therefore, it is expected that CABs will have similar measures in place under both regimes.   It is essential that competitors, authorised representatives and suppliers are also included in the identification, analysis and resolution of potential conflicts of interests.  \nI.6. May CAB provide pre-certification services?  \nPre-certification services are not allowed before an application is lodged by the \nmanufacturer (e.g. review of clinical data or assessment of the quality management system aside from regulatory standards such as ISO 13485) and therefore these services have to take place under the scope of the application.  \nEvery activity carried out once an application has been submitted will be considered \npart of the conformity assessment activities and therefore if the manufacturer withdraws its application after this process has started, the notified body has to inform the other notified bodies through Eudamed according to Article 53(2) of the MDR / 49(2) of the IVDR. Whenever these activities consist in providing solutions to the manufacturer, they fall under the definition of consultancy and therefore the notified body impartiality policy and procedure(s) will need to cover that these pre-certification activities could be seen as consultancy. The CAB has to implement in their policy and/or procedures how it prevents that pre-certification activities carried out as part of the conformity assessment activities are falling into consultancy. \nServices provided by the CAB that could fall under the definition of conformity \nassessment activities are not allowed outside of an application as they would be regarded as consultancy (e.g. gap analysis, check of MDR/IVDR readiness, use of mock-up files produced instead of \u201creal\u201d TD assessments). Nevertheless, general Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 4 of 14 \n training activities that are not client specific and that relate to regulation of devices or \nto related standards are allowed. \nI.7. Can the CAB accept applications prior to being notified? \nNo, applications under the MDR / IVDR cannot be accepted before the designation of \nthe CAB became valid, i.e. the day after the notification is published in NANDO. \nI.8. How are the conditions on remune ration to be assessed within the \nmeaning of 1.2.5 of Annex VII? \nThe MDR/IVDR establishes that remuneration cannot depend on the results of the \nassessments. Both direct and indirect correlations between results of the assessments and remuneration are prohibited. Hence an individual examination is needed. Special care has to be applied with regard to bonuses. Bonuses on the basis of general objectives, even when not directly linked to the result of the individual conformity assessments, might still be problematic if they indirectly \ncorrelate to the average result of assessments. In the context of a joint-assessment, sampling of contracts or agreements covering remuneration (sheets) should take place. The sampling should cover different grades of influence, e.g. project handlers, final reviewers/decision makers, or head of the CAB / medical devices' certification.  \nI.9. Are declarations of absence of conflict of interests sufficient to \nensure compliance with legal re quirements for impartiality? \nNo, declarations are not sufficient in isolation to ensure compliance. CABs should \ndefine their own system to comply with the legal requirements for independence and \nimpartiality, but a system based on analysis of risk and control measures should be \ngenerally in place. This system will usually  include a comprehensive risk analysis of \nthe CAB's activities, its staff (including top- level management) and the activities of its \norganisation or related bodi es. Risks posed to impartialit y from each individual should \nbe assessed with regard to past employment, consultancy services and financial interests. For instance, shares in companies certified by the notified body or in competitors of these companies (investment  funds can be seen differently) as well as \nrelatives of the person under analysis. Also, the risks linked to subcontractors/suppliers (1.2.1) of the manufacturer need to be assessed.  \nSection 2.4 of Annex VII also requires, as part of this system, a \u201cmulti-level\u201d \nstatement. Firstly, a general one, listing any existing or prior association with clients or devices or processes under assessment. This general one needs to be renewed from time to time (e.g. annually). In addition, there is a need for a written statement and verification by the notified body within each conformity assessment project.  \nAny involvement in processes (e.g. design, risk management, manufacturing \nprocesses) being related with the devices and quality management systems for economic operators covered by the application/designation needs to be seen as consultancy. Other activities not specifically linked with the product will be also regarded as consultancy (e.g. internal audi ts to manufacturers or client specific \ntraining).  Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 5 of 14 \n I.10. Does a CAB that is part of a larger organisation need \nindividual liability insurance? \nThe CAB is responsible for taking out liability insurance and therefore there must be \nevidence that the legal entity is covered by a liability insurance that fulfils the legal \nrequirements. The contract with the insurance company can be signed by other legal entity of a larger organisation (i.e. mother company) provided that the contract gives the CAB the individual right to  be protected against liabilit y claims. The notified body \nmust be able to invoke that right directly towards the insurance company, and not only indirectly via the company which has signed the contract (this is important e.g. in case of insolvency of the signing company or  in case of unwillingness or inability of \nthe signing company to effectively invo ke the insurance contract towards the \ninsurance company). Furthermore, the signing legal entity must involve the notified body in any change of insurance conditions affecting the medical devices conformity assessment activities of the CAB so that the notified body has the possibility to react if it considers that the coverage is insufficient. \nAny change on the liability insurance which may affect the compliance of the notified \nbody with the requirements set out in Annex VII should be communicated by the body to the authority responsible for notified bodies in accordance with articles 44 (1) of the MDR / 40(1) of the IVDR.  \n \nII. QUALITY MANAGEMENT SYSTEM \n \nIII. RESOURCES REQUIREMENTS \nIII.1. Is a complete re-author ization of existing personnel \nnecessary to document satisfaction of the new qualification criteria under section 3 of Annex VII?  \nYes, all personnel that will be used to per form conformity assessment tasks under \nthe MDR/IVDR shall be authorized under the new criteria. For the satisfaction of the work experience criteria, the CAB can accept previous experience in a notified body but it cannot automatically grandfather authorisations (i.e. transfer authorisations) granted by other notified body or by the same notified body under the Directives. However, the experience in a notified body needs to be extensive and traceable and always specific to the tasks to be carried out and the specific technology or product \n(specific codes) in order to satisfy the MDR/IVDR qualification criteria. In addition, comprehensive and objective evidence of such previous experience in a notified body in the relevant scope shall be part of the personnel files.    \nIII.2. What is the meanin g of \u201cpermanent ava ilability of sufficient \npersonnel\u201d within Section 3.1.1 of Annex VII?  \nIn respect to the availability of personnel, MDR / IVDR Annex VII Section 3.1.1 do not \nestablish the number of auditors / reviewers per code to ensure permanent availability of sufficient personnel. As a ve ry minimum, it is considered that notified \nbody should have one person available and authorised per applied-for scope code Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 6 of 14 \n and role as per Section 3.2 of Annex VII at the time of the joint assessment. \nNevertheless, it is recommended that the notified body has two product reviewers/auditors authorised per code to ensure a sufficient capacity to allow fulfilment of other related requirements such as rotation of personnel. When this is not the case, an observation may be raised at the joint assessment in order to flag that for certain codes the available resources are limited.   \nThe notified body is expected to have 2 auditors / reviewers available and authorised \nper applied-for scope in order to fulfil the legal requirements under Section 3.1.1 of Annex VII at the moment of its re-assessment joint assessment.   \nIII.3. What is the meaning of \u201cpossess or have access to all \nequipment and facilities\u201d needed to perform its tasks within the meaning of Section 3.1.1 of  Annex VII of the MDR? \nThis question refers to the requirements in relation to possessing or having access to \nsufficient equipment and facilities to properly perform the conformity assessment activities within the CAB's applied-for scope. It is expected that the CAB would have internal testing facilities or access to testing subcontractor(s) (e.g. by a framework agreement) for device tests in support of the codes for which it seeks designation under Annex X and Annex XI(B).  \nIn order to be designated under Annex X and XI(B), the CAB's personnel needs to \nhave the technical knowledge to identify and select all the tests needed; the CAB must have implemented detailed procedures ensuring the identification of the  relevant tests; and have access to at least some of the tests to be performed within the scope of designation. In particular, for each MDA or MDN code for which the CAB applies under Annex X or XIB it should identify at least the basic tests to be performed and the corresponding testing fac ilities (internal or subcontracted). The \nCAB should be able to demonstrate how t he facilities available are linked to the \ncodes the CAB applies for.  \nNevertheless, the CAB is not expected to hav e testing equipment and facilities (either \nin house or a framework agreement) covering all possible tests within a code under \nAnnex X or XI(B) or as part of surveillanc e or unannounced audits as some of the \ntests are very specific or rarely used. For these purposes, the CAB should have procedures in place in order to find additional subcontractors whenever needed or to define under which circumstances the CAB will perform witness testing (i.e. when the \ntest equipment needed is very specialised)\n \nIII.4. What is the meaning of \"two  years' professional experience\" \nin cases where the experience h as been gained within a CAB \nunder section 3.2.5 of Annex VII? \nAccording to MDR/IVDR Annex VII 3.2.5 product reviewers have to demonstrate two \nyears\u2019 professional experience in the design, manufacture, testing or use of the device or technology to be assessed or related to the scientific aspects to be assessed. Experience related to the scientific aspects to be assessed could include, Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 7 of 14 \n but not be limited to, extensive experience in conformity assessment activities in a \nspecific type of device or technology gained within a CAB3 . \nIn such case, when professional experience \u2013 based on a relevant background \neducation \u2013 is to be proven by activities only within a CAB, this experience should have been gained during at least two years. As a guideline if one individual has carried out at least five full technical documentation assessments of devices in the relevant code (or aspects to be assessed) or under the equivalent code under the Directives, during at least 2 years, this can be accepted as a valid work experience within the meaning of 3.2.5 of Annex VII.  Nevertheless, based on the assessment of the educational background and specific work experience of the individual, the CAB has always to analyse if additional assessments must be performed (i.e. under supervision). \nIn addition, in situations where the objective evidence for the experience gained \nduring technical file reviews is insufficient (e.g. if the staff was authorised for the code \nin a different CAB without detailed supporting evidence), as a guideline, the technical documentation assessments on the code (or aspects to be assessed) to which the individual wishes to be authorised have to be carried out under close supervision of an experienced product reviewer (e.g. mirror review\n4).  At least five of these \nassessments should be related to a full assessment. In addition to technical documentation assessments or product tests,  product-related audit activities can be \nconsidered as work experience as long as  they are not used solely and they are \nadequately documented and assessed by the authorising personnel of [or within] the CAB.  \nIn all of the cases above, the CAB has to analyse individual training needs (e.g. on \nrelevant standards) especially when the work experience was gained a few years ago in the past or when the individual has experience related to a very similar technology. Before authorisation, the authorising personnel needs to ensure that all the qualification criteria under 3.2.5 of Annex VII are fulfilled and their satisfaction fully documented (including an adequate justification in the exceptional cases where the criteria cannot be fully demonstrated as established in 3.3.1 of Annex VII) and that the knowledge is state-of-the-art. \nFor codes (MDR/IVDR) comprising a broad range of devices, the CAB has to ensure \nthat the individual has carried out technical documentation assessments in different devices covered by the code or the authorisation to the code is to be granted with appropriate limitations. \nIII.5. Does the CAB need to defi ne qualification criteria for \nmonitoring and maintenance of competences in accordance with Section 3.5 of Annex VII? \n                                                           \n3 As defined in section 6.2.2. of NBOG BPG 2017-2 \n4 Mirror review is to be understood as a review carried out simultaneously by two product reviewers of the notified body, one \nbeing on training and the other one being an experienced product reviewer on that code. Once the review is finalised from the two reviewers, the most experienced will assess and document the quality of the review carried out by the person in training.\n Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 8 of 14 \n Yes. The CAB\u2019s personnel competence needs to be maintained and therefore \nreviewed at regular intervals. For this purpose, the authorising personnel5 (as per \n3.2.3 of Annex VII) needs to define qualification criteria for monitoring and maintenance of competence of its entire staff (internal and external, as well as \nsubcontractors), involved in conformity assessment activities. Such \"re-qualification\" \nor \"maintenance\" criteria will be used as a basis for re-authorisation of personnel to \ncodes and roles.  \nIn respect of monitoring of competence, such criteria should be defined for personnel \ninvolved in conformity assessment activities, at least for personnel with relevant clinical expertise, product reviewers, site auditors and final reviewer / decision-maker, \nand authorising personnel. \nIII.6. What is the meaning of the term \u201cemployed\u201d in MDR Article \n36(1) / IVDR Article 32(1)? \nThe personnel referred to in Article 36(1) MDR / Article 32(1) IVDR carries out the \nkey functions within the notified body, and therefore the Regulations expressly \nrequire that this personnel is employed by the notified body. This requirement is estimated to be complied with when the contractual relationship between the notified \nbody and the individual meets at the minimum the following criteria: \n\u0081 direct employment contract between the notified body and the employee \nsetting out the rights and obligations of the latter; \n\u0081 control and supervision over the activities of the employee by the notified body \n\u0081 direct reporting obligations of the employee towards the notified body; and  \n\u0081 a direct paid remuneration by the notified body to the employee for the work \ncarried out, accompanied by the payment of any relevant taxes and social security contributions. \nAny reference to \u201cinternal activities\u201d sha ll be intended as activities being carried out \nby personnel employed by the Notified Body. \nN.B. Whenever needed and appropriate, any action from the Notified Bodies aimed \nat ensuring compliance with those requirements should be taken throughout the designation period as soon as possible and completed at the latest by the time of \ntheir first re-assessment. \nIII.7. What is the meaning of \u201cpe rmanent availability of personnel \nwith relevant clinical expertise\u201d in accordance with sections 3.2.4 and 3.1.1 of Annex VII? \nWith regard to \u201cpersonnel with relevant clinical expertise\u201d, in order to fulfil the tasks \ncovered in Section 3.2.4 of Annex VII it is expected that the CAB has at least one \n\"internal clinician\" who, where possible, has to be employed by the CAB. This does \n                                                           \n5 Short term used in NBOG BPG 2017-2 to refer to \"personnel responsible for establishing qualification criteria and for \nauthorising other personnel to perform specific conformity assessment activities\" according to Section 3.2.3 of Annex VII.  Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 9 of 14 \n not preclude the possibility to subcontract su ch a role, provided that the notified body \nproduces a justification as to why it is not possible to employ the person(s).  In any case, when the CAB does not have the possi bility of employing that person(s), it \nshould at least ensure that she/he is fully integrated throughout the conformity \nassessment and the decision-making process, which means that the person is \ninvolved in the CABs assessment and decision-making process in the same way as an employed staff. However, it should be noted that when the internal clinician is a subcontractor even if this person will suppo rt the final review and decision making \nprocess as indicated in 3.2.4 (e.g. in case an external clinical expert has been \ninvolved making a recommendation to the final reviewer or decision maker) they cannot be authorised as final reviewer or decision maker as these personnel should be employed by the notified body itself as required in Art. 36 of the MDR and Art. 32 \nof the IVDR.  \nAccordingly, all \u201cinternal clinicians\u201d are integrated, whereas some internal clinicians \nare not employed. Given that the term \"internal clinician\" is widely spread and it has \nbeen used to defined personnel carrying out tasks established in Section 3.2.4 of \nAnnex VII it is assumed that when the term \"internal clinician\" is used, it could refer \neither to an employee of the CAB or not. \n \nIV. PROCESS REQUIREMENTS \nIV.1. Do devices certified under the Directives need to be subject \nto a full conformity assessment under the new Regulations if the manufacturer applies for certifi cation under the MDR / IVDR?  \nThe conformity assessment activities described under Article 52 / Article 48 apply to \nany certificate issued under the new regulations. As no exceptions were established under the regulations for the migration or transfer of MDD/AIMDD/IVDD certificates to the MDR / IVDR the general provisions should apply. Therefore, all devices to be certified under the MDR / IVDR should be subject to an initial certification according to the applicable annex. The notified body should ensure that all requirements under the MDR / IVDR are fulfilled. It may not restrict its procedures to gap audits or gap file reviews.  \nIt should be noted that MDD/AIMDD/IVDD certificates will remain valid until their \nexpiration date and at the latest on 27 May 2024 as long as conditions laid down in Article 120(3) of the MDR and 110 (3) of the IVDR  are complied with.  \nIV.2. What should be the criter ia for auditing suppliers and \nsubcontractors? \nThe MDR/IVDR established  that the audit of the manufacturer pr emises must include \nan audit on the premises of subcontractors and/or suppliers if appropriate. Therefore, the notified body should have criteria for auditing these actors on the basis of their criticality. At the very least, the criteria defined in Section 4.5.2(b) of Annex VII should Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 10 of 14 \n be applied (i.e. the control over the supplier/subcontractor and its influence on the \nconformity of the device is essential whereas the sole existence of a certificate against ISO 13485 is not sufficient).  \nIV.3. What is the meaning of \"examinations and tests\" to be \nincluded in a certificate in accordance with Section 10 of Annex XII of the MDR / IVDR?\n6 \nCertificates do not need to include reference to relevant common specifications or \nharmonised standards as long as such information on all examinations and tests performed is traceable and available from e.g. report(s) which are mentioned in the certificate.  \nIV.4. What are the applicable requirements for voluntary \ncertificate transfer under MDR Article 58 / IVDR Article 53?  \nWhile MDR Article 58(1) / IVDR Article 53(1) sets out the requirements for a transfer \nagreement, it does not specify the conformity assessment activities to be performed by the incoming NB.  \nhe incoming NB may decide not to carry out full conformity assessment activities \naccording to Article 52 MDR / Article 48 IVDR, as long as it does have sufficient information in respect to the conformity ac tivities performed by the outgoing NB. \nFor quality management system certificates, the incoming NB needs to perform \nappropriate on-site audit(s) and assessments to ensure that the manufacturer in question applies the approved QMS and the post-market surveillance plan prior to \nthe issue of any certificate. In respect to the assessment of technical documentations \non a sampling basis, the oncoming NB shall review the previous assessment results together with a sample of a technical documentation and draw up or amend a sampling plan.  \nFor product certificates (Annex IX Chapter II/Annex X), new certificates without a \ncomprehensive (initial) review may be issued as long as the documentation received does not identify ongoing existing or other concerns. \nThe incoming NB assumes full responsibility for the new certificates issued following \nthe transfer. \nIV.5. What are the applicable requirements for OBL \nmanufacturers? \nThe MDR / IVDR does not distinguish between OBL\n7 and other manufacturers. There \nare just \"manufacturers\" and therefore OBL manufacturers must comply with the legal requirements, as any other manufacturer\n8.  \n                                                           \n6 See also Q&A IV.8  \n7 OBL\u201d (own brand label manufacturer) is a term used in the fiel d that describes manufacturer that are supplied with the finish ed medical \ndevice by their supplier, who often is called \u201cOEM\u201d (original e quipment manufacturer). Neither of both are defined in the MDR (or ever \nwere defined in the Directives).  Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 11 of 14 \n IV.6. What is the role of the intern al or integrated clinician in the \nnotified body\u00b4s assessment and decision-making process?   \nThe internal or otherwise integrated clinici an is responsible to identify when specialist \ninput is required for the assessment of the clinical evaluation as defined in Section 3.2.4 of Annex VII of the MDR and IVDR. This decision will be made by the internal \nor integrated clinician on a case-by-case basis, based on the products covered by the applications lodged by the manufacturer and the clinical expertise available. The internal clinician or integrat ed clinician will be responsible fo r this process in all cases \nwhere the conformity of the device to the requirements of annex I is achieved also by clinical data. In cases where demonstration of conformity to requirements of Annex I based on clinical data is not deemed appropriate (in accordance with Article 61(10)) the internal or integrated clin ician will also examine the ju stification provided in order \nto assess its adequacy.  The internal or otherwise integrated clinicians will decide if the review of clinical evaluation is to be carried out by themselves, to be delegated to other qualified staff or if it necessitates the input of external clinical experts. This process is also defined in Section 4.3 of Annex IX of the MDR and Section 5.4 of NBOG\u2019s best practice guide 2017-2 as endorsed by the MDCG. \nSection 3.2.4 of Annex VII defines that there must be a clinician who is either internal \n(= employee) or otherwise integrated into the CAB's assessment and decision-making process. To be regarded as integrated, a clinician (who is not an employee) must have access to all the information, required to perform its activities, circulating in the CAB and must be involved in the internal processes in the same way as an employee, the only difference to an employee being that there is no employment contract, but a service contract and therefore this person should not be considered final reviewer or decision-maker as per 3.2.7 of Annex VII.  \nIn addition to this, the internal or otherwise integrated clinician will clinically judge the \nopinion provided by  any external expert (including verificati on of comparability and \nconsistency of the assessments of clinical evaluations conducted by clinical experts) \nand will be responsible to make a recommendation to the decision maker on the adequacy of the clinical evaluation. \nIV.7. What is the meaning of  allocation of resources under \nSection 4.4 of Annex VII? \nAllocation of resources is to be understood as the allocation of appropriately \nauthorised and qualified perso nnel and means (including eq uipment and facilities) for \na given project (application), as stated in second paragraph of Section 4.4 of Annex VII \"appropriate resources including personnel\". Section 4.4 of Annex VII describes the assignment of tasks within a project to \u201cindividuals\u201d, starting with the individual responsible for ensuring that the assessment of that application is conducted in accordance with the relevant procedures and for ensuring that the appropriate resources including personnel are utilised for each of the tasks of the assessment \n                                                                                                                                                                                     \n8 Including but not limited to having: full and permanent access  to the technical documentation; (ability for) post-market surv eillance \nincluding post market clinical follow-up; sufficient technical competence; and control of the quality system (control of the d esign, \nmanufacture and/or final verificat ion and testing of the device s). Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 12 of 14 \n (often referred to as project leader) and following with the identification of individual \npersonnel that will carry out each task of a given project.  \nThe assessment of the resources needed for each application is a key function that \nhas to be fulfilled as part of the internal activities of the CAB as indicated in Section 4.1 of Annex VII and any changes on such allocation should be documented. \nIV.8. How can a CAB ensure that information on \"examinations \nand tests\" in accordance with Section 10 of Annex XII of the MDR / IVDR is available to all interested parties (as referred to in Section IV.3 of this document)? \nAccording to Annex XII information on tests and examinations performed as part of \nthe conformity assessment activities need to be included on the  certificates issued by notified bodies. This information might be of interest for competent authorities and third parties.   \nIf the certificates do not include explicitly references to relevant common \nspecifications, harmonised standards or other standards or referential but include a reference to the relevant report(s), the CAB should ensure that competent authorities and interested parties can have access this information on request.  For example, the certificate may  include a sentence like \"information on examinations and tests as per Annex XII, section 10 is available on reques t\" and possibly provide a contact (e.g. e-\nmail). \nIV.9. Which changes need prior approval by the CAB? \nThe Regulations - in Annex VII and in the specific conformity assessment annexes \n(i.e. Annex IX, X and XI) -establish the need for the manufacturer to notify certain planned changes.  Section 4.9 of Annex VII contains general requirements for notified bodies in respect to changes.  \nFor manufacturers, the specific conformity assessment annexes (i.e. Annex IX, X and \nXI) detail such requirements e.g. asking for plans for \u201cany\u201d changes (e.g. MDR Annex IX, 5.2 f), 5.3.1 d) or Annex X 5.2), for  changes could affect the safety and performance of the device or the conditions prescribed for use of the device (e.g. MDR Annex IX 4.10) or for \u201csubstantial\u201d changes only (e.g. MDR / IVDR Annex IX 2.4). With regard to the latter, the CAB needs to make clear in its communication to the manufacturer (e.g. in the terms and conditions) what it considers as \u201csubstantial changes\u201d to the quality management system or the device-range covered. \nIn order to fully comply with all the relevant requirements the CAB must have \ndocumented procedures defining how different changes need to be notified and assessed prior to their implementation and how the assessment will be documented. In particular, the CAB will define in its procedures when the approval of such changes will take the form of a supplement of the previously issued certificate. \nIV.10. What is the frequency of surveillance audits according to \nthe Regulations? \nAccording to the Regulations (Section 3.3 of Annex IX and Section 7 of Annex XI), \nsurveillance audits have to be carried out at least every 12 months. This means that Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 13 of 14 \n the audit planning defined in Section 4.5.2 and 4.10 of Annex VII will need to take \ninto consideration that surveillance audits have to be scheduled on at least an annual basis with a maximum of 12 months after the previous surveillance audit was carried out The first surveillance audit should be scheduled  taking as a reference the certification decision date. \nIV.11. What is the meaning of the last sentence in Section 4.5.1 of \nAnnex VII with regard to the need  for notified bodies  to take into \nconsideration standards and guidance even if the manufacturer does not claim compliance? \nCABs need to consider all the availabl e guidance, common specifications and \nharmonised standards to carry out its assessments.  This means, that CABs will have \nto consider this documentation when developing its own procedures and processes (including checklists and report templates) and when assessing the manufacturers \nQMS (e.g. by taking into consideration EN ISO 13485) and technical documentation.  \nFor instance, in order to assess if the solutions adopted by the manufacturer are \nstate of the art and in line with expectations, the CAB need to use the available guidance documents and standards. It should be noted that non-conformities will not \nbe raised against standards or guidance but need to be phrased against legal \nrequirements. For instance, Annex I Chapter I Section 1 of the Regulation which states that \u201cdevices shall be safe and effective [\u2026] taking into account the generally acknowledged state of the art\u201d can be used when the technical documentation does \nnot follow standards or guidance. \nIV.12. What are the applicable requirements for re-certification?   \nConformity assessment activities to be carried out in case of renewal of \ncertificates/re-certification are laid down in Article 56(2) of the MDR / Article 51(2) of \nthe IVDR, where the Regulations establish that the notified body can extend the validity of the certificate for further periods based on a re-assessment in accordance with the applicable conformity assessment procedures (i.e. as described in annexes \nIX-XI). In addition, Section 4.11 of Annex VII states that the notified body must use \nthe same methods and principles for the decision on re-certification as for the initial \ncertification decision.   \nWhile for EU Technical documentation assessment certificates and EU type \nexamination, Section 4.11 of Annex VII establishes a targeted conformity assessment (i.e. focusing in certain elements of the technical documentation review), this is not \nthe case for the quality management system certificates.  \nThe notified body will ensure that all relevant Regulation requirements for conducting \naudits (i.e. those covered in Section 4.5.2 of Annex VII, and sections 2.2 and 2.3 of Annex IX) are assessed in its entirety at le ast once after issuin g the certificate and \nbefore its expiry date.  In addition, prior to the renewal of a QMS certificate, it is \nrequired that the notified body will assess the results of the surveillance audits carried Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 14 of 14 \n out during the period of validity of the certificate in accordance with section 4.10 of \nAnnex VII, also including any unannounced audits and all audits carried out at \nsubcontractors and suppliers.   \nThis review must include the manufacturer\u00b4s system for vigilance, post-market \nsurveillance, PMCF and risk management as well as all open non-conformities   Furthermore, re sults of the notified body\u00b4s ev aluation of additio nal scientific and \nclinical data and clinical evaluations and post-market information as well as the \noutcome of latest technical documentation assessments on sampling basis and product tests have to be considered. \n \nV. OTHER REQUIREMENTS \nV.1. Are activities described under arti cles 16 and 17 of the Medical \ndevices Regulation (MDR) and Article 16 of the in vitro medical devices Regulation (IVDR) will be covered during joint assessments? \nConformity assessment bodies (CABs) can i ssue certificates following the process \ndescribed in articles 16 and 17 of the MDR and Article 16 of the IVDR but these are not considered conformity assessment activities covered by Chapter IV and Annex VII of the Regulations and therefore w ill not be part of joint assessments. \nV.2. What is the meaning of \u201cpublicly available\u201d as regards the list of \nstandard fees of a notified body under Article 50 MDR / Article 46 IVDR?  \nWhenever the Regulations require certain information to be made \u201cpublicly available\u201d, \nthat implies that a member of the public can access this information at any point in time, without the need for additional steps. In view of the public functions carried out by notified bodies, this requirement supports transparency of their activities. \nNot only Article 111 MDR / Article 104 IVDR re fer to different type of fees (i.e. fees \nlevied by Member States), but also it uses different wording. It cannot therefore be used to support the interpretation of Article 50 MDR / Article 46 IVDR. Moreover, public availability of fees levied by Member States will usually result from the official publication of national laws setting out such fees (therefore, there will be no need to request information on such fees)."}, {"title": "mdcg_2020_4_nb_audits_covid-19_en.pdf.txt", "text": "Medical Device       \nMedical Device  Coordination Group Document   MDCG  20 20-4   \nPage 1 of 6 \n  \n \n \n \n \nMDCG  20 20-4 \nGuidance on temporary extraordinary  \n measures related to medical device Notified \n Body audits during COVID -19 quarantine orders \n and travel restrictions  \n             \n \n April  2020 \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commission document and it cannot be regarded \nas reflecting the official position of the European  Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  Medical Device       \nMedical Device  Coordination Group Document   MDCG  20 20-4   \nPage 2 of 6 \n  \n \n1.  Introduction  \nIn the context of the current COVID -19 global outbreak as well as the rapid spread of \nthe virus across various regions of the globe, the resulting travel and quarantine \nrestrictions have significantly affected the ability of notified bodies to conduct \nmandatory on -site audits under the medical devices legislation. Theref ore, in the \ninterest of public health, this document has been developed to outline temporary \nextraordinary measures for notified bodies to follow in this interim period  in order to \nallow continued  availability of safe medical devices to the market and as sist in the \nprevention of  the risk of medical device shortages. In this context,  it is considered \nthat alternative solutions to carrying out on -site audits by notified bodies under the \nmedical devices Directives1 should be allowed under specific circumst ances, \nincluding the possibility to perform remote audits under certain conditions.  \nThis guidance takes immediate effect and is valid for the whole period of duration of \nthe pandemic COVID -19 as declared by the World Health Organisation.  \n2.  Scope  \nThis guida nce is intended to cover the following audits notified bodies are requested \nto carry out as part of medical devices conformity assessments:  \n\uf0b7 surveillance audits under the medical devices Directives,  \n\uf0b7 audits conducted for re -certification purposes under the medical devices \nDirectives,  \n\uf0b7 in cases where a manufacturer submits a change notification to a notified body \nthat would typically require on -site audit or verification,  \n\uf0b7 in cases where a manufacturer terminates (voluntarily or involuntarily) its \ncontract with a notified body and enters into a contract with another notified \nbody in respect of the conformity assessment of the same device(s).  \nAlthough this guidance applies to the medical device Directives only, for Regulations \n(EU) 2017/745 (MDR) and 2017/746  (IVDR) in the event that the availability of \ndevices is affected by COVID -19 restrictions the principles in this guidance may \napply.  \n \n \n                                                           \n1Directive 90/385/EEC, the AIMDD; Directive 93/42/EEC, the MDD; Directive 98/79/EC, the IVDD.  Medical Device       \nMedical Device  Coordination Group Document   MDCG  20 20-4   \nPage 3 of 6 \n  \nThe temporary extraordinary measures proposed in this guidance should not apply to \nunannounced audits, or, to special a udits which require on -site assessment (such as \nthe verification of implementation of specific corrective actions which can only be \nassesed on -site). This does not prevent the use of the alternative measures for these  \ntypes of audits in cases where doubt has been raised on the conformity / safety  of a \ndevice and it is not in the interest of public safety to wait  until the end of the \nrestrictions put in place due to the COVID -19 pandemic.  \nIn general, initial certification audits or audits to extend the s cope of certification \nunder the Directives should not be performed using these temporary extraordinary \nmeasures. However, notified bodies may apply these extraordinary measures on a \ncase -by-case basis for such audits in cases where devices are considered r elevant to \nensure medical care, especially if clinically necessary during the period of COVID -19 \nrestrictions.  \n3.  Proposed temporary alternative extraordinary measures and \narrangements to on -site audits  \nNotified bodies may introduce temporary alternative extraordinary measures in place \nof on -site conformity assessment audits that have been impacted by COVID -19 \nrestrictions and that are within the scope of section 2 above.  \nNotified bodies should have documented procedures detailing the alternative \ntemporary measures to be utilised and should define the criteria for implementing \nsuch measures (e.g. procedure for \u201cforce majeure\u201d). The relevant procedures should \nalso take into account the technologies to be used during such audits and also \naddress the impact of the alternative measures on the audit duration.  \nThese temporary alternative extraordinary measures may include the following \nprinciples and arrangements:  \n\uf0b7 Postponement of  on-site surveillance audits under the Directives in line with \ndocumented procedures of the notified body for force majeure.  \n\uf0b7 On-site audits may be replaced by remote audits using the most advanced \navailable Information and Communication Technologies as ap propriate in \naccordance with legislation on information security and data protection.  \n\uf0b7 Assessment of all relevant and required documents/records off -site by the \nnotified body.  \n\uf0b7 To take into account existing recent results from  MDSAP audits (or other \napprop riate audits) in lieu of Directive audits, where available  \n\uf0b7 To consider published international guidance such as those issued by the \nInternational Accreditation Forum (IAF) e.g. on how to use information and  \n \n \n Medical Device       \nMedical Device  Coordination Group Document   MDCG  20 20-4   \nPage 4 of 6 \n  \ncommunication technologies2 and for alternat ive auditing methods in \nextraordinary circumstances3. \n4.  Eligibility criteria and procedural aspects  \nTo be eligible for these temporary alternative extraordinary measures the audits must \nbe covered within the scope of section 2 above.  \nThe possibility to make use of temporary alternative extraordinary measures to on -\nsite audits should be carefully assessed and documented by notified bodies on a \ncase -by-case basis and performed using a risk -based approach. In particular, when \ndetermining the possibility to use t hese alternative measures, the risk assessment \nshould take into account the experience gained with a manufacturer. For example,  \nmanufacturers who have a history of a high number and/or critical non -compliances \nrelated to production/operational control  ma y have an impact on the appropriateness \nto conduct such temporary measures. However, in these cases an alternative \nmeasure could be performed as a temporary measure to assess the progress of the \nmanufacturer and should be be supplemented by an on -site audi t once travel \nrestrictions are lifted.  \nIn order to assess which alternative extraordinary measure (as outlined in section 3 \nabove) is most appropriate, the notified body should review their files relating to the \nstatus and operations of the manufacturer re lated to the audit in question, for \nexample the activities conducted at the site to be audited,  its quality management \nsystem, and its level of compliance from previous audits. Following this review, a risk \nanalysis should be made as to whether or not the  audit could be performed with \nalternative measures. Where a postponement cannot be justified, the notified body \nshould assess which alternative extraordinary measure should be performed (e.g. \nremote audit; off -site document review; conference calls with r elevant personnel of \nthe manufacturer).  \nFor remote audits, both the notified body and the manufacturer must have the \nrequired information and communication technologies or tools available and \nestablished (e.g. web conferences with document sharing, use of  web cams for \naudits of production lines). Confidentiality of intellectual property aspects shall be \nsafeguarded.   Notified bodies should clearly document and communicate any such \nrequirements for their audits with their auditees, along with the required \ndocumentation to be shared before and within such audits, including the necessary \ndata protection and cybersecurity measures . The technological capability of the  \nmanufacturer to ensure that such an audit can be accomplished should be verified by \nthe notified body in advance of the audit.  \n \n                                                           \n2 Requirements on how to use information and communication technologies to support and maintain the \nintegrity of the audit/assessment process may be found in International Accreditation Forum document IAF MD \n4 (Mandatory Document for the Use of Information and Communication Technology (ICT) for \nAuditing/Assessment Purposes).  \n3 ID3:2011  (IAF Informative Document For Management of Extraordinary Events or Circumstances Affecting \nABs, CABs and Certified Organizations)  Medical Device       \nMedical Device  Coordination Group Document   MDCG  20 20-4   \nPage 5 of 6 \n  \nDesignating Authorities may request to observe/witness such remote audits  via \ninformation and  communication technologies or to ols available and established.  \nWhen establishing the audit plan, the notified body should adjust the duration for \nreview of the areas on the audit plan, along with the overall duration of the audit, in \ncoordination with the manufacturer in order to make ef fective use of these alternative \nextraordinary measures. The audit plan should also clearly indicate which alternative \nextraordinary measures will be used and what will be conducted remotely. When \nissuing their audit reports the notified body should also c learly indicate that the audit \nwas conducted remotely and the method(s) used for such audits should also be \nspecified.  \nRemote surveillance audits should cover all of the surveillance tasks that can be \nverified remotely, including an off -site review of all  documents that would normally be \nassessed on -site.  \nFollowing such an alternative extraordinary measure the notified body should review \nand adjust the audit programme for each manufacturer to ensure that all required \nelements are assessed during the certi fication cycle.   \n5.  Decisions taken on certification  \nRemote audits undertaken for re -certification purposes should cover all of the \nmandatory re -certification tasks that can be verified remotely. Subsequent to a \nsucccessful remote audit a notified body may r e-issue the certification with the \ncondition that such audits should be followed up by an on -site verification audit at the \nnext available opportunity to verify the elements that could not be assessed remotely \n(the timeline for the on -site verification aud it should be justified by the notified body). \nAt the request of the notified body, the manufacturer may provide the notified body \nwith records (e.g. product release documentation) on an ongoing or regular basis,. If \nthe re -certification remote audit is uns uccessful, the certification should be \nsuspended or should expire as appropriate.   \nRemote audits conducted by the incoming notified body in the context of cases \nwhere a manufacturer terminates its contract with a notified body and enters into a \ncontract with another notified body in respect of the conformity assessment of the \nsame device (s), should also cover all of the tasks that can be verified remotely to \nallow the incoming notified body to ensure a proper assessment of the conformity of \nthe device. If the remote audit is unsuccessful (as per the notified body\u2019s procedures \nfor unsucces sful audits), the incoming notified body should not issue the certification.  \nIn the exceptional circumstance of the issuance of  an initial or extended scope \ncertificate under these alternative extraordinary measures (as per section 2 Scope \nabove), the no tified body should consider the clinical risk / benefit of their decision \nand should clearly document their rationale for these decisions. At the request of the \ndesignating authority the notified body should inform the national authority of any \nsuch decisi ons and provide any supporting documentation.  Medical Device       \nMedical Device  Coordination Group Document   MDCG  20 20-4   \nPage 6 of 6 \n  \n \nNote: A  task force established in March 2020 under the MDCG NBO working group \nis tasked with the development of guidance to define the operational implementation \ndetails of this guidance document."}, {"title": "Guidance on significant changes &amp; annexes.pdf.txt", "text": "1 \n Medical Device       \nMedical Device Coordination Group Document    MDCG 2020 - 3    \n \n \n \n       \n   MDCG 2020 -3 \nGuidance on significant changes regarding  \n   the transitional provision under Article 120  \n       of the MDR with regard to devices covered  \n       by certificates according to MDD or AIMDD            \n \n             March 2020  \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) established by \nArticle 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member States \nand it is chaired by a representative of the European Commission.  \nThe document is not a European Commission document and it ca nnot be regarded as reflecting the \nofficial position of the European Commission. Any views expressed in this document are not legally \nbinding and only the Court of Justice of the European Union can give binding interpretations of Union \nlaw. \n \n    \n2 \n  \nGuidance on  significant changes  regarding the \ntransitional provision under Article 120 of the \nMDR with regard to devices covered by \ncertificates  according to MDD or AIMDD1 \n \n1 Introduction  \nArticle 120( 2) and 120( 3) of the  Medical Device Regulation  (EU) 2017/745 (MDR) states that \ndevices which  have a valid certif icate issued by a notified body under the Active Implantable \nMedical Devices Directive 90/385/EEC  (AIMDD) or the Medical Devices Directive 9 3/42/EEC \n(MDD) may be placed on the market or put into service after th e date of application of the MDR \nunder certain conditions  and no later than  26 May 2024.  \nQuestions 8 and 9 of the CAMD Transition Sub Group  guidance : \u201cFAQ \u2013 MDR Transitional \nprovisions, V1.0 of 17. January 2018\u201d2 state that the certificates  covered by MDR Article 120(3) \ninclude \u201call certificates which are commonly issued by notified bodies with reference to the \nCouncil Directives MDD and AIMDD\u201d . \nConditions referred to in the first paragraph require that no  significant change s in design or \nintended purpose  of a device  be performed  after the date of application of the MDR . Therefore, it \nis important for manufacturers and notified bodies to get clarity on the significant changes to be \nconsidered under  MDR Art icle 120(3).  \nIt is also important that the AIMDD and MDD certificates remain valid following changes that are \nnot significant with regard  to design or intended purpose , provided that the required surveillance \nis carried out  by the notified body that issued the certificate. See also Question 17 of the above \nmentioned CAMD guidance2. \n2 Scope  \nThis guidance document is intended to provide clarification on the changes to a device that \nshould be considered a \u201csignificant change in design or a significant change in the intended \npurpose\u201d under  MDR Art icle 120(3). Assessment s should  be made on a case -by-case basis.  \n                                                           \n1 The principles  outlined in this guidance can be applied also for class I devices requiring the involvement of a \nnotified body for the first time.  \n2 https://www.camd -europe.eu/wp -content/uploads/2018/05/FAQ_MDR_180117_V1.0 -1.pdf    \n3 \n This guidance document does not elaborate on the process for manufacturers\u2019 submission and  \nnotified bodies\u2019  assessment of such changes as these should be part of the conformity \nassessment process  and surveillance  defined by the relevant notified body under the MDD or \nAIMDD. It is expected that manufacturers adjust their change not ification procedures, i.e. their \nprovisions to inform their notified body on changes, in accordance with the principles outlined in \nthis guidance until the date of application of the MDR. The adjusted procedures will be subject to \nnotified body assessment within their surveillance activities according to MDR Art. 120(3).   \n3 Changes to Directive  certificate s \nIt is important to highlight that no issuing of new MDD/AIMDD certificates, including modified,  \namended  or supplemented certificates , is allowed under MDR Article 120(3).  In particular, i f the \nmanufacturer wishes to make a  \u201csignificant chang e in design or intended purpose\u201d under MDR \nArticle 120(3), the implementation of such a  change would  prevent the manufacturer from \ncontinuing to place that device on the market  under the Directives . \n4 Assessment of changes' significance  in accordance with MDR \nArticle 120(3)  \nIn line with agreed arrangements for notification of changes between the manufacturer and the \nnotified body  according to the AIMDD/MDD  (e.g. contractual relationships, approved  procedures)  \nchanges and their implementation will be verified by the notified body as part of the surveillance \nactivities, or following a manufacturer\u2019s  submission for prior approval . The outcome of this \nverification will determine whether a certificate in accordance with AIMDD/MDD remains valid \naccording to Article 120 MDR. To use this derogation from Article 5 MDR manufacturers are not \nallowed to make s ignificant change s in design or a significant changes in the intended purpose. \nIn case of doubt whether a change is significant they should ask their notified body .  \nFor instance, administrative changes of organisations are considered in principle as non -\nsignificant. This includes changes of the manufacturer\u2019s name , address or legal form  (legal entity \nremains) or changes of the authorised representative.  \nFurthermore, all changes not having an impact on the design or the intended purpose of the \ndevice can be regarded as not significant  in the meaning of MDR Article 120(3) .  This is the case \nfor example of relocation or addition of new manufacturing sites, including when it affects \nsubcontractors  or suppliers , or of certain changes of the quality management system, provided \nthat the conditions for which the conformity assessment certification was granted are maintained. \nNevertheless, such changes continue to be subject to the agreed notification procedure identified \nin the first paragraph of the current secti on. T he manufacturer should always remain responsible \nfor providing evidence that all the above -mentioned changes do indeed neither  affect the design \nnor the intended purpose.     \n4 \n On the other hand, when the change is likely to affect the design or the inten ded purpose of the \ndevice, the significance of such a change must be assessed on a case -by-case basis.  \nTo facilitate a harmonised judgement of the significance of changes flowcharts (see Annex) have \nbeen developed.  \nIf a change is not a significant chang e in design or intended purpose  under MDR Article 120(3), \nthe implementation of such a change  is therefore  allowed during the transitional period. Acc. to \nsection 3 the certificate should not be amended.  \nThe notified body that issued the AIMDD or MDD certif icate may confirm in writing (after having \nreviewed manufacturer\u2019s description of the (proposed ) change) that the implementation of the \nchange does not represent a significant change in design or intended purpose under MDR Article \n120(3) and that the relat ed AIMDD or MDD certificate remains valid after the date of application \nof the MDR, but no longer than its expiry date or 26 May 2024, whichever comes first. Such \nwritten confirmation corrects or complements information on an existing certificate but does not \nrepresent the issuance of a \u201csupp lemented certificate\u201d as this is prohibited as mentioned in \nSection 3 . In case of requests from authorities the manufacturer should number such letters \nreceived from the notified body and submit them together with the certificate.   \nIn relation to class I medical devices requiring the involvement of a notified body for the first time, \nmanufacturers of such devices must be able to justify their decision when the changes are \nconsidered to be non -significant. The justificat ion shall be documented and made available when \nrequested.  \nThis guidance document provides in its Annex several flowcharts based on NBOG\u2019s Best \nPractice Guide 2014 -3: \u201cGuidance for manufacturers and Notified Bodies on reporting of Design \nChanges and Change s of the Quality System\u201d . In particular, Chart C , which is specific to \nsoftware, draws inspiration  from Annex VI, Part C, section  6.5 of the MDR to identify \nmodifications that are considered as significant change in (software) design.  \nThe assessment of a proposed change by using the main flowchart and any of the applicable  \nsub-charts in the Annex, is intended to assist  manufacturers and notified bodies  in deciding  \nwhether or not a change is to be considered significant in the design or intended purpose of the \ndevice under MDR Art icle 120(3).  \nThe flowcharts are divided into a main chart and five sub -charts (A to E) . There are six \ncategorical questions in the main chart that are linked to  one or more sub -charts with more \ndetailed questions . The change is considered a non -significant change of design or intended \npurpose per MDR Art icle 120(3)  if the answer to every  question in a sub -chart leads to \u201c non-\nsignificant change \u201d also when returnin g to the main chart. On the contrary, if any  sub-chart   \n5 \n delivers the result \u201csignificant change\u201d , the change being assessed is a \u201c significant chang e in \ndesign or intended purpose\u201d  of a device according to the MDR Article 120(3).  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n   \n6 \n Annex  \nDesign Changes and Changes of the Intended Purpose  \nWhich may be Considered \u201cSignificant\u201c When Interpreting the \nFirst Sentence of MDR Art. 120(3)   \n     Main Chart   \nChange of an existing Medical Device  \ncertified under MDD or AIMDD  \nChange of the  \nIntended Purpose?  \nSoftware change?  \nChart A  \nChart B  \nChart C  \nYes  \nYes  \nYes  \nNo \nNo \nIf non -significant  \nIf non -significant  \nIf non -significant  \nA \nB \nC \nChange of the  \ndesign or  \nperformance  \nspecification?  \nNo \nNo \nX \nDesign change related  \nto corrective  \nactions*?  \n*assessed and  \naccepted by the  \nrelevant Competent  \nAuthority acc. to  \nCAMD FAQ no 17  \nYes    \n7 \n Design Changes and Changes of the Intended Purpose  \nWhich may be Considered \u201cSignificant\u201c When Interpreting the \nFirst Sentence of MDR Art. 120(3)   \nMain Chart (ctd.)  \n \n \n \n \n \n \n \n \nChange of a  \nMaterial*?  \nChange  \nof terminal  \nsterilization method of  \ndevice or packaging design  \nwith impact to the  \nsterilisation?  \nChart D  \nChart E  \nThe change is considered a  \nnon \n- \nsignificant change  \nper MDR Art. 120(3)  \nYes  \nYes  \nNo \nNo \nNo \nIf non -significant  \nD \nE \n*The termmaterial  \nincludesany  \nsubstance  \n( \nsynthetic, natural,  \nbiological, chemical,  \nphysical, medicinal,  \n...) \n that is used to  \nmake or compose  \nthe device    \n8 \n Design Changes and Changes of the Intended Purpose  \nWhich may be Considered \u201cSignificant\u201c When Interpreting the \nFirst Sentence of MDR Art. 120(3)   \nChart A  \n \nFromMain  Chart:  \nChange of the IntendedPurpose*  \nThe changeisconsidered  \nsignificantper MDR Art. 120(3)  \nExtension  \nor change of the  \nIntended Purpose?  \nNew user or  \npatient population?  \nChange of  \nclinical use**?  \nYes  \nYes  \nYes  \nNo \nNo \nNo \nLimitation of the  \nIntended  \nPurpose?  \nReturn toMain Chart  \nQuestionX  \nYes  \nNo \nA1 \nA2 \nA3 \nA4 \n** Example:  \n- \nChange in the  \nanatomical site;  \n- \nChange in the access  \nsite or deployment  \nmethods;  \n*  Labellingchangesshouldbe  \nassessedtoensuretheyarenot  \npotentiallysignificantwhen  \nlinkedtothe intendeduse(e.g.  \ncontraindicationsandwarnings).   \n \n \n \n Design Changes and Changes of the Intended Purpose  \nWhich may be Considered \u201cSignificant\u201c When Interpreting the \nFirst Sentence of MDR Art. 120(3)   \n \nChart B  \n \n \nFromMain Chart:  \nChange of theDesignorPerformance Specification*  \nYes  \nNo \nNo \nB1 \nChange  \nof built -in control  \nmechanism, operating  \nprinciples, source  \nof energyor  \nalarms  \n? \nYes  \nNo \nReturn toMain Chart  \nQuestionC (or move directly to E  \nif Chart D was previously used)  \nYes \nB3 \nThe changeisconsidered  \nsignificantper MDR Art. 120(3)  \nbetakeninto  \n not \n * Itshall  \naccounthowthe changeis  \nachieved. A changein specification  \nmaybetriggeredby, but isnot  \nlimited to, changeof hardwareor  \nsoftware, includingchangeof a  \ncomponent.  \nDoes the  \nchange require  \nfurther clinical or  \nusability data to support  \nsafety and perfor - \nmance?  \n** \nDo new risks  \nrequire control measures  \nor are existing risks  \nnegatively  \naffected?  \nB2 \n** Compare  \nMEDDEV 2.7/1 rev.4  \nforfurtherguidance   \n \n \n \n Design Changes and Changes of the Intended Purpose  \nWhich may be Considered \u201cSignificant\u201c When Interpreting the \nFirst Sentence of MDR Art. 120(3)   \nChart C  \n \n \n \n \n \nFromMain Chart:  \nSoftware Change  \nNew or modified  \narchitecture or database  \nstructure, change of  \nan algorithm?  \nRequired  \nuser input replaced  \nby closed loop  \nalgorithm  \n? \nYes  \nYes  \nNo \nNo \nNew or major  \nchange of operating  \nsystem or any  \ncomponent?  \nNo \nYes  \nC1 \nC2 \nC3 \nNew diagnostic or  \ntherapeutic feature,  \nor new channel of  \ninter-operability  \n? \nYes \nC4 \nNo  \n \n \n \n Design Changes and Changes of the Intended Purpose  \nWhich may be Considered \u201cSignificant\u201c When Interpreting the \nFirst Sentence of MDR Art. 120(3)   \n \nChart C (ctd.)  \n \n \n \n \nThe changeisconsidered  \nsignificantper MDR Art. 120(3)  \nYes \nNo \nReturn toMain Chart  \nQuestionD  \nC5 \nNo \nNew user interface or  \npresentation of data*?  \n*\u201cPresentationof data\u201c  \ngoesbeyondthe  \nappearanceof theuser - \ninterface whichmayinclude  \nnewlanguages, layoutsor  \ngraphicsandisconsidered  \na minor change.  \nItisconnectedtomedical  \ndatawhicharepresentedin  \na newformatorby a new  \ndimensionormeasuring  \nunit.  \nYes \n*Minor changeswithout  \nimpacttodiagnosisor  \ntreatmentdeliveredmay  \ninclude:  \n- \ncorrectionof an error  \nwhichdoesnot posea  \nsafetyrisk(bugfixes),  \n- \nSecurity update (e.g.  \ncyber -security  \nenhancements,  \nlongevitycalculations),  \n- \nappearanceof the user  \ninterface,  \n- \noperatingeffeciencies.  \n- \nChangestoenhancethe  \nuserinterfacewithout  \nchangesin performance  \nMinor Change*?  \nC6  \n \n \n \n Design Changes and Changes of the Intended Purpose  \nWhich may be Considered \u201cSignificant\u201c When Interpreting the \nFirst Sentence of MDR Art. 120(3)   \n \nChart D  \n \n \n \n \n \n \nFromMain Chart:  \nChange of a Material*  \nChange to a  \nmaterial of human/animal  \norigin including addition of  \nnew materials?  \nNo \nYes  \nChange  \nto a material  \ncontaining a MS**  \nortothe MS  \nitselfor, a change which may  \nimpact the quality, safety or  \nefficacy of a MS  \n*** \n? \nYes  \nNo \nD1 \nD2 \n**MS: Substancewhich,  \nif used separately, would  \nbe considered to be a  \nmedicinal substance  \n***Including a change in  \nits manufacturing process,  \nwhich result in changes to  \nthe existing specification  \nof the medicinal  \nsubstance.  \n* These relate to changes  \ninvolving existing  \ningredients and materials.   \n \n \n \n Design Changes and Changes of the Intended Purpose  \nWhich may be Considered \u201cSignificant\u201c When Interpreting the \nFirst Sentence of MDR Art. 120(3)   \n \nChart D (ctd.)  \n \n \n \n \n \nIngredient  \nnew \n ormaterial from  \nuppliermeetsexisting  \n s \nspecification?  \nThe changeisconsidered  \nsignificantper MDR Art. 120(3)  \nNo \nYes  \nYes \nChanged  \ningredientor  \nmaterial fromexisting  \nsuppliermeetsexisting  \nspecification?  \nNo \nReturn toMain Chart  \nQuestionE  \nD3 \nD4 \nChange tobeassessedin  \naccwithChart B   \n \n \n \n Design Changes and Changes of the Intended Purpose  \nWhich may be Considered \u201cSignificant\u201c When Interpreting the \nFirst Sentence of MDR Art. 120(3)   \nChart E  \n \n \nFromMain Chart:  \nChange of terminal sterilization method  \nof device or packaging design  \nwith impact to the sterilization  \nDesign Change  \nwhich affects or  \nchanges the sterility  \nassurance**?  \nYes  \nNo \nNo \nYes  \nChange in  \npackaging design which  \naffects functionality, safety,  \nstability or  \nseal integrity?  \nE2 \nE3 \nShelf-life change  \nvalidated by protocols  \napproved by the notified body  \n***? \nThe changeisconsidered  \nsignificantper MDR Art. 120(3)  \nThe change is considered a  \nnon-significant change  \nper MDR Art. 120(3)  \nNo \n Yes  \nE4 \n** Guidance on assessing  \nchanges for their impact on  \nthe effectiveness of the  \nsterilization process is  \nprovided in the respective  \nsterilization standards such  \nas: \n\uf0a7 \nEN ISO 11135 (Ethylene  \nOxide),  \n\uf0a7 \nEN ISO 11137 -1  \nRadiation),  \n ( \n\uf0a7 \nEN ISO 17665 -1 (Moist  \nHeat),  \n\uf0a7 \nEN ISO 13408 -1 (Aseptic  \nProcess).  \nChange* of  \nterminal sterilization  \nmethod?  \nNo \nYes  \nE1 \n* Includes change from  \nnon-sterile to sterile or a  \nchange to the sterilisation  \nmethod. Changes of cycle  \nparameters under the  \napproved quality  \nmanagement system are  \nnot deemed as significant in  \nthe meaning of Art. 120(3)  \nMDR  \n***In principle, an increase  \nin shelf life can be  \nconsidered non -significant  \n( \ne.g. the increase is made  \nfollowing the completion of  \na real time test whose  \nmethod and end -point was  \nvalidated and previously  \nassessed by the notified  \nbody)."}, {"title": "md_application-transitional-provisions-certificates_en.pdf.txt", "text": "Medical Device       \nMedical Device  Coordination Group Document   MDCG  201 9-10 rev.1   \nPage 1 of 2 \n  \n \n \n \n \nMDCG  201 9-10 rev. 1  \n Application of transitional provisions concerning     \n validity of certificates issued in accordance to \n Directives 90/385/EEC and 93/42/EEC     \n            \n \n October  2019   \n July 2020 rev. 1 \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is \ncomposed of representatives of all Member States and it is chaired by  a \nrepresentative of the European Commission.  \nThe document is not a European Commission document and it cannot be regarded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only  the Court of Justice of the European \nUnion can give binding interpretations of Union law.  \n \n  Medical Device       \nMedical Device  Coordination Group Document   MDCG  201 9-10 rev.1   \nPage 2 of 2 \n  \nMDCG 2019 -10 revision 1 changes  \nMDR postponement dates: from 2020 to 2021  \nApplication of transitional provisions concerning validity \nof certificates issued in accordance to Directives \n90/385/EEC and 93/42/EEC1 \nAccording to Article 120(2) of Regulation (EU) 2017/475 on Medical Devices (the MDR), certificates \nissued in accordance with Directives 90/385/EEC and 93/42/EEC  (the Directives ) will remain valid \nuntil 26 May 2024 at the latest. However, Article 120(3) establishes specific conditions that such \ncertificates, and the related devices thereof, have to comply with.  In particular, it is required that the  \nnotified body that issued the certificate \u2013 under a valid designation \u2013 continues to be responsible for \nthe appropriate surveillance activities with respect to all of the applicable requirements related to \nthe devices it has certified and that it has the possibility to take any necessary measure in relation to \nthose. \nIt has to be noted that, as reported in FAQ n.17 of the MDR transitional provision document \npublished by the  CAMD Transition Sub Group, the contract between the manufacturer and the \nnotified body who issued the certificate under the relevant Directive  shall include provisions allowing \nthe appropriate performance of such surveillance activities.  \nIn order to allow manufacturers to take advantage of Art. 120( 2) and Art. 120(3) of the MDR, it needs \nto be ensured that Authorities  responsible for notified bo dies have the right to and do monitor those \nnotified body\u2019s activities to the extent appropriate and necessary. For this purpose, Article 120(3) \nand Article 122(1) of the MDR provide the necessary legal basis for Member States to establish the \nnecessary le gal empowerments2 by means of National law to carry out the needed  monitoring \nactivities in relation to Notified Bodies. All this is regardless of whether the Notified Body has applied \nor not to be designated under the MDR  and/or it has a still valid desig nation under the Directives \nduring the validity of certificates issued in accordance to the Directives . \nConcerning information published in the NANDO database, in accordance to Article 120(1) of the \nMDR, any publication of a notification in respect of a no tified body in accordance with the Directives \nwill become void  as from 26 May 2021 .  Therefore, NANDO will only be used in relation to the  \nDirectives for information purposes after 25 May 2021 . NANDO will therefore list those notified \nbodies  that have bee n designated under the Directives with a clear  message that they are not able to \nissue new certificates but only  allowed to carry out  surveillance activities for valid certificates in the \ntransitional period, as established in  Article 120 of the MDR.  \n                                                           \n1  This document specifically refers to transitional provisions laid down in Regulation (EU) 2017/745  but can \nbe applied by analogy to Regulation (EU) 2017/746.  \n2  It should be noted that  relevant legal empowerments might be already available by means of National law \nwhich build on different EU pieces of legislation."}, {"title": "md_2020-14-guidance-mdsap_en.pdf.txt", "text": "1 \n  \nMedical Devices \nMedical Device Coordination Group Document                             MDCG 2020-14         \n \n \n \n \n \n \nMDCG 2020-14 \n  \nGuidance for notified bodies on the use of \nMDSAP audit reports in the context of \nsurveillance audits carried out under the \nMedical Devices Regulation (MDR)/ In Vitro  \nDiagnostic medical devices Regulation (IVDR)  \n \n \nAugust 2020 \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is composed of representatives of all Member States and a representative of the European Commission chairs it. The document is not a European Commission document and it cannot be regarded as reflecting the official position of the European Commission. Any views expressed in this document are not legally binding and only the Court of Justice of the European Union can give binding interpretations of Union law. \n  2 \n Guidance for notified bodies on the use of MDSAP audit \nreports in the context of surveillance audits carried out under \nthe Medical Devices Regulation (MDR)/ In Vitro  Diagnostic \nmedical devices Regulation (IVDR) \n \nBackground \nIn fulfilling the EU\u2019s commitment to encourage notifi ed bodies to make use of audit reports from the \nMedical Device Single Audit Program (MDSAP) in a manner that is compatible with EU legislative \nrequirements, the Medical Device Coordination Group (MDCG) endorsed this guidance which has been developed by a group of experts comprised of interested Member State representatives, notified \nbody associations and stakeholders.  \nScope \nThe purpose of this document is to provide guidance to notified bodies on how to take into account MDSAP Medical Device Regulatory Audit Reports\n1 (from hereafter \u201cMDSAP audit reports\u201d) issued \nby MDSAP auditing organisations2 when performing surveillance audits under Regulation (EU) \n2017/745 \u2013 Medical Devices Regulation (MDR) and Regulation (EU) 2017/746 \u2013 In Vitro  Diagnostic \nmedical devices Regulation (IVDR). This is of particular use when a manufacturer has undergone an \nMDSAP audit and wishes to present this audit report (including the associated attachments) in context \nof the regular surveillance audits performed in accordance to the MDR or IVDR.  \nGeneral regulatory considerations \nUnder the MDR/IVDR, most conformity assessme nt procedures consist of both the quality \nmanagement system audit and the assessment of a device\u2019s safety and performance. Notified body\u2019s \nconformity assessment activities, which are a prerequisite for the manufacturer\u2019s declaration of \nconformity, when concluded successfully result in a conformity assessment certificate, a pre-market requirement for most classes of medical devices and IVDs. In that regard, notified bodies designated \nunder the MDR/IVDR fulfil roles, which correspond to combined functions of both MDSAP auditing \norganisations and MDSAP participating regulatory authorities.\n3 Therefore, the roles performed by \nnotified bodies and MDSAP auditing organisations differ as the latter solely perform quality \nmanagement system audits which are then utilised by regulatory authorities in their evaluation of a \nproduct\u2019s safety and performance for the purpose of issuing a marketing authorisation.   \n \n                                                      \n1 MDSAP audits are recorded using the Medical Device Regulatory Audit Report form (MDSAP AU F0019.1). Final \nMDSAP audit reports are signed in section 18 of the form. \n2 Auditing Organization: An organization that audits a medical  device manufacturer for conformity with quality management \nsystem requirements and other medical device regulatory re quirements. Auditing Organizati ons may be an independent \norganization or a Regulatory Authority which perform regulatory audits. (IMDRF/MDSAP WG/N3 FINAL:2016) \n3 Regulatory Authority: A government body or other entity that exercises a legal right to control the use or sale of medical \ndevices within its jurisdiction, and that may take enforcemen t action to ensure that medical products marketed within its \njurisdiction comply with legal requirements. (GHTF/SG1/N78:2012, cited from IMDRF/MDSAP WG/N3 FINAL:2016)  3 \n Requirements of  the MDR/IVDR \nThe MDR/IVDR clearly state that all manufacturers need to have a quality management system in \nplace so as to ensure that devices manufactured in se ries are in conformity with the requirements of the \nrespective regulation and that experience from the use of devices is taken into account in the \nproduction process (MDR Recital 32/IVDR Recital 31). This becomes an explicit requirement for \nmanufacturers to establish, document, maintain, keep up to date and continually improve quality management systems so that to ensure compliance with the Regulations (MDR Article 10 (9)/IVDR \nArticle 10(8)). \n Notified bodies are charged with the assessment of quality management systems of devices in \naccordance with MDR Article 52 and IVDR Article 48. Specifically, notified bodies are responsible \nfor auditing and certifying manufacturers\u2019 quality management systems (MDR/IVDR Annexes IX and XI and Annex VII section 4.5 ), following up with  appropriate surveillance audits (MDR/IVDR Annex \nIX section 3 and Annex VII section 4.5.1, 4.10) as well as conducting unannounced audits \n(MDR/IVDR Annex VII section 4.5.1). Notified bodies are also responsible for the development of their appropriate procedures for conformity assessments according to the MDR /IVDR.  \n \nThe MDR/IVDR specifically state that notified bodie s\u2019 audit programmes should clearly identify the \nnumber and sequence of activities required to demonstrate complete coverage of a manufacturer\u2019s \nquality management system (MDR/IVDR Annex VII 4.5.2) and that surveillance audits need to be \ncarried out on at least an annual basis (MDR/IVDR Annex VII section 4.10 and Annex IX section 3.3). For each surveillance audit identified in the audit programme, the objectives, criteria and scope of \nthe surveillance audit are defined in an audit plan which adequately addresses and takes into account \nspecific requirements for the devices, technolog ies and processes involved (MDR/IVDR Annex VII \nsection 4.5.2(a) \u2013 third bullet point). Surveillance audits are expected to gather sufficient information \nto verify the proper implementation of the quality management system and ensure that it continues to \ncomply with the requirements of the MDR/IVDR. \n \nWhen and how to take MDSAP audit reports into account \nIt is important to stress that the MDR/IVDR remain applicable in their entirety. The use of MDSAP audit reports within the EU legislative framework is possible only where the MDSAP audit covers similar or equivalent MDR/IVDR requirements. Designated notified bodies maintain the full authority \nover their judgement, conclusion and final decision about the conformity of quality management \nsystems to the relevant provisions of the MDR/IVDR and the safety and performance of medical devices and IVDs intended to be placed on the market in the EU. \n \nGiven that surveillance audits, their periodicity and EU auditors\u2019 competencies are mandated by law, yearly surveillance audits need to be maintained. Ho wever, it could be possible to take into account \nthe scope and outputs of manufacturers\u2019 recent MDSAP audit reports as an input for developing \nsurveillance audit programmes. The taking into account of MDSAP audit reports could define in a more precise manner the activities to be performed during a surveillance audit. For example, the \npositive quality management system conformity appraisal through MDSAP might lead to a reduction 4 \n of the focus on aspects already covered by MDSAP audit reports. The notified body may then focus \ntheir surveillance audit on specific MDR/IVDR requirements which are either not covered or only \npartially covered by the MDSAP audit report. Non-exhaustive list of examples (alphabetical order):  \n- clinical evaluation/performance evaluation process (including post-market \nclinical/performance follow-up),  \n- EU authorised representative contractual provisions,   \n- EU UDI assignments within the quality management system,  \n- manufacturer financial coverage in respect of potential liability,  \n- person responsible for regulatory compliance qualification and role,  \n- records control,  \n- system for risk management,  \n- vigilance and post market surveillance activities, including the associated corrective actions \nand preventive actions. \n \nSimilarly, non-conformities identified in recent MDSAP audit reports can trigger the notified body to pay particular attention to those aspects in the MDR/IVDR planned surveillance audit.  \n \nIt is important to highlight the following details: \n- The taking into account of MDSAP audit reports is not applicable to initial quality \nmanagement system audits required for the issuing of EU QMS certificates. Notified bodies \ndesignated under the MDR/IVDR would always need  to conduct these audits in their entirety.  \n- The taking into account of MDSAP audit reports is not applicable to MDR/IVDR \nunannounced audits.  \n- Reports of MDSAP unannounced audits or special audits should not be taken into account in \nthe narrowing of focus in MD R/IVDR surveillance audits. \n- Regular surveillance audits would still take place on a yearly basis. However, the positive \nQMS conformity appraisal through an MDSAP audit may lead to a limitation of the surveillance focus from aspects already covered by the MDSAP audit reports. \n- When MDSAP audit reports are considered as input to the planning of an MDR/IVDR \nsurveillance audit, these reports should be taken into account in their complete form, including all associated attachments. Both positive and negative statements about the conformity of the \nmanufacturer should be incorporated in the planning of the MDR/IVDR audit. \nIf there is concern about the functioning of the quality management system, for instance due to \ninformation gathered through the assessment of vigilance cases or post market activities, previous \nsurveillance audits  or technical documentation assessments, a complete surveillance audit should be \ncarried out.  \nNotified bodies may wish to determine and establish additional guidance in order to support their \nprocedures for evaluating MDSAP audit reports.  Such guidance could for example specify the content details of MDSAP audit reports considered acceptable (i.e. may be taken into consideration) in the \nnotified body assessment programme and what modifications may be done to the notified body \nassessment programme after the taking into consider ation of the MDSAP audit report (to ensure that 5 \n any specific assessment items that are not covered in the MDSAP audit reports are performed by the \nnotified body). \n The notified body shall remain fully responsible for its decision, to whether or not, and to what extent, \nan MDSAP audit report can be taken into account. \n The Annex to this guidance identifies and analyses aspects within MDSAP audit reports that are \nrelevant in relation to the EU requirements. Part I focuses on providing an explanation of where to find \nrelevant information in MDSAP audit reports that could be used to a greater or lesser extent as supporting evidence for MDR/IVDR quality management system requirements. Part II provides \nexamples on how correlations between MDR requirem ents to sections of MDSAP audit reports may \nbe established in the notified bodies\u2019 additional guidance or procedures. Although the examples in Part II focus on MDR requirements, the same methodology could be applied for the IVDR. \n \n \n 6 \n Annex  \n \n \nPart I \u2013 Explanation of relevant information in MDSAP audit report \n \nThe following table shows where information with relevance for MDR/ IVDR quality management system audits can be found in MDSAP audit reports and \nhighlights specifics that should be understood by notified bodies when taking into account such information.   \nA comprehensive description of MDSAP audit report content can be  found in MDSAP AU P0019 MDSAP Me dical Device Regulatory Audit Reports and MDSAP \nAU G0019 Medical Device Regulatory Audit Report Form Guidelines\n4  \n \nSections of MDSAP audit report Relevant information  \nSection 1 \u2013 Audit Information Name of MDSAP auditin g organisation, audit dates and duration, audit team \nSection 2 \u2013 Audited Facility Audited facility name and address. \nIn case of a multi-site audited organization, a separate audit report is generally required for each audited \nfacility.  This means, the audited facility described in Section 2 is not necessarily the manufacturer \nresponsible for the overall product.  Also see Section 4. \nSection 3 \u2013 Certification Schemes, Scopes & Criteria, Audit Types Certification schemes with scope of certification, audit type and audit criteria. \nIn some cases, a list of medical devices covered in the scope is attached to the audit report. \nThe \u201cCE marking\u201d scheme may be referenced, but this is not mandatory.   \nFor unannounced audits, it is important to understand that they are commonly performed to verify \neffectiveness of corrective actions on non-conformities, and their content is not the same as that of \nunannounced audits under MDR/IVDR.  \n                                                      \n4 Both documents are available in the \u201cMDSAP Documents\u201d / \u201cMDSAP Audit Procedures and Forms\u201d section of the MDSAP program homepag e (https://www.fda.gov/medical-devices/cdrh-\ninternational-programs/medical-device-single-audit-program-mdsap , accessed on 2020-03-25). \n 7 \n Sections of MDSAP audit report Relevant information  \nSection 4 \u2013 Certification Holder and Multi-\nsite Organization Relationship between audited facilities and reference to other audited facilities included in the audit. \nCertification Holder is the main facility shown on the title page of the certificate. \nCampus is a group of facilities that can be described in one audit report by derogation from general requirement of \nseparate audit reports for each facility.  \nRelated sites are other audited facilities that are described in separate audit reports. \nCorporate Information describes the use of multiple names and identities by the organization and its significant \nrelationships of the manufacturer with related companies in the context of the audited QMS and its associated \nactivities and devices. \nSection 5 \u2013 Audit Objectives Additional audit objectives applying  to schemes other than MDSAP may be included, but this is not mandatory. \nSection 6 \u2013 Audited Facility Description Regulatory Roles of th e audited facility are indicated separately for each MDSAP parti cipating country.  It may \nadditionally include the roles in other countries, such as Europe, but this is not mandatory. \nActivities at the Audited Facility describe what is actually done at the audited site. \nActivities not included in the Scope of Certification are activities performed at the facility which are not required \nto be listed in the MDSAP certificate. \nSection 7 \u2013 Critical Suppliers Critical suppliers of the audited facility that are relevant to the scope of audit, including pr oducts or services \nobtained from them and indication whether this audit extended to visit a supplier. \nInstead of a detailed description in this section, the list may be attached to the report. \nSection 8 \u2013 Audit History Outcomes of previ ous audits that have been taken into consideration in preparation for this audit. \nSection 9 \u2013 Exclusion and Non-\nApplications of requirements in the QMS Exclusion and non-application of ISO 13485 requir ements in the QMS of the audited facility. \nSection 10 \u2013 Outcome of Pre-Audit \nActivities Outcome of the preceding documentation review and/or stage 1 audit, if applicable.   \nInstead of detailed description in this section, additional records may be attached to the report. 8 \n Sections of MDSAP audit report Relevant information  \nSection 11 \u2013 Audit Findings Sections 11.1-11.7 describe audit findings and ev idence related to ISO 13485 and country-specific \nrequirements.  Please refer to MDSAP Audit Model and details of requirements5 for more information. \nSection 11.7A is only included, if the critical suppliers we re visited as part of the audit, to describe the audit \nfindings made at the visited supplier locations. \nSection 11.8 may include findings according to scheme s other than MDSAP, but this is not mandatory. \nSection 12 \u2013 Non-conformities List of non-conformities, references to which are made in Section 11.  \nGrade is a numeric classification of significance of non-conformity between 1 and 5 according to \nGHTF/SG3/N19:2012 - Quality Management System - Medical Devices \u2013 Non-conformity Grading System \nfor Regulatory Purposes and Information Exchange \nSection 13 \u2013 Significant Deviations from the Audit Plan Circumstances that lead to deviations from the audit plan and obstacles experienced by the audit team during the \naudit. \nSection 14 \u2013 Follow-up of Past Non-conformities Results of audit team\u2019s evaluation of effectiveness of ac tions taken in response to non-conformities identified \nin prior audits with the possible status Closed, Superseded of Left Open. \nA record with the details of this evaluation may be attached to the report. \nSection 15 \u2013 Summary of Major Changes to \nthe Audited Facility Summary description of major changes since previous audit, especially those changes not described in \nSection 11. \nSection 16 \u2013 Conclusions Extensive conclusion of the audit, including the statement on the conformity of the QMS with the audit \ncriteria and recommendations of the audit team. \nSection 17 \u2013 Attachments List of records th at are considered as part of the audit report, including those referenced in Section  6 (list of \nmedical devices), Section 7 (list of critical suppliers), Section 10 (outcome of pre-audit activities), Section 11.2 \n(review of sampled technical documentation), Section 14 (updated non-conformity report relative to past non-\nconformities). \nSection 18 \u2013 Audit Report Approval Date and signature of review and approval of the final audit report. \n                                                      \n5 The MDSAP Audit Model can be found in the \u201cMDSAP Documents\u201d / \u201cMDSAP Audit Procedures and Forms\u201d section of the MDSAP program homepage ( https://www.fda.gov/medical-\ndevices/cdrh-international-programs/medical-device-single-audit-program-mdsap , accessed on 2020-03-25). 9 \n Part II \u2013 Examples on how correlations between MDR requirements to sections of MDSAP audit reports may be established  \n \nThe following examples of established correlations between MDR qua lity management system requirements and the MDSAP Audit Model  show how certain \noverlapping requirements may be covered in MDSAP audit reports, and what specific MDR requirements are not covered. The referen ces direct to MDSAP audit \nprocesses and tasks that overlap with MDR requirements and are linked to same or similar ISO 13485 requirements.  \n \nIt is recommended that notified bodies develop more detailed gu idance for determining the extent  in which MDR/IVDR quality mana gement system requirements \ncorrelate to those covered in MDSAP audit reports. Any such fully  developed correlation should be revised in the event of a pub lication of changes to any basic \ncriteria document including EN ISO 13485, MDSA P Audit Model and MDR/IVDR, or any documen t utilised to establish correlation, su ch as CEN/TR 172236. \n \nThe examples provided in the below table cover only the following  three blocks of MDR requirements: Clinical evaluation, Suppli er controls, and Post-market \nsurveillance. \n \nMDR requirement Sections of MDSAP audit report addressing this topic(s) Particular MDR requirements \nnot covered in an MDSAP audit \nClinical evaluation \nMDR Article 10, paragraph 3 \nMDR Annex IX, Chapter I, 2.1, indents 10-11 \nMDR Annex XI, Part A, 6.1 indent 17 Section 11.5 \u2013 Design and Development, Task 11 Specifics of Article 61 and Annex \nXIV Part A \nClinical evaluation plan and \nprocedures to keep up to date the \nclinical evaluation plan \nSupplier controls \nMDR Article 10, paragraph 9 (d) \nMDR Annex IX, Chapter I, 2.2 paragraph 2 b) \nindent 3 Section 11.1 \u2013 Management, Task 5 \nSection 11.3 \u2013 Measurement, Analysis and Improvement, Tasks 2, 7, 13 Section 11.5 \u2013 Design and Development, Tasks 1, 7, 8, 16 \nSection 11.6 \u2013 Production and Service Controls, Tasks 7, 14, 19, 21, 22 \nSection 11.7 \u2013 Purchasing, all tasks  Annex II 3. (c) \n                                                      \n6 CEN/TR 17223:2018 Guidance on the relationship between EN ISO 13485: 2016 (Medical devices \u2013 Quality management systems \u2013 Requ irements for regulatory purposes) and European Medical \nDevices Regulation and In Vitro  Diagnostic Medical Devices Regulation. \n7 MDR Annex XI, Part A, 6.1 indent 1 refers back to MDR Annex IX, Chapter I, 2.1 10 \n MDR requirement Sections of MDSAP audit report addressing this topic(s) Particular MDR requirements \nnot covered in an MDSAP audit \nPost-market surveillance \nMDR Article 10, paragraph 10 \nMDR Annex IX, Chapter I, 2.1 indent 8-9 MDR Annex XI, Part A, 6.1 indent 1\n8 \nMDR Annex XI, Part B, 13 Section 11.3 \u2013 Measurement, Analysis and Improvement, Task 12, 14, \n15 \nSection 11.4 \u2013 Medical Device Adverse Events and Advisory Notices \nReporting, Tasks 1, 2 Specific requirements on the PMS \nsystem incl. PMS plan, PMS report, \nPSURs, and PMCF plan (Articles 83-86 and Part B of Annex XIV as \nwell as obligations resulting from \nthe provisions on vigilance \n(Articles 87 to 92) \n \n \n \n                                                      \n8 MDR Annex XI, Part A, 6.1 indent 1 refers back to MDR Annex IX, Chapter I, 2.1"}, {"title": "mdcg_2019_13_sampling_MDR_IVDR.pdf.txt", "text": "1 \n Medical Device       \nMedical Device Coordination Group Document                           MDCG  2019 -13   \n \n \n \n \n \n \n \nMDCG  2019 -13 \n        Guidance on sampling of MDR Class  IIa / Class IIb  \n        and IVDR Class B / Class C devices  \n        for the assessment of the technical documentation\n              \n \n           Decem ber   2019  \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) \nestablished by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of \nrepresentatives of all Member States and it is chaired by a representative of the \nEuropean Commission.  \nThe document is not a European Commission document and it cannot be regarded as \nreflecting the official  position of the European Commission. Any views expressed in this \ndocument are not legally binding and only the Court of Justice of the European Union \ncan give binding interpretations of Union law.  \n   \n2 \n Guidance on s ampling of MDR Class IIa /  \nClass IIb and IVDR Class B /  Class C devices \nfor the assessment of the technical \ndocumentation  \n1 Introduction  \nRegulation (EU) 2017/745 on medical devices (MDR) and Regulation  (EU) \n2017/746 on in vitro  diagnostic medical devices (IVDR)  establish the \nrequirements for sampling of Class IIa / Class IIb and Class B /  Class C devices \nfor the assessment of the technical documentation.  \nArticle 52(4) and (6) of the MDR and Article 48( 7) and ( 9) of the IVDR est ablish \nthe need to assess the technical documentation of at least one representative \ndevice per generic device group  (for Class IIb and Class C) and for each \ncategory of devices  (for Class IIa and Class B) prior to issuing the certificate.   \nSection 2.3 and 3.4 of Annex IX of both Regulations (and section 10 of Annex XI  \nof the MDR ) defines that the quality management system assessment has to be \naccompanied by the assessment of technical documentation for devices selected \non a representative basis . \nSection  4.5.2(a) of Annex VII of both Regulations1 requires the notified body to \ndraw up and keep up to date, a sampling plan for the assessment of technical \ndocumentation as referred to in Annexes II and III prior to the audit .  \nSection 4.5.2(b) of Annex VII requires the notified body to assess t he technical \ndocumentation as preparation for the audit (s). This assessment is expected to be \nfinalised in due time of such  audit (s). \n \n2 Scope  \nThis guidance is intended to define  the requirements of sampling for Class IIa \nand Class IIb devices  under the MDR and Class B and Class C devices under \nthe IVDR for the purpose of assessing the technical documentation .   \nThis guidance defines and further elaborates  on the sampling criteria and use of \nsuch criteria for drawing up  and maintaining a sampling plan.  \nIn addition, th is guidance clarifies th e tasks to be performed by the notified body \nincluding the  applicability of Chapter II of Annex IX of both Regulations and the \nextent of  the technical documentation assessment.   \nSee Section 5.3 for exemptions for specific types of devices.  \n \n                                                      \n1 Hereafter referred to as \u201cAnnex VII\u201d  for both, the MDR and the IVDR.    \n3 \n 3 Definitions  \nThe Regulations do not contain definitions of certain terms applicable to \nsampling , and in some instances  certain definitions given cannot be used on an \noperational level. Therefore , only for th e purpose of this  guidance  the \nfollowing definitions apply : \n \n3.1. Category  of devices : category  of devices  should be understood as the \nrelevant M DA/MDN codes (MDR) or IV R code s (IVDR)  according to \nRegulation (EU) 2017/2185 on the codes for the designation of notified \nbodies .  \n \n3.2. Generic device group2:  is to be understood : \n\uf0b7 in respect of the MDR3,4 as the 4th level of the European \nNomenclature  on Medical Devices (EMD N) 5, 6 (i.e. combination of \none letter plus 6 digits ), and  \n\uf0b7 in respect of the IVDR as the 3rd level of the EMD N (i.e. \ncombination of one letter plus 4 digits respectively)  in combination \nwith the most appropriate  IVP code.  \n \n3.3. Device  range:  device range is to be understood as all \u201cdevice \ncategories\"  for Class IIa and Class B devices and all \u201cgeneric device \ngroups \u201d for Class IIb and Class C devices  covered in a certificate .   \n \n3.4. Device : device should be understood as the device(s) associated with \none Basic UDI -DI7.  \n \n3.5. QMS certificates:  QMS certificates are EU q uality management system \ncertificates  (MDR and IVDR) , EU quality assurance certificates  (MDR) \nand EU production quality assurance certificates  (IVDR)  issued by \nnotified bodies as a result of conformity assessments .  \n \n                                                      \n2 \"A set of devices having the same or similar intended purposes or a commonality of technology allowing \nthem to be classified in a generic manner not reflecting specific characteristics\" (Art. 2 (7) MDR  and \nArt. 2(8) IVDR).  \n3 In cases, where the 4th level for the MDR do es not exist the notified body should use the next higher \nlevel . \n4 If the notified body considers that  for a particular device level 4  for the MDR/level 3 for the IVDR is not \nsufficiently specific to define a generic device group, it can use the next lower level if available.  \n5EMDN  nomenclature  can be found currently at : \nhttp://www.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_15_file. pdf \n6 In case where more than one EMDN  code applies to one device, only the most appropriate  one of these \nEMD N codes will be assigned for sampling purposes. The technical documentation related to that \nparticular device will be assessed in its entirety.  \n7 As defined in MDCG 2018 -1 v2 Guidance on BASIC UDI-DI and changes to UDI -DI.  \n4 \n 4 Sampling criteria  \nThe Regulation s establish minimum requirements for sampling prior to issuing \nthe certificate and during its validity.  The notified body will ensure that these \nrequirements  will be complied with when drawing up a sampling plan.  In \naddition, other considerations have to be observed in order to ensure an \nadequate coverage of devices on a representative basis.  \n4.1. Quantitative Sampling Criteria  \n \n4.1.1.  Sampling prior  to issuing a QMS certificate  \nThe Regulations establish the need for the notified body to assess technical \ndocumentation for a number of  devices prior to issu ing the QMS certificate :  \n- For Class IIb and Class C the technical documentation of at least one \nrepresentative device per generi c device group  (as per Article 52(4) of the \nMDR and Article 48( 7) of the IVDR ).  This means that the notified body \nshou ld asses s how many generic device groups as per 3.2 are covered in \nthe application  (how many nomenclature's 4th levels for MDR /  3rd levels  \nin combination with applicable IVP  codes  for the IVDR8), select per group  \nat least one representative device covered by a Basic UDI -DI and assess \nthe technical documentation  for the device(s) selected .   \n- For Class IIa and Class B the technical documentation of at least one \nrepresentative device per category  of devices  (as per Article 52(6) of the \nMDR and Article 48( 9) of the IVDR ).  This means that the notified body \nshould asses how many categories of devices as per section 3.1, (how \nmany  MDA/M DN or IVR codes ), are covered by the ma nufacturer\u2019s \napplication, select per category at least one representative device covered \nby a Basic UDI -DI (MDA/MDN or IVR code ) and assess the technical \ndocumentation  for the device(s) selected . \nThe outcome of these assessments is an essential input for the final review \naccording t o Annex VII section 4.7 of the R egulations  prior to issuing of the \ncertificate .  \n4.1.2.  Sampling during surveillance  \nAfter issuing the certificate, the notified body will continue to assess technical \ndocumentation in line with the sampling plan. Section 3.5 of Annex IX of both \nRegulations indicates that surveillance assessment shall also include an \n                                                      \n8 Generic device groups for Class C devices will consist on an EMDN  + an IVP code. Therefore, when \ndifferent products are covered under the same EMDN  but corresponds to different IVP codes, the \nnotified body will assign the most appropriate IVDP code to each device.    \n5 \n assessment of the tech nical documentation9 which means that at least one \ntechnical documentation must  be reviewed each year .  \nIn addition, notified bodies will ensure that the entire device range is covered \nduring the period of validity of the certificates  as required by Section 4.5.2 (a) of \nAnnex VII . This means that at least one device per each category, in case of \nClass IIa and Class B  devices , and at least one device per each generic device \ngroup, in case of Class IIb and Class C devices, should be samp led and the \nrelevant technical documentation assessed between the issue of a certificate \nand its expiry date.  \nFurthermore, in addition to  the above -mentioned criteria , the number of samples  \nto be assessed need to be selected on a representative basis ( as per Annex VII \n4.5.1 9th indent MDR, An nex IX 2.3  3rd paragraph MDR / IVDR,  and An nex VII \n4.5.1 8th indent IVDR). Therefore, in developing the sampling plan (see section \n6), the notified body should also ensure that the number of devices sampled is \nproportionate to the total number of devices contained in the certificate. For this \npurpose, it is expected that 15%10 of devices from  each category and from each \ngeneric device group covered in the certificate will be sampled during its validity  \n\u2013 taking into account the maximum validity of 5 years . \nIn cases where the certificate contains very few devices and the technical \ndocumentation s of these have been already reviewed, it is expected that during \nsurveillance audit s the notified body will focus on the review of the technical \ndocumentation related to post -market surveillance in accordance with Annex III .  \nNormally, the devices to be sampled after the certificate has been issued would \nbe spread evenly during the validity of the certificate. However, the notified body \nmight decide to perform different number s of reviews in a given year for different \nreasons (e.g. workload , vigilance concern ) as long as throughout the surveillance \nperiod all initially determined assessments are performed . Such an approach is \nacceptable as long as the minimum requirements mentioned in the first \nparagraph of this section are complied with.  \n4.2. Qualitative  Sampling Criteria  \nSection 2.3 of Annex IX of both Regulations establishes qualitative criteria to be \nused when drawing up sampling plans. While s ome of these criteria such as \nsimilarities in design, technology and manufacturing and sterilisation methods \nmay be covered already by the fact that devices belong to the same category or \ngeneric device group , all the criteria defined in Section 2.3 of Annex IX including  \nnovelty of the technology  intended purpose  or the results of any previous \nrelevant assessments such as with regard to physical, chemi cal, biological or \nclinical properties must be individually considered when prioritising the review of \none device over another.  This prioritisation should take into account the inherent \nrisk of  the different devices included in the relevant category  of devices  / generic \n                                                      \n9 The follow -up of change notifications according to Section 4.9 of Annex VII (e.g. \u201cthe device range \ncovered\u201d in Annex IX section 2.4), and other surveillance activities as laid down in Section 4.10 of \nAnnex VII are to be carried out in addition to sampling during surveillance . \n10 For the first certification cycle under the MDR/IVDR the 15% may be decreased to a minimum of 5%.   \n6 \n device group which means that , for instance, novel devices, will usually  be \nprioritised over well -known technologies (unless there are specific concerns over \nthe latter).  Additional criteria may be also taken into consideration by the  notified \nbody11. As required by the Regulation, the notified body must  document its \nrationale for the samples taken , in particular, mentioning what specific criteria \nhave been taken into account.  \nIt should be noted, that as long as there are devices that have  not been sampled , \neach device should only be sampled once  during the period of validity of the \ncertificate  unless vigilance cases or other information which  have been brought \nto the notified body \u2019s attention will require it .  \n \n5 Assessment of the technical documentation  \n \n5.1. Depth of the assessment  \nThe depth and extent of the technical documentation assessment of Class IIa / \nIIb and Class B / Class C devices will be the same as the  depth of assessment \ncarried out for Class III and Class IIb implantable  and Class D devices .  \nThis means that the technical documentation of a device shall be assessed \nagainst all General Safety and Performance Requirements (Annex I) and \nrequirements of Annex II and III. Records of the assessment shall be prepared \nwhich allow  a third party to understand the functionality of the device and all \naspects of the assessment including judgements made by the assessor . \nIt should be taken into account that every device (i.e. Basic UDI -DI) might include \ndifferent variants, models or sizes. In that case, the review of the technical \ndocumentation will also include the assessment of how the differences among \nthese have been addressed in the technical documentation and whether all of \nthem are in line with the relevant requirements.  \n5.2. Applicability of Chapter II, Section 4 of Annex IX   \nTaking into account the wording of article s 52(4) and 52(6) of the MDR and \nArticle 48(7) and 48(9) of the IVDR, as combined with annex es VII and IX, the \ntasks to be carried out by the notified body as part of the conformity assessment \nactivities described in Chapter II , Section 4  of Annex IX comprise t he complete \nreview of the technical documentation  in accordance with Annexes II and III .  \nIn addition, the manufacturer  will grant access to the technical documentation as \nreferred to in Section 2.2 of Annex IX and the  notified body will  provide the \nmanufacturer with a report on the technical documentation assessment. For \nClass IIa / IIb and Class B / Class C the notified body will neither require  an \napplication nor issue an EU technical documentation assessment certificate  (see \n5.3 for exceptions) .  \n                                                      \n11 For instance, where controls or calibrators are specifically intended to be used in conjunction with a  \nspecific IVD device, these controls or calibrators will preferably be assessed alongside that device   \n7 \n 5.3. Additional requirements for s pecific types of devices under the MDR \nand the  IVDR  \nFor class IIb  implantable devices12, Article 52(4) second subparagraph  of the \nMDR establish es the need to review the technical documentation in accordance \nwith the complete Section 4 of Annex IX for every device,  therefore  an \napplication as well as the issuance of an EU technical documentation \nassessment certificate  are req uired . They are exempt from sampling.  \nAccording to Article 54 , Class IIb active devices intended to administer and/or \nremove a medicinal product falling into rule 12 of Annex VIII are subject to the \nclinical evaluation consultation procedure  prior to issuing of the certificate . These \ndevices can be subject to sampling  but according to Article s 54(3) and 55 the \nnotified body must ensure that at least the clinical evaluation assessment report \n(CEAR) for each device  is uploaded in Eudamed prior to issuing the QMS \ncertificate.   This means that the sampling will not apply to the clinical evaluation \nas it has to be assessed for every device.  \nArticle 48  (7, 8 and 9) and Section 5 of Annex IX of the  IVDR establish  that class \nB and C devices for self -testing, near-patient testing  and companion diagnostics \nare exempt from sampling . The manufacturer will lodge an application as per \nsections 5.1  (a) and 5.2 (a) of Annex IX of the IVDR , and , as described in section \n5.1 (c-e) and 5.2 ( a-e), the notified bod y will review the technical documentation \nof all the devices covered in the certificate  and will issue an EU technical \ndocumentation assessment certificate.   \n5.4. Reporting  \nThe technical documentation assessment of Class IIa / IIb and Class B /  Class C  \ndevices and its reporting should follow the principles established in Annex VII \nand the applicable provisions of the conformity assessment annexes  and should \nuse or be similar to those procedures and checklists developed by the notified \nbody for the assessment of Class III / IIb implantable devices  and Class D \ndevices .  \nIn order to fulfil the legal requirements, the reporting requirements established in \nSection 4.6. of Annex VII will apply.  \n \n6 Drawing up and keeping up to date a sampling plan  \nAccording to Section 4.5.2(a) of Annex VII  the notified body shall draw up and \nkeep up to date a sampling plan . This plan should contain at least the devices  \ncovered by the certificate, their Basic UDI -DI, the generic device group (in case \nof Class IIb ), the generic device group plus the IVP code (in case of  Class C \ndevices) or the category of devices (in case of Class IIa / Class B devices) , the \nidentifier of the respective technical documentation , the (planned) assessment \ndates and the status of such asse ssments .  \n                                                      \n12 Except fo r sutures, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips \nand connectors,  which are subject to sampling   \n8 \n  \nThe notified body should update the sampling plan whenever needed on the \nbasis of the criteria defined in this guidance  as well as on the basis of its post -\ncertification activities laid down in Section 4.10 of Annex VII. In particular, the \noutco me of the screening of relevant sources of scientific and clinical data and \npost-market information relating to the scope of their designation , or the review of \nvigilance data should be taken into account.  \nIf the manufacturer makes a change in the product range during the period of \nvalidity of the certificate, the notified body should review the sampling plan \naccordingly. When a dding new devices to the scope of the certificate which do \nnot fall into the alrea dy covered generic device groups / categories  of devices , \nthe initial sampling criteria (section 4.1) apply.  \nIf the manufacturer applies for re -certification, the notified body should update \nthe sampling plan with the samples to be assessed during the upc oming \ncertification period according to the principles laid down under section 4.1.2 \nSampling during surveillance and keep the sampling plan up to date as \ndescribed above."}, {"title": "11 MDCG 2020-11 Guidance on the renewal of designation and monitoring of notified bodies under Directives 90385EEC and 9342EEC.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-11  \n \n \n1 \n  \n \n \n \n \n \n \nMDCG 2020-11 \n  \nGuidance on the renewal of designation and \nmonitoring of notified bodies under Directives \n90/385/EEC and 93/42/EEC to be performed in \naccordance with Commission Implementing \nRegulation (EU) 2020/666 amending Commission \nImplementing Regulation (EU) 920/2013   \n             \n \nMay 2020 \n \n \n  \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission. The document is not a European \nCommission document and it cannot be regarded as reflecting the official position of \nthe European Commission. Any views expressed in this document are not legally \nbinding and only the Court of Justice of the European Union can give binding \ninterpretations of Union law. \n \n  Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-11  \n \n \n2 \n Guidance on the renewal of designation and monitoring of \nnotified bodies under Directives 90/385/EEC and 93/42/EEC \nto be performed in accordance with  Commission \nImplementing Regulation (EU) 2020/666 amending \nCommission Implementing Regulation (EU) 920/2013  \n \n1. Introduction \nThe COVID-19 pandemic has created extraordinary circumstances that demand substantial \nadditional resources, as well as a continued availability of vitally important medical devices, \nthat could not reasonably have been anticipated at the time of adoption of Medical Devices \nRegulation (EU)  2017/745 (hereafter referred to as \u2018MDR\u2019). In order to allow Member States, \nhealth institutions and economic operators to prioritise the fight against the COVID-19 \npandemic it was considered necessary to defer the application of certain MDR provisions by \none year (i.e. until 25 May 2021)1. To ensure the continuous presence of a functioning \nregulatory framework for medical devices it was necessary to also defer by one year the date \nof repeal of the Medical Devices Directives 90/385/EEC and 93/42/EEC (hereafter referred to \nas \u2018the Directives\u2019). \nThe deferral of the date of repeal has a consequential impact on the designations of certain \nnotified bodies under the Directives, including their ability to carry out their obligations and \nbe operational until 25 May 2021. The current COVID-19 pandemic also affects the way in \nwhich designating authorities are able to perform the required appropriate surveillance and \nmonitoring activities over notified bodies. To take account of these extraordinary \ncircumstances, the Commission and the Member States, on 18 May 2020, adopted \nCommission Implementing Regulation (EU) 2020/666 amending Commission Implementing \nRegulation (EU) 920/2013 as regards the renewal of designations and the surveillance and \nmonitoring of notified bodies (hereafter referred to as \u2018the Implementing Regulation\u2019)2. The \namendment provides for a derogation from certain requirements on the renewal of \ndesignations of notified bodies and for alternative surveillance and monitoring activities that \ndesignating authorities should carry out.  \nIn particular, in the interest of health and patient safety, and, to ensure consistency among the \nactivities performed by designating authorities, this guidance document has been developed to \noutline common criteria for the renewal of designations of notified bodies under the \nDirectives until 25 May 2021. In addition, this document intends to provide clarification on \nthe appropriate activities performed by designating authorities over notified bodies in order to \nensure an adequate level of surveillance in accordance with Article 5 paragraph 1, third \nsubparagraph, of the Implementing Regulation. \n                                              \n1 OJ L 130, 24.4.2020, p. 18\u201322. \n2 OJ L 156, 19.5.2020, p. 2\u20135  Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-11  \n \n \n3 \n 2. Scope \nThis guidance covers the following activities performed by designating authorities under \nexceptional circumstances, as referred to in Article 4(6) of the Implementing Regulation: \n\uf0b7 renewal of designation under the Directives of notified bodies whose designation \nexpires in the period from 26 May 2020 to 25 May 2021; \n\uf0b7 surveillance activities to be performed by designating authorities in accordance with \nthe Implementing Regulation under COVID-19 related restrictions, notably \nquarantine orders and travel restrictions. \nThis guidance does not apply to the procedure for the initial designation of a notified body \nunder the Directives nor to the procedures for extensions of the scope of a notified body nor \nthe lifting of limitations to the scope of a notified body3. \n3. Renewal of designation of a notified body until 25 May 2021 \nWhen deciding upon the renewal of the designation as a notified body in accordance with \nArticle 4(6) of the Implementing Regulation, designating authorities should perform an \nappropriate assessment of the continuous competence of the notified body and its ability to \naccomplish the tasks for which it has been designated. \nDesignating authorities should base their decision to renew a designation on a review of \ndocuments, resources and activities, which lay ground for the verification of the criteria for \ndesignation as set out in the Directives and in Annex I to the Implementing Regulation. \nThis review should include in particular the following: \n\uf0b7 assessment of relevant quality management system procedures, forms and records, in \nparticular qualification criteria, procedures for selection and authorisation of persons \ninvolved in conformity assessment activities, procedures to ensure independence, \nobjectivity and impartiality of the notified body\u2019s activities; \n\uf0b7 assessment of an appropriate number of the notified body\u2019s reviews of the \nmanufacturer\u2019s technical documentation, including clinical evaluations; \n\uf0b7 assessment of an appropriate number of the notified body\u2019s personnel files; \n\uf0b7 discussion of the results of the assessments of quality management documents and \nrecords with responsible personnel, including management responsible for the \nimplementation and update of the quality management system as well as the notified \nbody\u2019s assessors responsible for product review, including clinical evaluation, final \nreview and decision-making processes; \n\uf0b7 review of the outcome of the most recent on-site surveillance assessments and \nobserved audits  as well as of recent extraordinary assessment activities conducted by \nthe designating authority \n                                              \n3 See Article 11 of Directive 90/385/EEC and Article 16 of Directive 93/42/EEC. Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-11  \n \n \n4 \n When performing the above-mentioned review, the designating authority could also consider, \nif relevant, the outcome of the most recent joint assessment carried out in accordance with \nArticle 3 of the Implementing Regulation as well as joint assessments recently carried out in \naccordance with the MDR. \nIn order to ensure a sufficient assessment the selection of the appropriate number of \nmanufacturer\u2019s technical documentation reviews and personnel files to be reviewed should \ntake into account the volume of the activities performed by the notified body, its scope of \ndesignation and any relevant vigilance data. The designating authority should be able to \njustify the number and type of files selected. The designating authority should ask the notified \nbody to implement appropriate measures to correct any non-conformities found during the \nreview \nNormally, the renewal should include an on-site assessment. However, when exceptional \ncircumstances prevent a designating authority from carrying out such an on-site assessment, \nalternative assessment measures should be used. Principles and arrangements of alternative \nmeasures described in Section 5 of this document concerning surveillance activities may \napply. \nThe results of the assessment performed by the designating authority should be documented \nand the final decision on the renewal of a designation should be substantiated. \n4. Notification and information to be provided to the Commission \nIn accordance with Article 4(6) of the Implementing Regulation, any decision by a Member \nState on the renewal of a designation as a notified body should be notified to the Commission \nand the other Member States through the New Approach Notified and Designated \nOrganisations information system (NANDO)  on or before the date of designation expiry. In \nline with the ordinary procedure, this should take place by means of submitting an update of \nthe existing notification under the relevant Directive. \nThe Commission may request further information relating to a decision taken by a designating \nauthority on the renewal of a designation. In particular, designating authorities should make \navailable, upon request from the Commission, the reports describing the assessments \nperformed in relation to the renewal of the designation and the relevant outcome as described \nin Section 3 of this guidance. This should clearly document the basis for the renewal decision \ndetailing the elements reviewed by the designating authority to substantiate the decision, \nincluding the results of any surveillance and monitoring activities as described in Section 5 of \nthis guidance. Relevant notified body\u2019s documentation should also be made available to the \nCommission on request. \n5. Surveillance activities to be performed under exceptional circumstances \nIn the context of the current COVID-19 pandemic, the resulting travel and quarantine \nrestrictions may significantly affect the ability of designating authorities to conduct their Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-11  \n \n \n5 \n mandatory surveillance and monitoring activities such as on-site assessments and observed \naudits of their notified bodies. Therefore, in accordance with Article 5(1) of the Implementing \nRegulation, in order to ensure an adequate level of surveillance, designating authorities should \nat least assess an appropriate number of notified body\u2019s reviews of the manufacturer\u2019s \ntechnical documentation, including clinical evaluations, and of personnel files, in addition to \ncarrying out alternative surveillance measures. These alternative measures may include the \nfollowing principles and arrangements: \n\uf0b7 on-site surveillance assessments may be replaced by remote surveillance assessments \nusing the most advanced available Information and Communication Technologies as \ndeemed appropriate in accordance with Union legislation on information security and \ndata protection; \n\uf0b7 assessment of all relevant and required documents/records off-site. \nIn order to ensure a sufficient assessment, the selection of the appropriate number of notified \nbody\u2019s reviews of the manufacturer\u2019s technical documentation, including clinical evaluations, \nand personnel files to be reviewed, should take into account the volume of the activities \nperformed by the notified body, its scope of designation and any relevant vigilance data. The \ndesignating authority should be able to justify the number and type of files selected."}, {"title": "mdcg_2019_5_legacy_devices_registration_eudamed_en.pdf.txt", "text": "Medical Device       \nMedical Device  Coordination Group Document   MDCG  201 9-5   \nPage 1 of 4 \n  \n \n \n \n \nMDCG  201 9-5 \n Registration of legacy devices in EUDAMED  \n               \n \n April  2019  \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commission document and it cannot be regar ded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  \n \n  Medical Device       \nMedical Device  Coordination Group Document   MDCG  201 9-5   \nPage 2 of 4 \n  \nThis document deals with registration of devices, which can continue to be placed on \nthe market under Directive certificates by virtue of Article 120(3) of Regulation \n745/2017 (MDR), and Article 110(3) of Regulation 746/2017 (IVDR) after the relevant \nMDRs application dates. Those products are, for the purpose of this document, \nreferred to as \u201clegacy devices\u201d1. All following considerations, which are made in \nrelation to the MDR shall apply to the IVDR, mutatis mutandis.  \nArt 120(3) of the MDR lays down that t he requirements of the MDR relating to post -\nmarket surveillance, market surveillance, vigilance, registration of economic \noperators and of devices shall apply to legacy devices placed on the market after the \napplication date of the MDR in place of the corr esponding requirements of the \nDirectives.   \nThe MDR is not explicit in requiring that these \u201clegacy devices\u201d are subject to relevant \nUDI obligations. The MDR device registration requirements (Annex VI Part A Section \n2 and Part B that are complementary) mak e the Basic UDI -DI and UDI -DI the access \nkeys for device -related information in the future Eudamed, which is reflected in the \ndatabase design. Therefore, any registration of a device is normally possible in \nEudamed only if a proper Basic UDI -DI and UDI -DI are assigned to the device and \nregistered in the database together with the other device -related data.   \n \nIn light of this, taking all views heard into account, and considering that Article 120(3):  \n- Refers to legacy devices to be registered in line with MDR  provisions,  \n- Lacks any explicit reference to UDI obligations for legacy devices   \nthe MDCG considers it appropriate to adapt the Eudamed design to allow the \nregistration of legacy devices in Eudamed in the absence of a (Basic) UDI -DI.  \nThis is intended to prevent any technical constraint to the applicability of Art 120(3) \nfor legacy device registration in Eudamed.  \nA comprehensive description of the technical implications is provided in the Annex.   \n                                                           \n1 It shall be noted  that, in other contexts, the term \u201clegacy devices\u201d might be used with a different meaning.  Medical Device       \nMedical Device  Coordination Group Document   MDCG  201 9-5   \nPage 3 of 4 \n  \n \nAnnex  \nBasic considerations related to functioning of future registration of legacy \ndevices in Eudamed  \n1. Legacy devices \u2013 covered by a valid Directive certificate - that will continue to \nbe placed on the market after the MDR date of application should be \nregistere d in Eudamed without a Basic UDI -DI and UDI -DI. The registration \ndeadlines for those devices is clearly the one referred to in Article 123(3)(e):  \n18 months after the date of application (provided that Eudamed is fully \nfunctional on time)2.  \n2. However, in ca se of serious incident or field safety corrective action to be \nreported during the 18 months referred to in point 1, where the legacy devices \nhave not been registered in Eudamed yet, they must be registered at the \nmoment of the serious incident/field safet y corrective action reporting.   \n3. Point 1 will be applicable only to the devices that are not already registered as \nMDR devices.  \nNOTE: All the Directive -compliant devices which have been placed on the market \nahead of the general application dates and will not continue to be placed on the \nmarket afterwards, should be registered in Eudamed (without a Basic UDI -DI and \nUDI-DI) only if a serious incident report and/or a field safety corrective action report \n(with the field safety notice) occurs after the applica tion date.  \n \n \nTechnical implementation in Eudamed  \n4. Legacy devices that will be registered in Eudamed will need two other \nunique access keys (IDs) to replace the Basic UDI -DI and UDI -DI for the \nsake of the workability of Eudamed .  \n5. For this purpose, a Eudamed DI will be assigned to the device instead of the \nBasic UDI -DI and a Eudamed ID will be assigned by Eudamed instead of the \nUDI-DI allowing the system to work and to keep the design of Eudamed as \nclose as possible to the MDR design. These Eudamed DI and Eudamed ID will \nbe unique for a given legacy device.  \n6. The Eudamed DI could be either entirely generated by Eudamed or the \nmanufacturer could partly assign the DI code. On the other hand, the \nEudamed ID will be always automatically and fully generated b y Eudamed  \n                                                           \n2  It should be noted that all class I devices that are not sterile and/or with a measuring function under the \nDirectives, are not eligible for any grace period. When placed on the market after the MDR date of \napplication, they will have to be MDR compliant and be registered in EUDAMED  as MDR devices.   Medical Device       \nMedical Device  Coordination Group Document   MDCG  201 9-5   \nPage 4 of 4 \n  \n \nfrom the Eudamed DI. The proposed rules for the assignment (still under \ndiscussion) are that Eudamed DI start with character \"B\", where Eudamed ID \nwill start with character \"D\" (only difference between Eudamed DI and \nEudamed ID). Beside this f irst character, the Eudamed DI/ID will include the \nSRN of the manufacturer, a number (assigned by the manufacturer or \nEudamed) and a check digit.  \n7. The relationship between the Eudamed DI and a Eudamed ID will be one to \none.  \n8. Furthermore, the registration o f the legacy devices will require the \nmanufacturer to enter the directive certificate identification (NB number, \ncertificate number, revision number and expiry date) since they will not be \nregistered in Eudamed by the NBs.  \nIn case a legacy device has been already registered in Eudamed and that same \ndevice becomes at any point in time an MDR compliant device, that MDR device \nshould be considered as a new device requiring a new registration (due to the \nchange in the applicable  legislation) with a Basic UDI -DI and UDI -DI in Eudamed. \nHowever, only a UDI -DI should be entered, if another device with the same Basic \nUDI-DI has already been registered. Eudamed should facilitate this (copy) process \nand allow the linking between the  MDR  device and the corresponding legacy device ."}, {"title": "mdcg_2019_4_devices_registration_eudamed_en.pdf.txt", "text": "Medical Device       \nMedical Device  Coordination Group Document   MDCG  201 9-4   \nPage 1 of 2 \n  \n \n \n \n \nMDCG  201 9-4 \nTimelines for registration of device  \n data elements in EUDAMED  \n                 \n \n April  2019  \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commission docum ent and it cannot be regarded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  \n Medical Device       \nMedical Device  Coordination Group Document   MDCG  201 9-4   \nPage 2 of 2 \n  \n\u201cWith regard to timelines for device registration, the text of the MDR presents an \ninconsistency. On the one hand, Article 123(3)(d) lists the full Article 29 as being \napplicable from the application dates or, if EUDAMED is not functional on time, six \nmont hs after the date of publication of the notice referred to in Article 34(3). On the \nother hand, Article 123(3)(e) grants an additional 18 -month transitional period for \nobligations contained in Article 29(4).  \nTaking into account:  \n- the declared will of the c o-legislator to grant an 18 -month additional \ntransitional period for device registration and registration of certificates,  \n- the logical correspondence and complementary character of device data \nelements in Part A (Section 2) and Part B of Annex VI,  \n- the nee d to ensure that information on devices in EUDAMED is not displayed \nto public in a partial or misleading nature,  \nthe obligation for registration in EUDAMED of device data elements listed in \nboth part A, Section 2, and Part B of Annex VI, shall be applicabl e as from the \ntimelines indicated in Article 123(3)(e) (meaning from 18 months after the \ngeneral application date or, if EUDAMED is not fully functional on time, from 24 \nmonths after the date of publication of the notice referred to in Article 34(3)).  \nThis is without prejudice to the fact that the obligation related to the operation of \nassignment of Basic UDI \u2014DI and UDI -DI to devices remains applicable as from the \ngeneral application dates.  \nThis is also without prejudice to the fact that at any time after the general application \ndate, for MDR compliant devices, the full registration of devices (Article 29) remains a \npre-condition for the possible registration of their relevant serious incident in \nEUDAMED  \nThese considerations apply mutatis mutandis  to the IV DR\u201d."}, {"title": "2020-15-position-paper-actor-registration-module_en.pdf.txt", "text": "Medical Devices \nMedical Device Coordination Group Document                                                  MDCG 2020-15       \n \n  \n \n \nMDCG 2020-15 \n  \nMDCG Position Paper on the use of the \nEUDAMED actor registration module and \nof the Single Registration Number (SRN) \nin the Member States  \n \nAugust 2020 \n \n  \n \nThis document has been endorsed by the Medical Device Coordinat ion Group (MDCG) \nestablished by Article 103 of Regulation (EU) 2017/745.  \nThe MDCG is composed of representatives of all Member States an d a representative of the \nEuropean Commission chairs it. The document is not a European C ommission document and \nit cannot be regarded as reflecting the official position of th e European Commission. Any \nviews expressed in this document are not legally binding and on ly the Court of Justice of the \nEuropean Union can give binding interpretations of Union law.   Medical Devices \nMedical Device Coordination Group Document                                                  MDCG 2020-15       \n \n MDCG Position Paper \non the use of the EUDAMED actor registratio n module and of the Single Registration \nNumber (SRN) in the Member States \n \nArticle 33 of Medical Devices Regulation (EU)  2017/745 of the European  Parliament and of \nthe Council of 5 April 2017 (her eafter: \u2018MDR\u2019) sets out that the Commission, after consulting \nthe MDCG, shall set up, maintain and manage the European database on medical devices (EUDAMED). EUDAMED shall be composed of  multiple electronic systems (so called \n\u2018modules\u2019), including an elect ronic system on registration of economic operators, also \nreferred to as the actor registration module .  \nIn accordance with Article 30(1) MDR, the actor registration module shall allow for the \ncreation of a unique single registration number (\u2018SRN\u2019)  referred to in Article 31(2) and to \ncollate and process information that is necessary and proportionate to identify the manufacturer (including producer s of system/procedure packs)  and, where applicable, the \nauthorised representative and the importer. As such, the actor registra tion module forms a pre-\nrequisite for the use of the other EUDAMED  modules and facilitates a secure way of \naccessing EUDAMED. The responsibility to assign  SRNs to economic operators lies with the \nMember States. To that end, Artic le 31(2) stipulates that, after having verified and validated \nthe data entered by an economic operator, the competent authority of a Member State shall obtain an SRN from the actor registration m odule and approve the issuing of it to the \nrequesting manufacturer, authorised representative or importer. \nOn 30 October 2019, the Commission published a notice by which it concluded that the full \nfunctionality of EUDAMED require s the availability and full opera tion of all six modules in \naccordance with the technical specifications and confirmed by an audit as referred to in Article 34. The notice foresees the launch of a fully functional EUDAMED for May 2022. \nHowever, at its meeting of 12 March 2020 th e MDCG agreed that the Commission makes \navailable to Member States each EUDAMED module on a gradual basis as soon as it is \noperational. \nIn line with the MDCG decision referred to above, the Commissi on has confirmed its \nreadiness to deploy the actor registration module as of 1 December 2020. The members of \nthe MDCG  strongly encourage the use of the actor registration module by all relevant \nactors on their territories,  including the use of the single registration number  by actors as \nstipulated in the MDR (e.g. indicating the SRN on certificates). \nThe members of the MDCG agree that double registration requirements for actors should \nbe avoided as much as possible . Therefore, actors that obtai n an SRN should be considered \nin compliance with the actor registration requirements (for manufacturers, authorised \nrepresentatives, importers, system/procedure pack producers) to the extent that national laws accommodate for this. In such cases, thos e actors should follow the obligations and \nrequirements of the MDR related to both the registration of relevant actors (via the actor \nregistration module) and the us e of their SRN as required."}, {"title": "05 MDCG 2020-5 Guidance on Clinical Evaluation - Equivalence.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document   MDCG  2020-5  \n \n  \n \n \n \nMDCG 2020-5 \n  \n Clinical Evaluation - Equivalence \nA guide for manufacturers and notified bodies \n               \n \n April 2020 \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) \nestablished by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of \nrepresentatives of all Member States and it is chaired by a representative of the \nEuropean Commission.The document is not a European Commission document and it \ncannot be regarded as reflecting the official position of the European Commission. Any \nviews expressed in this document are not legally binding and only the Court of Justice \nof the European Union can give binding interpretations of Union law. \n   \nPage 2 of 20 \n  \n \n \n \n \n \n \n \nClinical Evaluation - Equivalence  \nA guide for manufacturers and notified bodies  \n   \nPage 3 of 20 \n 1 Table of contents \n \n1. Introduction .......................................................................................................... 4 \n2. Scope ................................................................................................................... 5 \n3. Equivalence ......................................................................................................... 5 \n3.1 Technical characteristics ............................................................................... 5 \n3.2 Biological characteristics ............................................................................... 6 \n3.3 Clinical characteristics ................................................................................... 9 \n4. Demonstration of equivalence ............................................................................ 10 \n5. Use of data from similar devices ........................................................................ 14 \n6. Clinical data identification ................................................................................... 15 \nAnnex I \u2013 Equivalence table ..................................................................................... 16 \n \n   \nPage 4 of 20 \n 1. Introduction \n \nThis guidance document is not legally binding. It has been put together following \ncontribution from national competent authorities, industry and relevant stakeholders \nand it should therefore be recognised as best practice.  \nThe Regulation (EU) 2017/745 on medical devices1, hereafter referred to as the MDR \n(medical device regulation), provides a possibility to use clinical data related to an \nequivalent device in the clinical evaluation required for a device under conformity \nassessment2. \nWhilst carrying out a clinical investigation is the most direct way to generate clinical \ndata concerning the safety and performance of medical devices for the purpose of CE \nmarking, clinical data can also be sourced from3 \n\uf02d clinical investigation(s) or other studies reported in scientific literature, of a \ndevice for which equivalence to the device in question can be demonstrated, \n\uf02d reports published in peer reviewed scientific literature on other clinical \nexperience of either the device in question or a device for which equivalence to \nthe device in question can be demonstrated \n \nEquivalence shall be demonstrated according to the MDR requirements4. \nThe European Commission has published a guide on clinical evaluation under the \ndirectives 93/42/EEC and 90/385/EEC; MEDDEV 2.7/1 rev. 45. This MEDDEV guide \nshould be used also during the process of demonstrating equivalence under the MDR. \nHowever, it has been recognised that some of the requirements set out in MEDDEV \n2.7/1 rev. 4 are not fully aligned with the MDR and that further guidance to address the \ndifferences would be of benefit to industry and other stakeholders. Only the text of the \nMDR is legally binding. In cases of divergence between the MEDDEV 2.7/1 rev. 4, this \nMDCG guidance and the MDR, the MDR shall take precedence. \nThis MDCG guidance does not introduce any new requirements. \nThe demonstration of equivalence does not remove the requirement to always conduct \na clinical evaluation in accordance with the MDR. It is the demonstration of \nequivalence6 that allows the manufacturer to let clinical data from an equivalent device \nenter the clinical evaluation process of the device in question for the purpose of \nconfirmation of conformity with relevant general safety and performance \n                                                             \n1 Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices \nhttp://eur-lex.europa.eu/legal-content/EN/TXT/?uri=OJ:L:2017:117:TOC   \n2 MDR, Article 61 and Annex XIV Part A. \n3 MDR, Article 2 (48) 2nd and 3rd indent. \n4 MDR, Annex XIV, Part A (3). \n5 MEDDEV 2.7/1 revision 4, Guidelines on medical devices, clinical evaluation: A guide for manufacturers and \nnotified bodies under directives 93/42/EEC and 90/385/EEC \nhttps://ec.europa.eu/growth/sectors/medical-devices/current-directives/guidance_en   \n6 MDR, Annex XIV, Part A (3).  \nPage 5 of 20 \n requirements7. There may also be other sources of clinical data than from an \nequivalent device8 to include in the process of clinical evaluation. \n2. Scope \nThis MDCG guidance covers the demonstration of equivalence, based on data \npertaining to an already existing device on the market9, for the purpose of CE-marking \nunder the MDR.  \nOne of the purposes of this document is to highlight the differences between the MDR \nand the MEDDEV 2.7/1 rev.4 specifically with regards to equivalence. It is also \nintended to provide additional guidance and support a harmonised approach to the \ndemonstration of equivalence across the EU. \nIn addition, non-exhaustive guidance and references have been provided with respect \nto device considerations for medical devices incorporating an ancillary medicinal \nproduct.  \nThis MDCG guidance also covers products without an intended medical purpose listed \nin Annex XVI of the MDR. \n3. Equivalence  \nThe MDR requires10 that technical, biological and clinical characteristics are \nconsidered when demonstrating equivalence to another device. Whilst these general \ncharacteristics are described in the MEDDEV 2.7/1 rev. 4 Appendix 1 and are aligned \nwith the MDR requirement, there are differences in the criteria that are set out for each \nof the three characteristics. Differences in criteria between the MDR and the MEDDEV \n2.7/1 rev. 4 are highlighted below and are accompanied by some explanatory text.  \n3.1 Technical characteristics \n \nMDR, Annex XIV Part A (3) MEDDEV 2.7/1 rev 4, Appendix A1 \nThe device is of similar design;  \nis used under similar conditions of use ;  \nhas similar specifications and properties including \nphysicochemical properties such as intensity of \nenergy, tensile strength, viscosity, surface \ncharacteristics, wavelength and software \nalgorithms ;  \nuses similar deployment methods, where relevant;  \nhas similar principles of operation and critical \nperformance requirements. - be of similar design, and \n- used under the same conditions of use , and \n- have similar specifications and properties (e.g. \nphysicochemical properties such as type and intensity \nof energy, tensile strength, viscosity, surface \ncharacteristics, wavelength, \nsurface texture, porosity, particle size, nanotechnology, \nspecific mass, atomic inclusions such as \nnitrocarburising, oxidability), and \n- use similar deployment methods (if relevant), and \n- have similar principles of operation and critical \nperformance requirements \n \n                                                             \n7 MDR, Article 61 (1) and (3 (a)). \n8 MDR, Article 2 (48) 1st and 4th indent. \n9 Whether the \u2018market\u2019 is presumed to be the EU market or not is related to requirements in Article 61. See \nsection 4 (d) and (e) in this document for further guidance. \n10 MDR, Annex XIV Part A (3).  \nPage 6 of 20 \n (a) The MDR requires that technical characteristics shall be taken into \nconsideration for the demonstration of equivalence including that the device in \nquestion and the device presumed to be equivalent are \u201cused under similar \nconditions of use\u201d. MEDDEV 2.7/1 rev. 4, however, specifies use under the \nsame conditions with regard to technical characteristics11. The conditions of use \nshall be similar to the extent that there would be no clinically significant \ndifference in the safety and clinical performance between the device in question \nand the device presumed to be equivalent. For further guidance on the \nassessment of \u2018similar\u2019, see also section 4 of this document.  \n \n(b) Different examples are given for specifications and properties of the device \nwhen considering technical characteristics across the two definitions. These are \nexamples only and are to be considered as such. They must not be interpreted \nas an exhaustive list of specifications and properties of technical characteristics \nwhen considering equivalence to another device. Note however that the MDR \nspecifically points out that software algorithms  shall be similar in the device \npresumed to be equivalent. This includes software algorithms in software driving \nor influencing the use of a device, and in software intended to be used alone12. \nIt is the functional principle of the software algorithm, as well as the clinical \nperformance(s) and intended purpose(s) of the software algorithm, that shall be \nconsidered when demonstrating the equivalence of a software algorithm. It is \nnot reasonable to demand that equivalence is demonstrated for the software \ncode, provided it has been developed in line with international standards for \nsafe design and validation13 of medical device software. \n \nSoftware solely intended for the configuration of a device (e.g. presentation on \na graphical user interface etc), and not related to any medical purpose14  (e.g. \ndiagnosis, treatment etc), does not need to be similar when considering \nequivalence as long as it can be justified to not negatively affect the usability, \nsafety or clinical performance. \n3.2 Biological characteristics  \n \nMDR, Annex XIV Part A (3) MEDDEV 2.7/1 rev. 4, Appendix A1 \nThe device uses the same materials or substances in \ncontact with the same human tissues or body fluids \nfor a similar kind and duration of contact and \nsimilar release characteristics of substances, \nincluding degradation products and leachables  \n Use the same materials or substances in contact with \nthe same human tissues or body fluids. \nExceptions  can be foreseen for devices in contact \nwith intact skin and minor components of devices; in \nthese cases risk analysis results may allow the use of \nsimilar materials taking into account the role and \nnature of the similar material. \n                                                             \n11 \u201cConditions of use\u201d with regard to technical characteristics may e.g. be environmental factors such as \nmagnetic fields, temperature, moisture, conditions during transport of device in use etc.  \nSee section 3.3 in this document regarding use for the same clinical condition or purpose. \n12 See MDCG 2019-11 Guidance on Qualification and Classification of Software in Regulation (EU) 2017/745 - \nMDR and Regulation (EU) 2017/746 \u2013 IVDR. \n13 E.g. IEC 62304 Medical device software \u2013 Software life cycle processes, and IEC 82304-1 Health software \u2013 \nPart 1: General requirements for product safety. \n14 MDR, Article 2(1).  \nPage 7 of 20 \n (a) Manufacturers must consider the additional text in the MDR and adequately \nspecify all applicable characteristics. The exceptions, outlined in the MEDDEV \n2.7/1 rev 4, to not use the same materials are NOT acceptable under the MDR. \n \nThe MDR requires that biological characteristics shall be taken into \nconsideration for the demonstration of equivalence, i.e. the device uses the \nsame materials or substances  in contact with the same human tissues or body \nfluids for a similar kind and duration of contact, and with similar release \ncharacteristics of substances, including degradation products and leachables, \nas the presumed equivalent device. The distinction between \u201csame materials or \nsubstances\u201d and \u201csimilar release characteristics of substances\u201d is made to \naccount for the fact that processing, design and the use environment may \nintroduce small changes even when the raw materials are the same.  \n \nProcessing can make materials more susceptible to degradation by changing \nproperties of the material and/or by inducing different stresses. For example, \nsmall changes in pH or oxidative stress can increase or decrease release \ncharacteristics. For this reason, it is the final device that shall be assessed. \n \n(b) The principles outlined in ISO 10993 series of standards for the biological \nevaluation of medical devices can be adopted, in particular the ISO 10993-1 for \na risk-based approach to biological evaluation15 and also for material \ncharacterization.  \n \nIn addition, the ISO 10993-18 which covers chemical characterization of \nmaterials can be adopted to specify the identity of materials and to estimate the \ntype and quantity of leachables from the final device.  Annex C of this standard \naddresses biological equivalence. The ISO 10993-17 includes principles on the \ntoxicological risk assessment of leachables. Leachables may include \ndegradation products or other substances from the materials or substances that \nthe device is made of, but also other constituents for example residuals from \nthe manufacturing process or sterilisation, any contaminations etc. Therefore, \nfor the consideration of equivalence, it is the properties and characteristics of \nthe final device that shall be taken into account. \n \nFor degradable materials, ISO 10993, Parts 13, 14 and 15 address the \nidentification and quantification of degradation products. Note, that there may \nbe further parts in the ISO 10993 series of standards that are relevant for the \ndevice in question.  \n \n(c) The MDR has additional requirements16 for devices that are composed of \nsubstances or of combinations of substances  that are intended to be \nintroduced into the human body, and that are absorbed by or locally dispersed \n                                                             \n15 ISO 10993-1 Biological evaluation of medical devices \u2013 Part 1: Evaluation and testing within a risk \nmanagement process, and collateral standards in the 10993 series. \n16 MDR, Annex I, (12.2).  \nPage 8 of 20 \n in the human body. For the consideration of equivalence, the substances shall \nbe the same. \n \nThose devices are not medicinal products, but for the conformity assessment \nthey shall comply with the relevant requirements laid down in Annex I to \nDirective 2001/83/EC17 for the evaluation of absorption, distribution, \nmetabolism, excretion, local tolerance, toxicity, interaction with other devices, \nmedicinal products or other substances and potential for adverse reactions. This \nmeans that for the demonstration of equivalence under the MDR, those aspects \nshall also be taken into consideration. \n \nNote that the requirement18 that the notified body shall seek a scientific opinion \nfrom a competent authority for medicinal products or the EMA, for the device or \nits products of metabolism, that are systemically absorbed by the human body \nin order to achieve their intended purpose, on the compliance with the relevant \nrequirements laid down in Annex I to Directive 2001/83/EC, always applies for \nthe device under evaluation even if equivalence has been demonstrated under \nthe MDR. \n \n(d) The demonstration of equivalence may also concern medical devices with an \nancillary medicinal substance , for example drug-eluting stents or heparin-\nbonded central venous catheters.  \n \nThe MDR requires19 that biological characteristics shall be taken into \nconsideration for the demonstration of equivalence, including that the device in \nquestion and the device presumed to be equivalent, use \u201cthe same materials or \nsubstances in contact with the same human tissues or body fluids\u201d. This applies \nalso to the medicinal substance and any related excipients/coatings.  \n \nExcipients/coatings may potentially have a significant effect for example on the \nrelease characteristics of the medicinal substance intended only for a local \neffect from a stent, and thereby a significant effect on the clinical performance. \n \nIn all cases, concerning the device under evaluation, the notified body shall20   \n\uf02d verify the usefulness of the substance as part of the device, taking \naccount of the intended purpose of the device, and \n\uf02d seek a scientific opinion from a competent authority for medicinal \nproducts or the EMA to ensure that the quality, safety and benefit/risk of \nusing the ancillary medicinal product, including whether the \nmanufacturing process have been adequately assessed. \n \n                                                             \n17 Directive 2001/83/EC relating to medicinal products for human use. \n18 MDR, Annex IX, Chapter II, 5.4 (b). \n19 MDR, Annex XIV Part A (3)  second indent. \n20 MDR, Annex IX, Chapter II, 5.2. (b) and (c).  \nPage 9 of 20 \n Note that medical devices with an ancillary medicinal substance are class III \ndevices21. In cases where a manufacturer intends to claim equivalence to a \ndevice not manufactured by him, the MDR requires that the two manufacturers \nhave a contract in place that explicitly allows the manufacturer of the second \ndevice full access to the technical documentation on an ongoing basis22 . \n \nManufacturers cannot claim equivalence of a device with an ancillary medicinal \nsubstance to a device without an ancillary medicinal substance and vice versa. \nFor example, the manufacturer of a heparin coated catheter shall not claim \nequivalence to a drug-free catheter even if both catheters are otherwise \nidentical23 . See also section 4 of this document.  \n \nSimilarly, manufacturers shall not claim equivalence of the ancillary medicinal \nsubstance to a \u2018standalone\u2019 medicinal substance. \n \n3.3 Clinical characteristics \n \nMDR, Annex XIV Part A (3)  MEDDEV 2.7/1 rev . 4, Appendix A1  \nThe device is used for the same clinical condition or \npurpose , including similar severity and stage of \ndisease, at the same site in the body, in a similar \npopulation, including as regards age, anatomy and \nphysiology;  \nhas the same kind of user ;  \nhas similar relevant critical performance in view of the \nexpected clinical effect for a specific intended \npurpose. - used for the same clinical condition (including when \napplicable similar severity and stage of disease, same \nmedical indication ), and \n- used for the same intended purpose, and \n- used at the same site in the body, and \n- used in a similar population (this may relate to age, \ngender, anatomy, physiology, possibly other aspects), \nand \n- not foreseen to deliver significantly different \nperformances (in the relevant critical performances such \nas the expected clinical effect, the specific intended \npurpose, the duration of use , etc.) \n \n(a) The MDR additionally requires that, for manufacturers to compare clinical \ncharacteristics, the device shall have the same kind of user . The MDR clearly \npoints out that a user means any healthcare professional or lay person who \nuses a device24, and that a lay person means an individual who does not have \nformal education in a relevant field of healthcare or medical discipline25. \nManufacturers must therefore take into consideration whether the intended \nuser\u2019s competence or knowledge can have any implication for the safety, clinical \nperformance and outcome when considering equivalence between the device \nin question and the presumed equivalent device. For example, a device \nintended for professional use and a device intended for home use, but for the \nsame clinical condition or purpose, may have a different safety and performance \nprofile due to the environment in which they are intended to be used.  \n                                                             \n21 MDR, Annex VIII, Rule 14. \n22 MDR, Article 61 (5). \n23 MDR, Annex XIV Part A (3). \n24 MDR, Article 2 (37). \n25 MDR, Article 2 (38).  \nPage 10 of 20 \n  \n(b) The MDR does not explicitly state that the medical device needs to be used for \nthe same medical indication, gender and duration of use  as the equivalent \ndevice. However, it is understood that in general, this is covered by the MDR \nrequirement that both devices should be used for the same clinical condition \nor purpose  including similar severity and stage of disease and also have similar \nrelevant critical performance which is also outlined in the MEDDEV 2.7/1 rev. 4. \nThis is supported by the definitions in the MDR of the \u2018intended purpose\u201926, and \nthe ability of the device to achieve its intended purpose by the \u2018clinical \nperformance\u201927 including measurable \u2018clinical benefit\u201928.  \n4. Demonstration of equivalence   \n \nMDR, Annex XIV Part A (3) MEDDEV 2.7/1 rev. 4, Appendix A1 \nThe characteristics listed in the first paragraph shall be \nsimilar to the extent that there would be no clinically \nsignificant difference in the safety and clinical \nperformance of the device. Considerations of \nequivalence shall be based on proper scientific \njustification .  \n For assuming equivalence, \n- all three characteristics (clinical, technical, biological) \nneed to be fulfilled; \n- similar means that no clinically significant difference \nin the performance and safety of the device would be \ntriggered by the differences between the device under \nevaluation and the device presumed to be equivalent. \n \nThere are a number of prerequisites that shall be fulfilled for the demonstration of \nequivalence: \n(a) The overall considerations of equivalence shall conclude whether the listed \ntechnical, biological and clinical characteristics in the MDR29 are similar to the \nextent that there would be no clinically significant difference in the safety and \nclinical performance of the device. Note that some of the listed characteristics \nin the MDR shall be the same, not only similar. The corresponding wording from \nMEDDEV 2.7/1 rev. 4 is presented for information above. Consideration must \nbe given to the characteristics mentioned above and a gap analysis should be \nconducted by the manufacturer to evaluate any clinically significant \ndifference(s). \nModifications30 of a device may be implemented for a variety of reasons. If the \ndifferences have been introduced to address specific safety and/or performance \nissues it shall be duly justified, that there would be no clinically significant \ndifference in the safety and clinical performance other than the intended \nimprovements related to the specific issue that triggered the modification / \ndifference. For all modifications and concomitant claims of equivalence, there \nmust be no additional risks or potential of negatively altered performance related \nto the introduced modifications. \n                                                             \n26 MDR, Article 2 (12). \n27 MDR, Article 2 (52). \n28 MDR, Article 2 (53). \n29 MDR, Annex XIV Part A (3). \n30 MDR, Article 61 (4).  \nPage 11 of 20 \n See a template example of an Equivalence table in the Annex I of this document. \n \nA manufacturer of a medical device shall not claim equivalence to a product \nwithout an intended medical purpose listed in the MDR Annex XVI. \n \n(b) Manufacturers may identify more than one equivalent device to the device under \nevaluation, but each device shall be equivalent to the device under evaluation \nin all the listed technical, biological and clinical characteristics31. Equivalence to \neach device shall be fully investigated, described and demonstrated in the \nclinical evaluation report.  \nThis means that manufacturers shall not use different parts of different devices \nto claim equivalence to the device under evaluation. The MEDDEV 2.7/1 rev. 4 \nis in line with this approach. \nIn exceptional cases, a deviation from this principle may be considered. There \nmay be device systems comprised of several more or less \u201cstand alone\u201d \ndevices, where it may be justified to consider equivalence of a device in the \nsystem to a presumed equivalent device in a device system already on the \nmarket (by the same manufacturer) provided that all technical, biological and \nclinical characteristics are same/similar32, and that the devices in the system do \nnot affect the safety and performance of each other. This should be duly \ninvestigated and documented both on the level of potential interference between \nthe devices in the system, as well as on the overall safety and clinical \nperformance of the device system. \n \n(c) Regarding the clinical evaluation, the MDR requires33 that the manufacturer \nshall specify and justify the level of clinical evidence necessary to demonstrate \nconformity with the relevant general safety and performance requirements. That \nlevel of clinical evidence shall be appropriate in view of the characteristics of the \ndevice and its intended purpose34. In addition, considerations of equivalence \nshall be based on proper scientific justification35.  \n \nThis implies that technical, biological and clinical characteristics shall be duly \ninvestigated and documented. The manufacturer is expected to fully identify and \ndisclose any differences between the two devices.  \n \nPre-clinical data for the consideration of equivalence should allow a scientifically \nsound evaluation of technical and biological characteristics. Examples of data \nsources: \n                                                             \n31 MDR, Annex XIV Part A (3), the requirement refers to only \u201ca device\u201d and \u201cthe device\u201d. \n32 MDR, Annex XIV Part A (3). \n33 MDR, Article 61 (1) second paragraph. \n34 MDR, Article 61 (1) second paragraph  \nIt may under certain circumstances be justified to demonstrate conformity without support of clinical data, see \nMDR, Article 61 (10), but note that this is not applicable for implantable devices or class III devices. \n35 MDR, Annex XIV Part A (3) \nFor guidance see also MEDDEV 2.7/1 rev 4, Annex A6, Appraisal of clinical data - examples of studies that lack \nscientific validity for demonstration of adequate clinical performance and/or clinical safety.  \nPage 12 of 20 \n \uf02d data from the technical documentation of a manufacturer\u2019s own \npresumed equivalent device (specifications, test-results, \nchemical/physical/biological analyses, data from pre-clinical \ninvestigations etc) \n\uf02d data published in the scientific literature, e.g. animal or other pre-clinical \ndata \nThe assessment of whether any differences in characteristics would result in \nclinically significant difference in safety and clinical performance shall also be \nduly substantiated and based on proper scientific justification. This assessment \nmay be supported by e.g. clinical data from the scientific literature, common \nspecifications (CS)36, harmonised standards or other established technical \nspecifications. \nFurthermore, for the assessment of safety, a risk-based approach37 is expected, \nboth for the identification of characteristics that may affect safety as well as for \nthe final assessment of equivalence regarding safety. \n \nIt is important for the consideration of equivalence that pre-clinical data and any \nclinical data relate to the actual device under evaluation, and to a defined \ngeneration/version of the actual device considered for equivalence, bearing in \nmind that there may be significant differences between different generations of \nthe other device.   \n \nIf a manufacturer is not able to demonstrate sufficient levels of access to the \ndata38 relating to the presumed equivalent device and needed for the \nconsideration of equivalence, equivalence claims cannot be made for the \npurpose of conformity assessment. \n \n(d) The MDR notes specific requirements in addition to the demonstration of \nequivalence in order not to perform a clinical investigation which must be taken \ninto account. \n \nA manufacturer of implantable devices and class III devices  shall perform \nclinical investigations except if the device has been designed by modifications \nof a device already marketed by the same manufacturer  and equivalence can \nbe demonstrated according to the MDR39. In this context, a marketed device is \nconsidered to be a device already placed on the market and CE marked with \nrespect to either the MDR or the directives 93/42/EEC or 90/385/EEC. The CE \nmarking should still be valid, should be based on an updated clinical evaluation, \nand the benefit/risk ratio for this device should be favourable. \n \n                                                             \n36 MDR, Article 2, (71) \u2018common specifications\u2019 (CS) means a set of technical and/or clinical requirements, other \nthan a standard, that provides a means of complying with the legal obligations applicable to a device, process or \nsystem. \n37 ISO 14971 Medical devices \u2013 Application of risk management to medical devices, and also other related \nstandards as applicable e.g. ISO 10993-1 and ISO 10993-18. \n38 MDR, Annex XIV Part A (3) last paragraph. \n39 MDR, Article 61 (4), and Annex XIV (3).  \nPage 13 of 20 \n For a manufacturer of implantable devices and class III devices  claiming \nequivalence to an already marketed device not manufactured by him , in \naddition to the requirements in MDR Article 61(4), the manufacturer must have \na contract in place that allows full access to the technical documentation on an \nongoing basis40. Furthermore, the MDR also requires that the original clinical \nevaluation of the equivalent device has been performed in compliance with the \nrequirements of the MDR. This implies that the presumed equivalent device is \ncertified under the MDR. As such, it will not be possible to claim equivalence to \na device certified with respect to the Directives 93/42/EEC or 90/385/EEC. \n(e) For devices other than implantable devices and class III devices  and where \nthe manufacturer wants to claim equivalence, MDR Article 61 (3) is applicable. \nThis requirement does not specify whether the device is presumed to be \nmarketed within the EU. Therefore, it will be possible to claim equivalence to a \ndevice certified with respect to the Directives 93/42/EEC or 90/385/EEC or the \nMDR.  \nHowever, exceptions can be considered, and equivalence claimed to a device \nthat is not CE-marked, provided all relevant MDR requirements regarding \nequivalence and clinical evaluation can be met. This includes  \n\uf02d that the manufacturer shall have sufficient levels of access to the data \nrelating to devices with which they are claiming equivalence41 . In the \ncircumstance that the presumed equivalent device is from another \nmanufacturer, there is no MDR requirement of a contract between the \nmanufacturers for regulating the access to the technical documentation. \n\uf02d that clinical investigations were conducted in accordance with \ninternational guidelines42  \n\uf02d that the clinical data meet the requirements of the MDR, and a \njustification is provided whether the clinical data are transferrable to the \nEuropean population.  \nThe regulatory status of the presumed equivalent device should be disclosed. \nSee MEDDEV 2.7/1 rev. 4 Appendix A1 for further guidance.  \n \n(f) In case of products without an intended medical purpose  listed in MDR \nAnnex XVI clinical investigations shall be performed for those products unless \nreliance on existing clinical data from an analogous medical device is duly \njustified43. An analogous device, in this context, is understood as a medical \ndevice which is similar in terms of functioning and risks profile and has a medical \npurpose44. To duly justify reliance on existing clinical data from an analogous \n                                                             \n40 MDR, Article 61 (5). \n41 MDR, Annex XIV Part A (3) the last sentence. \n42 MDR, Recital (64) \nClinical investigation of medical devices for human subjects \u2013 Good clinical practice (ISO 14155), and \nWorld Medical Association Declaration of Helsinki on Ethical Principles for Medical Research Involving Human \nSubjects. \n43 MDR, Article 61 (9). \n44 MDR, Recital (12).  \nPage 14 of 20 \n medical device, the principles of demonstration of equivalence45 should be \napplied with the acceptance that the device under evaluation will only have an \naesthetic or another non-medical purpose whereas the analogous device has a \nmedical purpose. The general requirement to demonstrate a clinical benefit46 \nshall be understood as a requirement to demonstrate the performance of the \ndevice.  \n \nIn addition, since the common specifications (CS) for the products without an \nintended medical purpose may have requirements related to the clinical \nevaluation regarding safety47 these requirements must be taken into \nconsideration when demonstrating equivalence and concluding whether there \nwould be no clinically significant difference in the safety48. \n \nThere shall be no significant difference in the safety and performance between \nthe product and the presumed analogous medical device.  \n5. Use of data from similar devices \nThe term \u2018similar devices\u2019 may be understood as devices belonging to the same \ngeneric device group. The MDR defines this49 as a set of devices having the same or \nsimilar intended purposes or a commonality of technology allowing them to be \nclassified in a generic manner not reflecting specific characteristics. \nIn cases where equivalence cannot be demonstrated under the MDR, the data from \nsimilar devices may be useful for a variety of other purposes, for example: \n1. Ensuring that the risk management system is comprehensive by identifying \nrelevant hazards and clinical risks. \n2. Understanding the state of the art, the natural course of disease and \nalternative available treatment options. \n3. Helping to define the scope of the clinical evaluation, by identifying any design \nfeatures in similar devices that pose special performance or safety concerns. \n4. Provide input for clinical investigation design or post-market clinical follow-up \ndesign, and the post-market surveillance system. \n5. Identification of relevant and specified clinical outcome parameters for the \nintended clinical benefits, based on the published clinical data pertaining to the \nsimilar device(s). \n6. To define minimum requirements for a quantified clinical benefit that is \nconsidered clinically relevant, and/or to identify acceptable occurrence rates of \nrisks and adverse events. \n                                                             \n45 MDR, Annex XIV Part A (3). \n46 MDR, Article 61 and Annexes XIV and XV. \n47 MDR, Article 1 (2). \n48 MDR, Annex XIV Part A (3). \n49 MDR, Article 2 (7).  \nPage 15 of 20 \n 6. Clinical data identification \nA clinical evaluation of the device under assessment shall be made according to the \nMDR50. All the clinical data, both favourable and unfavourable shall be identified. This \napplies to clinical data from both the device in question and the device for which \nequivalence can be demonstrated. If the data meet the definition of clinical data as \ndefined in the MDR51, the data shall then progress to data appraisal and analysis in \norder to evaluate whether the clinical data are providing sufficient clinical evidence for \nthe purpose of confirmation of conformity with the relevant general safety and \nperformance requirements (GSPR)52.  \nFor identifying, appraising and analysing available clinical data from the scientific \nliterature to establish clinical evidence53, manufacturers will find facilitative guidance in \nsections 8-10 of MEDDEV 2.7/1 rev. 4.  \nIn the event that the data do not meet the MDR definition of clinical data these are not \nclinical data and cannot be subject to data appraisal, analysis and evaluation for the \npurpose of providing clinical evidence for the confirmation of conformity with the \nrelevant GSPR.  \n \n  \n                                                             \n50 MDR, Annex XIV Part A. \n51 MDR, Article 2 (48). \n52 MDR, Annex I. \n53 MDR, Article 2 (51).  \nPage 16 of 20 \n Annex I \u2013 Equivalence table \nA table, such as the table below, may be used to clearly demonstrate equivalence and \nto identify the supporting data on a device by device basis. The items in the first column \nof the table are examples only and are to be considered as such. They must not be \ninterpreted as an exhaustive list of specifications, properties, parameters and/or \naspects for demonstrating equivalence to another device. \nThe manufacturer should identify differences and place emphasis on the differences \nbetween the two devices rather than the similarities. Considerations shall include the \npotential additive effect of multiple small differences. For further considerations of \nequivalence, see sections 3 and 4 in this document.  \nScientific justifications shall be provided for the different characteristics when claiming \nno clinically significant difference in the safety and clinical performance of the device. \nWhere more than one device is assessed for equivalence, the table should be \ncompleted separately for each presumed equivalent device. The documentation of the \ndemonstration of equivalence shall be included in the clinical evaluation report. \n Medical Device       \nMedical Device Coordination Group Document   MDCG  2020-5  \n \n  \nEquivalence table \nfor the comparison of a device with a presumed equivalent marketed device for the purpose of demonstrating equivalence \n1. Technical \ncharacteristics  \n(add a separate row \nfor each of the \nassessed \ncharacteristics)  Device 1  (under clinical evaluation)  \nDescription of characteristics and  \nreference to specifying documents Device 2 (marketed device) \nDescription of characteristics and  \nreference to specifying documents  Identified differences or  \nconclusion that there are no differences in the \ncharacteristic \nDevice is of similar \ndesign   1.1 \nUsed under similar \nconditions of use \n   1.2 \nSimilar specifications \nand properties \nincluding \nphysiochemical \nproperties such as \nintensity of energy, \ntensile strength, \nviscosity, surface \ncharacteristics, \nwavelength and \nsoftware algorithms    1.3 \nUses similar \ndeployment methods \nwhere relevant   1.4 \nHas similar principles \nof operation and   1.5  \nPage 18 of 20 \n critical performance \nrequirements \nScientific justification why there would be no clinically significant difference in the safety and clinical performance of th e device, OR  \na description of the impact on safety and or clinical performance \n(use one row for each of the identified differences in characteristics, and add references to documentation as applicable) Clinically \nsignificant \ndifference \nYes / No  \n1.1  \n1.2  \n1.3  \n1.4  \n1.5  \n2. Biological \ncharacteristics   \n(add a separate row \nfor each of the \nassessed \ncharacteristics)  Device 1 \nDescription of characteristics and  \nreference to specifying documents Device 2 (marketed device) \nDescription of characteristics and  \nreference to specifying documents  Identified differences or  \nconclusion that there are no differences in the \ncharacteristic \nUses the same \nmaterials or \nsubstances in contact \nwith the same human \ntissues or body fluids     (The characteristic must be the same for the \ndemonstration of equivalence) \n2.1 \nSimilar kind and \nduration of contact \nwith the same human \ntissues or body fluids \n   2.2 \nSimilar release \ncharacteristics of \nsubstances including \ndegradation products \nand leachables   2.3 \nScientific justification why there would be no clinically significant difference in the safety and clinical performance of the device, OR  \na description of the impact on safety and or clinical performance \n(use one row for each of the identified differences in characteristics, and add references to documentation as applicable) Clinically  \nsignificant \ndifference \nYes / No   \nPage 19 of 20 \n 2.1  \n2.2  \n2.3  \n3. Clinical \ncharacteristics   \n(add a separate row \nfor each of the \nassessed \ncharacteristics)  Device 1 \nDescription of characteristics and  \nreference to specifying documents Device 2 (marketed device) \nDescription of characteristics and  \nreference to specifying documents  Identified differences or  \nconclusion that there are no differences in the \ncharacteristic \nSame clinical \ncondition or purpose, \nincluding similar \nseverity and stage of \ndisease   3.1 \nSame site in the body \n   (The characteristic must be the same for the \ndemonstration of equivalence) \n3.2 \n \nSimilar population, \nincluding as regards \nage, anatomy and \nphysiology    3.3 \nSame kind of user \n   (The characteristic must be the same for the \ndemonstration of equivalence) \n3.4 \nSimilar relevant \ncritical performance in \nview of the expected \nclinical effect for a \nspecific intended \npurpose \n   3.5 \nScientific justification why there would be no clinically significant difference in the safety and clinical performance of the device, OR \na description of the impact on safety and or clinical performance \n(use one row for each of the identified differences in characteristics, and add references to documentation as applicable) Clinically \nsignificant \ndifference \nYes / No   \nPage 20 of 20 \n 3.1  \n3.2  \n3.3  \n3.4  \n3.5  \nSummary  \nIn the circumstance that more than one non-significant difference is identified, provide a justification whether the sum of differences may affect the safety and clinical \nperformance of the device."}, {"title": "10-1 MDCG 2020-10-1 Guidance on safety reporting in clinical investigations.pdf.txt", "text": "Page 1 of 16 1 \n   \n \n \n \nMDCG 2020-10/1 \nSafety reporting in clinical investigations \nof medical devices under the  \nRegulation (EU) 2017/745  \n \n May 2020 \n \n \n  \n \n \n  \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) established by Article 103 of Regulation (EU) \n2017/745. The MDCG is composed of representatives of all Member States and it is chaired by a representative of the European \nCommission. \nThe document is not a European Commission document and it cannot be regarded as reflecting the official position of the Europea n \nCommission. Any views expressed in this document are not legally binding and only the Court of Justice of the European Union ca n \ngive binding interpretations of Union law.    \nPage 2 of 16 MDCG 2020-10/1 \nSafety reporting in clinical investigations of medical devices under the Regulation (EU) 2017/745\n \nMay 2020 \n \nTable of contents \n1 INTRODUCTION .................................................. ............................................................... ............................................................... ........................................................ 3  \n1.1 SAFETY REPORTING IN THE ABSENCE OF EUDAMED  .............................................................. ............................................................... ............................................................... ..... 3  \n2 SCOPE ......................................................... ............................................................... ............................................................... ............................................................... . 4 \n2.1 CLINICAL INVESTIGATIONS OF MEDICAL DEVICES  .............................................................. ............................................................... ............................................................... ......... 4  \n2.2 MEDICAL DEVICES USED IN CLINICAL TRIALS OF MEDICINAL PRODUCTS (DRUG TRIALS ) ............................................................. ............................................................... ........................ 4  \n3 DEFINITIONS ................................................... ............................................................... ............................................................... ............................................................ 5  \n3.1 INVESTIGATIONAL DEVICE  .............................................................. ............................................................... ............................................................... ...................................... 5  \n3.2 ADVERSE EVENT (AE) .......................................................... ............................................................... ............................................................... ............................................... 5  \n3.3 SERIOUS ADVERSE EVENT (SAE).......................................................... ............................................................... ............................................................... ................................. 5  \n3.4 DEVICE DEFICIENCY  .............................................................. ............................................................... ............................................................... .............................................. 5  \n4 REPORTING METHOD .............................................. ............................................................... ............................................................... ................................................... 6  \n4.1 TRANSITION TO REPORTING VIA EUDAMED  .............................................................. ............................................................... ............................................................... ............... 6  \n4.2 OVERVIEW OF FORMATS TO BE USED BY SPONSORS WHEN REPORTING TO NCA S .............................................................. ............................................................... ............................. 6  \n4.3 COLLECTING REPORTS FROM INVESTIGATORS  .............................................................. ............................................................... ............................................................... ............. 6  \n5 REPORTABLE EVENTS ............................................. ............................................................... ............................................................... .................................................... 7  \n5.1 EXCEPTIONS FOR PMCF  INVESTIGATIONS ACCORDING TO MDR  ARTICLE 74.1 .......................................................... ............................................................... ................................... 7  \n5.2 REPORTABLE EVENTS OCCURRING IN THIRD COUNTRIES  .............................................................. ............................................................... .............................................................. 7 \n5.3 TRANSITION PERIOD FOR REPORTABLE EVENTS IN PRE -MARKET CLINICAL INVESTIGATIONS INITIATED UNDER DIRECTIVES LEGIS LATION  .............................................................. ........................ 7  \n5.4 TRANSITION FOR REPORTABLE EVENTS IN PMCF  CLINICAL INVESTIGATIONS INITIATED UNDER DIRECTIVES LEGISLATION  .............................................................. .......................................... 8  \n6 REPORT BY WHOM ................................................ ............................................................... ............................................................... ..................................................... 8  \n7 REPORT TO WHOM ................................................ ............................................................... ............................................................... ..................................................... 8  \n8 REPORTING TIMELINES ........................................... ............................................................... ............................................................... .................................................... 8  \n8.1 REPORT BY SPONSOR TO NCA S............................................................... ............................................................... ............................................................... .............................. 8  \n8.2 REPORT BY THE INVESTIGATOR TO THE SPONSOR  .............................................................. ............................................................... ............................................................... ........ 9  \n9 CAUSALITY ASSESSMENT .......................................... ............................................................... ............................................................... .................................................. 9  \n10 REPORTING FORM ................................................ ............................................................... ............................................................... .................................................... 11  \n10.1 COMPLETION GUIDELINES : FORM HEADER  .............................................................. ............................................................... ............................................................... .............. 11  \n10.2 COMPLETION GUIDELINES : EVENT DETAILS  .............................................................. ............................................................... ............................................................... .............. 13  \n11 REFERENCES .................................................... ............................................................... ............................................................... ......................................................... 16  \n12 APPENDIX \u2013 CLINICAL INVESTIGATION SUMMARY SAFETY REPORTING FORM  .............................................................. ............................................................... .......... 16  \n   \nPage 3 of 16 1 Introduction \n \nSafety reporting in clinical investigations of medical devices shall be performed in line with the requirements of the Regulat ion (EU) 2017/745 \u2013 \nMedical Device Regulation (MDR) Article 80(2):   \nThe sponsor shall report, without delay to all Member States in  which the clinical investigation is being conducted, all of th e following by means of \nthe electronic system referred to in MDR Article 73:  \na) any serious adverse event that has a causal relationship with t he investigational device, the comparator or the investigation procedure or \nwhere such causal relationshi p is reasonably possible;  \nb) any device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention ha d not occurred, \nor circumstances had been less fortunate;  \nc) any new findings in relation to any event referred to in points  a) and b).  \nThe period for reporting shall take account of the severity of the event. Where necessary to ensure timely reporting, the spon sor may submit an \ninitial report t hat is incomplete followed up by a complete rep ort.  \nUpon request by any Member State in which the clinical investig ation is being conducted, the sponsor shall provide all informa tion referred to in \nparagraph 1. \nFor post-market clinical follow up (PMCF) investigations of CE- marked devices1 used within the intended use covered by the CE-marking, report ing \nrequirements of MDR Article 80(5) and (6) apply. This means tha t the vigilance provisions laid down in Articles 87 to 90 and i n the acts adopted \npursuant to Article 91 shall apply for PMCF clinical investigat ions. However, this guidance document is still relevant for PMC F clinical investigations \nas the reporting of serious adverse events where a causal relat ionship to the preceding investigational procedure has been est ablished shall follow \nthe reporting procedures of clin ical investigations as outlined  in Article 80. \n1.1 Safety reporting in the absence of Eudamed \nSince the electronic system referred to in Article 73 (Eudamed)  will not be available and fully functional at the Date of appl ication of the MDR this \nguidance outlines the procedures for safety reporting in clinic al investigations in the absence of Eudamed.  \nThis document defines Serious Ad verse Event (SAE) reporting mod alities and includes a summary tabulation reporting format. \n  \n                                                           \n1 The PMCF investigations referred to in MDR Article 74(1).  \nPage 4 of 16 2 Scope \n2.1 Clinical investigation s of medical devices \nThe reporting modalities and format set out in this guidance ap ply to:   \n\u0081 Pre-market clinical investigations  covered by Articles 62 and 74(2) of the MDR conducted with: \na) Non-CE marked devices, \nb) CE marked devices used outside the intended use(s) covered by t he CE-marking. \nc) The term pre-market clinical inv estigation may also include som e studies covered by MDR Article 82.  \n \nAs MDR Article 82 allows member states to define national requi rements for such clinical investigations, sponsors are encourag ed to check \nwith the applicable NCA2 whether this guidance or other reporting procedures should be applied. \nIn situations where a clinical investigation has started using a non-CE marked device, and the right to bear the CE marking ha s been obtained \nbefore the end of the clinical investigation, the SAE reporting  continues  until  completion of the investigation, according  to the clinical \ninvestigation plan and these guidelines apply throughout the SA E reporting period. \n \nFor pre-market clinical investigations involving CE marked comp arator devices used within their intended purpose, SAEs occurri ng in or to \nsubjects that are in the comparator arm of an investigation sha ll also be reported in accordance with these guidelines.  \n \nNote: SAEs concerning CE marked devices which meet the vigilanc e reporting criteria also need to be handled under the post-mar ket \nsurveillance/vigilance system.  \n \n\u0081 Those Post-Market Clinical Follow Up (PMCF) investigations  that involve procedures additional to those performed under th e normal \nconditions of use of the device, and where those additional pro cedures imposed by the clinical investigation plan are invasive  o r  \nburdensome, covered by MDR Article 74(1). For these clinical in vestigations the safety reporting for events pertaining to MDR Article 80(6) \nfollow the Serious Adverse Event reporting process only, and ar e outlined in this guidance. Events pertaining to MDR Article 8 0(5) are \nreported following the vigilance process only and are outside t he scope of this guidance. \n \n\u0081 Note that other post-market clinical investigations may be subj ect to safety reporting requirements in line with this guidance  due to \nnational requirements following MDR Article 82, but there is no  such general requirement. Sponsors are encouraged to check wit h the \napplicable NCA whether this guidance or other reporting procedu res should be applied. \n \n\u0081 Due to the transitional provisions in MDR Article 120(11) this guidance also covers clinical investigations which have started  to be conducted \nin accordance with Article 10 of Directive 90/385/EEC (AIMDD) o r Article 15 of Directive 93/42/EEC (MDD) prior to 26 May 2021.  These \ninvestigations may continue to be conducted after date of appli cation of the MDR, but the reporting of serious adverse events and device \ndeficiencies shall be carried out in accordance with the MDR re quirements from 26 May 2021 and onwards.  \n2.2 Medical devices used in clinical  trials of medicinal products ( drug trials)  \n\u0081 A CE-marked device which is used outside its intended purpose, or a non-CE marked device in a clinical drug trial would implic itly have to \nbe assessed for safety and performance and the study shall foll ow both MDR (Chapter VI) and the applicable legislation for cli nical drug \ntrials. This guidance document is then relevant for compliance with the MDR regarding safety reporting.  \n \n                                                           \n2 For the purpose of this guidance,\" NCAs\" encompasses the Natio nal Competent Authorities of the EEA, Switzerland and Turkey.   \nPage 5 of 16 \u0081 If a drug-device study (or a drug trial) is not undertaken to a ssess the safety or performance of a device used in the study, the reporting \nrequirements of MDR Article 80 do not apply, as long as the dev ice is CE marked and used within its intended purpose. This gui dance is not \napplicable, but the vigilance re porting provisions of MDR apply  in those situations, as for any commercially available device.  Sponsors \nshould make sure that the device manufacturer is notified about  any incidents related to the device and the legal manufacturer  of the \ndevice is responsible for the subsequent vigilance reporting.  \n \n3 Definitions  \n3.1 Investigational device  \nA device that is assessed in a  clinical investigation  \n(MDR Article 2(46)) \n \nNote: An investigational device can be a non-CE marked device o r a CE marked device. The definition in MDR Article 2(46) does not differentiate \nbetween different regulatory statuses of devices. However, the reporting requirements are different depending on whether the c linical \ninvestigation is done for purposes described in Article 62, 74 or 82. The definition is understood to cover also the devices i nvestigated in PMCF \ninvestigations, even if they are not subject to notification pe r Art 74.1. \n3.2 Adverse Event (AE)  \nAny untoward medical occurrence, unintended disease or injury o r any untoward clinical signs, including an abnormal laboratory  finding, \nin subjects, users or other persons, in the context of a clinic al investigation, whether or not related to the investigational  device.  \n(MDR Article 2(57)) \nNote:  \na. This definition includes events that are anticipated as well as  unanticipated events \nb. This definition includes events occurring in the context of a c linical investigation related to the investigational device, th e comparator or \nthe procedures3 involved. \n3.3 Serious Adverse Event (SAE)  \nAny adverse event that led to any of the following:  \na) death,  \nb) serious deterioration in the health of the subject, that result ed in any of the following:  \ni. life-threatening illness or injury,  \nii. permanent impairment of a body structure or a body function,  \niii. hospitalisation or prolongation of patient hospitalisation,  \niv. medical or surgical intervention to prevent life-threatening il lness or injury or permanent impairment to a body structure or a body \nfunction,  \nv. chronic disease,  \nc) foetal distress, foetal death or a congenital physical or menta l impairment or birth defect \n(MDR Article 2(58)) \n3.4 Device deficiency  \nAny inadequacy in the identity, quality, durability, reliabilit y, safety or performance of an i nvestigational device, includin g malfunction, use errors \nor inadequacy in information supplied by the manufacturer.  \n                                                           \n3 For the purpose of safety reporting all activities related to the use of a medical device may be considered procedures  \nPage 6 of 16 (MDR Article 2(59)) \n \n4 Reporting method \nA new template for the Summary Reporting Form should be used fo r all studies from 26 May 2021. The tabular format featured in the Appendix \nneeds to be filled in/updated for each reportable event or for new findings/updates to already reported events. It shall be tr ansmitted to all NCAs \nwhere the clinical investigation is being performed. \nFor more details on how to complete the form refer to section 10. Reporting form .  \n4.1 Transition to reporting via Eudamed \nOnce Eudamed is available and fully functional the obligations and requirements that relate to performing safety reporting via  Eudamed shall apply \nfrom the date corresponding to six months after the date of pub lication of the notice referred t o in Article 34(3) of the MDR.  \n4.1.1 Ongoing events at time of transition to Eudamed \nIt is acknowledged that at the time of transition to reporting via Eudamed, there will be ongoing events for which initial rep orts have been made \naccording to the procedures described in this document. For the se reportable events follow-up and final reports will be submit ted to the NCAs by \nthe same procedure, but all new reportable events shall be ente red in Eudamed.  \nWhether retrospective uploading of previous event reports to Eu damed will be possible is not clear at the time this guidance i s issued.  \n4.2 Overview of formats to be used b y sponsors when reporting to NC As \n \nUnder directives legislation \nUntil May 25th, 2021: The tabular format from MEDDEV 2.7/3 Appe ndix I should be used  \nTransition period \nFrom May 26th, 2021 \nand until Eudamed is \navailable The Tabular format of this guidance (Appendix- Summary Reporting  \nForm) should be used.  \nWhen Eudamed is \navailable but not yet mandatory and until the timepoint when Eudamed becomes mandatory Either the Tabular format of this guidance (Appendix- Summary \nReporting Form) or the Eudamed web form can be used.  Note: Once the shift to Eudamed reporting has been made for a s pecific \nclinical investigation, Eudamed should continue to be used for reporting \nall new events and updates to those events throughout the remai nder \nof the clinical investigation. \nFrom the timepoint when Eudamed is mandatory*\n*From the date corresponding to six months after the date of publication of the notice referred to in Article 34(3) of the \nMDR. Web form via Eudamed shall be used for all new events, and upda tes to \nthose events.  \nThe Tabular format of this guidance (Appendix- Summary Reporting  \nForm) can be used only to transmit follow-up reports/final repo rts to \nthe NCAs on events which were in itially reported in this format .  \n \n \n4.3 Collecting reports from investigators \nThe format in which sponsors wish to receive single event repor ts from investigators will be up to the sponsor to design and t hey may be adapted \nto an individual clinical investigation. When sponsors design s uch reporting forms, they should consult this guidance document  to  e ns ure  al l  \nrelevant details are captured in the reports from the investiga tor, so that the sponsors can fu lfil their reporting obligation s.  \nPage 7 of 16  \n5 Reportable events  \nFor the purpose of this guidance and based on the definitions a bove, the following events are considered reportable events in accordance \nwith MDR Art. 80(2):  \na) any serious adverse event that has a causal relationship with t he investigational device, the comparator or the investigation procedure or \nwhere such causal relationship is reasonably possible;  \nb) any device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention ha d not \noccurred, or circumstances had been less fortunate;  \nc) any new findings in relation to any event referred to in points  a) and b).  \nSerious adverse events related to a CE marked device which is p art of the investigation procedure (for example a CE-marked imp lanting tool used \nin combination with a non-CE marked investigational device) are  reportable per MDR Article 80(2) if there is a causal, (or rea sonably possible) \nrelationship to the device, the comparator or the investigation  procedure. The reporting procedures described in this guide sh ould then be \nfollowed in addition to the normal vigilance reporting procedur es for CE marked devices.  \nAll causality assessments should be made using the guidance in section 9. Only causality level 1 (i.e. \u201cnot related\u201d) is exclu ded from reporting. If \neither the sponsor or the investigator has assigned a higher ca usality level than \"not related\", the event should be reported.  \n5.1 Exceptions for PMCF investigatio ns according to MDR Article 74. 1 \nFollowing Article 74.1 the SAE reporting for these PMCF clinica l investigations is governed b y Articles 80(5) and 80(6).  \nThis means that the provisions o f vigilance laid down in Articl es 87-90 and acts adopted pursuant to Article 91 shall apply. H owever, the SAEs \nwhere a causal relationship between the serious adverse event a nd the preceding investigational procedure has been established  shall follow the \nreporting procedures of clinical investigations as outlined in Article 80.  \nFor the purpose of this guidance reportable events in PMCF clin ical investigations are thus those serious adverse events where  a causal relationship \nbetween the serious adverse event and a preceding investigation al procedure has been established.  \n\u201cPreceding investigational procedure\u201d shall be understood as a procedure which is imposed by th e Clinical Investigation Plan a nd which has taken \nplace before (or coincided in time) with the serious adverse ev ent. This includes but is not limited to the burdensome or inva sive procedure(s) \nwhich defines whether the study is subject to notification requ irements following MDR article 74(1).  \n5.2 Reportable events occurring in Third Countries \nReportable events occurring in Third Countries4 in which a clinical investigation is performed under the same clinical investigation plan \nhave to be reported in accordance with this guidance to the NCA (s) of the European countries in which the clinical investigati on is being \nconducted.  \n\u0081 The NCA shall start receiving the reportable events occurring i n Third Countries as soon as the clinical investigation is auth orised to start in \nthat Member State.  \n\u0081 Events occurring in Third Countries after the participating Eur opean sites have closed shall continue to be reported.  \n5.3 Transition period for reportable events in pre-market clinical investigations initiated und er directives legislation \nIt is acknowledged that the MDR implies changes to the reportin g requirements compared to the directives\u2019 requirements where a ll SAEs should \nbe reported regardless of relatedness. Under MDR sponsors are n o longer obliged to report SAEs that are \u201cnot related\u201d to the c linical investigation \n                                                           \n4 Countries other than Switzerland, Turkey and those belonging t o the EEA.  \nPage 8 of 16 procedures or the investigational device. At the date of applic ation for MDR there will be ongoing events for clinical investi gations initiated under \ndirectives legislation. As from the 26th of May 2021 sponsors are no longer expected to submit follow-u p reports to NCAs for events that have been \ndeemed \u201cnot related\u201c (see section 9 of this document for guidan ce on causality assessment). For ongoing events that have a cau sality assessment \nother than \u201cnot related\u201d follow up reports will still have to b e provided.  \nTo facilitate the transition and give time for sponsors to upda te Clinical Investigation Plans and study procedures in clinica l investigations a sponsor \nmay continue to report all SAEs t o NCAs until Eudamed reporting  is mandatory (see section 4.1 Transition to reporting via Euda med). This applies \nonly to studies which have started to be conducted5 in accordance with Article 10 of Directive 90/385/EEC or Artic le 15 of Directive 93/42/EEC \nprior to 26 May 2021.  \n5.4 Transition for reportable events in PMCF clinical investigation s initiated under dire ctives legislation  \nIn case of PMCF studies which required SAE reporting according to the Pre-MDR national legislations, MDR article 80 (5) and 80 (6) shall apply from \nMay 26th, 2021.  \n \n6 Report by whom  \nReportable events have to be reported by the sponsor of the cli nical investigation, which could be the manufacturer, the legal  representative \nor another person6 or entity,. \n \n7 Report to whom  \nReportable events must be reported at the same time to all NCAs  where the clinical investigation has commenced using the summary tabulation \nfeatured in the Appendix.  \nA list of clinical investigation contact points within the NCAs  is published at the Commission's homepage. \nFor the purpose of this guidance, an investigation is considere d to have commenced in an individual Member State: \n\u2022 For investigations under the directives: When the sponsor is au thorized to start the investigation in accordance with the noti fication \nprocedures in that Member State. \n\u2022 For investigations started under the MDR: When the sponsor is a uthorized to start the investigation in that Member State in ac cordance \nwith the provisions laid out in the MDR. \nMember States may also require separate reporting to the Ethics  Committee(s). \n \n8 Reporting timelines  \n8.1 Report by sponsor to NCAs.  \nThe sponsor must report to all NCAs where the clinical investig ation is authorised to start: \n\u2022 For all reportable events as described in section 5 which indic ate an imminent risk of death, serious injury, or serious illne ss and that \nrequires prompt remedial action for other patients/subjects, us ers or other persons or a new finding to it: Immediately, but not later \n                                                           \n5 For the purpose of safety reporting this is defined as \u201cAuthor ised to start in the individual Member State in line with appli cable directives legislati on, regardless of whether \nany subjects have been recruited in the Member State or not.\u201d  \n6 Contact person established by the sponsor in line with Article  62(2) if accepted by Member State.   \nPage 9 of 16 than 2 calendar days after awareness by sponsor of a new report able event or of new information in relation with an already re ported \nevent. \nThis includes events that are of significant and unexpected nat ure such that they become alarming as a potential public health  hazard. It \nalso includes the possibility of multiple deaths occurring at s hort intervals. \nThese concerns may be identified by either the NCA or the manuf acturer. \n \n\u2022 Any other reportable events as described in section 5 or a new finding/update to it: Immediately, but not later than 7 calendar days \nfollowing the date of awareness by the sponsor of the new repor table event or of new information in relation with an already r eported \nevent.  \nIn some cases, a different periodicity or different modalities may be agreed between the participating NCAs and the sponsor ac cording to the \ninvestigation\u2019s design and to the pathology under clinical inve stigation. This would allow implementation of adequate provisio n for clinical \ninvestigations in which SAE frequency is expected to be high du e to the natural progression of the disease (e.g. palliative on cology). \n8.2 Report by the investigator to the sponsor  \nThe sponsor shall implement and maintain a system to ensure tha t the reporting of the reportable events as defined under chapt er 5 will be \nprovided by the investigator to the sponsor immediately, but no t later than 3 calendar days after investigation site study per sonnel\u2019s \nawareness of the event.  \n9 Causality assessment  \nThe relationshi p between the use of the medic al device7 (including the medical - surgical procedure) and the occurrence  of each adverse event \nshall be assessed and categorized.  \nD u r i n g  c a u s a l i t y  a s s e s s m e n t  a c t i v i t y ,  c l i n i c a l  j u d g e m e n t  s h a l l  be used and the relevant documents, such as the Investigator\u2019s Brochure, the \nClinical Investigation Plan or the Risk Analysis Report shall b e consulted, as all the foreseeable serious adverse events and the potential risks are \nlisted and assessed there8. The presence of confounding factors, such as concomitant medi cation/treatment, the natural history of the underlying \ndisease, other concurrent illness or risk factors shall also be  c o n s i d e r e d .  \nThe above considerations apply also to the serious adverse even ts occurring in the comparison group. \nFor the purpose of harmonizing reports, each SAE will be classi fied according to four different levels of causality: \n1. Not related \n2. Possible \n3. Probable \n4. Causal relationship \nThe sponsor and the investigators will use the following defini tions to assess the relationship of the serious adverse event t o the investigational \ndevice, the comparator or the investigation procedure. \n1. Not related: Relationship to the device, comparator or procedur es can be excluded when: \n- the event has no temporal relationship with the use of the inve stigational device, or the procedures related to application of  the \ninvestigational device; \n                                                           \n7 Intended as both investigational device and comparator.  \n8 For a comparator device, the Operator\u2019s Manual could be a rele vant document.  \nPage 10 of 16 - the serious adverse event does not follow a known response patt ern to the medical device (if the response pattern is \npreviously known) and is biologically implausible; \n- the discontinuation of medical device application or the reduct ion of the level of activation/exposure - when clinically feasi ble - \nand reintroduction of its use (or increase of the level of acti vation/exposure), do not impact on the serious adverse event; \n- the event involves a body-site or an organ that cannot be affec ted by the device or procedure; \n- the serious adverse event can be attributed to another cause (e .g. an underlying or concurrent illness/ clinical condition, an  effect \nof another device, drug, treatment or other risk factors); \n- the event does not depend on a false result given by the invest igational device used for diagnosis9, when applicable; \nIn order to establish the non-relatedness, not all the criteria  listed above might be met at the same time, depending on the t ype of \ndevice/procedures and the serious adverse event. \n2. Possible: The relationship with the use of the investigational device or comparator, or the relationship with procedures, is w eak but \ncannot be ruled out completely. Alternative causes are also pos sible (e.g. an underlying or concurrent illness/ clinical condi tion or/and \nan effect of another device, drug or treatment). Cases where re latedness cannot be assessed, or no information has been obtain ed \nshould also be classified as possible. \n3. Probable: The relationship with the use of the investigational device or comparator, or the relationship with procedures, seem s \nrelevant and/or the event cannot be reasonably explained by ano ther cause. \n4. Causal relationship: the serious  adverse event is associated with the investigational device, co mparator or with procedures beyond \nreasonable doubt when: \n- the event is a known side effect of the product category the de vice belongs to or of similar devices and procedures; \n- the event has a temporal relationship with investigational devi ce use/application or procedures; \n- the event involves a body-site or organ that \no the investigational device or procedures are applied to; \no the investigational device or procedures have an effect on; \n- the serious adverse event follows a known response pattern to t he medical device (if the response pattern is previously known) ; \n- the discontinuation of medical device application (or reduction  of the level of activation/exposure) and reintroduction of its  use \n(or increase of the level of activation/exposure), impact on th e serious adverse event (when clinically feasible); \n- other possible causes (e.g. an underlying or concurrent illness / clinical condition or/and an effect of another device, drug o r \ntreatment) have been adequately ruled out; \n- harm to the subject is due to error in use; \n- the event depends on a false result given by the investigationa l device used for diagnosis10, when applicable; \nIn order to establish the relatedness, not all the criteria lis ted above might be met at the same time, depending on the type of \ndevice/procedures and the serious adverse event. \n                                                           \n9 If an investigational device gives an incorrect diagnosis, the  patient might, for example, receive an unnecessary treatment a nd incur all the risks that accompany that \ntreatment, or might be incorrectly diagnosed with a serious dis ease. In other cases, the patient might not receive an effectiv e treatment (thereby missing out on the benefits \nthat treatment would confer) or might not be diagnosed with the  correct disease or condition. \n10 If an investigational device gives an incorrect diagnosis, the  patient might, for example, receive an unnecessary treatment a nd incur all the risks that accompany that \ntreatment, or might be incorrectly diagnosed with a serious dis ease. In other cases, the patient might not receive an effectiv e treatment (thereby missing out on the benefits \nthat treatment would confer), or might not be diagnosed with th e correct disease or condition.  \nPage 11 of 16 The sponsor and the investigators will distinguish between the serious adverse events related to the investigational device an d those related to \nthe procedures (any procedure specific to the clinical investig ation). An adverse event can be related both to procedures and the investigational \ndevice. Complications caused by concomitant treatments not impo sed by the clinical investigation plan are considered not relat ed. Similarly, \nseveral routine diagnostic or patient management procedures are  applied to patients regardless of the clinical investigation p lan. If routine \nprocedures are not imposed by the clinical investigation plan, complications caused by them are also considered not related.  \nIn some particular cases the event may not be adequately assess ed because information is insufficient or contradictory and/or the data cannot \nbe verified or supplemented. The sponsor and the Investigators will make the maximum effort to define and categorize the event  a n d  a v o i d  \nthese situations. Where an investigator assessment is not avail able and/or the sponsor remains uncertain about classifying the  serious adverse \nevent, the sponsor should not exclude the relatedness; the even t should be classified as \u201cpossible\u201d and the reporting not be d elayed.  \nParticular attention shall be given to the causality evaluation  of unanticipated serious adverse events. The occurrence of una nticipated events \nrelated could suggest that the clinical investigation places su bjects at increased risk of harm than was to be expected before hand. \n \n10 Reporting form  \nThe reporting form template for the summary SAE tabulation is g iven in the Appendix of this document.  \nThe reporting form is study specific and covers only a given cl inical investigation, defined by a distinct clinical investigat ion plan. English is the \nrecommended language for the reporting form. The report form ca n be modified in any applicable software (not only Microsoft Ex cel) but \nthe file needs to be compatible with Microsoft Excel when sent to the participating NCAs.  \nThe template form contains inserted filters and functionality t o facilitate use of preferred terminology in the reporting. The se are important for the \nanalysis and should be maintained. \nSponsors who generate the excel report file by automated proces ses may implement other technical features in their systems for  e x c e l  f i l e  \ngeneration to ensure the preferred terms listed in metadata are  used.  \nThe table gives a cumulative overview of the reportable events per clinical investigation and will be updated and transmitted to participating \nNCAs each time a new reportable event or a new finding to an al ready reported event is to be reported. More detailed informati on has to be \nprovided on request of an NCA, if so requested by using the ind ividual study specific reporting form (see further section 4.3 Collecting reports \nfrom investigators ).  \n10.1 Completion guidelines: Form header \n10.1.1  EUDAMED/CIV-ID \nThe union-wide Single Identification Number mentioned in MDR Ar ticle 70(1) will not be possible to generate until Eudamed for MDR is fully \nfunctional. For the transition period, clinical investigations will get tracking numbers (CIV-ID) upon registration in the Eud amed2 database which \nis performed by the NCA upon receipt of an application. This CI V ID is provided to the sponsor during the NCA\u2019s handling of th e initial application \nfor the clinical investigation and should be entered on the saf ety reporting form.  \nThe CIV ID should already be available for a clinical investiga tion started under the directives\u2019 legislation, where it should  be indicated on the \nMEDDEV 2.7/3 reporting form etc. Sponsors who are not aware of the CIV ID of their clinical inv estigations are invited to cont act the concerned \nNCA to get this information.  \nPage 12 of 16 10.1.2  Title of Clinical Investigation  \nThe identifying title of the Clinical Investigation. The title indicated here should be consistent with other title entries (s uch as in clinical investigation \napplication form, clinical inves tigation plan cover page etc).  \n10.1.3  CIP number/code \nThe unique identification code or short name assigned to the sp ecific clinical investigation pl an by the Sponsor (numeric, alp hanumeric or acronym) \nshould be indicated.  \n10.1.4  Contact person \nName, address, e-mail and telephone number should be provided f or the person who is sponsor\u2019s point of contact in case NCA hav e follow up \nquestions regarding submitted safety report forms.  \n10.1.5  MS+NCA Reference numbers \nFor each participating Member State indicate the country code11 and the NCA\u2019s national reference number for the clinical inves tigation.  \nExample:  \nSE 5.1-20YY-XXXXXX DK 20YYXXXXXX \n10.1.6  No. of subjects enrolled to date total \nIndicate the total number of subjects who have been enrolled (p er date of report) in the clinical investigation globally.  \n10.1.7  No. of subjects enrolled to date per country \nList all countries where the clinical investigation has been au thorised by date of report and indicate the number of subjects who have been enrolled \nin the clinical investigation (per date of report) in each coun try.  \n10.1.8  Device type \nIndicate the type of device(s) assessed in the clinical investi gation (e.g. pacemaker, coronary stent, hip implant).  \n10.1.9  Reference Member State \nIndicate the name of the Member State which drew the unique EUD AMED/CIV ID (normally the first Member State receiving an appli cation for \nthe clinical investigation). Once the coordinated assessment pr ocedure (per MDR Article 78) is up and running, the coordinatin g Member State \nshould be indicated here.  \n10.1.10  No. of investigational devices used to date total \nIndicate the total number of investigational devices which have  been used (per date of report) in the clinical investigation g lobally.  \n10.1.11  No. of investigational devic es used to date per country \nList all countries where the clinical investigation has been au thorised by date of report and indicate the number of investiga tional devices which \nhave been used in the clinical investigation (per date of repor t) in each country. \n10.1.12  Date of report \nIndicate the date when the report is compiled for transmission to NCAs. Format DD/MM/YYYY.  \n                                                           \n11 Use ISO-3166-1 alpha-2 codes, i.e.two-letter country codes as defined in ISO 3166-1  \nPage 13 of 16 10.2 Completion guidelines: Event details \nEach unique reportable event is presented in a separate line. U pdates to a previously reported event should be made by changin g the information \nin the same line, and clearly identified according to the princ iples described below.  \nAny new information added in the form should be highlighted in bold and/or colour. This includes any new lines added and any c hanges made \nto the information in an already existing line.  \nIn the initial report, in any given line, no fields shall be le ft intentionally blank. To meet this requirement, preliminary i nformation should be filled \nin, despite the need of further updating.  \n10.2.1  Status  \nThe sponsor shall identify the new/updated information in the s tatus column as: \nA = added = new reportable event; M = modified = new finding/update to an already reported event;   \nU = unchanged. \n10.2.2  Date Sponsor received report of SAE/DD \nIndicate the date when the sponsor was first notified by the in vestigation site about the event. This date is checked for comp liance with reporting \ntimelines as outlined in section  8 Reporting timelines .  \nFormat DD/MM/YYYY. \n10.2.3  Country code \nIndicate the country code\n11 for the country in which the subject associated with the event  has been enrolled. \n10.2.4  Investigation site \nName identifying institution or site where the clinical investi gation is carried out.  \n10.2.5  Subject ID code \nThe study specific subject ID code, i.e. the link between study  data and the actual subject identity (which is not to be provi ded in this form).  \n10.2.6  SAE ID code \nThe investigator, sponsor or manufacturer should assign a uniqu e ID to each SAE that has occurred, This number shall remain un changed \nthroughout all other alterations of the particular SAE-reportin g due to ongoing assessment. \n10.2.7  Date of procedure/First use \nIndicate the date of the relevant procedure or the date when th e subject was exposed to the dev ice for first use. Format DD/MM /YYYY. \n10.2.8  Date of event onset \nThe date when the first signs of an event were noticed may be d ifferent (earlier) than the date when the event fulfilled the s eriousness criteria \n(see further the definition in section 3.3 Serious Adverse Even t (SAE)). The date when the event became an SAE should be repor ted as Date of \nevent onset. In case of Device Deficiencies which did not lead to an SAE, the date the DD was discovered should be indicated.  \nFormat DD/MM/YYYY. \n10.2.9  SAE or DD \nChoose one option from SAE(Seriou s Adverse Event) or DD (Device  Deficiency).  \nDo not add other options.  \nPage 14 of 16 10.2.10  Age \nThe subject\u2019s age at date of event onset should be indicated.  \nIn cases where exact date of birth is not available as a basis for age calculation, it is acknowledged that an approximate age  at date of event onset \ncould be calculated based on the age at enrollment.  \nNormally the Age should be indicated in Years, although for pae diatric/neonatal populations it may be more relevant to indicat ed age in months, \nweeks or days. When a different unit than years is used, the un it should be indicated as appropriate. \n10.2.11  Patient gender \nChoose one option from the following list (do not add other opt ions):  \n\u0081 Female \n\u0081 Male \n\u0081 Other \n\u0081 Unknown \n10.2.12  Location of device \nFor this field, it is the location of the device at the time th e report is submitted to NCA is of interest (i.e not at the tim e of investigator or sponsor \nawareness of the event). Changed location of the device is in i tself not a reason to provide an updated report. However, whene ver an update/final \nreport is provided for other reasons, it is relevant to update this field if the device for example has reached the sponsor by  then. \nChoose one option from the following list (do not add other opt ions): \n\u0081 Investigational/study site \n\u0081 Sponsor \n\u0081 Subject \n\u0081 Manufacturer \n\u0081 Remains implanted \n\u0081 Discarded \n\u0081 Unknown \n\u0081 Other \n10.2.13  Classification of event \nChoose one option from the following list of consequence charac teristics (do not add other options):  \n\u0081 Death \n\u0081 Life-threatening illness or injury \n\u0081 Permanent impairment/ Chronic disease \n\u0081 Hospitalization \n\u0081 Medical or surgical intervention \n\u0081 Foetal distress, f\u0153tal death or congenital physical or mental o r birth defect \n\u0081 Not applicable (Note that this option is only to be selected in  case of reportable Device deficiencies that did not lead to an  SAE)  \nPage 15 of 16 It is acknowledged that for a specific event two or more option s may be equally applicable, e.g. \u201d Hospitalization\u201d and \u201cmedica l intervention\u201d. The \nhighest-ranking classification should be indicated, using the f ollowing ranking order: 1) Death , 2) life threatening, 3) foeta l distress, 4) permanent \nimpairment, 5) Medical or surgic al intervention 6) hospitalizat ion. \n10.2.14  Description of event \nProvide a description of the event in free text. Below is a non -exhaustive list of items that  could be relevant to cover:  \n\u0081 Nature of the observed symptoms \n\u0081 Duration and severity of the symptoms \n\u0081 Date of onset of first signs of the event (before it became a S AE) \n\u0081 Medical background of the patient \n\u0081 Medical care of the patient \n\u0081 Comments on the event in relation to already known safety data \nUse of standardised terminology corresponding to relevant IMDRF  codes is encouraged. \n10.2.15  Action/treatment /outcome \nProvide information in free text on actions taken, treatment(s)  administered and the outcome.   \n10.2.16  Relationship to procedure \nChoose one option from the foll owing list of causality levels ( for explanatory texts see sect ion 9 Causality assessment): \n\u0081 Not related \n\u0081 Possible \n\u0081 Probable \n\u0081 Causal \nPlease report the assessments by sponsor and investigator in th e respective columns.   \n10.2.17  Relationship to device \nChoose one option from the foll owing list of causality levels ( for explanatory texts see sect ion 9 Causality assessment) \n\u0081 Not related \n\u0081 Possible \n\u0081 Probable \n\u0081 Causal \nPlease report the assessments by sponsor and investigator in th e respective columns.  \n10.2.18  Unanticipated SADE \nChoose option Yes or No \nAn Unanticipated Serious Adverse Device Effect12 is an effect which by its nature, incidence, severity or outco me has not been identified in the \ncurrent risk assessment. Procedure s associated with the use of a device should be addressed in the risk assessment, which make s it possible to \n                                                           \n12 An adverse device effect is an adverse event related to the us e of an investigational device. A serious adverse device effect  is an adverse device effect that has resulted in \nany of the consequence characteristics of a serious adverse eve nt.   \nPage 16 of 16 determine whether the procedure related SAEs are Unanticipated Serious Adverse Device Effect or not. SAEs related to procedure s imposed by \nthe clinical investigation plan but not with the use of the dev ice should not be considered Serious Adverse Device Effects.  \n10.2.19  Investigation arm \nChoose one option from the following list: \n\u0081 Test group \n\u0081 Comparison group \n\u0081 Blinded \n\u0081 Not applicable \nNote: For some study designs it might be more relevant to add n ame of device; i.e. in a clinical  investigation with several te st groups it might be \nuseful to differentiate which investigational device that the s ubject has been exposed to.  \n10.2.20  Event status \nChoose one option from the following list (do not add other opt ions): \n\u0081 Resolved \n\u0081 Resolved with Sequelae \n\u0081 Ongoing \n\u0081 Death \n10.2.21  Date of event resolution \nAdd date in format DD/MM/YYYY. If event status is \u201cOngoing\u201d ent er Not Applicable.  \n \n11 References \n1. R e g u l a t i o n  ( E U )  2 0 1 7 / 7 4 5  o f  t h e  E u r o p e a n  P a r l i a m e n t  a n d  o f  t h e  council of 5 April 2017 on medical devices, amending Directive \n2001/83/EC, Regulation (EC No 178/2002 and Regulation (EC) No 1 223/2009 and repealing Council Directives 90/385/EEC and 93/42/ EEC.  \n2. Council Directive 90/385/EEC of 20 June 1990 on the approximati on of the laws of the  Member States relating to active implantable medical \ndevices, last amended by Directive  2007/47/EC. \n3. Council Directive 93/42/EEC of 14 June 1993 concerning medical devices, last amended  by Directive 2007/47/EC. \n4. Codes for the representation of names of countries and their su bdivisions \u2013 Part 1: Country codes (ISO 3166-1) published by In ternational \nOrganisation for Standardization (ISO). \n \n12 Appendix \u2013 Clinical Investigation Sum mary Safety Reporting Form"}, {"title": "08 MDCG 2020-8 Guidance on PMCF Evaluation Report Template.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n1 \n  \n \n \nMDCG 2020-8 \n  \n Post-market clinical follow-up (PMCF) Evaluation Report Template \nA guide for manufacturers and notified bodies                \n \n April 2020 \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) established by Article 103 of Regulation (EU) \n2017/745. The MDCG is composed of representatives of all Member States and it is chaired by a representative of the European \nCommission.The document is not a European Commission document and it cannot be regarded as reflecting the official position of the \nEuropean Commission. Any views expressed in this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law. Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n2 \n  \n \n \n \n \n \n \nPost-market clinical follow-up (PMCF) Evaluation Report Template  \nA guide for manufacturers and notified bodies \n \n  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n3 \n  \nContents \nIntroduction  ........................................................................................................................................................................................................................................... 4 \nPost-market clinical follow-up evaluation report Template  ............................................................................................................................................................ 4 \nSection A. Manufacturer contact details ....................................................................................................................................................................................... 5 \nSection B. Medical Device description and specification  .......................................................................................................................................................... 5 \nSection C.   Activities undertaken related to PMCF: results  ..................................................................................................................................................... 7 \nSection D.  Evaluation of clinical data relating to equivalent or similar devices  .................................................................................................................... 7 \nSection E. Impact of the results on the technical documentation  ............................................................................................................................................ 7 \nSection F.  Reference to any common specification(s), harmonized standard(s) or guidance document(s) applied  ...................................................... 9 \nSection G. Conclusions  .................................................................................................................................................................................................................. 9 \n \n  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n4 \n Introduction \n \nThe Medical Device Regulation (EU) 2017/745 (MDR) considers the post-market clinical follow-up (PMCF) as a continuous process that \nupdates the clinical evaluation and that shall be addressed in the manufacturer\u2019s post-market surveillance plan. The MDR reinforces the \nPMCF process by the manufacturer, devoting part B of Annex XIV to it and providing a set of requirements for developing a PMCF plan \nand its evaluation report, necessary to its implementation.  \n \nThe manufacturer shall analyse the findings coming from the activities foreseen in the PMCF plan and document the results in this PMCF \nevaluation report that shall be part of the clinical evaluation report and the technical documentation. \n  \nThe conclusions of the PMCF evaluation report shall be taken into account to update eventually the clinical evaluation, the risk \nmanagement documentation, the post market surveillance plan and the SSCP, if applicable. \n \nThe purpose of the present templates is to guide manufacturers in complying with the requirements of the MDR with respect to the \ncompilation of  the PMCF evaluation report. This would assist manufacturers in a harmonised and complete presentation of post market \nclinical data and facilitate the activity of notified bodies and competent authorities in finding the information in an organized format. \n \nPost-market clinical follow-up evaluation report Template  \nPost-market clinical follow- up (PMCF) plan corresponding to the present evaluation report \nPMCF plan number and version: \n \nPost-market clinical follow- up (PMCF) Evaluation Report \nPMCF report number: \nPMCF report date: \nPMCF report version:  \nRevision history  \nRev Revision date Description of change Revised by \n    Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n5 \n     \n \n \n Section A. Manufacturer  contact details \nLegal manufacturer name: \nAddress: \nSRN: \nPerson responsible for regulatory compliance: \nE-mail: \nPhone: \nFax: \nAuthorised representative (if applicable): \nAddress: \nContact person:  \nE-mail: \nPhone: \nFax: \n \nSection B. Medical Device description and specification \nRefer to section B from PMCF plan, if there are no changes.  \nIf there are changes from PMCF plan, please fill in the different requested fields highlighting those changes.  \nProduct or trade name: \nModel and type: \nGeneral description of the device: Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n6 \n Intended purpose1 \nIntended users \nBasic UDI-DI: \nIntended patient population: \nMedical condition(s)2: \nIndications: \nContraindications: \nWarnings:  \nList and description of any variants and/or configurations covered by this plan: \nList of any accessories covered by this plan: \nCertificate number (if available): \nCND code(s)3:  \nClass: \nClassification rule: \nExpected lifetime4  \nNovel product                                \u2610  yes    \u2610  no \nNovel related clinical procedure:   \u2610  yes    \u2610  no \nExplanation of any novel features: \n \n \n                                                             \n1 Intended purpose means the use for which a device is intended according to the data supplied by the manufacturer on the label in the instructions for use or in promotional or sales \nmaterials or statements and as specified by the manufacturer in the clinical evaluation (MDR, Article 2(12)).  \n2 It refers to the clinical condition that is to be diagnosed, prevented, monitored, treated, alleviated, compensated for, replaced, modified or controlled by the medical device. \n \n4 The expected lifetime is to be defined during the design input phase by considering the current state of the art for a specific intended use and indication of a device.  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n7 \n Section C.   Activities undertaken related to PMCF: results  \nIn this section the manufacturer shall report all the activities described in section C of the PMCF plan which have been performed, all the collected \nclinical data obtained from those completed activities, as well as any justification of deviations from the plan.  \n \nThe discussion shall include the analysis of the findings, whether positive or negative and also the potential impact on the different documents (clinical \nevaluation report, risk management file, SSCP, etc\u2026) initially reviewed during the conformity assessment.  \n \nIt is expected for each activity performed, a description in different subsections, related to the type of activities (device registry, PMCF studies, real \nworld evidence, surveys about the use of device, etc\u2026), and for each subsection, a description about the quality of data collected.5 \n \nSection D.  Evaluation of clinical data relating to equivalent or similar devices  \n \nIn this section the manufacturer shall report all the clinical data collected relating to an equivalent device or selected similar device(s), provide an \nanalysis and conclusions, and whether changes of the state of the art, or newly identified hazards would have an impact on the devices benefit-risk \ndetermination, the clinical evaluation and/or the PMCF plan.  \n \n \n \nProduct name of \nequivalent / similar \ndevice Results discussed References used to get the \nresults (publications, part of \ntechnical documentation from \nthis equivalent / similar device) \n \n \n \n Section E. Impact of the results on the technical documentation  \n \n                                                             \n5 For the analysis and assessment of the clinical data collected, some parts of section 9.3.1 from Meddev 2.7/1 rev.4 could be used to assess the quality of data. \n Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n8 \n In this section, the manufacturer shall discuss the aggregate results coming from each PMCF activity planned and performed, described in section C, \nbut also results coming from equivalent and/or similar device, described in section D, which are considered to impact the technical documentation and \nat least the following documents shall be considered: \n \n1. Clinical evaluation report - CER (date and version)  \n \n\u2610   No relevant information from the clinical evaluation report have been considered. \n \nIf applicable, it is expected from manufacturer to describe why some information that might have an impact on the CER have not been considered. \n \nRelevant information analyzed and monitored: \n- \n- \n \nAnalysis of the outcome is to be reported in the updated clinical evaluation report. \n \n \n2. Risk management file (date and version) \n \n\u2610   No relevant information from the risk management file have been considered \n \nIf applicable, it is expected from manufacturer to describe why some information that might have an impact on the risk management file have not been \nconsidered. \n \n \n \nRelevant information analyzed and monitored: \n \n- \n- \n- \n \n Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n9 \n Analysis outcome to be reported in the risk management file updated: \n- \n- \n \n \n \n \n \nSection F.  Reference to any common specification(s), harmonized standard(s) or guidance document(s) applied  \n \nIn this section the manufacturer should point out whether the collected clinical data related the device in question still confirm adherence to applied \ncommon specifications and/or applied harmonized standards, and/or guidances listed in the PMCF plan. \n \nCommon Specification(s) applied \n(Title, date and version) \n \nHarmonised standard(s) applied \n(Title, date and version) \n \nGuidance(s) followed \n(Title, date and version ) \n \n \nSection G. Conclusions  \n \n \nIn this section, it is expected that the manufacturer shall provide an overall conclusion of the findings and relate them to the aims of the PMCF \nplan. The conclusions shall be taken into account in the following clinical evaluation and in the risk management. Finally, this conclusion shall \nhighlight if any need for preventive and/or corrective measures has been identified. The conclusion may also give input to the next PMCF plan. Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n10"}, {"title": "07 MDCG 2020-7 Guidance on PMCF Plan Template.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n1 \n  \n \n \n \nMDCG 2020-7 \n  \n Post-market clinical follow-up (PMCF) Plan Template \nA guide for manufacturers and notified bodies                \n \n April 2020 \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) established by Article 103 of Regulation (EU) \n2017/745. The MDCG is composed of representatives of all Member States and it is chaired by a representative of the European \nCommission.The document is not a European Commission document and it cannot be regarded as reflecting the official position of the \nEuropean Commission. Any views expressed in this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law. \n  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n2 \n  \n \n \n \n \n \nPost-market clinical follow-up (PMCF) Plan Template  \nA guide for manufacturers and notified bodies \n  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n3 \n  \nContents \nIntroduction  ........................................................................................................................................................................................................................................... 4 \nPost-market clinical follow-up plan Template  .................................................................................................................................................................................. 5 \nSection A. Manufacturer contact details ....................................................................................................................................................................................... 5 \nSection B. Medical Device description and specification  .......................................................................................................................................................... 6 \nSection C. Activities related to PMCF: general and specific methods and procedures  ........................................................................................................ 7 \nSection D. Reference to the relevant parts of the technical documentation  .......................................................................................................................... 9 \nSection E. Evaluation of clinical data relating to equivalent or similar devices  .................................................................................................................... 10 \nSection F. Reference to any applicable common specification(s), harmonized standard(s) or applicable guidance document(s)  ............................. 11 \nSection G. \u2013 Estimated date of the PMCF evaluation report  .................................................................................................................................................. 12 \n \n  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n4 \n Introduction \n \nThe Medical Device Regulation (EU) 2017/745 (MDR) considers the post-market clinical follow-up (PMCF) as a continuous process that \nupdates the clinical evaluation and that shall be addressed in the manufacturer\u2019s post-market surveillance (PMS) plan. The MDR \nreinforces the PMCF process by the manufacturer, devoting part B of Annex XIV to it and providing a set of requirements for developing \na plan, necessary to implement PMCF.  \n \nA PMCF plan shall specify the methods and procedures set up by the manufacturer, to proactively collect and evaluate clinical data from \nthe use in or on humans of a CE marked medical device, placed on the market or put into service within its intended purpose, as referred \nto in the relevant conformity assessment procedure. \n  \nThe aim of the PMCF plan is: \n\uf0b7 confirming the safety1 and performance, including the clinical benefit if applicable, of the device throughout its expected lifetime; \n\uf0b7 identifying previously unknown side-effects and monitor the identified side-effects and contraindications; \n\uf0b7 identifying and analysing emergent risks on the basis of factual evidence; \n\uf0b7 ensuring the continued acceptability of the benefit-risk ratio, referred to in Section 1 and 9 of Annex I in the MDR;  \n\uf0b7 identifying possible systematic misuse or off-label use of the device, with a view to verifying that the intended purpose is correct. \n \nThe PMCF plan shall be part of the post-market surveillance plan.  \n \nThe findings of the PMCF shall be analysed by the manufacturer who shall document the results in a PMCF evaluation report. The \nPMCF evaluation report shall be part of the clinical evaluation report and the technical documentation. The adequateness of the PMCF \nplan and its application is subject to assessment by the notified body. The notified body\u2019s assessment of the clinical evaluation shall also \ncover the manufacturer\u2019s procedures and documentation of the PMCF,  as well as the justification in relation to non-performance of \nPMCF. \n  \nThe purpose of the present template is to guide manufacturers in complying with the requirements of the MDR with respect to the \ncompilation of the PMCF plan. This would assist manufacturers in a harmonised and complete presentation of post market clinical data \nand facilitate the activity of notified bodies and competent authorities in finding the information in an organised format. \n                                                             \n1 The confirmation of the safety includes the acceptability of identified risks and particularly residual risks.  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n5 \n  \nPost-market clinical follow-up plan Template \n \nPMCF plan number: \nPMCF plan date: \nPMCF plan version:  \nRevision history  \nRev Revision date Description of change  Revised by  \n    \n    \n \nSection A. Manufacturer  contact details \nLegal manufacturer name: \nAddress: \nSRN: \nPerson responsible for regulatory compliance: \nE-mail: \nPhone: \nFax: \nAuthorised representative (if applicable): \nAddress: \nContact person:  \nE-mail: \nPhone: \nFax: \n Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n6 \n Section B2. Medical Device description and specification \nProduct or trade name: \nModel and type: \nGeneral description of the device:  \nIntended purpose3: \nIntended users \n Basic UDI-DI: \nIntended patient population: \nMedical condition(s)4: \nIndications: \nContraindications: \nWarnings: \n \n \nList and description of any variants and/or configurations covered by this plan: \n \nList of any accessories covered by this plan: \nCertificate number (if available): \nCND code(s)5:  \nClass: \nClassification rule: \n                                                             \n2 MDR, Annex II, 1,1. \n3 Intended purpose means the use for which a device is intended according to the data supplied by the manufacturer on the label in the instructions for use or in promotional or \nsales materials or statements and as specified by the manufacturer in the clinical evaluation (MDR, Article 2(12)).  \n4 It refers to the clinical condition that is to be diagnosed, prevented, monitored, treated, alleviated, compensated for, replaced, modified or controlled by the medical device \n5 Per article 26 of MDR.  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n7 \n Expected lifetime:6  \nNovel product:                              \u2610 yes   \u2610  no \nNovel related clinical procedure:  \u2610 yes   \u2610 no \nExplanation of any novel features: \n \nSection C. Activities related to PMCF: general and specific methods and procedures  \n \nIn this section it is expected to describe the different activities that will be conducted in post-market, including general and specific methods / procedures \nto conduct  in relation to the product covered by the scope of PMCF, also the aim of each activity described and the rational for the appropriateness of \nthe chosen general and specific methods to achieve those objectives as well as the known limitations of the planned activities such as for example \nincomplete follow up, missing data and so on. The timelines of those activities shall be also defined quarterly or at least yearly.  \nHere are some examples of different activities related to PMCF: \n\uf0b7 A manufacturer device registry  (specific for the type of device or the group of the medical devices the product belongs to) can be indicated \ntogether with a description and a summary of the plan. A pre-specification of what quality and quantity data \u2013 based on the risk of the device(s) \nand the associated accessories \u2013 to be collected and analysed shall be included. Any possible evaluation of suitable national public registries  \nwith clinical data on the manufacturer\u2019s own device and/or on  similar devices could be specified in this section, identifying the expected quantity \nand quality of data to be gathered and the search protocols to be adopted.  \n\uf0b7 PMCF studies  planned could be indicated in this section, together with a summary of the plan including the design, sample size, the endpoints, \nthe inclusion/exclusion criteria (e.g. extended follow up of patients included in the pre-market clinical investigations, new clinical investigations \nwithin the intended use, retrospective studies). In case of implantable devices and class III devices where clinical investigations have not been \nperformed pursuant to Article 61 (4), the PMCF plan shall include post market studies to confirm the safety and performance of the device. \n\uf0b7 Planned Real-world evidence  (RWE) analyses could be indicated in this section, together with a summary of the plan including the design, \nsample size, the endpoints, and analysis population. The real-world data (RWD) from which these analyses are based on should be of sufficient \nquality and come from reliable data sources. \n\uf0b7 Surveys  planned to collect information about the use of the concerned medical device could be described.  \nEach activity will be developed in a different subsection (e.g.  C.1,  C.2, \u2026), and for which the manufacturer will: \n                                                             \n6 The expected lifetime is to be defined during the design input phase by considering the current state of the art for a specific intended use and indication of a device.  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n8 \n \uf0b7 Define where the need of conducting the PMCF activity is coming from (requested by notified body, clinical evaluation report, PMS, risk \nmanagement report, previous PMCF report, etc\u2026) \n\uf0b7 Provide the description of activity, and if it is a general or specific procedure / method. \n\uf0b7 Define the aim of this activity:  \no confirming the safety of the medical device \no confirming the performance of the medical device \no identifying previously unknown side-effects (related to the procedures or to the medical devices). \no monitoring the identified side-effects and contraindications \no identifying and analysing emergent risks \no ensuring the continued acceptability of the benefit-risk ratio \no identifying possible systematic misuse or off-label use of the device \n \n\uf0b7 Describe the different procedures which will be used as part of PMCF: \no screening of scientific literature and other sources of clinical data  \no post-market studies  \no collecting data in registries \no survey from health care professional \no survey from patients/users \no review of case reports which may reveal misuse or off-label use \n \n\uf0b7 Describe the rationale for the appropriateness of the chosen methods/procedures, including:  \no the justification for sample size, timescales and endpoints \no justification for comparator, on the basis of intended purpose and state of the art \no justification of the study design on the basis of all of the above, and why it is sufficient to ensure representative patient populations and \nprovide for adequate controls on sources of bias (an evaluation of the potential sources of bias should form part of this) \no a statistical justification for the expected quality of outcomes, and justification for why this is satisfactory in light of the residual risks. This \nis an important consideration. For example, retrospective surveys with no justification other than \u201cthis should demonstrate the expected \nquality of evidence that we require,\u201d but without showing a statistical rationale, are not acceptable.  \n \n\uf0b7 Provide the timelines of the activity. A detailed and adequately justified time schedule for PMCF activities, such as the analysis of PMCF data and \nreporting, shall be described.  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n9 \n A summary table of the different PMCF activities foreseen by the manufacturer is provided below: \nNumber \nof \nactivity Description of activity Aim of the activity  \nRationale and known \nlimitations of the activity Timelines of the activity \n   \n   \n \n \n \nSection D. Reference to the relevant parts of the technical documentation  \n \nIn this section the manufacturer is required to include references to the relevant information from the clinical evaluation report and  from the risk \nmanagement file, which need to be analysed, followed up, and evaluated in this plan. As an alternative, the manufacturer is required to state that there is \nno relevant information from the clinical evaluation report and/or from the risk management file to be considered in this plan.  \n \nClinical Evaluation Report (date and version) \nRelevant information to be further analysed and monitored: \n- \n- \n- \n \nRisk Management File (date and version) \nRelevant information to be further analysed and monitored: Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n10 \n - \n- \n- \n \n\u2610 No relevant information from the clinical evaluation report to be considered in this plan \n \n \n\u2610  No relevant information from the risk management file to be considered in this plan \n \nSection E. Evaluation of clinical data relating to equivalent or similar7 devices \n \nThe manufacturer shall gather in this section information regarding equivalent / similar devices for which clinical data will be further evaluated and \npresented in the PMCF report. \nPlease note that PMCF data intended to demonstrate continuing safety and performance should be sourced from the device under evaluation.  \nData from equivalent or similar devices may be used, for example to update the information relating to the state of the art, to identify and further assess \nrelevant safety outcomes etc. \nThe selected devices shall be consistent throughout the technical documentation. Indicate whether the selected device is demonstrated to be equivalent \nor is a similar device. For each device listed, a clear reference to the pertinent parts of the CER can be made. \nThe following items of each equivalent and/or similar devices would be at least provided, in a table format: \n                                                             \n7 Section 5, MDCG 2020-5 Clinical Evaluation \u2013 Equivalence, A guide for manufacturers and notified bodies.  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n11 \n Product name of \nequivalent / similar \ndevice Intended purpose Intended users Intended patient population Medical condition Indication Reference to clinical \ndata evaluation in \nthe CER ( date, \nversion and location in \nthe text) \n \n  \n \n \nSection F. Reference to any applicable common specification(s), harmonized standard(s) or applicable guidance \ndocument(s)  \n \n \nCommon specification(s) to comply with, if applicable: \n(Title, date and version) \n \n \n \nHarmonised standards to apply, if applicable \n(Title, date and version) \n \n \nGuidance on PMCF, if applicable Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n12 \n (Title, date and version) \n \n \n \n \nSection G. \u2013 Estimated date of the PMCF evaluation report  \n \nWhen the manufacturer plans to have the first report. The timelines shall be defined quarterly or at least yearly."}, {"title": "06 MDCG 2020-6 Guidance on Sufficient Clinical Evidence for Legacy Devices.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document   MDCG  2020-6  \n  \n \n \n \n \n \n \n \n \nMDCG 2020-6 \n  \n         Regulation (EU) 2017/745: Clinical evidence needed for  \n        medical devices previously CE marked under \n        Directives 93/42/EEC or 90/385/EEC   \n \nA guide for manufacturers and notified bodies  \n             \n \n April 2020 \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) \nestablished by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of \nrepresentatives of all Member States and it is chaired by a representative of the European \nCommission.The document is not a European Commission document and it cannot be \nregarded as reflecting the official position of the European Commission. Any views \nexpressed in this document are not legally binding and only the Court of Justice of the \nEuropean Union can give binding interpretations of Union law. \n   \n \nPage 2 of 22  \n \n  \n \n \n \n \n \n \n \nRegulation (EU) 2017/745: Clinical evidence needed for medical devices \npreviously CE marked under Directives 93/42/EEC or 90/385/EEC  \n \nA guide for manufacturers and notified bodies  \n   \n \nPage 3 of 22  \n \n  \nTable of contents  \n1. Definitions ...................................................................................................................................................... 4  \n1.1. Terms defined in MDR Article 2 .................................................................................. 4  \n1.2. Additional terms not defined in MDR Article 2 ............................................................ 4  \n2. Reference documents ............................................................................................................................... 6  \n3. Scope ................................................................................................................................................................ 6  \n4. Introduction and context ......................................................................................................................... 7  \n5. General aspects ............................................................................................................................................ 8  \n6. Guidance on specific aspects of clinical evaluation for legacy devices ........................... 10  \n6.1. Annex XIV Part A Section 1a: Establish or update a clinical evaluation plan .............. 10  \n6.2. Annex XIV Part A Section 1b: Identify available clinical data .................................... 11  \n6.2.1. Pre-market sources of clinical data ...................................................................... 12  \n6.2.2. Post-market sources of clinical data ..................................................................... 12  \n6.3. Annex XIV Part A Section 1c: Appraisal of the clinical data ...................................... 12  \n6.4. Annex XIV Part A Section 1d: Generation of new clinical data .................................. 13  \n6.5. Annex XIV Part A Section 1e: Analysis of the clinical data ........................................ 14  \nAppendix I - Sections of MEDDEV 2.7/1 rev. 4 which are still relevant under the MDR for \nthe application of this guidance ................................................................................................................. 18  \nAppendix II \u2013 Clinical Evaluation Plan for Legacy Devices .............................................................. 19  \nAppendix III \u2013 Suggested hierarchy of clinical evidence for confirmation of conformity \nwith relevant GSPRs under the MDR ........................................................................................................ 20  \n \n \n   \n \nPage 4 of 22  \n \n This guidance document is not legally binding. It has been put together following \ncontribution from national competent authorities, industry and relevant stakeholders and \nit should therefore be recognised as best practice. It also intends to support a harmonised \napproach with respect to clinical data providing sufficient clinical evidence necessary to \ndemonstrate conformity with the relevant General Safety and Performance Requirements \n(GSPR) across European Union Member States. \n \n1. Definitions \n \n1.1. Terms defined in MDR Article 2 \nThe following terms are used as defined in the Medical Device Regulation (EU) 2017/745 \n(MDR): \n\uf0b7 \u2018performance\u2019;1  \n\uf0b7 \u2018risk\u2019;2  \n\uf0b7 \u2018intended purpose\u20193 \n\uf0b7 \u2018benefit-risk determination\u2019;4 \n\uf0b7 \u2018clinical evaluation\u2019;5 \n\uf0b7 \u2018clinical investigation\u2019;6 \n\uf0b7 \u2018clinical data\u2019;7 \n\uf0b7 \u2018clinical evidence\u2019;8  \n\uf0b7 \u2018clinical performance\u2019;9  \nIt should be noted that clinical performance may arise from either \u2018direct or indirect \nmedical effects\u2019 \u2018leading to a clinical benefit for patients\u2019; see comments for \nrelevance to clinical benefit below \n\uf0b7 \u2018clinical benefit\u2019.10  \nIt should be noted that clinical benefits may be either direct or indirect; for example \ndevices such as guidewires may assist other medical devices in achieving their \nintended purpose, without having a direct therapeutic or diagnostic function \nthemselves. \n\uf0b7 \u2018generic device group\u2019.11 \n \n1.2. Additional terms not defined in MDR Article 2 \nAdditional terms which are not explicitly defined in Article 2 of the MDR, but which are \nessential to evaluation of benefit-risk and clinical evaluation conclusions: \n                                                \n \n1 MDR, Article 2(22). \n2 MDR, Article 2(23). \n3 MDR, Article 2(12). \n4 MDR, Article 2(24). \n5 MDR, Article 2(44). \n6 MDR, Article 2(45). \n7 MDR, Article 2(48). \n8 MDR, Article 2(51). \n9 MDR, Article 2(52). \n10 MDR, Article 2(53).  \n11 MDR, Article 2(7).  \n \nPage 5 of 22  \n \n \uf0b7 \u2018legacy devices\u2019: this is considered to include all devices previously CE marked \nunder the European Medical Devices Directive 93/42/EEC (MDD) or Active \nImplantable Medical Devices Directive 90/385/EEC (AIMDD) \n\uf0b7 \u2018well-established technology\u2019: this terminology is used in Article 52(5) and Article \n61(8) of the MDR, but is not defined in these articles. The term is not restricted to \nthe devices listed in Article 61(6b); Article 61(8) explicitly states that this includes \ndevices similar to  the exempted devices listed in Article 61(6b), which might be \nadded to that list in future. The common features of the devices which are well-\nestablished technologies are that they all have: \no relatively simple, common and stable designs with little evolution; \no their generic device group has well-known safety and has not been \nassociated with safety issues in the past;  \no well-known clinical performance characteristics and their generic device \ngroup are standard of care devices where there is little evolution in \nindications and the state of the art; \no a long history on the market. \nTherefore, any devices that meet all these criteria may be considered \u201cwell-\nestablished technologies\u201d. \n\uf0b7 \u2018scientific validity\u2019, \u2018scientifically valid\u2019: this terminology is used in the MDR in \nreference to clinical data planning, evaluation and conclusions12. Clinical \nevaluations must follow a \u201cdefined and methodologically sound procedure\u201d13, for \nwhich expectations of scientific validity are implicit. Embedded in the term \n\u2018scientific validity\u2019 are concepts including adequacy of study design and controls \nfor bias, appropriateness and relevance of research questions, adequacy of \nsample sizes and statistical analyses, completeness of data, adequacy of follow \nup period, and appropriateness of conclusions on the basis of objective evidence. \nSection 9.3.1 of MEDDEV 2.7/1 rev. 4 provides guidance for the evaluation of \nmethodological quality and scientific validity under the MDD/AIMDD which are \nequally valid under the MDR which can be considered to apply when referencing \n\u2018scientific validity\u2019 in this guidance. \n\uf0b7 \u2018level of clinical evidence\u2019:  this terminology is used in the MDR with respect to \nrequirements for demonstration of conformity with the relevant GSPR and overall \nbenefit-risk14. It is understood to encompass the amount and quality of evidence \n(i.e. its characterisation by quality, quantity, completeness and statistical validity, \netc.) required to demonstrate safety, performance and the benefit-risk conclusion \nof a medical device. It should not be confused with the term \u2018levels of evidence\u2019 \n(as used in evidence-based medicine) which is used to rank study designs, and is \nonly a part of the concept \u2018level of clinical evidence\u2019. Regarding the assessment of \nthe level of clinical evidence for the device in question, see sections 6.3 and 6.5d \nof this document. \n\uf0b7 \u2018state of the art\u2019: IMDRF/GRRP WG/N47 provides the following definition: \nDeveloped stage of current technical capability and/or accepted clinical practice in \nregard to products, processes and patient management, based on the relevant \nconsolidated findings of science, technology and experience.  \n                                                \n \n12 MDR Annex XV, Chapter I, Article 2(2.1) and (2.6). \n13 MDR Article 61(3). \n14 MDR Article 61(1), Annex IX section 5.1.   \n \nPage 6 of 22  \n \n Note: The state-of-the-art embodies what is currently and generally accepted as \ngood practice in technology and medicine. The state-of-the-art does not \nnecessarily imply the most technologically advanced solution. The state-of-the-art \ndescribed here is sometimes referred to as the \u201cgenerally acknowledged state-of-\nthe-art \n\uf0b7 \u2018intended use\u2019: The MDR defines \u2018intended purpose\u2019, but not \u2018intended use\u2019. \n\u2018intended use\u2019 should be considered to have the same meaning as \u2018intended \npurpose\u2019.  \n\uf0b7 \u2018indication\u2019, \u2018indication for use\u2019: refers to the clinical condition that is to be \ndiagnosed, prevented, monitored, treated, alleviated, compensated for, replaced, \nmodified or controlled by the medical device. It should be distinguished from \n\u2018intended purpose/intended use\u2019, which describes the effect of a device. All devices \nhave an intended purpose/intended use, but not all devices have an indication (e.g. \nmedical devices with an intended purpose of disinfection or sterilisation of \ndevices). \n\uf0b7 \u2018similar device\u2019: devices belonging to the same generic device group. The MDR \ndefines this as a set of devices having the same or similar intended purposes or a \ncommonality of technology allowing them to be classified in a generic manner not \nreflecting specific characteristics15.  \n    \n2. Reference documents \nThis document provides facilitative guidance to the requirements of MDR Chapter VI and \nAnnex XIV, and references the following MDD/AIMDD guidance documents: \n\uf0b7 MEDDEV 2.7/1 rev. 4: Clinical Evaluation: A Guide for Manufacturers and Notified \nBodies under Directives 93/42/EEC and 90/385/EEC \n\uf0b7 MEDDEV 2.12/2 rev 2: Post Market Clinical Follow-Up Studies: A Guide for \nManufacturers and Notified Bodies \n \n3. Scope \nThis document seeks to provide guidance for clinical data providing sufficient clinical \nevidence necessary to demonstrate conformity with the relevant GSPR, as per Article \n61(1) MDR, for legacy devices CE marked with respect to Directives 93/42/EEC (MDD) \nor 90/385/EEC (AIMDD). \nThis document aims to provide guidance for manufacturers and notified bodies to prepare \nfor the conformity assessment procedure according to the MDR.  \nThis document does not provide comprehensive guidance with respect to the process or \nmethodology relating to clinical evaluation. It is general and not restricted to any particular \ndevice technology or risk class. Following on from the principles described in Section 3 \nhowever, special attention is given to those described in Article 61(6). \n \n                                                \n \n15 MDR, Article 2(7).   \n \nPage 7 of 22  \n \n 4. Introduction and context  \nThis section is intended to provide an introduction and context, and not to modify the \ninterpretation of the MDR. \nMDR Article 61(1) states: \nConfirmation of conformity with relevant general safety and performance \nrequirements set out in Annex I under the normal conditions of the intended use of \nthe device, and the evaluation of the undesirable side-effects and of the \nacceptability of the benefit-risk ratio referred to in Sections 1 and 8 of Annex I, shall \nbe based on clinical data providing sufficient clinical evidence, including where \napplicable relevant data as referred to in Annex III.  \nThe manufacturer shall specify and justify the level of clinical evidence necessary \nto demonstrate conformity with the relevant general safety and performance \nrequirements. That level of clinical evidence shall be appropriate in view of the \ncharacteristics of the device and its intended purpose.  \nTo that end, manufacturers shall plan, conduct and document a clinical evaluation \nin accordance with this Article and Part A of Annex XIV. \n \nMDR Article 61(4) states that clinical investigations shall be performed for Class III and \nimplantable devices, but distinct exemptions from this requirement are identified both in \nthis article and in Articles 61(5) and 61(6). The common theme of these exempted devices \nis that they have been previously marketed (Article 61(6)) or have been demonstrated to \nbe equivalent to devices previously marketed (Article 61(5)).  \nArticle 61(6a and b) further distinguishes between legacy devices (Article 61(6a)) which \nhave been previously marketed under 93/42/EEC or 90/385/EEC and a specific subset \nof well-established technologies (WET) (Article 61(6b)). \nThe following should be noted: \n\uf0b7 all such exemptions from clinical investigations require that the clinical evaluation \nis based on \u201csufficient clinical data\u201d; \n\uf0b7 the basic clinical evaluation requirements for the legacy devices described in \nArticle 61(6a) and the devices of Article 61(6b) are the same: \u201csufficient clinical \ndata\u201d and compliance to common specifications where these exist. The distinction \nbetween the two is that the devices listed in Article 61(6b) are not explicitly required \nto have had prior certification under the Directives to be exempted from the \nrequirement for clinical investigations that otherwise apply to Class III and \nimplantable devices; \n\uf0b7 both the Directives and the MDR require the quantity and quality of clinical data to \nbe sufficient to demonstrate safety, performance and the acceptability of the \nbenefit-risk ratio: both the Directives and the MDR require clinical evidence to be \nsound and the conclusions derived from this evidence to be scientifically valid.  \nArticle 61(10)16 allows for the use of non-clinical data for demonstration of conformity with \nGSPRs: \nWithout prejudice to paragraph 4,where the demonstration of conformity with \ngeneral safety and performance requirements based on clinical data is not deemed \n                                                \n \n16 See MDCG guidance on the CEAR template for notes related to use of Article 61(10).  \n \nPage 8 of 22  \n \n appropriate, adequate justification for any such exception shall be given based on \nthe results of the manufacturer's risk management and on consideration of the \nspecifics of the interaction between the device and the human body, the clinical \nperformance intended and the claims of the manufacturer. \nArticle 61(10) cannot be applied to Class III or implantable devices. In exceptional cases \nArticle 61(10) may be applied for all other device classifications. \n5. General aspects \n\u201cSufficient clinical evidence\u201d is not defined in the MDR. The definition of \u201cclinical evidence\u201d \nitself contains the word \u201dsufficient\u201d but it is related to the amount and quality of the clinical \ndata and the clinical evaluation results which \u201callow a qualified assessment of whether \nthe device is safe and achieves the intended clinical benefits when used as intended by \nthe manufacturer\u201d.17 Sufficient clinical evidence is also mentioned in the MDR Article 61 \nwhere  it is provided that the confirmation of conformity with the relevant GSPR shall be \nbased on sufficient clinical evidence. Therefore, \u201csufficient clinical evidence\u201d is \nunderstood as \u201cthe present result of the qualified assessment which has reached the \nconclusion that the device is safe and achieves the intended benefits\u201d. It is important to \nnote that clinical evaluation is a process where this qualified assessment has to be done \non a continuous basis.  \nCompared to Directives 93/42/EEC and 90/385/EEC, MDR provides greater detail and \nadditional requirements with respect to the process of clinical evaluation, for the purpose \nof confirmation of conformity with relevant GSPR. The generation of clinical data and their \nevaluation providing sufficient clinical evidence is part of a lifecycle approach to medical \ndevices.  \nThe MDR reinforces a number of important factors which are relevant to clinical \nevaluation. This includes: \n\uf0b7 Consideration of available alternative treatment options  is required for the \nconfirmation of the acceptability of the benefit-risk ratio.18 \n\uf0b7 The acceptability of the benefit-risk ratio must be based upon clinical data \nproviding sufficient clinical evidence including where applicable relevant data from \npost-market surveillance.19 \n\uf0b7 The term \u201cclinical evidence\u201d is introduced and the level of clinical evidence  \nmust be specified and justified by the manufacturer, taking the characteristics of \nthe device and the intended purpose into account.20 \n\uf0b7 The incorporation of post market surveillance (PMS) data in particular the \npost-market clinical follow-up (PMCF) data into the process of clinical evaluation.21 \nManufacturers are required to establish a post-market surveillance plan in \naccordance with Annex III of the MDR and the clinical data arising from this PMS \nshall be incorporated into the clinical evaluation. \n\uf0b7 The definition of equivalence is now included in the text of the MDR,22 and the \nprocess to demonstrate equivalence is defined23. \n                                                \n \n17 MDR, Article 2(51).  \n18 MDR, Article 61(3)(c). \n19 MDR, Article 61(1) and Annex III. \n20 MDR, Article 61(1). \n21 MDR, Article 61(1) and (11). \n22 MDR, Annex XIV, Part A, section 3. \n23 MDCG 2020-5 Clinical Evaluation \u2013 Equivalence, A guide for manufacturers and notified bodies.  \n \nPage 9 of 22  \n \n \uf0b7 A definition of \u201cclinical data\u201d  is provided.24 \nWhen it comes to the first MDR conformity assessment of a legacy device the pre-market \nand post-market clinical data generated for the purpose of MDD/AIMDD can be taken into \naccount. As requirements and guidance developed over time, it is not necessarily the \ncase that the clinical data used for conformity assessment under the Directives is clinical \ndata providing sufficient clinical evidence for the purpose of MDR requirements. Legacy \ndevices which have been placed on the market have been subjected to conformity \nassessment and therefore are presumed to have been supported by clinical data25. Post-\nmarket clinical data together with the clinical data generated for the conformity \nassessment under the MDD/AIMDD will be the basis of the clinical evaluation process for \nlegacy devices under the MDR. \nDuring the period of validity of the MDD/AIMDD certificates, the MDR requirements for \nthe PMS apply from the MDR date of application. Legacy devices are therefore not \nexempted from the additional requirements in MDR concerning PMS, including PMCF. \nPMS data and clinical evaluation plans and reports need to be produced and updated. \nThe MDR compliant clinical evaluation for a legacy device must contain the identification \nof available clinical data as well as their appraisal / analysis / evaluation and shall lead to \na demonstration of conformity to the MDR GSPR based on clinical data providing \nsufficient clinical evidence as part of a lifecycle approach. \nThe European Commission guidance MEDDEV 2.12/2 regarding PMCF studies notes \ndifferent instances where a PMCF study may have been justified:26  \n\uf0b7 Route chosen for clinical evaluation : where CE marking for legacy devices was \nbased upon equivalence, PMCF studies may have been necessary. The European \nCommission guidance MEDDEV 2.12/2 regarding PMCF also notes that in the \ncase that clinical evaluation was based exclusively on clinical data from equivalent \ndevices for initial conformity assessment, the certifying notified body shall verify \nthat PMCF studies have been conducted,27 in accordance with the relevant \nprovisions of the Directives.28  \n\uf0b7 Device related factors : There are a number of device-related factors where \nPMCF studies may have been necessary.29 \nWhen assessing the conformity of legacy devices under the MDR, it is important to verify \nwhether PMCF studies considered necessary under the MDD/AIMDD (and where \napplicable, during the transition period, under the MDR), have been appropriately \nconducted, and results are taken fully into account for in the clinical evaluation for the \nconformity assessment under MDR. \nGuidance on the general process of conducting clinical evaluation is also available in the \nMEDDEV 2.7/1 rev. 4. This guidance was written with respect to the MDD and AIMDD to \nprovide practical guidance on several scientific and clinical aspects that are relevant for \nconducting clinical evaluation. However only the text of the MDR is authentic in law, \nsections relevant to the MDR are listed in Appendix I to this document. \n                                                \n \n24 MDR, Article 2(48). \n25 Except where non-clinical testing were demonstrated to be adequate (MDD, Annex X, 1.1(d); AIMD, Annex 7, 1.5). \n26 MEDDEV 2.12/2, section 5 https://ec.europa.eu/growth/sectors/medical-devices/current-directives/guidance_en   \n27 MEDDEV 2.12/2, section 8. \n28 Annex II.4, Annex II.7, Annex III, Annex V.6 and Annex VI.6 of Directive 93/42/EEC and Annex II.4, Annex II.7, Annex III and Annex \nV.6 of Directive 90/385/EEC. \n29 MEDDEV 2.12/2, section 5.  \n \nPage 10 of 22  \n \n 6. Guidance on specific aspects of clinical evaluation for legacy devices \nSections 6.1 \u2013 6.5 below provide guidance on each stage of the clinical evaluation \nprocess of MDR Annex XIV Part A Section 1. \n6.1. Annex XIV Part A Section 1a: Establish or update a clinical evaluation plan30 \nManufacturers are required to document a clinical evaluation plan to meet the \nrequirements of MDR Annex XIV Section 1a.  \nPremarket elements of the plan as described in the final indent of MDR Annex XIV Section \n1a (first-in-man studies, feasibility and pilot studies) are not generally relevant to legacy \ndevices which are unchanged in design or indications. However, the context for the plan \nas described in indents 1-7 and the basis for the PMCF as described in indent 8 of MDR \nAnnex XIV Section 1a are considered relevant and necessary for demonstration of \ncompliance to the MDR.  Appendix II of this guidance document suggests a minimum \ncontent for clinical evaluation plans for legacy devices. Further advice regarding specific \nsub-indents of MDR Annex XIV Section 1a are provided below. \na. Identification of the relevant GSPRs (indent 1 of MDR Annex XIV Section 1a): \nclinical evaluation planning under the Directives required an identification of the \nrelevant Essential Requirements (ER) for which demonstration of conformity \nrequired clinical data. The manufacturer should conduct an analysis with respect \nto the GSPRs of the MDR, to determine if additional data to support the clinical \nevidence are required to meet additional MDR requirements. This could be \nachieved either through a gap analysis with respect to new MDR requirements, or \nby creation of an entirely new analysis for the MDR. As noted in Section 3, Article \n61(10) cannot be applied to Class III or implantable devices, but may be applied \nto some or all requirements for confirmation of conformity with relevant GSPRs for \nall other device classifications if adequately justified. \nb. Specification of the intended purpose, target groups, indications, contraindications \n(indents 2-3 of MDR Annex XIV Section 1a):  Appendix A3 of MEDDEV 2.7/1 rev. \n4 lists additional information to Annex II of the MDR about device description that \ncan be relevant for planning clinical evaluations. The manufacturer needs to \nensure that inputs for the clinical evaluation plan are in line with the device\u2019s \u201clabel, \ninstructions for use, promotional or sales materials or statements\u201d31 and with the \ndevice\u2019s updated risk management documents.  \nc. Detailed description of intended clinical benefits with relevant and specified clinical \noutcome parameters (indent 4 of MDR Annex XIV Section 1a): MEDDEV 2.7/1 rev. \n4 Appendix A7.2 Section b provides relevant additional information with respect to \nthe definition of clinical benefits. MEDDEV 2.7/1 rev. 4 Appendix A7.2 Section c \nprovides relevant information with respect to the quantification of benefits and \ndetermination of relevant outcome parameters, which may be useful for clinical \nevaluation planning.   \nd. Specification of qualitative and quantitative aspects of clinical safety and \nperformance (indents 5-7 of MDR Annex XIV Section 1a): The level of clinical \nevidence required for the device under evaluation needs to be determined by the \nmanufacturer and verified by the notified body. The level of clinical evidence shall \n                                                \n \n30 MDR, Annex XIV, Part A, section 1.  \n31 MDR, Article 2 (12).  \n \nPage 11 of 22  \n \n be appropriate in view of the characteristics of the device and its intended \npurpose.32  \nThe proposed level of clinical evidence should take into account the specification \nof methods to be used for examination of qualitative and quantitative aspects of \nclinical performance and clinical safety with clear reference to the determination of \nresidual risks and side-effects. MEDDEV 2.7/1 rev. 4 appendix A6 describes \nexamples of studies that lack scientific validity for the demonstration of adequate \nclinical performance and/or clinical safety. MEDDEV 2.7/1 rev. 4 section 9.3.2 also \nprovides relevant guidance. It also has to take into account the intended clinical \nbenefits to patients with relevant and specified clinical outcome parameters as well \nas  an indicative list and specification of parameters to be used to determine, based \non the state of the art in medicine, the acceptability of the benefit-risk ratio for the \nvarious indications and for the intended purpose or purposes of the device.33 \nFor medical devices which have been subject to conformity assessment according \nto Directives, it should be possible to provide a clear justification for the level of \nclinical evidence required to reach a demonstration of conformity based on clinical \ndata providing sufficient clinical evidence at the end of the data analysis stage. \nManufacturers should identify benefits and risks of the device under evaluation, \ntake into account available alternative treatment options and a clinical assessment \nof residual risks associated with the device before justifying the level of clinical \nevidence. As an outcome of this step, it should be possible to conclude if the device \nis one which has a clearly positive benefit\u2013risk determination, when alternatives \nare considered, or a marginal one. Special attention is required, with respect to \ndevices with a marginal benefit-risk, at both the stage of initial conformity \nassessment and when designing the post-market surveillance or clinical follow-up \nof the device. \nAccording to the MDR, parameters to be used to \u201c determine\u2026. the acceptability of \nthe benefit-risk ratio for the various indications and for the intended purpose or \npurposes of the device\u201d  need to be based on the state of the art in medicine.34 \nSection 8.2. of MEDDEV 2.7/1 rev. 4 indicates how data on the current state of the \nart in medicine can be identified. \n6.2. Annex XIV Part A Section 1b: Identify available clinical data35  \nIt is important to identify all available sources of clinical data from both the pre-market \nand post-market phases. This will include all of the clinical data which is generated and \nheld by the manufacturer as well as clinical data for equivalent or similar devices36. \nClinical data is defined in the MDR and the sources of data are specified in Article 2(48). \nSections 6.2.1 and 6.2.3 below provide additional guidance with respect to the use of \nthese data sources for legacy devices. \nIt should be noted that, apart from devices for which Article 61(10) may be applied, the \nMDR requires confirmation of conformity with the relevant GSPRs to be based on clinical \ndata as defined in Article 2(48). However, other types of data may provide supportive or \nclarifying information: this may include data derived through evaluation of state of the art, \n                                                \n \n32 MDR, Article 61(1). \n33 MDR, Annex XIV, Part A, section 1 (a) 5th indent. \n34 MDR, Annex XIV, Part A, section 1.  \n35 Guidance with respect to identification of clinical data is provided in section 8 and Appendix A4 and A5 of MEDDEV 2.7/1 rev. 4. \n36 Section 5, MDCG 2020-05 Clinical Evaluation \u2013 Equivalence, A guide for manufacturers and notified bodies.  \n \nPage 12 of 22  \n \n evaluation of clinical data for similar devices (as described in Section 1.2 of this \ndocument), usability or simulated use testing, etc. A summary of considerations related \nto use of clinical and non-clinical data sources is provided in Appendix III of this document. \n6.2.1. Pre-market sources of clinical data \nFor the purpose of legacy devices, pre-market sources of clinical data may include: \n\uf0b7 Clinical investigation reports of the device concerned; \n\uf0b7 Clinical investigation reports or other studies reported in scientific literature, of a \ndevice for which equivalence to the device in question can be demonstrated in \naccordance with the MDR; \n\uf0b7 Reports published in peer reviewed scientific literature on other clinical experience of \neither the device in question or a device for which equivalence to the device in \nquestion can be demonstrated; \n\uf0b7 Other pre-market data, e.g. case reports on experience with the use of the device in \nquestion, such as compassionate or humanitarian exceptional use reports. Note that \nthis kind of pre-market data may be more prone to bias, compared to those listed \nabove. \nIt should be noted that MDR Article 2(48) provides a narrower definition of what \nconstitutes clinical data sources as compared to the Directives which allow unpublished \nreports on other clinical experience to contribute to the clinical evaluation. Such data \nsources may provide informative context for the clinical evaluation of legacy devices. \n6.2.2. Post-market sources of clinical data \nPost-market sources of clinical data refer to data collected following the initial CE marking \nunder the Directives (or prior to introduction of a new indication or design variant). This \nmay include: \n\uf0b7 PMS clinical data, complaint and incident reports; \n\uf0b7 PMCF studies, including post-market clinical investigations; \n\uf0b7 Independent clinical studies conducted using the device37; \n\uf0b7 Device registries;  \n\uf0b7 Data retrieved from the literature. \nFor well-established technologies the clinical evaluation can be based on data coming \nfrom similar devices, under the conditions detailed in paragraph 6.5 (e). With respect to \nlegacy devices, when clinical data from equivalent devices is used, equivalence must be \ndemonstrated according to the requirements of the MDR.38,39 \n6.3. Annex XIV Part A Section 1c: Appraisal of the clinical data \nThe clinical data sets should be subject to an appraisal with respect to their relative \ncontribution to the overall clinical evaluation. It is important to perform analysis of the \nmethodological quality of data obtained from different sources to identify and assess the \nlevel of evidence, bias, other inherent weakness or other possible shortcomings. \nClinical investigations, other sources of clinical data and post-market sources of clinical \ndata can be of variable methodological quality and therefore an appraisal of the design of \n                                                \n \n37 Including for example devices used during clinical trials of pharmaceutical substances, or accessories to other medical devices, \nwhere the device is clearly identified. \n38 MDR, Annex XIV and Article 2(48). \n39 MDCG 2020-5 Clinical Evaluation \u2013 Equivalence, A guide for manufacturers and notified bodies.   \n \nPage 13 of 22  \n \n these studies is important. Examples of studies that lack scientific validity for \ndemonstration of adequate clinical performance and / or clinical safety can be found in \nAppendix A6 General principles of clinical evaluation of MEDDEV 2.7/1 rev. 4. The use \nof vigilance data, in general is appropriate for identification of any new risks, events in \nsubpopulations, examining trends in PMS reports etc. With respect to the utilisation of \npost-market surveillance data for the purpose of conformity assessment, it is important to \nrecognise that uncontrolled sources of clinical data \u2013 for example complaint or incident \nreport data \u2013 cannot always provide reliable data with respect to the incidence of risks \nand cannot provide an estimate of uncertainty i.e. a confidence interval. Due to limitations \nof complaints reporting, the use of estimates such as [number of incidents or complaints] \n/ [number of device sales] cannot generally be considered sufficient to provide proof of \nsafety; their use should be limited to cases where data from pre-market or post-market \nclinical investigations or PMCF studies are not deemed appropriate. \nAdditional information on the use of information derived from vigilance data, device \nregistry data, case series, patient dossiers and other use data can be found in section \n9.3.1 (c) of MEDDEV 2.7/1 rev. 4. \nClinical data appraisal should be conducted using verified/validated assessment tools. \nExamples include methodological quality assessment tools developed by medical \nresearchers and scientists to assess published clinical data such as Appendix F of IMDRF \nMDCE WG/N56 on Clinical Evaluation, Cochrane Collaboration\u2019s tool for Randomized \nControlled Trials (RTC), MINORS (Methodological index for non-randomized studies), \nReisch tool (for non-randomized interventional studies), Newcastle-Ottawa Scale (NOS) \nfor assessing the quality of nonrandomised studies in meta-analyses. Their detailed \ndescription, the inclusive list of major components of each tool is included in the paper by \nZeng X, Zhang Y, Kwong JS et al. \u201cThe methodological quality assessment tools for \npreclinical and clinical studies, systematic review and meta-analysis, and clinical practice \nguideline: a systematic review\u201d40. This list is not exhaustive. Additional validated tools \nmay become available in the future. \n6.4. Annex XIV Part A Section 1d: Generation of new clinical data \nLegacy devices following the MEDDEV 2.12/2 guidance for PMCF should normally have \ncollected data on the devices themselves in the post-market phase. In the event that the \npostmarket data on the device itself (including PMCF) is not adequately comprehensive \nto provide sufficient clinical evidence, and the demonstration of equivalence is no longer \npossible under the definition of equivalence in the MDR, new data may need to be \ngenerated prior to CE-marking under the MDR.  \nIn general, there shall be sufficient clinical evidence to confirm safety, performance and \nthe acceptability of the benefit-risk determination in relation to the state of the art for the \nlegacy devices prior to CE-marking under the MDR, and such demonstration should not \nrely on new PMCF studies started under the MDR to bridge gaps (e.g. indications not \nsupported by clinical evidence). Where other evidence, for example results of pre-clinical \ntesting etc. as described in MDR Article 61(10), is used for confirmation of safety and \nperformance, PMCF studies may be undertaken to confirm these conclusions. \n                                                \n \n40 J Evid Based Med. 2015 Feb;8(1):2-10. doi: 10.1111/jebm.12141. Review. https://www.ncbi.nlm.nih.gov/pubmed/25594108   \n \nPage 14 of 22  \n \n 6.5. Annex XIV Part A Section 1e: Analysis of the clinical data \nThe aim of this stage is the determination if all clinical data collected and appraised, as \ndescribed in previous stages, demonstrate together conformity with relevant GSPR. In \norder to determine the benefit-risk ratio, it is necessary to identify the benefits and risks \nassociated with the device and the alternatives (if any). Practical guidance is available in \nsection 10 of MEDDEV 2.7/1 rev. 4.41  \nDemonstration of compliance with the GSPR, relevant for the device in question have to \nbe based on: \n\uf0b7 The usage of reliable, justified and sound analytical methods (where applicable \nqualitative, quantitative, or both);  \n\uf0b7 Results of performed comprehensive analysis; \n\uf0b7 Identification of any missing data and/or gaps; \n\uf0b7 Determination of PMCF needs.    \n \na. Clinical benefits \nClinical benefit means \u201cthe positive impact of a device on the health of an individual, \nexpressed in terms of a meaningful, measurable, patient-relevant clinical outcome(s), \nincluding outcome(s) related to diagnosis, or a positive impact on patient management or \npublic health\u201d.42 The type of clinical benefit associated with a device depends upon the \ndevice under evaluation and its intended purpose. Examples of clinical benefits and their \nquantification can be found in Appendix A7.2 letters (b) and (c) of MEDDEV 2.7/1 rev. 4. \nIt should be noted that while direct clinical benefits should be supported by clinical data, \nindirect clinical benefits may be demonstrable by other evidence such as: \n\uf0b7 pre-clinical and bench test data (eg compliance to product standards or common \nspecifications); \n\uf0b7 real world data such as registries, information deriving from insurance database \nrecords, etc; \n\uf0b7 data from another device that is used with the subject device which does have \ndirect clinical data (eg, data from a stent used to justify safety and performance of \na guidewire).  \nA determination of the level of clinical evidence required to demonstrate an indirect clinical \nbenefit should be made on the basis of a thorough risk assessment and evaluation of \nshort, medium and long term clinical risks (for example, a guidewire, although used \ntransiently, may have long term clinical risks if it leads to vessel dissection). \n \nb. Risks \nRisk means the combination of the probability of occurrence of harm and the severity of \nthat harm.43 The MDR requires manufacturers to establish, document, implement and \nmaintain a system for risk management.44 The standard ISO 1497145 provides such a \nprocess for managing risks associated with medical devices, as part of an ongoing, \n                                                \n \n41 This chapter includes references to the MDD, MDR requirements should be used instead, ie. reference to \u2018Essential requirements\u2019 \nshould be replaced by GSPR and reference to PMCF should be replaced by the relevant MDR requirements, i.e. in Annex XIV, part B.  \n42 MDR, Article 2(53). \n43 MDR, Article 2(23). \n44 MDR, Article 10(2). \n45 Medical devices \u2014 Application of risk management to medical devices.  \n \nPage 15 of 22  \n \n lifecycle approach. The Annex I of the MDR require that manufacturers reduce risks as \nfar as possible, and to do this, manufacturers must estimate and evaluate the risks \nassociated with, and occurring during, the intended use and during reasonably \nforeseeable misuse.46 \nThe determination as to which risks require the generation of clinical data to support either \nthe probability and severity of a particular harm, or the effectiveness of a risk control \nmeasure, is one which must be reached upon a case by case basis,47 and the decision \nas to when it is necessary to generate further clinical data is not addressed by ISO 14971 \nand should be an output of the process of clinical evaluation. \nConsiderations on aspects of risk evaluation, and considerations on the number of \npatients needed to obtain sufficient data can be found in Appendix A7 of MEDDEV 2.7/1 \nrev. 4. \n \nc. Benefit-risk determination, state of the art, alternative treatment options \nThe MDR requires that any risks which may be associated with the use of the device are \n\u201ccompatible with a high level of protection of health and safety, taking into account the \ngenerally acknowledged state of the art\u201d48 and that the determination of the acceptability \nof the benefit-risk ratio is \u201c based on the state of the art in medicine \u201d.49  \nIt is important to remember that a medical device may be used for an indication for which \nthere are many alternative medical options. This may include the use of medicinal \nproducts, other medical devices, other medical or allied health professional interventions, \na combination of any of these or no intervention. As such, in order to determine a benefit-\nrisk ratio, up-to-date alternatives must be considered for legacy devices. The \nappropriateness and relevance of an alternative treatment option depends upon a wide \nrange of factors, including the nature of the healthcare system and patient preferences. \nTo help to describe alternatives, it is necessary to describe the \u2018state of the art\u2019 for the \ntreatment of the indicated clinical condition taking alternative treatments into account. The \nstate of the art in this context can be taken to mean the generally accepted most effective \ntreatment option, for the intended purpose relevant to the device under consideration. \nOccasionally, this may be subject to differences of opinion between clinical evaluators as \nto what is the state of the art, and where such differences exist, these should be described \nand taken into account insofar as is possible. In such cases, a thorough evaluation of the \nresults from published clinical studies of high methodological quality shall be taken into \naccount. Moreover, where applicable, particular attention shall be paid to therapy \nguidelines grounded on principles of evidence based medicine. Novel and innovative \ndevice technology may be subject to a rapidly evolving state of the art for a particular \nindication, and where this exists, it should also be noted. \nAspects that influence the acceptability of benefits and risks can be found in Appendix \nA7.2 letter (e) and in Appendix A7.4 of MEDDEV 2.7/1 rev. 4. \n \n                                                \n \n46 MDR, Annex I, Chapter 1, section 3(c). \n47 ISO14971:2007, page v, notes that an individual\u2019s perception of risk can depend upon a range of factors including their cultural \nbackground, the socio-economic and educational background of the society concerned, the actual and perceived state of health of \nthe patient, and many other factors. \n48 MDR, Annex I, Chapter 1, Section 1. \n49 MDR, Annex XIV, Part A, Section 1(a).   \n \nPage 16 of 22  \n \n d. The level of clinical evidence available to demonstrate conformity based on clinical \ndata providing sufficient clinical evidence \nThe MDR requires that the level of clinical evidence is justified and specified by the \nmanufacturer. The required level of clinical evidence has to be identified, specified and \njustified by the manufacturer during the clinical evaluation process. This level has to be \nappropriate to demonstrate conformity with the relevant GSPR.  \nTo reach a determination of sufficiency, when considering the available level of clinical \nevidence, the manufacturer may use widely available and validated tools when examining \nclinical data. These tools are methodological quality assessment tools developed by \nmedical researchers and scientists to assess published clinical data.50 Examples of these \ntools include the Cochrane Collaboration\u00b4s tool for RCT or NOS checklist for analytical \nstudies (see Footnote 40). See MEDDEV 2.7.1 rev 4, Section 9.3.2 \u2018How to determine \nthe relevance of a data set for the clinical evaluation\u2019, for further information. \n \ne. Lack of clinical data providing sufficient clinical evidence  \nManufacturers should conduct a gap analysis with respect to the MDR requirements. If \ndata gaps have been identified, there are different possibilities to bridge those gaps.    \nWhile controlled clinical investigations might be the preferred method for collecting clinical \ndata as part of the PMCF studies for some products, there are other possibilities to gather \nrelevant clinical data in the field in order to close the clinical data gap. Other alternatives \ninclude, but are not limited to systematic reviews of clinical data published in the literature, \nevaluation of results from PMCF studies such as clinically relevant scientifically sound \nquestionnaires51 or registries. Scientifically sound studies will normally include (note, this \nis not a complete list): \n\uf0b7 Clearly stated research question(s), objective(s) and related endpoints; \n\uf0b7 An evaluation of potential sources of bias or study distortion, and the impact of \nthese factors on the potential validity of results; \n\uf0b7 Design with an appropriate rationale and statistical analysis plan; \n\uf0b7 A plan for an analysis of the data and for drawing appropriate conclusion(s). \nIf there is not sufficient supportive clinical evidence with regard to the declared intended \npurpose52 including the indications and claims as appropriate, manufacturers shall narrow \nthe intended purpose of the device under evaluation until it is supported by the available \nclinical evidence. \nAs noted in Section 4, some legacy devices may have limited clinical data, particularly if \nthey were marketed prior to the publication of the Directives. In some cases, it may be \nnecessary for the manufacturer to undertake PMCF to generate new data for these legacy \ndevices prior to CE marking under the MDR, whereas in other cases, particularly for low \nrisk standard of care devices where there is little evolution in the state of the art, it may \nbe possible to demonstrate conformity with the relevant GSPRs with a more limited \nclinical data set. \nDevices previously certified under the Directives might not be considered to have \nsufficient clinical data for certification under the MDR. Reasons may include: \n                                                \n \n50 The suggested tools may also be relevant for unpublished data. \n51 Clinically relevant and where possible validated.  \n52 MDR, Article 2(12).  \n \nPage 17 of 22  \n \n \uf0b7 changes in the state of the art  \n\uf0b7 data arising from PMS may identify new risks or provide additional clarity with \nrespect to indications and contraindications  \n\uf0b7 devices previously certified under Quality System annexes of the Directive may \nnot have been sampled prior to an application for MDR certification, and the \nclinical evidence therefore not subject to Notified Body scrutiny \n\uf0b7 the MDR introduces new requirements on the use of equivalence, which may \nreduce the overall volume of data available for demonstration of conformity with \nthe relevant GSPRs \n\uf0b7 the MDR has a more explicit definition of what constitutes clinical data, which may \nremove some data sources previously used \nAlthough the Directives indicate that data shall be collected in the post-market phase for \nall devices53, in practise the data collected may not meet MDR criteria, if the devices were \nconsidered standard of care and were not associated with safety concerns. Stable, well-\nestablished technologies that perform as intended and are not associated with safety \nconcerns, and where there has been no innovation, are less likely to be the subject of \nresearch, and therefore literature data may be limited or non-existent. In some cases, it \nmay be necessary for the manufacturer to undertake PMCF to generate new clinical data \nfor these devices prior to certification under the MDR, even if they are well-established \nand have been on the market for several decades, to enable an evaluation of their safety \nand clinical performance in relation to an evolving state of the art.  \nIn exceptional cases, particularly for low risk standard of care devices where there is little \nevolution in the state of the art, and the device is identified as belonging to the group of \n\u2018well-established technologies\u2019 (see section 1.2 and Appendix III in this document) a lower \nlevel of clinical evidence may be justified to be sufficient for the confirmation of conformity \nwith relevant GSPRs. This may be supported by clinical data from the PMS provided that \nthere has been a quality management system in place to systematically collect and \nanalyse any complaints and incident reports, and that the collected data support the \nsafety and performance of the device. \n \n                                                \n \n53 MDD, Annex II(3.1) indent 7, Annex IV(3), Annex V(3.1) indent 8, Annex VI(3.1) indent 8, Annex VII(4).  \n \nPage 18 of 22  \n \n Appendix I - Sections of MEDDEV 2.7/1 rev. 4 which are still relevant under the MDR \nfor the application of this guidance \n \nThe identified sections of MEDDEV 2.7/1 rev. 4 are considered relevant to MDR as they \ncontain helpful information regarding how to perform activities associated with clinical \nevaluation: \n\uf0b7 6.4. Who should perform the clinical evaluation? \n\uf0b7 8. Identification of pertinent data (Stage 1) \n\uf0b7 9. Appraisal of pertinent data (Stage 2) \n\uf0b7 10. Analysis of the clinical data (Stage 3). This chapter includes references to the \nMDD, MDR requirements should be used instead \n\uf0b7 A3. Device description - typical contents \n\uf0b7 A4. Sources of literature \n\uf0b7 A5. Literature search and literature review protocol, key elements \n\uf0b7 A6. Appraisal of clinical data - examples of studies that lack scientific validity for \ndemonstration of adequate clinical performance and/or clinical safety \n\uf0b7 A7.2. Conformity assessment with requirement on acceptable benefit/risk profile \n\uf0b7 A7.3. Conformity assessment with requirement on performance \n\uf0b7 A7.4. Conformity assessment with requirements on acceptability of undesirable \nside-effects \n\uf0b7 A10. Proposed checklist for the release of the clinical evaluation report. \n   \n \nPage 19 of 22  \n \n Appendix II \u2013 Clinical Evaluation Plan for Legacy Devices54 \nA modified Clinical Evaluation Plan for legacy devices should include at least:55 \n\uf0b7 An identification of the GSPR that require support from relevant clinical data.   \n\uf0b7 A specification of the intended purpose of the device.56 \n\uf0b7 A clear specification of intended target groups with clear indications and contra-\nindications.   \n\uf0b7 A detailed description of intended clinical benefits to patients with relevant and \nspecified clinical outcome parameters. \n\uf0b7 A strategy to identify, analyse and assess alternative treatments57.  \n\uf0b7 A specification of methods to be used for examination of qualitative and \nquantitative aspects of clinical safety with clear reference to the determination of \nresidual risks and side-effects; \n\uf0b7 An indicative list and specification of parameters to be used to determine, based \non the state of the art in medicine, the acceptability of the benefit-risk ratio for the \nvarious indications and for the intended purpose or purposes of the device.  \n\uf0b7 An indication how benefit-risk issues relating to specific components such as use \nof pharmaceutical, non- viable animal or human tissues, are to be addressed.  \n\uf0b7 A strategy and methodology to identify, analyse and appraise all relevant available \nclinical data in light of the changed definition for clinical data. \n\uf0b7 Evidence for equivalence, if clinical data from an equivalent device is included in \nthe clinical evaluation. \n\uf0b7 A definition of the required level of clinical evidence, which shall be appropriate in \nview of the characteristics of the device and its intended purpose.58 59 60 \n\uf0b7 A strategy and methodology to systematically collect, summarise and assess post \nmarket surveillance data to demonstrate continuing safety and performance, and \nto what extent complaints with regards to safety and performance have been \nobserved with the legacy devices.61  \n                                                \n \n54 MDR, Annex VII, 4.11. \n55 Appendix A3 of MEDDEV 2.7/1 rev. 4 lists information that can be relevant for planning clinical evaluations. The manufacturer needs \nto make sure that input for the clinical evaluation plan are in line with the device\u2019s \u201clabel, instructions for use, promotional or sales \nmaterials or statements\u201d and with the device\u2019s updated risk management documents. \n56 In order to fully identify the intended purpose(s) of a legacy device, the manufacturer needs to consider the data that is foreseen on \nthe label, in the instructions for use or in promotional or sales materials or statements that are foreseen for the device. Typical elements \nof the intended purpose can be found in Appendix A3 of MEDDEV 2.7/1 rev. 4. \n57 MDR, Article 61(3)(c). \n58 MDR, Article 61(1). \n59 The proposed level of clinical evidence should take into account the specification of methods to be used for examination of qualitative \nand quantitative aspects of clinical safety with clear reference to the determination of residual risks and side-effects. \n60 To determine the level of clinical evidence it is necessary to identify benefits and risks of the device under evaluation and to take \ninto account available alternative treatment options, and a clinical assessment of failure modes associated with the device. \n61 MDR Article 83 and MDR Annex III.   \n \nPage 20 of 22  \n \n Appendix III \u2013 Suggested hierarchy of clinical evidence for confirmation of \nconformity with relevant GSPRs under the MDR \nSources of pre- and post- market clinical data are described in Sections 6.2.1 and 6.2.2 \nof this document. Reference is also made to clinical evidence which may provide \ncontextual, supportive or clarifying information for demonstration of conformity with the \nrelevant GSPRs. A suggested hierarchy of evidence and considerations to apply is \nprovided in the table below, ranked roughly in order from strongest to weakest (some \nvariations may apply dependent on the device, GSPR for which evidence is required, and \nquality of individual data sources): \nRank Types of clinical data and \nevidence Considerations / comments \n1 Results of high quality62 \nclinical investigations \ncovering all device variants, \nindications, patient \npopulations, duration of \ntreatment effect, etc This may not feasible or necessary for certain \nwell-established devices with broad indications \n(eg Class IIb legacy sutures, which could be \nused in every conceivable patient population) \n2 Results of high quality \nclinical investigations with \nsome gaps  Gaps must be justified / addressed with other \nevidence in line with an appropriate risk \nassessment, and clinical safety, performance, \nbenefit and device claims. \nAssuming the gaps can be justified, there should \nbe an appropriate PMCF plan to address \nresidual risks.  \nOtherwise, manufacturers shall narrow the \nintended purpose of the device until sufficient \nclinical data has also been generated. \n3 Outcomes from high quality \nclinical data collection \nsystems such as registries63 Is there sufficient evidence of the quality of the \ndata collected by the registry64, 65? \nAre the devices adequately represented? \nAre the data appropriately stratified? \nAre the endpoints appropriate to the safety, \nperformances and endpoints identified in the \nclinical evaluation plan? \n4 Outcomes from studies with \npotential methodological \nflaws but where data can still \nbe quantified and \nacceptability justified66 Many literature sources fall into this category, \ndue to limitations such as missing information, \npublication bias, time lag bias, etc. This applies \nequally to publications in the peer-reviewed \nscientific literature. However, for legacy devices \n                                                \n \n62 Refer to data appraisal considerations described in Section 6.3 of this guidance. \n63 Please note that the Considerations / Comments listed in point 2 also apply to these studies.  \n64 http://www.imdrf.org/docs/imdrf/final/technical/imdrf-tech-170316-methodological-principles.pdf   \n65 http://www.imdrf.org/docs/imdrf/final/technical/imdrf-tech-160930-principles-system-registries.pdf   \n66 Please note that the Considerations / Comments listed in point 2 also apply to these studies.  \n \nPage 21 of 22  \n \n where no safety or performance concerns have \nbeen identified, these sources can be sufficient \nfor confirmation of conformity to the relevant \nGSPRs if appropriately appraised and the gaps \nare identified and handled.  \nHigh quality surveys may also fall into this \ncategory. \nClass III legacy devices and implantable legacy devices which are not well-established \ntechnologies should have sufficient clinical data as a minimum at level 4. Those devices \nwhich are well-established technologies may be able to confirm conformity with the \nrelevant GSPRs via an evaluation of cumulative evidence from additional sources as \nlisted below. Reliance solely on complaints and vigilance is not sufficient. \n5 Equivalence data (reliable / \nquantifiable) Equivalence must meet MDR criteria.  \nIt is normally expected that manufacturers \nshould gather data on their own devices in the \npost-market phase, therefore reliance on \nequivalence should be duly justified, and linked \nto appropriate PMCF or proactive PMS. \n6 Evaluation of state of the art, \nincluding evaluation of \nclinical data from similar \ndevices as defined in \nSection 1.2 of this document  This is not considered clinical data under the \nMDR, but for well-established technologies only \ncan be considered supportive of confirmation of \nconformity to the relevant GSPRs. \nData from similar devices may be also important \nto establish whether the device under evaluation \nand similar devices belong to the group of \ndevices considered as \u201cwell established \ntechnologies\u201d (WET). See section 1.2 in this \ndocument for the criteria for WET. Data from \nsimilar devices may be used, for example, to \ndemonstrate ubiquity of design, lack of novelty, \nknown safety and performance profile of a \ngeneric group of devices, etc. \n7 Complaints and vigilance \ndata; curated data This falls within the definition of clinical data \nunder MDR Article 2(48), but is not generally \nconsidered a high quality source of data due to \nlimitations in reporting. It may be useful for \nidentifying safety trends or performance issues. \nHigh volume data collected within a robust \nquality system may provide supportive evidence \nof device safety. \n8 Proactive PMS data, such \nas that derived from surveys  This falls within the definition of clinical data \nunder MDR Article 2(48), but is not generally \nconsidered a high quality source of data due \nlimitations associated with sources of bias and \nquality of data collection. It may be useful for  \n \nPage 22 of 22  \n \n identifying safety concerns or performance \nissues. \n9 Individual case reports on \nthe subject device This falls within the definition of clinical data \nunder MDR Article 2(48), but is not considered a \nhigh quality source of data due to limitations in \ngeneralising findings to a wider patient \npopulation, reporting bias, etc. It may provide \nsupportive or illustrative information with respect \nto specific claims. \n10 Compliance to non-clinical \nelements of common \nspecifications considered \nrelevant to device safety and \nperformance  Common specifications which address clinical \ninvestigation or data requirements directly would \nrank higher in this hierarchy. Common \nspecifications may address clinically relevant \nendpoints through non-clinical evidence such as \nmechanical testing for strength and endurance, \nbiological safety, usability, etc. \n11 Simulated use / animal / \ncadaveric testing involving \nhealthcare professionals or \nother end users67 This is not clinical data, but may be considered \nevidence of confirmation of conformity to \nrelevant GSPRs, particularly in terms of \nusability, such as for accessories or instruments.  \n12 Pre-clinical and bench \ntesting / compliance to \nstandards62 Pre-clinical and bench testing may address \nclinically relevant endpoints through non-clinical \nevidence such as mechanical testing for \nstrength and endurance, biological safety, \nusability, etc. \n \n                                                \n \n67 This may be of interest in the case of application of Article 61(10)."}, {"title": "mdcg_clinical_evaluationtemplate_en.pdf.txt", "text": "Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n0 \n   \n \n \n \n \n \n \nMDCG 2020-13 \n  \nClinical evaluation assessment report template   \n \nJuly 2020 \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) established \nby Article 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member States and a representative of the European Commission chairs it. The document is not a European Commission document and it cannot be regarded as reflecting the official position of the European Commission. Any views expressed in this document are not legally binding and only the Court of Justice of the European Union can give binding interpretations of Union law. \n  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n1 \n  \nContents \n \nIntroduction ............................................................................................................................... ....... 3  \nScope ......................................................................................................................... ..................... 3  \nApproach to Template .......................................................................................................... ........... 4  \nTemplate CEAR ................................................................................................................. ............. 6  \nSection A: Administrative particulars (notified body, manufacturer, product and clinical \nevaluation report reference) .................................................................................................. ....... 6  \nSection B: Reviewers involved in the notified body assessment of the clinical evaluation ........... 7  \nSection C: Device description, classification, clinical evaluation plan, information materials \nsupplied by the manufacturer, common specifications and harmonised standards applied, equivalence and state of the art .............................................................................................. ..... 8\n \nSection D: Clinical literature review.......................................................................................... .. 15  \nSection E: Clinical investigations and related documentation .................................................... 18  \nSection F: PMS, PMCF and the plan for updates ...................................................................... 20  \nSection G: IFU, SSCP, labelling and other information supplied with the device ....................... 21  \nOverall Conc lusions: .......................................................................................................... ........ 24  \nSpecific Considerations ....................................................................................................... .......... 25  \nSection I: Clinical evaluation c onsultation procedure for certain class III and class IIb devices \n(Article 54) .................................................................................................................. ............... 25  \nSection J: Where demonstration of conformity based on clinical data is not deemed appropriate \n(Article 61(10)) .............................................................................................................. ............. 28  \nSection K: The voluntary clinical consultation on the clinical development strategy (Article 61(2))\n .............................................................................................................................. ..................... 30  \n \n \n  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n2 \n  \nList of acronyms \nCEAR   Clinical Evaluation Assessment Report \nCECP   Clinical Evaluation Consultation Procedure CER   Clinical Evaluation Report CIP   Clinical Investigation Plan EUDAMED  European Databank on Medical Devices IFU   Instructions for Use MDR   Medical Device Regulation (Regulation (EU) 2017/745 on me dical devices) \nPMCF   Post-Market Clinical Follow-up PMS   Post-Market Surveillance PSUR   Post-Market Surveillance Update Report \nSRN   Single Registration Number \nSSCP   Summary of Safety and Clinical Performance  TDAR   Technical Documentation Assessment Report  UDI-DI   Unique Device Identification Device Identifier \n  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n3 \n Introduction  \nA  c l i n i c a l  e v a l u a t i o n  a s s e s s m e n t  r e p o r t  ( C E A R )  i s  a  r e p o r t  u s e d  b y  t h e  n o t i f i e d  b o d y  t o  c l e a r l y  d o c u m e n t  t h e  \nconclusions of its assessment of the clinical evidence presente d by the manufacturer in the clinical evaluation report \n(CER) and the related clinical evaluation that was conducted \u2013 a core requirement of the Medical Device Regulation \n(EU) 2017/745 (MDR).   The clinical evaluation must be a part of the manufacturer's qu ality management. It should also be aligned with and \nreflected in other aspects of the technical documentation, such  as: \n\u2022 The interface of the clinical eva luation with the risk manageme nt process and its appraisal and analysis of the pre-\nclinical and clinical evaluation and their relevance for the de m o n s t r a t i o n  o f  c o n f o r m i t y  w i t h  t h e  r e l e v a n t  \nrequirements in Annex I.\n1 \n\u2022 Post-market surveillance including  any corrective and preventiv e actions involving the device. \n\u2022 Post-market clinical follow-up pl an and where appropriate the p ost-market clinical follow-up report. \n\u2022 Instructions for use, which provide adequate information on int ended purpose, proper use and warnings about \nrisks to patients and healthcare practitioners. \n As part of its conformity assessment activities the notified bo dy shall examine, validate and verify that manufacturers' \nprocedures and documentation adequately address the requirement s relating to the technical documentation\n2 and \nclearly document its assessment3.  \n \nThe notified body shall review the clinical evidence presented by the manufacturer in the clinical evaluation report \nand the related clinical evaluation that was conducted, which i ncludes4:  \n \n\u0081 Assessing the suitability of using data from claimed equivalent  devices, taking into account factors such as new \nindications and innovation. The notified body shall clearly doc ument its conclusions on the claimed equivalence, \nand on the relevance and adequacy of the data for demonstrating  conformity. For any characteristic of the device \nclaimed as innovative by the manufacturer or for new indication s, the notified body shall assess to what extent \nspecific claims are supported by specific pre-clinical and clin ical data and risk analysis. \n\u0081 Verifying that the clinical evidence and the clinical evaluatio n are adequate and shall verify the conclusions drawn \nby the manufacturer on the conformity with the relevant general  safety and performance requirements. That \nverification shall include consideration of the adequacy of the  benefit-risk determination, the risk management, \nthe instructions for use, the user training and the manufacture r's post-market surveillance plan, and include a \nreview of the need for, and the adequacy of, the PMCF plan prop osed, where applicable. \n\u0081 Considering the clinical evaluation and the benefit-risk determ ination, and whether specific milestones need to be \ndefined to allow the notified body to review updates to the cli nical evidence that result from post-market \nsurveillance and PMCF data.   \n The outcome of this assessment must be clearly documented in th e CEAR.\n5 A harmonised CEAR template provides a \nstandardised method for documenting the notified body\u2019s assessm ent of the manufacturer\u2019s clinical evaluation and \nrelated documents. CEARs in this format will also support specific additional requirements  such as the clinical \nevaluation consultation procedure6 and reviews by designating authorities.7  \nScope \nThis template applies to MDR Annexes IX section 4 and Annex X s ection 3. It also applies to assessments of technical \ndocumentations on a sampling basis for class IIa/IIb devices in  accordance with Annex IX sections 2.3 and 3.5 and \n                                            \n1 MDR, Annex VII Section 4.5.1 and 4.5.5 \n2 MDR, Annexes II and III \n3 MDR Annex VII Section 4.5.5 and 4.6  \n4 MDR, Annex IX Sections 4.4 to 4.7  \n5 MDR, Annex IX 4.8   \n6 MDR, Article 54 \n7 MDR, Article 45 Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n4 \n Section 10 of Annex XI(A).8 Aspects related to the clinical evaluation assessment are also  laid down in Section 4.5.5 \nan d  oth er r ele van t s ecti on s of A n n e x V II.   It als o ap p lies to  m ed ical d e vice s fo r wh ich  clin ical d at a is n o t  d ee med  \nappropriate,9 to demonstrate conformity with Annex I, and the demonstration of an adequate justification for this.10 \nApproach to Template \nPlease note that the explanatory text under each heading provid es brief descriptions of the type of information which \nwill be included by the  notified body, however it is not an all -inclusive list and further detail may be required depending \nupon the device or the intended purpose for which it will be us ed. This template represents the minimum  content  for \na CEAR and needs to be incorporated into the process and proced ures of the notified body.11 The CEAR shall also make \na recommendation to support a final review and a final decision  to be taken by the notified body.  \n \nAny non-compliances identified during the assessment of the asp ects described in the relevant sections of the \ntemplate, as well as the appropriate follow up actions taken by  the manufacturer to close them need to be \ndocumented. This template may be used by the notified body to d ocument the non-compliance/deficiencies and \nqueries raised during the assessment and the assessment of resp onses received. It is important to note that the \ncompleted CEAR may not necessarily contain comprehensive inform ation regarding the non-compliance/deficiencies, \nwhich were raised by the notifie d body during the course of the  assessment. The CEAR shall document the outcome12 \nand the conclusions13 of the assessment.  \n Designating authorities shall assess whether the clinical evalu ation assessment was conducted appropriately, \nconsidering the assessment, procedures, associated documentatio n and the conclusions;\n14 Designating authorities will \nhave access to the complete \u2018audit trail\u2019 of the notified body.   \n \nExpert panels who are conducting a clinical evaluation consulta tion procedure shall assess the CEAR, however they \nmay not have access to the complete conformity assessment for t he device and associated procedures and \ndocumentation. To enable the expert panel work, the CEAR shall provide sufficient information with respect to the \nclinical evidence provided by the manufacturer, in particular c oncerning the benefit-risk determination, the \nconsistency of that evidence with the intended purpose, includi ng the medical indication or indications and the PMCF \nplan.15 Expert panels may also request the notified body to present it s conclusions regarding the clinical evaluation \nassessment report.16  \n \nIt is only once all the non-compliances have been closed out th at the relevant tick-box should be completed to signal \nt h a t  t h e  a s s e s s m e n t  i s  p o s i t i v e .  I n  t h e  r a r e  e v e n t  t h a t  t h e r e  i s one or more open minor non-compliances at the \nconclusion of the assessment stage, this must be clearly descri bed in the template, together with appropriate follow-\nu p  a c t i o n s  t o  c l o s e  t h e m ,  a n d  e x p e c t e d  c o m p l e t i o n  t i m e l i n e s  t o  be followed by the manufacturer under the \nsupervision of the notified body.  \n \nThe sections covered in Annex I of this template are generally applicable depending on the type of assessment. The \nsections covered in Annex II may be applicable, depending upon the device under evaluation. All applicable sections \nshould be completed, relevant conclusions reached and correspon ding boxes ticked for the report to be complete . \nThe CEAR should be signed-off by the relevant personnel in acco rdance with the quality management system of the \nnotified body. When making available the CEAR to third parties,  the notified body should treat the personal data within \n                                            \n8 MDCG 2019-13  \n9 Article 61(10) \n10 Based on the results of the manufacturer's risk management and  on consideration of the specifics of the interaction between \nthe device and the human body, the clinical performance intende d and the claims of the manufacturer. \n11 MDR, Annex VII Section 4.6  \n12 MDR, Annex IX Section 4.8 \n13 MDR, Annex VII Section 4.6 \n14 MDR, Article 45(3) \n15 MDR, Annex IX Section 5.1(c) \n16 MDR, Annex IX Section 5.1(b)  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n5 \n it as per its procedures for the management of personal data, i n compliance with Regulation (EU) 2016/679 General \nData Protection Regulation.  \n \n Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n6 \n Template CEAR \n \nSection A: Administrative particulars (notified body, manufactu rer, product and clinical evaluation report reference)  \nMedical device name model and type:  \n\u2610 Basic UDI-DI(s) (if available): \n \n\u2610 Certificate number (if applicable): \n Project number:  Risk Class:  \n \nApplicable code(s) per Commission Implementing \nRegulation (EU) 2017/2185: \n Manufacturer(s) name and SRN:\n  \n Authorised representative (if applicable) \nname and SRN: \n \n  Notified body:  \n Notified body number:  \n \nE-mail contact of NB: \n Telephone contact of NB:   \n Parts of this template which have been \napplied \n \nGeneral considerations\n17 \n\u2610 Section A: Administrative particulars  \n\u2610 Section B: Reviewers involved  \n\u2610 Section C: Device description, \nclassification, clinical evaluation plan, \ninformation materials supplied by the \nmanufacturer, common specifications and harmonised standards applied, equivalence and state of the art \n\u2610 Section D: Clinical literature review \n\u2610 Section E: Clinical investigations and \nrelated documentation \n\u2610 Section F: PMS and PMCF \n\u2610 Section G: IFU, SSCP, labelling and other \ninformation supplied with the device \n\u2610 Section H: Summary of all available data \nand conclusions \n\u2610 Overall Conclusions \n \nSpecific Considerations Type of assessment:  \n\u2610 Initial conformity assessment  \n\u2610 Assessment of changes18 and update of the clinical \nevaluation19 \n\u2610 Re-certification assessment \n\u2610 Assessment of technical documentation for class IIa \n/ IIb devices on a sampling basis \n Intended purpose: \n Check of clinical evaluation report authors \n\u2610 CER dated and signed \n\u2610 CVs provided for CER author(s) \n \nComments: \nConfirm CVs are up to date \nConfirm CER authors have full range of \nrequired expertise represented (e.g. research methods, information \n                                            \n17 These must be completed in all cases \n18 MDR, Annex IX Section 4.10 \n19 For example in accordance with Annex VII, Section 4(10) Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n7 \n According to Annex / section:   \nInsert the Annex and section  management, regulatory requirements, \ndevice technology, diagnosis and \nmanagement of conditions to be treated) \nCVs are considered acceptable: \u2610 \n \u2610 Section I: Clinical evaluation \nconsultation procedure for certain class III and class IIb devices (Article 54) \n\u2610 Section J: Where demonstration of \nconformity based on clinical data is not deemed appropriate (Article 61(10)) \n\u2610 Section K: The voluntary clinical \nconsultation on the clinical development strategy (Article 61(2)) \nTechnical file identification number and technical documentatio n assessment report (TDAR) reference if available or any other references that allow the correlation between TDAR and \nCEAR: \n \nDocuments assessed: \nFor example, clinical evaluation report, clinical investigation  plan, clinical investigation re port, ethics committee approval , Competent Authority approval, post market surveillance data, \npublications. \nInclude the title, version number/reference and date of the doc uments.  \nWhen the CER has been updated verify that this update correspon ds to the most recently updated PMS/PMCF reports and any condit ions set on the first certification, if applicable. \nNote that references to the technical documentation should be m ade in order to ensure document control. \n \n \n \nSection B: Reviewers involved in the notified body assessment o f the clinical evaluation  \nProvide the name or the employee code of the personnel with rel evant clinical expertise (as  per 3.2.4 of annex VII): \n \nRelevant clinical expertise:  \n \nHave additional reviewers been involved? Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n8 \n \u2610Yes \n\u2610No  \nProvide a justification: \n \nAdditional reviewers assigned to review the clinical evaluation  \nNumber of additional reviewers \nNames of additional reviewers: \nSeparate the internal and external clinical \nreviewers. \nYou may use employee codes \n Specific aspects assessed (by each additional reviewer): For example, rationale \nfor the design and chosen statistical methodology of clinical i nvestigation etc.  Competence area / codes: List of relevant MDR codes \nor area this person is authorised to, according to the \nAuthorisation Matrix, as of Annex VII, 3.3.2)  \nRelevant expertise:  \n \n \n \nSection C: Device description, classification, clinical evaluat ion plan, information materials supplied by the manufacturer, c ommon specifications and harmonised standards applied, \nequivalence and state of the art \nDevice description  \nDescribe the device and comment on the intended purpose, includ ing:  \n\u0081 The intended patient population and medical conditions to be di agnosed, treated and/or monitored.  \n\u0081 A general description of the key functional elements: its parts /components (including software if appropriate), its formulatio n, its composition, its functionality and, where relevant, \nits qualitative and quantitative composition.  \n\u0081 The principles of operation of the device and its mode of actio n; explanation of any novel features. \n \nClassification \nList the applicable classifica tion rule(s) and indents. \n Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n9 \n Device configurations/variants included in this application: \nInclude the manufacturers description of the sizes, differences  in design features, different configurations etc.  \nInclude an image of the device where possible.  \nIf applicable, include the manufacturers description of the dev ice history and/or changes in the device since its last assessm ent. \nWhere relevant, include the manufacturers description of the re ason for differences in design variants with illu strative image s where possible. \n \nAccessories or compatible devices: Describe any accessories or compatible devices if any or state,  \u201cnone\u201d). \nInclude component devices in case of system/procedure pack. If the use of accessories or compatible devices has an impact o n clinical safety or performance or the scope or validity of th e clinical evaluation,  identify this here.  \nIf it is necessary to understand the usage of the device, inclu de images or other relevant inf ormation such as diagrams. \n \nPrevious generations of the device and similar devices (if appl icable):  \nVerify that the manufacturer has provided:  \n\u0081 an overview of the previous generation or generations of the de vice produced by the manufacturer, where such devices exist. \n\u0081 an overview of identified similar  devices available on the Unio n or international markets, where such devices exist, including  length of time on the market, sales volume etc. \nNon-compliances identified and resolved for this section may be  briefly described in this box \nDevice details, intended purpose and classification are:  \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 \n \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \nClinical evaluation plan Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n10 \n Briefly summarise the manufacture r\u2019s clinical evaluation plan a nd confirm that it meets the requirements of Annex XIV Part A S ection 1a, highlighting the areas which require particular \nattention for this assessment: \n\u0081 an identification of the general safety and performance require ments that require support from relevant clinical data; \n\u0081 a specification of the intended purpose of the device;  \n\u0081 a clear specification of intended target groups with clear indi cations and contra-indications;  \n\u0081 a detailed description of intended clinical benefits to patient s with relevant and specified clinical outcome parameters;  \n\u0081 a specification of methods to be used for examination of qualit ative and quantitative aspects of  clinical safety with clear re ference to the determination of residual risks and side-\neffects;  \n\u0081 an indicative list and specification of parameters to be used t o determine, based on the state of the art in medicine, the acc eptability of the benefit-risk ratio for the various indication s \nand for the intended purpose or purposes of the device;  \n\u0081 an indication  how benefit-risk issues relating to specific components such a s use of pharmaceutical, non-viable animal or human tissues, ar e to be addressed; and  \n\u0081 a clinical development plan indi cating progression from explora tory investigations, such as first-in-man studies, feasibility and pilot studies, to confirmat ory investigations, such as \npivotal clinical investigations, and a PMCF as referred to in P art B of Annex XIV of MDR, with an indication of milestones and  a description of potential acceptance criteria. \nA detailed description of the clinical development plan is not required for the purpose of this template unless there are spec ific concerns.  \nAdd the manufacturer\u2019s reference and version and date of the cl inical evaluation plan. \nClinical performance \nSummarise the clinical data to d emonstrate the ability of the d evice, resulting from any direc t or indirect medical effects wh ich stem from its technical or functional characteristics, incl uding \ndiagnostic characteristics, to achieve its intended purpose as claimed by the manufacturer, thereby leading to a clinical bene fit for patients, when used as intended by the manufacturer. \nDescribe the clinical benefits. \nSafety \nDoes the clinical evaluation adequately addresses the qualitati ve and quantitative aspects of clinical safety with clear refer ence to the determination of residual risks and undesirable sid e-\neffects and the confirmation of the relevant safety and perform ance requirements provided for in Annex I? \nSummarise the clinical data regarding safety, and also describe  residual risks and any undesirable side- effects. \nDoes the clinical evaluation spec ify the methods to be used for  examination of qualitative and quantitative aspects of clinica l safety with clear reference to the determination of residual risks \nand undesirable side-effects? \nIf relevant, briefly summarise any  significant complaint, trend s or vigilance issues associated w ith earlier device iterations , which may be equivalent or similar devices, and explain wheth er \nor not they have any impact on the clinical evaluation assessme nt. \nNon-compliances identified and resolved for this section may be  briefly described in this box Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n11 \n The clinical evaluation plan is: \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 \n \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \nCommon specifications, harmonised standards or other solutions applied \nAre there common specifications relevant to the device under ev aluation? \nHave they been complied with? If not:\n20  \n\u0081 Explain any deviations and how t hese might affect the validity of the clinical evaluation and its conclusions, and any equival ence claims. \n\u0081 Confirm that the manufacturer has adopted solutions that ensure  a level of safety and performanc e that is at least equivalent thereto in accordance with Article 9(3). \n \nAre there harmonised standards relevant to the clinical evaluat ion of the device under evaluation? \nHave they been applied? If partially applied add the manufacturers justification and co nfirm that the manufacturer has adopted solutions that ensure a  level of safety and performanc e required by the Regulation \n(EU) 2017/745. \nIf there are deviations explai n any deviations and how these mi ght affect the validity of the clinical evaluation and its conc lusions, and any equivalence claims. \nIs the most up-to-date revision being used by the manufacturer?  (state which revision was used) \n \nAre there other solutions that have been applied? \nDescribe any standards, guidance or other solutions that have b een applied, and the manufacturers justification  \nNon-compliances identified and resolved for this section may be  briefly described in this box \n                                            \n20 Excluding devices listed in Annex  XVI which must comply with th e relevant common specifications  in accordance with Article 9(4 ). Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n12 \n The application of CS, harmonised standards or other solutions is:  \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 \n \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \nThe demonstration of equivalence \nIs the clinical evaluation based upon clinical investigation(s)  or other studies reported in scientific literature, of a devic e for which equivalence to the device in question can be \ndemonstrated? \nState Yes / No Device(s) to which equivalence has been claimed: \n \nIs the clinical evaluation based upon reports published in peer  reviewed scientific literature on a device for which equivalen ce to the device in question can be demonstrated?  \nState Yes / No \nIf yes, specify the source(s) of the data, if it is the device in question, or an equivalent device, or both. \n \nDevice(s) to which equivalence has been claimed:  \n \nDevice which is most relevant: \n \nAssessment of equivalence \n1. Equivalence rationales: \nIndicate which devices are/are not equivalent, and confirm that  data relating to devices which are not equivalent have been ex cluded from the analysis of clinical data for the purposes for \ndemonstrating safety and performance. \n \nIf equivalence has been claimed to more than one device, each d emonstration of equivalence can only be based on a single devic e. Each equivalent device must meet all three equivalence \ncriteria (clinical, technical, biological). \n \n2. Are the devices equivalent in accordance with Section 3 of Anne x XIV including technical, biologi cal and clinical characterist ics? \nState Yes / No \nIdentify any differences in these parameters, and verify why th ese are not expected to adversely affect the safety and perform ance of the medical device under evaluation. Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n13 \n Non-compliances identified and resolved for this section may be  briefly described in this box \nThe demonstration of equivalence is:  \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 \n \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \nAccess to data  \nComment on the manufacturer\u2019s access to data, relating to devic es with which they are claiming equivalence in order to justify  their claims of equivalence. \nFor implantable and Class III device s, if equivalence is claime d with a device marketed by another manufacturer, confirm that there is a current valid contract between the two \nmanufacturers allowing ongoing access to the technical document ation in accordance with Article 61 (5) of the MDR. \nHas the original clinical evaluat ion been performed in complian ce with the requirements of Regulation 2017/745, and has the ma nufacturer of the second device provided clear evidence \nthereof? \n State Yes / No  \nConfirm that access to data is sufficient to provide the manufa cturer with enough information about the equivalent devices to support equivalence claims, in cluding any testing which may \nhave been undertaken to confirm equivalence of specifications/p erformance/etc.  \n \nAny other limitations with re spect to equivalent devices: \nComment on any other limitations with respect to the equivalent  devices or manufacturer\u2019s equivalence claims, and the extent t o which these limitations impact the manufacturer\u2019s clinical \nevaluation and conclusions. \n \nNon-compliances identified and resolved for this section may be  briefly described in this box \nManufacturer demonstration of equivalence and access to data is : \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n14 \n  \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \nState of the art \nBenchmark devices, state of the art and other available treatme nt options: \nDescribe the alternative availabl e treatment options identified  by the manufacturer which could offer comparable safety and pe rformance for the same treatment indications / patient \npopulations, etc. \n \nBriefly describe how benchmarks for safety and performance have  been identified by the manufacturer in terms of the state of t he art. Benchmarks will norma lly be based on aggregate data \nfrom several devices considered to have acceptable performance (e.g. systematic reviews or registry analysis); if individual d evices are selected as benchmarks for safety and performance, a  \nsuitable rationale should be provided. \n Confirm that the manufacturer's description of the state of the  art is based upon an appropriate literature search (see sectio n D)?  \n \nFor devices previously marketed, is the description of the stat e of the art still accurate? Can the device still be considered  to be state of the art? \n Safety, performance and benefit-risk claims - requirements in t erms of the state of the art: \nWhat performance and safety endpoints has the manufacturer iden tified? \nIn light of the outcomes achievable with benchmark products and  other treatment options, are these endpoints appropriate and c linically relevant? Have surrogate endpoints been \nadequately justified? \n \nHas the manufacturer adequately described an indicative list an d specification of parameters used to determine, based on the s tate of the art in medicine, the  acceptability of the benefit-\nrisk ratio for the various indications and for the intended pur pose or purposes of the device? \n \nNon-compliances identified and resolved for this section may be  briefly described in this box \nManufacturer demonstration of state of the art is: \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n15 \n  \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \nNovelty \nInclude the manufacturer\u2019s explanation of any novel features of  the device and/or the related  clinical procedures and their pu rpose.  \nWhat is the possible clinical or health impact in terms of bene fit/risk? \nIs novelty adequately addressed? \u2610 \n \n \nSection D: Clinical literature review  \nWith respect to the search criteria  of the literature review, does it: \n\u2610 Address all device sizes, variants, model and accessories? \n\u2610 Address the same clinical condition? \nFurther information regarding literature search methods is avai lable in MEDDEV 2.7/1 revision 4, section A5. \nSearches for the device in question, equivalent devices and oth er devices (for example to support a description of the state o f the art) should be described separately. \n With respect to the selection criteria  of the literature review, does it relate to both below: \n\u2610 The device under evaluation or to a device demonstrated to be equivalent? \n\u2610 The state of the art or alternative available treatment option ? \nThe clinical evaluation should c learly describe the selection c riteria with respect to the regulatory purpose to which it will  apply. The CER should clearly differentiate between the two ty pes \nof data referenced above. If the data does not relate to either  of the above, provide a rationale with respect to its inclusio n.  \n \nLiterature search protocol21 \nProvide a brief summary of the literature search strategy appli ed, commenting on: \n                                            \n21 For general guidance on a literat ure search, see MEDDEV 2.7/1 r evision 4, A5. Literature search and literature review protocol , key elements.  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n16 \n \u2022 The adequacy of search terms: for example, it should be suffici ently broad to establish benchmarks, determine the general stat e of the art, determine potential risk, adverse \nevents, undesirable side-effects, etc.  \nNote that a search which is restricted to the manufacturer\u2019s ow n product or the name of their chosen equivalent could miss imp ortant information and therefore is not \nacceptable. \n\u2022 Databases used (to minimize bias multiple databases should be u sed). \n\u2022 Acceptability of inclusion and exclusion criteria.  \n\u2022 Both favourable and unfavourable data included. \n\u2022 Strategies for avoiding duplication of data (for example, acros s different publications or between manufacturer and published data). \n\u2022 Literature search and review protocol (i.e. how did the manufac turer test this protocol to ensure comprehensive identification  of relevant data / demonstrate that all relevant \ndata has been retrieved?). \n\u2022 Any deviations from the manufacturer\u2019s literature search protoc ol. \n\u2022 Overall conclusions regarding the adequacy of search methods, l ikelihood of having retrieved all relevant data, and methods us ed to avoid bias. \nComment if systematic search and review methods such as the fol lowing have been used: \n\u2022 PICO (patient characteristics, type of intervention, control, a nd outcome queries). \n\u2022 Cochrane Handbook for Systematic Reviews of Interventions. \n\u2022 PRISMA (The Preferred Reporting Items for Systematic Reviews an d Meta-Analyses) Statement. \n\u2022 MOOSE Proposal (Meta-analysis Of Observational Studies in Epide miology). \n\u2022 Other (specify or describe). \nLiterature searc h documentation: \n\u2610 Literature search protocol provided \n\u2610 Literature search reports provided \n\u2610 Full list of retrieved articles provided \n\u2610 Full list of excluded articles provided, with reasons for excl usion \n\u2610 Full text copies of relevant documents available \n Comments: \nProvide rationale if any of the above has not been provided. Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n17 \n Nota bene: \n\u2022 A literature search and other retrieval of data should be carri ed out based on a search protocol. The search protocol should d ocument the planning of the search before execution.  \n\u2022 Once the searches have been executed, the adequacy of the searc hes should be verified and a literature search report should be  compiled to present details of the execution, any \ndeviations from the literature search protocol, and the results  of the search. \n\u2022 It is important that the literature search is documented to suc h degree that the methods can be appraised critically, the resu lts can be verified, and the search reproduced if \nnecessary. \n\u2022 Abstracts lack sufficient detail to allow issues to be evaluate d thoroughly and independently, but may be sufficient to allow a first evaluation of the relevance of a paper. Copies of \nthe full text papers and documents should be obtained for the a ppraisal stage. \n\u2022 The literature search protocol(s), the literature search report (s), and full text copies of relevant documents using URL links , become part of the clinical evidence and, in turn, the \ntechnical documentation for the medical device. \nNon-compliances identified and resolved for this section may be  briefly described in this box  \nLiterature search protocol and outputs are: \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 \n \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \nData appraisal: \nProvide a brief summary of the manufacturer\u2019s data appraisal me thods (i.e. how they determine whether the data from a given st udy or other source of data is of sufficient quality and \nrelevance to be included in the clinical evaluation. This inclu des evaluation of criteria incl uding study design, sources of b ias, peer review, relevance to subject device, etc. Retrieved s tudies \nand data sets should be weighted on the basis of scientific qua lity and relevance to the scope and objectives of the clinical evaluation for the subject devices). \nJustify the acceptability of the appraisal in terms of: \n\u2022 Methodological quality and scient ific validity of articles retr ieved and evaluated appropriately. \n\u2022 Relevance of the information to the clinical evaluation determi ned and documented. \n\u2022 Contribution of each data set to the clinical evaluation weight ed according to systematic criteria. Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n18 \n   \nNon-compliances identified and resolved for this section may be  briefly described in this box  \nData appraisal is:  \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 \n \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer.  \n \n \nSection E: Clinical investigations and related documentation  \nHas the manufacturer conducted clinical investigation(s)?  \nState Yes / No \n Has the manufacturer conducted pre-market or post-market clinic al investigations? \nProvide detail \n If the manufacturer has not conducted clinical investigation: What is the rationale?  \nWhy is this acceptable / unacceptable? \n Has the manufacturer provided a c opy of all clinical investigat ion reports? \nState Yes / No \n \nWere all clinical investiga tions publicly registered? \nState Yes / No \n \nHave been verified that clinical investigations conducted with respect to Regulation (EU) 745/ 2017 publicly registered on EUDA MED? \nState Yes / No Provide the EUDAMED single regist ration number where available.  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n19 \n  \nDid the clinical investigations result in a publication in a sc ientific journal? \nState Yes / No If yes, does the clinical investigation report reflect the resu lts of clinical investigation(s) or other studies reported in s cientific literature, or reports published in peer reviewed sci entific \nliterature on other clinical experience? If there are any diffe rences describe these and summarise the rationale provided by t he manufacturer. \n \nHas the manufacturer provided all Competent/Regulatory Authorit y correspondence (from all countries, including outside of EU) \nState Yes / No \n \nAre the conclusions drawn by the manufacturer, based upon the r esults of the clinical investiga tion, valid in the light of the  approved clinical investigation plan? \nProvide detail  \nIf clinical investigations not performed under Regulation (EU) 745/2017 were not publicly registered or published: \n\u0081 Confirm that a rationale was provided. \n\u0081 Confirm that the SSCP and where relevant the IFU (for example w ith respect to the description of clinical benefits) adequately  provide information for the intended user and if \nrelevant, the patient. \nClinical Investigation  Plan (CIP) reference \n CIP complies with MDR, Annex XV, and EN ISO 14155 Annex A  \nState Yes / No \n CIP scope and study design  \nAdequacy of CIP scope and study design for demonstration of saf ety, performance and benefit risk of subject devices: \n\u0081 Study design. \n\u0081 Devices identified.  \n\u0081 Patient population. \n\u0081 Patient numbers. \n\u0081 Objectives and endpoints. \n\u0081 Length of follow up and intervals. \n\u0081 Study locations. \n\u0081 Overall conclusions. \nNon-compliances identified and resolved for this section may be  briefly described in this box Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n20 \n Manufacturer clinical investigati ons and related documentation are: \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 \n \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \n \nSection F: PMS, PMCF and the plan for updates \nDocuments reviewed, where relevant: \n\u2610 PMS Plan  \n\u2610 PMS Report (where relevant)  \n\u2610 PMCF Plan  \n\u2610 PMCF Report (where relevant)  \n\u2610 PSUR (if available) \nInclude references to the above documents. The demonstration of equivalence and the link to post-market cl inical follow-up \nDescribe how the manufacturer will verify the presumption that there would be no clinically significant difference in the safe ty and clinical performance of the device under evaluation \ncompared with the equivalent device by post market surveillance  or post market clinical follow-up? \n Is there a post-market clinical follow-up planned? \nState Yes / No \n Is this an implantable or class III device for which clinical i nvestigations have not been perfo rmed in accordance with Articl e 61(4)? \nState Yes / No \nFor these devices the PMCF plan should include post market clin ical studies to demonstrate the safety and performance of the d evice. \n Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n21 \n Clinical evaluation updates: \nIdentify when updates to the clinical evaluation report shall b e assessed during the surveillance and post certification monit oring activities and which frequency should be considered.  \nProvide further detail taking into account the manufacturer's P MCF plan and the post-market surveillance plan.  \nNon-compliances identified and resolved for this section may be  briefly described in this box \nThe PMS, PMCF and the plan for updates are: \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 \n \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \n \n \nSection G: IFU, SSCP, labelling and other information supplied with the device \n \nInformation materials supplied by the manufacturer and the inst ructions for use: \nDescribe what has been reviewed \u2013 IFU, promotional materials (i f available), SSCP, labelling etc.  In case several documents ha ve been assessed, identify answers to the questions below for \neach of the documents.22  \n \n                                            \n22 Note that the SSCP requires a separate validation report. Comments on appropriateness of PMS/PMCF Plan: \n \nIf no PMCF is planned, has the manufacturer provided an accepta ble justification for not conducting a PMCF? \nState Yes / No  \n Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n22 \n Intended purpose: \nDoes the clinical evidence support this? \nIntended patient population: Who is the intended patient population?  Does the clinical evidence support this? \nAre all the appropriate/relevant restrictions, warnings or cont raindications in place?  \n \nIntended users: \nIs the device to be used by healthcare professionals or lay use rs? Does the IFU provide all the appropriate/relevant informati on for the intended user?  \nHas the manufacturer taken into account the technical knowledge , experience, education, training and use environment, where ap plicable, and the medical and physical conditions of \nintended users (design for lay, professional, disabled or other  users). \nIs any training for users required as a risk control measure? I f not, is this justified with respect to the risk management fi le and the clinical evaluation? \n \nLimitations: \nHas the manufacturer adequately/clearly described any limitatio ns for the device use? \nDoes the device require any specific limitations? \n \nContraindications: Have contraindications been adequately/clearly described? \nAre any further contraindications necessary?  \n \nWarnings and precautions:  \nHave warnings, precautions and/or measures to be taken in the e vent of malfunction of the device or changes in its performance  that may affect safety been adequately descried? \n \nDoes the information supplied by the manufacturer adequately/cl early provide the safety and performance information relevant t o the user, or any other person, as appropriate/relevant? \nIs the estimation of associated risks and residual risk adequat e? Is this estimation quantitative (i.e. a percentage rate or r ate with a confidence interval) or qualitative? Is the descript ion \nappropriate for patients and users? Is the information provided to the end user written in a clear and understandable way (instruction s of use, indications, and w arnings)? \n \nIs the IFU and other information materials supplied by the manu facturer aligned with the other parts of the technical document ation? \nConsider: \n\u2022 the clinical evaluation (the dev ice description used for the cl inical evaluation, other content s of the clinical evaluation re port).  \n\u2022 the available clinical data (such as the public registration an d results of clinical investigations, publications, PMCF studie s, etc.). Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n23 \n \u2022 PMS report or PSUR. \n\u2022 the risk management file. \n \nNon-compliances identified and resolved for this section may be  briefly described in this box \nIFU, promotional materials, labelling are:  \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 \n \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \n \n \nSection H: Summary of all available data and conclusions  \nHas the manufacturer conducted clinical investigation(s) for th e device under evaluation? \nState Yes / No  \nHas the manufacturer demonstrated equivalence with respect to s ection 3 of Annex XIV of the MDR?  \nState Yes / No \n \nIf the manufacturer conducted CIs, does clinical data from clin ical investigations of the device under evaluation adequately d emonstrate compliance with the relevant general safety and \nperformance requirements? \nState Yes / No  \nHas the reliability of the sourc e of clinical investigation dat a been assured through monitoring activities and verification o f the application of appropriate clinical research standards? \nState Yes / No  \nIf the manufacturer demonstrated equivalence with respect to se ction 3 of Annex XIV of the MDR does the data from an equivalen t device demonstrate compliance with Annex I? State Yes / \nNo Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n24 \n Provide a summary of safety data (with reference to the relevan t section of the CER). \n \nProvide a summary of performance data (with reference to the re levant section of the CER) \n \nDoes the clinical data provide su fficient clinical evidence to:23 \n\u2022 Demonstrate compliance with the relevant general safety and per formance requirements? State Yes  / No, and provide additional i nformation if relevant  \n\u2022 Support the intended purpose, the claims and the information in  the IFU and SSCP?  State Yes / No, and provide addi tional information if relevant  \n \nWhat are the remaining unanswered questions regarding the devic e under evaluation? \nDescribe these with respect to the plan for PMS / PMCF  \n \n \n \nOverall Conclusions:  \nBenefit-risk conclusions: \nSummarise the clinical benefits. D escribe them briefly in relat ion to the meaningful and measu rable patient relevant clinical outcomes, including outcome(s) related to diagnosis. Describe \ntheir positive impact on patient management or public health.  \nSummarise the risks with clinical relevance (e.g uncertainties or limitations of clinical data, undesirable side-effects, pote ntial for misuse, etc) and provide a short description (e.g. in cidence, \nseverity, duration, vulnerable patient subgroups, dose-response  relationship where relevant, etc). \nDiscuss the impact of risks (as described above) in relation to  the clinical benefits taking into account the factors describe d and in particular the uncertain ties in relation to available clinical \ndata. \n \nHave all the risks that could have a significant impact on the benefit-risk analysis' been identified in the clinical evaluati on?  \nIs there alignment between the risk management and clinical eva luation? \n \n                                            \n23 For legacy products, see MDCG 2020-6  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n25 \n State Yes / No \nDescribe how the clinical benefits outweigh the risks also cons idering the current state of the art.  \n \nHave all deficiencies/non-compliances been raised and satisfact orily addressed in the course of this clinical evaluation asses sment?  \n \nState Yes / No \n \nIs it possible to follow the changes that have been made to add ress them?  \nOverall conclusion on the assessment of the manufacturer's clin ical evaluation including a clinical judgement of the opinion p rovided by any external expert. \nMake a clear recommendation to the  notified body's decision mak er in regards to the conclusions of this assessment for the pur pose of granting certification, stating in addition: \n\u2022 whether the post-market surve illance plan, including the PMCF p lan, is adequate.  \n\u2022 specific milestones to be set for further review of the up to d ate clinical evaluation by the notified body.  \n\u2022 considerations to define the period of certification. \n\u2022 additional conditions on the cer tification to be considered.  \n \nSufficient information are prov ided to demonstrate acceptabilit y of benefit-risk conclusions and confirm that the relevant MDR  requirements are met : \u2610 \n \nSpecific Considerations \n \nSection I: Clinical evaluation consultation procedure for certa in class III and class IIb  devices (Article 54) \n \nIs the procedure required by Article 54(1) to be applied? State Yes / No Provide further information where necessary with respect to thi s justification \n \nIf this procedure is not to be applied, with respect to Article  54(2) what is the reason?\n24 \n                                            \n24 See MDCG 2019-3, Interpretation of Article 54(2)b  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n26 \n (a) renewal of a certificate issued under the MDR; \u2610 \n(b) the device has been designed by modifying a device already marketed by the same manufacturer for the same intended purpose , and the manufacturer has demonstrated to the \nsatisfaction of the notified body that the modifications do not  adversely affect the benefit-risk ratio of the device; \u2610 \n Provide a summary of the modification(s) that have been made to  the device? \nProvide a summary of the manufacturer\u2019s rationale demonstrating  that the benefit-risk ratio of the device is not adversely aff ected. \nHas the clinical data been provided to support the conclusions of the manufacturer regarding the benefit-risk of the modified device with respect to the previous version? \n For legacy devices, verify:  \n\u0081 that the modifications do not adversely affect the benefit-risk  ratio. \n\u0081 that the device in question had a valid certificate under the D irectives. \n\u0081 in case the certificate has been withdrawn, suspended\n25 or expired, if there is an impact on compliance with the gener al safety and performance requirements, and \n\u0081 that there is no pending assessment of changes for the device o r outstanding non-compliance. \n\u0081 the description of modifications provided and assess if these m odifications are limited only to those needed in order to compl y with the new legal requirements introduced by the MDR. \n \nNote: limitations of the intended purpose of the device should not trigger the consultation procedure in accordance to Art. 54 . \n \n(c) the principles of the clinical  evaluation of the device typ e or category have been addressed in a CS referred to in Articl e 9 and the notified body confir ms that the clinical evaluation  of \nthe manufacturer for this device is in compliance with the rele vant CS for clinical evaluation of that kind of device. \u2610 \nRelevant scientific panel and associated competence area(s)  \nIndicate your opinion on the r elevant scientific and associated  competence area(s)  for the device under assessment: \n \n  Medical area(s)  Associated competence-related areas  \n Orthopaedics, traumatology, rehabilitation, \nrheumatology   Joint replacements (hip, knee, shoulder) \n Spinal devices \n Non-articulating devices, rehabilitation \n Other \n                                            \n25 The devices for which the certificates were withdrawn or suspe nded due to lack of compliance wi th essential requirements will  require a clinical evaluation consultation procedure as this \nadversely affects the benefit-risk ratio of the device.  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n27 \n  Circulatory system: cardiovascular / lymphatic \nsystem   Prosthetic heart valves and devices for heart valve repair \n Cardiovascular stents (metallic and bioresorbable) and vascular  prostheses \n Active implantable cardiac devic es and electrophysiological dev ices \n Structural interventions and new devices (e.g. LAA/PFO occluder s, heart failure devices) \n Cardiac surgery including extracorporeal membrane oxygenation, cardiopulmonary bypass devices, artificial hearts (and \nleft ventricular assist devices) \n Other \n Respiratory, anaesthesiology, intensive care   Respiratory and anaesthetic devices \n Neurology   Central and peripheral nervous system devices \n Implants for hearing and vision (sensory recovery) \n Neurosurgical devices \n Other \n Endocrinology and diabetes   Endocrinology and diabetes (e.g. insulin delivery systems and c losed-loop systems, continuous glucose monitoring)  \nImplantable systems \n General and plastic surgery, dentistry   Surgical implants and general surgery \n Plastic surgery and wound care \n Maxillofacial surgery \n Dentistry (devices for dentistry  (oral surgery, implantology, d ental materials incl.)) \n Other \n Obstetrics & gynaecology including reproductive \nmedicine   Devices for obstetrics and gynaecology \n Gastroenterology & hepatology   Devices for gastroente rology and hepatology \n \n Nephrology & urology  Devices for nephrology and urology \n Ophthalmology  Devices for ophthalmology Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n28 \n  \nProvide further information necessary with respect to this just ification \n \n \nConclusion for certain class III and IIb devices to be consider ed by the expert panel \nNovel aspects \nSee section C, subsection \u2018Novelty\u2019 \n  \n \nBenefit-risk determination  See section H and the Overall Conclusion sections \n \nConsistency of clinical evidence with intended purpose and PMCF  \nProvide an assessment of the consistency of the clinical eviden ce with:  \n(a) the intended purpose, including medical indication(s),  \n(b) the post-market clinical follow-up (PMCF) plan. \n \n \n \nSection J: Where demonstration o f conformity based on clinical data is not deemed appropriate (Article 61(10)) \n \nHas the manufacturer claimed that the demonstration of conformi ty with general safety and performance requirements based on cl inical data is not deemed appropriate in accordance \nwith Article 61(10)? \nState Yes / No \nNota bene : A clinical evaluation is still required and the above informa tion and evidence-based justifica tion shall be presented in the  clinical evaluation report. \n Has the manufacturer provided a justification for reliance upon  Article 61(10)? \nState Yes / No \n If yes, describe the evidence which the manufacturer is relying on, w ith respect to: \n\u0081 Performance evaluation \n\u0081 Bench testing  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n29 \n \u0081 Pre-clinical evaluation \n \nConsider: \n\u0081 Has any available clinical data for the device or an equivalent  device been searched for and/or identified by the manufacturer ?  \nIf yes \u2013was the identified clinic al data integrated in the clin ical evaluation. \nThis should include an evaluation of clinical data identified f rom the literature, and an appraisal of their relevance to the device under evaluation. \n \n\u0081 Is clinical data available for si milar devices, does this provi de information with relevant to the safety and performance of t he device under evaluation? \nHas the manufacturer conducted an appropriate search of scienti fic literature?  \nIf clinical data for similar devi ces is available \u2013 this should  be included in the CER and evaluated and may be of particular relevance to post-market surveillance / PMCF planning. \n \n\u0081 The results of the manufacturer's risk management \nAre the results of the manufacturer's risk management supportiv e of the use of non-clinical testing methods? \n \n\u0081 Consideration of the specifics of the interaction between the d evice and the human body \nIs the device under assessment part of a system or stand-alone?  \nIs there sufficient information regarding this interaction avai lable from sources other than clinical data?  \n \n\u0081 The clinical performance intended \nWhat is the intended performance? Is it reasonable to rely upon  non-clinical data for the proposed intended performance? \n \n\u0081 The claims of the manufacturer  \nThe manufacturer should not make any claims which are not suppo rted by clinical data. \n \n Overall conclusion  \n \nNon-compliances identified and resolved for this section may be  briefly described in this box \nThe justification of the manufacturer for reliance upon Article  61(10) is:  \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n30 \n  \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \n \n \nSection K: The voluntary clinical consultation on the clinical development strategy (Article 61(2))  \nExpert Panel consultation reference: \n Expert Panel recommendations: \nHave the views of the expert panel been given due consideration  by the manufacturer? \nHas this been included in the  clinical evaluation report? \nIs there any divergence between the manufacturers clinical deve lopment strategy and the views of the expert panel? If yes \u2013 wh at is the justification for this? Is this acceptable? Explain \nwhy."}, {"title": "MDCG 2020-1.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document         MDCG  2020-1  \n  \n \n \n \n \n \nMDCG  2020-1  \n       Guidance on Clinical Evaluation (MDR) \n      / Performance Evaluation (IVDR) of  \n      Medical Device Software              \n \n             March 2020 \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) \nestablished by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of \nrepresentatives of all Member States and it is chaired by a representative of the European \nCommission. \nThe document is not a European Commission document and it cannot be regarded as reflecting \nthe official position of the European Commission. Any views expressed in this document are not \nlegally binding and only the Court of Justice of the European Union can give binding \ninterpretations of Union law.  \n \n  \nPage 1 of 21 \n  \n  Guidance on \nClinical Evaluation/  \nPerformance \nEvaluation of \nMedical Device \nSoftware \nMarch 2020  \n \nGuidance on Clinical Evaluation \n(MDR) / Performance Evaluation \n(IVDR) of Medical Device Software  \n  \nPage 2 of 21 \n Table of Contents \n \n1. Purpose ............................................................................................................................................ 3 \n2. Scope ............................................................................................................................................... 3 \n3. Background ..................................................................................................................................... 4 \n3.1. Abbreviations ........................................................................................................................... 5 \n3.2. Formats used within this document........................................................................................... 5 \n3.3. Definitions ............................................................................................................................... 5 \n4. General principles of the MDSW CLINICAL EVALUATION  (MDR) / PERFORMANCE EVALUATION  \n(IVDR) process ....................................................................................................................................... 9 \n4.1. Introduction ............................................................................................................................. 9 \n4.2. Determination of the valid clinical association / scientific validity .......................................... 12 \n4.3. Technical Performance /Analytical Performance .................................................................... 12 \n4.4. Clinical Performance .............................................................................................................. 13 \n4.4.1. Clinical investigations and clinical performance studies .................................................. 14 \n4.4.2. Where demonstration of conformity based on clinical data is not deemed appropriate ..... 15 \n4.5. Final analysis and conclusion of the clinical evaluation (MDR) / performance evaluation \n(IVDR) .............................................................................................................................................. 15 \n4.6. Continuous update of the clinical evaluation (MDR) / performance evaluation (IVDR)........... 15 \nAnnex I \u2013 Methodological principle for generation of CLINICAL EVIDENCE  ........................................ 17 \nAnnex II \u2013 Examples of CLINICAL EVALUATION (MDR) /  PERFORMANCE EVALUATION  (IVDR) \nstrategies ........................................................................................................................................... 18 \na) MDSW intended to analyse sleep quality data .................................................................... 18 \nb) MDSW intended for image segmentation ............................................................................ 19 \nc) MDSW intended to detect inflammatory bowel diseases (IBD) .......................................... 20 \nd) Active devices containing MDSW to enable their intended purpose .................................. 21 \ne) MDSW which provides an additional user-interface to control an insulin pump ............... 21 \nf) MDSW intended to analyse exhaled CO2 in a life-sustaining device in order to control \nventilator settings ......................................................................................................................... 21 \n \n   \nPage 3 of 21 \n 1. Purpose \nThe purpose of this guidance is to provide a framework for the determination of the appropriate level of \nCLINICAL EVIDENCE  required for MEDICAL DEVICE SOFTWARE  (MDSW) to fulfil the requirements set out \nin Regulation (EU) 2017/745 \u2013 Medical Devices Regulation (MDR) and Regulation (EU) 2017/746 \u2013 In \nVitro Diagnostic Medical Devices Regulation (IVDR).1  \nIn order to promote global convergence, this document takes into account certain concepts outlined in \nInternational Medical Device Regulators Forum (IMDRF) guidance documents (such as N41).2 \n2. Scope \nThis guidance should be applied to MDSW. For the purpose of this guidance, MDSW is software that is \nintended to be used, alone or in combination, for a purpose as specified in the definition of a \u201cmedical \ndevice\u201d in the medical devices regulation or in vitro diagnostic medical devices regulation.  \nIt should be noted that software can be associated3 with another medical device, by driving or influencing \nits use. The guideline MDCG 2019-11 clarifies that software which is driving or influencing is covered by \nthe medical devices regulations4 either as a part/component of a device or as an accessory for a medical \ndevice.  \nSoftware developers should refer to MDCG 2019-11 for guidance on the appropriate qualification and \nclassification of software prior to such software being introduced into the market. The same principles of \nCLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) apply to all MDSW. Conceptually, \nthe following models of software can be understood (whereas combinations may be possible, refer to Table \n1):  \na) Software for which the manufacturer claims a specific medical intended purpose. Such software \nhas a CLINICAL BENEFIT  and requires CLINICAL EVIDENCE  within its own conformity assessment. \nb) Software for which the manufacturer does not claim any medical intended purpose. Such software \nis intended to drive or influence a medical device. The CLINICAL EVIDENCE  is provided within the \ncontext of the driven or influenced device and is therefore out of the scope of this document. \nIt should be recognised that the concept of a CLINICAL BENEFIT  for MDSW may deviate from that which \napplies in the case of pharmaceuticals or other medical devices, since the benefit of MDSW may lie in \nproviding accurate medical information on patients, where appropriate, assessed against medical \ninformation obtained through the use of other diagnostic options and technologies, whereas the final clinical \noutcome for the patient is dependent on further diagnostic and/or therapeutic options which could be \navailable. \n                                                \n1 Depending on the device in question, the level of Clinical Evidence may differ and shall be assessed on a case by case basis.  \n2 International Medical Device Regulators Forum \u2013 IMDRF/SaMD WG/N41FINAL:2017 \u2013 Guidance on Software as a Medical \nDevice (SaMD): Clinical Evaluation  \n3 Associated medical device may be software or hardware. \n4  The use of \u201cThe Medical Devices Regulations\u201d from here on out refers to both Regulation (EU) 2017/745 \u2013 MDR and Regulation \n(EU) 2017/746 \u2013 IVDR.   \nPage 4 of 21 \n Model of Software CLINICAL EVALUATION (MDR) / \nPERFORMANCE EVALUATION \n(IVDR)  - scope \nMDSW \n(with independent intended purpose and claimed CLINICAL \nBENEFIT)  MDSW only \nMDSW \n(with intended purpose and claimed CLINICAL BENEFIT  related \nto driving or influencing a medical device for a medical \npurpose) MDSW and the driven or influenced \nmedical device Notes 1,2 \nSoftware driving or influencing the use of a medical device \n(with no independent intended purpose or independent claimed \nCLINICAL BENEFIT ) Driven or influenced medical device \nincluding the software (component or \naccessory) \nTable 1 Different MDSW and CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION  (IVDR) \nrequirements \nNote 1: If a software is driving/ influencing more than one medical device, an independent CLINICAL \nEVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) is required for each foreseen and clinically \nviable software \u2013 device combination. \nNote 2: Out of scope of this guidance (See MDCG 2019-11 for examples). \n3. Background \nArticle 61 (1) of the MDR and Article 56 (1) of the IVDR state the following: \n\u2018The manufacturer shall specify and justify the level of CLINICAL EVIDENCE  necessary to \ndemonstrate conformity with the relevant general safety and performance requirements. That level \nof CLINICAL EVIDENCE  shall be appropriate in view of the characteristics of the device and its \nintended purpose.\u2019 \nArticle 2 (51) of the MDR and Article 2 (36) of the IVDR define \u2018 CLINICAL EVIDENCE \u2019 as:  \n\u2018clinical data and CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) results \npertaining to a device of a sufficient amount and quality to allow a qualified assessment of whether \nthe device is safe and achieves the intended CLINICAL BENEFIT (S), when used as intended by the \nmanufacturer.\u2019 \nIn order to provide guidance relating to the level of CLINICAL EVIDENCE  required for MDSW and as set out \nin recital (5) of the MDR and IVDR, this guidance takes into account internationally converged principles \nadopted by an international group of regulators, IMDRF ( http://www.imdrf.org ). Adoption of these \nprinciples provides European regulators an initial framework when further developing MDR/ IVDR-\nspecific regulatory approaches and expectations for regulatory oversight. \nWhile this document describes a converged approach to CLINICAL EVALUATION (MDR) / PERFORMANCE \nEVALUATION (IVDR) for MDSW , it should be read in conjunction with other documents that aim to provide  \nPage 5 of 21 \n horizontal guidance for the CLINICAL EVALUATION  of medical devices or PERFORMANCE EVALUATION  of \nin vitro diagnostic medical devices.5 \nNote: Please be advised that this document is subject to revision upon the publication of the aforementioned \nhorizontal guidance.  \nClinical expertise and judgments are required at every step of the CLINICAL EVALUATION (MDR) / \nPERFORMANCE EVALUATION (IVDR), including literature search and appraisal. Each indication and \nclaimed CLINICAL BENEFIT  that is part of the intended purpose should be assessed individually and have \nthe supporting CLINICAL EVIDENCE . Systematic and explicit approach for the appraisal of supporting data \nallows achieving confident, scientifically substantiated conclusions and facilitates transparency of these \njudgments. \n3.1. Abbreviations \nGSPR General Safety and Performance Requirements  \nIMDRF International Medical Device Regulators Forum  \nIVDR In Vitro Diagnostic  Medical Devices Regulation; EU 2017/746  \nMDCG Medical Device Coordination Group  \nMDR Medical Devices Regulation; EU 2017/745  \nMDSW Medical Device Software  \nPMCF Post Market Clinical Follow -up \nPMPF Post Market Performance Follow -up \nPMS Post Market Surveillance  \nRWE Real-World Evidence  \nSaMD Software as a Medical Device  \nSOTA State-of-the-Art \nSSCP Summary of Safety and Clinical Performance  \nSSP Summary of Safety and Performance  \n \n3.2. Formats used within this document \nCursive A note to a text \nCAPITALIZED  Terms defined in this document or the Regulations  \nsubscript References  \n \n3.3. Definitions \nThe definitions elaborated within this section and utilised within this document are intended to apply \nsolely to Medical Device Software (MDSW) according to the MDR and IVDR. \n                                                \n5 These guidance documents are under development and will be published on the Commission\u2019s Medical Devices website.   \nPage 6 of 21 \n CLINICAL BENEFIT  Article 2 (53) MDR defines CLINICAL BENEFIT  as the positive impact \nof a device on the health of an individual, expressed in the terms of a \nmeaningful, measurable, patient-relevant clinical outcome(s), \nincluding outcome(s) related to diagnosis, or a positive impact on \npatient management or public health; whereas  \n \nArticle 2 (37) IVDR defines CLINICAL BENEFIT as the positive impact \nof a device related to its function, such as that of screening, \nmonitoring, diagnosis or aid to diagnosis of patients, or a positive \nimpact on patient management or public health.6 \nSource: EU 2017/745 (MDR), Article 2 (53); EU 2017/746 (IVDR), Article 2 (37) and IVDR recital (64)   \nCLINICAL DATA  (MDR) Information concerning safety or performance that is \ngenerated from the use of a device and is sourced from the following: \n- clinical investigation(s) of the device concerned, \n- clinical investigation(s) or other studies reported in scientific \nliterature, of a device for which equivalence to the device in \nquestion can be demonstrated, \n- reports published in peer reviewed scientific literature on \nother clinical experience of either the device in question or a \ndevice for which equivalence to the device in question can \nbe demonstrated, \n- clinically relevant information coming from post-market \nsurveillance, in particular the post-market clinical follow-up;  \nSource: EU 2017/745 (MDR)  \n(IVDR) Clinical Data, in particular:  \n- from relevant peer-reviewed scientific literature and \navailable consensus expert opinions or positions from \nrelevant professional associations relating to the safety, \nperformance, clinical benefits to patients, design \ncharacteristics, scientific validity, clinical performance and \nintended purpose of the device and/or of equivalent or similar \ndevices; or \n- other relevant clinical data available relating to the safety, \nscientific validity, clinical performance, clinical benefits to \npatients, design characteristics and intended purpose of \nsimilar devices, including details of their similarities and \ndifferences with the device in question \n- clinically relevant information coming from post-market \nsurveillance, in particular the post-market performance \nfollow-up; \nSource: Adopted from EU 2017/746 (IVDR) Annex XIV (2.4) and Annex VII (4.10) and (4.1 1) \n                                                \n6 IVDR recital (64) states : It should be recognised that the concept of clinical benefit for in vitro diagnostic medical devices is \nfundamentally different from that which applies in the case of pharmaceuticals or of therapeutic medical devices, since the benefit \nof in vitro diagnostic medical devices lies in providing accurate medical information on patients, where appropriate, assessed \nagainst medical information obtained through the use of other diagnostic options and technologies, whereas the final clinical \noutcome for the patient is dependent on further diagnostic and/or therapeutic options which could be available.   \nPage 7 of 21 \n CLINICAL DEVELOPMENT PLAN \n(MDR) A plan indicating progression from exploratory investigations, such \nas first-in-man studies, feasibility and pilot studies, to confirmatory \ninvestigations, such as pivotal clinical investigations and a PMCF \nwith an indication of milestones and a description of potential \nacceptance criteria. \nSource: EU 2017/745 (MDR), Annex XIV, part A  \nCLINICAL EVALUATION (MDR) A systematic and planned process to continuously generate, collect, \nanalyse and assess the clinical data pertaining to a device in order to \nverify the safety and performance, including CLINICAL BENEFITS , of \nthe device when used as intended by the manufacturer. \nSource: EU 2017/745 (MDR), Article 2 (44) \nCLINICAL EVIDENCE  Clinical data and CLINICAL EVALUATION (MDR) / PERFORMANCE \nEVALUATION (IVDR)  results pertaining to a device of a sufficient \namount and quality to allow a qualified assessment of whether the \ndevice is safe and achieves the intended CLINICAL BENEFIT (S), when \nused as intended by the manufacturer. \nSource: EU 2017/745 (MDR), Article 2 (51)); EU 2017/746 (IVDR), Article 2 (36) \nCLINICAL INVESTIGATION \n(MDR) Any systematic investigation involving one or more human subjects, \nundertaken to assess the safety or performance of a device. \nSource: EU 2017/745 (MDR), Article 2 (45) \nCLINICAL PERFORMANCE  Article 2 (52) MDR defines clinical performance as the ability of a \ndevice, resulting from any direct or indirect medical effects which \nstem from its technical or functional characteristics, including \ndiagnostic characteristics, to achieve its intended purpose as claimed \nby the manufacturer, thereby leading to a CLINICAL BENEFIT  for \npatients, when used as intended by the manufacturer; whereas \n \nArticle 2 (41) IVDR defines clinical performance as the ability of a \ndevice to yield results that are correlated with a particular clinical \ncondition or a physiological or pathological process or state in \naccordance with the target population and intended user.  \nSource: EU 2017/745 (MDR), Article 2 (52); EU 2017/746 (IVDR), Article 2 (41)  \nCURATED DATABASE / CURATED \nREGISTRY  For the purpose of this document, a curated database /curated registry  \nis any kind of structured repository such as a traditional database, an \nontology or an XML file, that is created and updated with a great deal \nof human effort through the consultation, verification, and \naggregation of existing sources, and the interpretation of new (often \nexperimentally obtained) raw data.  \nGENERALISABILITY  Generalisability  refers to the ability of a MDSW to extend the \nintended performance tested on a specified set of data to the broader \nintended population.  \nPage 8 of 21 \n HUMAN FACTORS ENGINEERING  Human factors engineering refers to the a pplication of knowledge \nabout human behaviour, abilities, limitations, and other \ncharacteristics to the design of and interactions with a MDSW to \nachieve adequate USABILITY . \nPERFORMANCE EVALUATION \n(IVDR) An assessment and analysis of data to establish or verify the \nSCIENTIFIC VALIDITY , the ANALYTICAL  and, where applicable, the \nCLINICAL PERFORMANCE  of a device. \nSource: EU 2017/746 (IVDR), Article 2 (44) \nPERFORMANCE STUDY (IVDR) A study undertaken to establish or confirm the analytical or CLINICAL \nPERFORMANCE  of a device. \nSource: EU 2017/746 (IVDR), Article 2 (42) \nREAL-WORLD PERFORMANCE  Information on real -world device use and performance from a wider \npatient population than a controlled study.  \nSource: Definition derived from IMDRF/SaMD WG/N41FINAL:2017  \nSTATE-OF-THE-ART Developed stage of current technical capability and/or accepted \nclinical practice in regard to products, processes and patient \nmanagement, based on the relevant consolidated findings of science, \ntechnology and experience.  \n \nNote: The STATE-OF-THE-ART embodies what is currently and \ngenerally accepted as good practice in technology and medicine. The \nstate-of-the-art does not necessarily imply the most technologically \nadvanced solution. The STATE-OF-THE-ART described here is \nsometimes referred to as the \u201cgenerally acknowledged STATE-OF-\nTHE-ART\u201d \nSource: Modified from IMDRF/GRRP WG/N47 FINAL:2018  \nTECHNICAL PERFORMANCE \n(MDR) /ANALYTICAL (IVDR))  \nPERFORMANCE  Capability of a MDSW to accurately and reliably generate the \nintended technical/analytical output from the input data.  \nSource:  IMDRF/SaMD WG/N41FINAL:2017 \nSource: EU 2017/746 (IVDR) Article 2 (40)  \n \nUSABILITY For the purpose of this document, usability refers to the c haracteristic \nof the user interface that establishes effectiveness, efficiency and ease \nof user learning and user satisfaction.   \nVALID CLINICAL ASSOCIATION \n(MDR) / SCIENTIFIC VALIDITY \n(IVDR) Means the association of an MDSW output with a clinical condition \nor physiological state. \nSource: Derived from IMDRF/SaMD WG/N41FINAL:2017 \nSource: EU 2017/746 (IVDR), Article 2 (38) \n \n  \nPage 9 of 21 \n 4. General principles of the MDSW CLINICAL EVALUATION  (MDR) / \nPERFORMANCE EVALUATION  (IVDR) process \n4.1. Introduction \nCLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) is an ongoing process, conducted \nthroughout the life cycle of a MDSW. It is a structured, transparent, iterative and continuous process which \nis part of the quality management system for a device. Software that qualifies as a MD or an IVD is subject \nto the same general CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) principles, laid \ndown in the applicable guidelines and regulatory documents, as other MDs/ IVDs, such as: \n- Establishing and maintaining a CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION \n(IVDR) plan and criteria applied to generate the necessary CLINICAL EVIDENCE  based on the \ncharacteristics of the device; \n- Identification of the relevant data pertaining to performance and/ or safety of the device and any \nremaining unaddressed issues or gaps in the data; \n- Appraisal of the relevant data in terms of quality and its contribution to the CLINICAL EVALUATION \n(MDR) / PERFORMANCE EVALUATION (IVDR); \n- Analysis of the available data and its relevance with regard to demonstrating conformity with the \nrelevant General Safety and Performance Requirements (GSPRs); \n- Documenting the relevant data, their assessment and the CLINICAL EVIDENCE  derived therefrom, in \nthe CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) report; \n- Updating the CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) and its \ndocumentation throughout the life cycle of the MDSW concerned with data obtained from \nimplementation of the manufacturer's Post Market Clinical Follow-up / Post Market Performance \nFollow-up (PMCF /PMPF) plan. \nThese methodological principles are depicted in Figure 1. \n \nFigure 1 Overview of the stages of the CLINICAL  EVALUATION (MDR) / PERFORMANCE  EVALUATION (IVDR) \n \nPage 10 of 21 \n The requirements for CLINICAL EVALUATION  and PERFORMANCE EVALUATION are outlined in Article 61 of \nthe MDR (including Annex XIV) and Article 56 of the IVDR (including Annex XIII), respectively. \nWhile the definition of CLINICAL EVALUATION  in the MDR and PERFORMANCE EVALUATION  in the IVDR \nare not identical (see section 0), there is a shared expectation for providing sufficient CLINICAL EVIDENCE  \nto demonstrate conformity with relevant GSPRs under the normal conditions of the device\u2019s intended use. \nCLINICAL EVIDENCE  should be sufficient and appropriate in view of the characteristics of the device, clinical \nrisks and its intended purpose. The level of CLINICAL EVIDENCE  necessary should be specified and justified \nby the manufacturer.  \nThree key components should be taken into account when compiling CLINICAL EVIDENCE  for every MDSW \n(Figure 1), and each is described below in further detail.  \nVALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY is understood as  the extent to which, the MDSW\u2019s \noutput (e.g. concept, conclusion, calculations) based on the inputs and algorithms selected, is associated \nwith the targeted physiological state or clinical condition. This association should be well founded or \nclinically accepted (e.g. existence of a scientific framework or sufficient level of evidence as further \nelaborated in section 4.2 of this document). The V ALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY  of \na MDSW should demonstrate that it corresponds to the clinical situation, condition, indication or parameter \ndefined in the intended purpose of the MDSW.  \nNOTE: The VALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY  seeks to establish that there are sound \nscientific principles underpinning the use of the MDSW in question. The information provided for the \nestablishment of the V ALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY  should put forward the case that \nthe MDSW has an association with a clinical condition or physiological state. This association may not \nalways be readily established. Thus, the C LINICAL PERFORMANCE  can serve as an additional input to the \nVALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY  from a clinical perspective for the specific intended \npurpose (see Annex I).    \nExample: MDSW that detects heart arrhythmia by analysing auscultation sound obtained by a digital \nstethoscope requires demonstrating VALID CLINICAL ASSOCIATION of the association between abnormal \ncardiac sounds and heart arrhythmia. \nEvidence supporting VALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY  can be generated e.g. through \nliterature research, professional guidelines, proof of concept studies, or manufacturer\u2019s own clinical \ninvestigations/clinical performance studies. \nValidation of the  TECHNICAL PERFORMANCE / ANALYTICAL PERFORMANCE is the demonstration of the \nMDSW\u2019s ability to accurately, reliably and precisely generate the intended output, from the input data. \nEvidence supporting T ECHNICAL PERFORMANCE  / ANALYTICAL PERFORMANCE can be generated through \nverification and validation activities, e.g. unit-level, integration, and system testing or by generating new \nevidence through use of curated databases, curated registries, reference databases or use of previously \ncollected patient data. \nValidation of the  CLINICAL PERFORMANCE  is the demonstration of a MDSW\u2019s ability to yield clinically \nrelevant output in accordance with the intended purpose. The clinical relevance of a MDSW\u2019s output is a \npositive impact  \nPage 11 of 21 \n - on the health of an individual expressed in terms of measurable, patient-relevant clinical \noutcome(s), including outcome(s) related to diagnosis, prediction of risk, prediction of \ntreatment response(s), or \n- related to its function, such as that of screening, monitoring, diagnosis or aid to diagnosis \nof patients, or \n- on patient management or public health. \nEvidence supporting C LINICAL PERFORMANCE can be generated by testing the MDSW under evaluation, \nor an equivalent device, in the target population and for the intended use. The applied methodology should \nbe appropriate in light of the device characteristics and intended purpose and may include pre-clinical \ntesting, a clinical investigation or a clinical performance study. \nSpecifically, for MDSW not claiming C LINICAL BENEFITS that can be specified through measurable, \npatient-relevant clinical outcome(s), clinically relevant outputs are achieved through demonstrated \npredictable and reliable use and USABILITY  (please refer to section 4.2 of this document).  \nIn addition, CLINICAL EVALUATION  or PERFORMANCE EVALUATION  of MDSW must consider the benefit-\nrisk ratio in light of the STATE-OF-THE-ART related to practice of medicine for diagnosis, treatment or patient \nmanagement. It is further expected that the assessment of MDSW considers all components of the CLINICAL \nEVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) (see Figure 1 and Annex 0). \nThe three components described above do not represent a distinct stepwise approach but rather portray a \nmethodological principle for the generation of CLINICAL EVIDENCE .  \nTo determine and justify the level of CLINICAL EVIDENCE , both amount and quality of supporting data \nshould be evaluated. This assessment may be guided by the following non-exhaustive questions: \nSufficient amount \n- Does the data support the intended use, indications, target groups, clinical claims and \ncontraindications? \n- Have the clinical risks and analytical performance/ clinical performance been investigated? \n- Have relevant MDSW\u2019s characteristics, such as the data input and output, the applied algorithms \nor type of interconnection been considered when generating the data to support the performance of \nthe device? \n- What is the grade of innovation/ history on the market (how big is the body of scientific evidence)? \n- Other, as applicable. \nSufficient quality \n- Were the type and the design of the study/ test appropriate to meet the research objectives? \n- Was the data set appropriate and actual (state of the art)? \n- Was the statistical approach appropriate to reach a valid conclusion? \n- Were all ethical, legal and regulatory considerations/ requirements taken into account? \n- Is there any conflict of interest?  \nPage 12 of 21 \n - Other, as applicable. \n4.2. Determination of the valid clinical association / scientific validity \nIn the first step, the manufacturer should verify the association between the output of the MDSW (based on \nthe inputs and algorithms selected) and the targeted physiological/ clinical condition, clinical situation or \nclinical parameter, as defined in the intended purpose of the MDSW. MDSW may include a multitude of \nclinical features governed by its intended purpose which require individual assessment.  \nThis association should be clinically accepted or well founded, which means accepted by the broad medical \ncommunity and/or described in scientific (peer-reviewed) literature.  \nVALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY can be demonstrated through the use of existing \nCLINICAL PERFORMANCE DATA  while taking into account the generally acknowledged STATE-OF-THE-ART. \nVALID CLINICAL ASSOCIATION  / SCIENTIFIC VALIDITY may further be demonstrated by the creation of new \nCLINICAL PERFORMANCE DATA  in the cases where existing data is not sufficient. For example, as a result \nof a gap analysis, the manufacturer could conclude that additional data may be required. \nExamples of existing data (in no particular order) \n- Technical standards \n- Professional medical society guidelines \n- Systematic scientific literature review  \n- CLINICAL INVESTIGATION s/ CLINICAL PERFORMANCE  STUDIES \n- Published CLINICAL DATA  (e.g. Summary of Safety and Clinical Performance (SSCP) / Summary \nof Safety and Performance (SSP), Registries and databases from authorities)  \nExamples of generating new evidence (in no particular order) \n- Secondary data analysis (Analysis of real-world data) \n- Perform CLINICAL INVESTIGATION / CLINICAL PERFORMANCE  STUDY \n4.3. Technical Performance /Analytical Performance \nThe manufacturer should verify that the MDSW reliably, accurately and consistently meets the intended \npurpose in real-world usage.  \nThe relevant performance characteristics, as part of the GSPRs and linked to the analytical and / or clinical \nfeatures, should be supported by evidence generated during verification and validation activities as part of \ngood manufacturing practices for software, or by generating new evidence through the use of curated \ndatabases, curated registries, reference databases or use of previously collected patient data.   \nPage 13 of 21 \n TECHNICAL PERFORMANCE  / ANALYTICAL PERFORMANCE  is confirmed by the examination and provision \nof objective evidence that the MDSW specifications conform to user needs and intended uses, and that the \nrequirements implemented can be consistently fulfilled.7 \nFor example, performance verification and validation in the intended computing8 and use environments9,10 \ncan be characterised by the demonstration of  \n- availability, \n- confidentiality, \n- integrity, \n- reliability, \n- accuracy (resulting from trueness and precision),  \n- analytical sensitivity,  \n- limit of detection,  \n- limit of quantitation,  \n- analytical specificity,  \n- linearity,  \n- cut-off value(s),  \n- measuring interval (range),  \n- GENERALISABILITY , \n- expected data rate or quality,  \n- absence of inacceptable cybersecurity vulnerabilities,  \n- HUMAN FACTORS ENGINEERING .  \nIdentification of gaps during the validation of the T ECHNICAL PERFORMANCE /ANALYTICAL \nPERFORMANCE  could require generation of new evidence, for example, to demonstrate generalisability with \nreal-life datasets or to extend the usability evaluation to omitted user groups.  \n4.4. Clinical Performance \nFor the validation of a MDSW\u2019s  CLINICAL PERFORMANCE , the manufacturer should demonstrate that the \nMDSW has been tested for the intended use(s), target population(s), use condition(s), operating- and use \nenvironment(s) and with all intended user group(s). Section 4.1 of this document further provides context \nthat validation of C LINICAL PERFORMANCE  includes the assessment of clinical safety, effectiveness, \nperformance and can support the demonstration of CLINICAL BENEFIT . Validation of the CLINICAL \nPERFORMANCE should be considered at each change of the software to a new release. If no validation is \nperformed, a justification should be stated in the technical documentation.  \nWith a validation of C LINICAL PERFORMANCE , it is demonstrated that users can achieve clinically relevant \noutputs through predictable and reliable use of the MDSW.  \n                                                \n7 Derived from Source: GHTF/SG3/N18:2010. \n8 Computing environment: e.g., hardware, memory size, processing unit, time zone, network infrastructure) under which the \nsoftware is to perform. \n9 Use environment: actual conditions and setting in which users interact with the medical device.  \n10 Example on operating environments with distinct requirements are cloud or remote networks.   \nPage 14 of 21 \n The manufacturer should consider the intended use(s), indication(s), desired clinical output(s) expressed as \nclaims, leading to expected CLINICAL BENEFIT s as part of the CLINICAL PERFORMANCE  validation.  \nA MDSW may have multiple features with only some features claiming a specific CLINICAL BENEFIT . \nCLINICAL PERFORMANCE  is only applicable to those features. Since MDSW can be modular in nature, \nvalidation of the C LINICAL PERFORMANCE  is also permissible on module level when the functionality of \nthe modules is independent of the other modules. This would allow the confirmation of a continuous benefit \n/ risk acceptability only for the MDSW modules that have changed. In cases where the final combination \nof modules changes product indications and intended purposes, the performance of that final product \nconfiguration should also be evaluated. Validation of the C LINICAL PERFORMANCE  can be characterised by \nthe demonstration of applicable C LINICAL DATA to the MDSW in question, such as (non-exhaustive): \n- clinical/ diagnostic sensitivity, \n- clinical/ diagnostic specificity, \n- positive predictive value, \n- negative predictive value, \n- number needed to treat (average number of patients that need to be diagnosed/ treated in order to \nhave an impact on one person), \n- number needed to harm (number of patients that need to be diagnosed/ treated in order have an \nadverse effect on one patient),  \n- positive likelihood ratio, \n- negative likelihood ratio, \n- odds ratio, \n- USABILITY / user interface, \n- confidence interval(s). \nCLINICAL DATA  can be obtained by one or multiple methods such as those referred to in \nGHTF/SG5/N7:2012 and IMDRF/SaMD WG/N41FINAL:2017. \nIn addition to the considerations above, C LINICAL EVALUATION  of class III and implantable devices \n(MDR), shall include data from a C LINICAL INVESTIGATION  unless the conditions of Article 61(4), (5) or \n(6) of the MDR have been fulfilled. \nFor MDSW falling under the IVDR, the evaluation of clinical performance requires the carrying out of \nclinical performance studies  regardless of the classification of the device, unless due justification is \nprovided for relying on other sources of clinical performance data. \nRelevant common specifications should be taken into account.    \n4.4.1. Clinical investigations and clinical performance studies \nThe practical and achievable benefits of a C LINICAL INVESTIGATION / CLINICAL PERFORMANCE STUDY \nshould be considered as part of determining what data are needed for demonstrating the safety and \nperformance of a new or modified MDSW.  The investigation or study should account for potential risks, \nshould follow appropriate ethical requirements, and should be compliant with all relevant legal and \nregulatory requirements.  \nPage 15 of 21 \n MDSW has specific characteristics that should be considered when setting up a clinical investigation or \nclinical performance study.  If the MDSW is used for the determination of a patient\u2019s future state (e.g. \npredisposition, prognosis, prediction) or if the output of the MDSW impacts clinical outcomes (e.g. \ntreatment efficacy) or patient management decisions, then a prospective study  may be required as part of \nthe device\u2019s CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR). In other situations, \nretrospective analysis may be more appropriate to generate the necessary data to support compliance with \nthe GSPRs, as there is no impact on patient management and the research does not introduce any risks to \nthe patients. Such an approach is only possible under condition that there is an adequate access to data sets \nof sufficient amount and quality and obtained from the target population. \nFormal requirements of MDR Articles 62 (1), 74 and 82 need to be met as far as appropriate for pre-market \nretrospective studies of MDSW falling under the MDR. \n4.4.2. Where demonstration of conformity based on clinical data is not deemed appropriate  \nIn line with the provisions of MDR Article 61 (1) and IVDR Article 56(1), the level of CLINICAL EVIDENCE  \nrequired should be appropriate in view of the device claims and characteristics. For medical devices, where \nthe demonstration of conformity with GSPRs based on clinical data is not deemed appropriate (MDR \nArticle 61 (10)), the manufacturer shall duly substantiate in the technical documentation why it is adequate \nto demonstrate conformity based on the results of non-clinical testing methods alone, including \nPERFORMANCE EVALUATION , bench testing and preclinical evaluation, and USABILITY  assessment. \nThe justification must be based on the output of the risk management process. This should include an \nevaluation of clinical STATE-OF-THE-ART, including alternative diagnostic and treatment options, including \nthose identified from literature, and an appraisal of their relevance to the device under evaluation. The \ndevice / body interaction, the CLINICAL PERFORMANCE s intended, and the claims of the manufacturer should \nbe specifically considered. \nA CLINICAL EVALUATION (MDR) is still required, and the above information and evidence-based \njustification should be presented in the clinical evaluation report. \nSimilarly for IVDs, where due to specific device characteristics, demonstration of conformity with GSPRs \nbased on clinical data is not deemed appropriate, a PERFORMANCE EVALUATION (IVDR) is still required \nand a justification shall be provided and documented in the Performance Evaluation Plan and the \ncorresponding Performance Evaluation Report. \n4.5. Final analysis and conclusion of the clinical evaluation (MDR) / \nperformance evaluation (IVDR) \nThe manufacturer should compile evidence, perform the benefit-risk analysis and document the CLINICAL \nor PERFORMANCE EVALUATION and its output in the CLINICAL EVALUATION (MDR) / PERFORMANCE \nEVALUATION (IVDR)  report.  \n4.6. Continuous update of the clinical evaluation (MDR) / performance \nevaluation (IVDR) \nThe safety, effectiveness and performance of the MDSW should be actively and continuously monitored \nby the manufacturer.   \nPage 16 of 21 \n Such data may include, but is not limited to post-market information such as complaints, PMCF/ PMPF \ndata, REAL-WORLD PERFORMANCE  data, direct end-user feedback or newly published research / guidelines \nand should be subject to the CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) \nprinciples depicted in Figure 1. \nThe unique level of connectivity of MDSW facilitates access to REAL-WORLD PERFORMANCE  data, which \ncan be used for multiple purposes, including, but not limited to \n- timely detection and correction of malfunctions; \n- detection of systematic misuse; \n- understanding user interactions; \n- to conduct ongoing monitoring of CLINICAL PERFORMANCE ; \n- to improve effectiveness; \n- develop the claims in the CLINICAL DEVELOPMENT PLAN (MDR) or future releases. \nMDSW can be released for CE marking with initially claimed and validated CLINICAL BENEFITS . \nMonitoring of REAL-WORLD PERFORMANCE  data can help formulate hypotheses about future MDSW \nfunctionalities and intended use(s).   \nPage 17 of 21 \n Annex I \u2013 Methodological principle for generation of CLINICAL EVIDENCE  \n \n \nPage 18 of 21 \n Annex II \u2013 Examples of CLINICAL EVALUATION (MDR) /  PERFORMANCE \nEVALUATION  (IVDR) strategies  \nThe high-level examples provided here are for guidance purposes only and aim to provide general \nindications on how to develop a CLINICAL EVALUATION / PERFORMANCE EVALUATION  strategy. The \nstrategy presented in each example is not a confirmation  of the pathway for a CLINICAL EVALUATION / \nPERFORMANCE EVALUATION  of the device, as other factors need to be considered.  \nMoreover, the proposed pathway reflects the specific intended purpose, or the healthcare context or \nsituation, in which the device is used as described in the example itself. Any change to the intended purpose \nor the healthcare context / situation in which that same device is used might result in a different approach. \nData source Examples \nPeer-reviewed, relevant scientific literature  - Existing data from studies conducted \nwith the subject device or equivalent \ndevice \nCLINICAL INVESTIGATION / CLINICAL \nPERFORMANCE  STUDIES - Prospective or retrospective studies \n- Existing manufacturer data  \n- Data from equivalent devices \n- Data from curated \ndatabases/registries/reference databases \n- Data from outside the EU with \njustification on applicability \n \nPublished experience gained by routine \ndiagnostic testing - REAL-WORLD PERFORMANCE DATA  \n- Data obtained from PMPF/ PMCF \n \n \na) MDSW intended to analyse sleep quality data \nAn independent MDSW intended to take into account accelerometer and microphone data to determine \nquality of sleep and to estimate the expected success rate of CPAP (continuous positive airway pressure) \ntreatment for sleep apnoea.  \nThe Manufacturer claims that the MDSW \n- determines the quality of sleep that impacts the general well-being. \n- monitors quality of sleep in patients with sleep disorders such as sleep apnoea (using phone \nsensors/wearable devices) \n- estimates the expected success rate of CPAP therapy. \nValid Clinical Association  \nTo establish VALID CLINICAL ASSOCIATION , review literature. \n- Objective quality of sleep is measured by sleep duration, efficiency and fragmentation.  It is further \nwell-established that quality of sleep impacts general well-being such as concentration, risk-factors \nfor cardiovascular disease, mood, cognitive abilities, etc.   \nPage 19 of 21 \n - It is not well-established that the success of CPAP therapy can be predicted by monitoring the \nquality of sleep. \n- Address the association of accelerometer and microphone data to established quality of sleep \nparameters (e.g. sleep duration, efficiency and fragmentation). \nThe VALID CLINICAL ASSOCIATION  has been not established without gaps for prediction of success of CPAP \ntherapy, which requires generation of missing clinical data. \nTechnical Performance  \n- Confirm with verification and validation tests that the app can reliably and reproducibly calculate \nsleep quality scoring. \n- Confirm compatibility between the MDSW and the device equipped with the sensors to ensure data \ncan be utilised in the intended way.  \nClinical Performance  \n- In addition to the USABILITY  assessment, the manufacturer would perform a retrospective study on \npreviously obtained data to confirm that success of CPAP therapy can be predicted based on the \nquality of sleep.  \nb) MDSW intended for image segmentation \nAn independent MDSW intended to allow automatic detection of organs and anatomical structures (such \nas the aorta) in CT scans with the accuracy of a radiologist. \nThe Manufacturer claims that the MDSW: \n- detects abdominal aortic aneurisms on abdominal CT scans, \n- detects compression fractures on vertebrae,  \n- detects liver cysts. \nValid Clinical Association  \nTo establish VALID CLINICAL ASSOCIATION , review literature. \n- The normal shape and size of anatomy is well established. \n- Segmentation techniques on cross-sectional images correlates well with the actual size and shape. \nThe VALID CLINICAL ASSOCIATION  has been established without gaps identified.  \nTechnical Performance  \n- Confirm with verification and validation tests the basic technical performance such as display, \nmodification, window levelling of images, measurements including confirmation of accuracy, \nsensitivity and reliability of the MDSW as per the expected performance. \n   \nPage 20 of 21 \n Clinical Performance  \n- USABILITY  assessment including the intended user groups in conjunction with the VALID CLINICAL \nASSOCIATION  and validation of T ECHNICAL PERFORMANCE  results has been determined as \nsufficient to demonstrate conformity with relevant GSPRs. \n- In cases where data is available, a retrospective analysis can be performed. In cases where data \ndoes not represent the variability of input parameters, for the CLINICAL PERFORMANCE  of the \nsegmentation algorithm, the missing data could be generated in a prospective CLINICAL \nINVESTIGATION .  \nc) MDSW intended to detect inflammatory bowel diseases (IBD) \nSelf-testing independent MDSW intended for the semi-quantitative detection of calprotectin from a faecal \nsample. Reagents are added to the sample resulting in a colour change. The sample is then photographed \non a smartphone, and the image is evaluated by an MDSW application (app) running on the phone. The \nMDSW app detects the colour change in the sample and interprets the concentration of calprotectin. The \ntest is intended as an aid in monitoring and staging of patients with inflammatory bowel disease (IBD). \nManufacturer\u2019s claims that the MDSW app \n- aids in monitoring and staging the disease level of patients with inflammatory bowel diseases \n(IBD). \n- aids in differentiation between IBD and functional bowel disorders.  \n- helps patients avoid unnecessary clinical visits.  \nScientific Validity  \nTo establish S CIENTIFIC VALIDITY, review literature.  \n- The SCIENTIFIC VALIDITY could address how the calprotectin level corresponds to the IBD level \nand stages. Furthermore, it should address, whether calprotectin levels are suitable to differentiate \nbetween IBD and functional bowel disorders. \n- It is well-established that calprotectin concentration in faecal matter can be reliably measured in \ntest strips by change of colour.  \n- The colour intensity is directly representative of the concentration of calprotectin.  \nAnalytical Performance  \n- Confirm the MDSW app can detect reliably and accurately the colour of the test strip compared to \nhuman observation, taking into account environmental factors.  \nClinical Performance  \n- The manufacturer should assess the initial performance and feasibility by creating CLINICAL \nPERFORMANCE  metrics, taking into account sensitivity, specificity and confidence intervals. \n- Any claims regarding CLINICAL BENEFIT  should be supported by sufficient clinical performance \ndata.   \n- USABILITY  should be confirmed by the manufacturer.   \nPage 21 of 21 \n d) Active devices containing MDSW to enable their intended purpose  \nActive devices, such as diagnostic or therapeutic devices, that include MDSW which drives the device in a \nway that, without the software it would not be able to fulfil its intended purpose. This software does not \nperform a medical purpose on its own.    \nThe CLINICAL EVALUATION  of the MDSW should not be performed independently but should be performed \ntogether with the driven device.  \ne) MDSW which provides an additional user-interface to control an insulin pump \nA MDSW intended to virtualise controls of an insulin pump additionally on a smartphone app by connecting \nto it.  \nAs the software is driving the insulin pump, it is not performing a medical purpose on its own, nor is it \ncreating information on its own for medical purposes.  \nThe CLINICAL EVALUATION  of the MDSW app should not be performed independently but should be \nperformed together with the driven insulin pump.  \nf) MDSW intended to analyse exhaled CO2 in a life-sustaining device in order to control \nventilator settings \nThe MDSW uses physiological data of the patient (e.g. exhaled CO 2, blood oxygen saturation) to control a \nventilation device (e.g. frequency, volume and pressure). \nThe MDSW allows the device to maintain the pre-set value at a desired target (defined by the clinician) \nwithout periodic user adjustments needed. This MDSW is part of a closed-loop system.  \nThe CLINICAL EVALUATION  should not be limited to the MDSW and should include pre-clinical and clinical \ninvestigations, encompassing the entire closed-loop system."}, {"title": "mdcg_2019_9_sscp_en.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  1(24)  \n \n \nMDCG  2019-9 \n \nSummary of safety and clinical performance \nA guide for manufacturers and notified bodies \n                \n \n \nAugust  2019 \n \n \n  \n \n \n  This document has been endorsed by the Medical Device Coordination Group (MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member States and it is chaired by a representative of the European Commission. The document is not a European Commission document and it cannot be regarded as reflecting the official position of the European Commission. Any views expressed in this document are not legally binding and only the Court of Justice of the European Union can give binding interpretations of Union law.  \n \n \n   \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  2(24)  \n \n \n \n \n \n \nMDCG 2019-9 \nSummary of safety and clinical performance  \nA guide for manufacturers and notified bodies  \n \nAugust 2019 \n \nTable of contents  \nIntroduction  .............................................................................................................................. ...............................3  \nAbbreviations  .............................................................................................................................. ...........................3  \nGeneral requirements and recommendations for the SSCP  ..........................................................................4  \nValidation and uploading of the SSCP  ...............................................................................................................7  \nGuidance for each of the required sections of the SSCP document  ...........................................................10  \n1. The identification of the device and the manufacturer, including the Basic UDI-DI and, if  \nalready issued, the SRN  .........................................................................................................................10  \n2. The intended purpose of the device and any indications, contraindications and target \npopulations  .............................................................................................................................. ..................11  \n3. A description of the device, including a reference to previous generation(s) or variants if      \nsuch exist, and a description of the differences, as well as, where relevant, a description of any accessories, other devices and products, which are intended to be used in combination with      \nthe device  .............................................................................................................................. ....................11\n \n4. Information on any residual risks and any undesirable effects,  warnings and precautions  ......12  \n5. The summary of clinical evaluation as referred to in Annex XIV, and relevant information on \npost-market clinical follow-up  .................................................................................................................15  \n6. Possible diagnostic or therapeutic alternatives  ...............................................................................18  \n7. Suggested profile and training for users  ...........................................................................................19  \n8. Reference to any harmonised standards and CS applied  .............................................................19  \n9. Revision history  .............................................................................................................................. ......19  \nReferences  .............................................................................................................................. .............................20  \nAppendix: Template for the SSCP  ....................................................................................................................21   \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  3(24)  \nIntroduction \n \nThe Regulation (EU) 2017/745 on medical devices (1) requires that the \nmanufacturer shall draw up a summary of safety and clinical performance (SSCP) for implantable devices and for class III devices, other than custom-made or \ninvestigational devices. The SSCP shall be validated by a notified body (NB) and made available to the public via the European database on medical devices (Eudamed)\n1. \n The SSCP is intended to provide public access to an updated summary of clinical data\n2 and other information about the safety and clinical performance of the medical \ndevice. The SSCP will be an important source of information for intended users \u2013 both healthcare professionals and if relevant for patients. It is one of several means intended to fulfil the objectives of the Medical Device Regulation (MDR) to enhance transparency and provide adequate access to information\n3. \n The SSCP is not intended to: \n\u0081 give general advice on the diagnosis or treatment of particular medical \nconditions, nor \n\u0081 replace the instructions for use (IFU) as the main document that will be \nprovided to ensure the safe use of a particular device, nor \n\u0081 replace the mandatory information on implant cards\n4 or in any other \nmandatory documents. \n The main purpose of this document is to provide guidance on the presentation, content and validation of the SSCP. The word \u201cshall\u201d is used when there is a corresponding \u201cshall\u201d in the MDR, otherwise \u201cshould\u201d or \u201crecommended\u201d etc. is used indicating the interpretation of the MDR.  \nAbbreviations \n \nCIV ID clinical investigation identification number, generated by Eudamed for  \nclinical investigations under the Medical Device Directives (2) (3) \nCMR carcinogenic, mutagenic or toxic to reproduction CS \u2018common specifications\u2019 as defined in the MDR\n5 \nEU European Union  Eudamed European database on medical devices FSCA field safety corrective action\n6 \nFSN field safety notice7 \n                                                 \n1 MDR, Article 32 (1) \n2 MDR, Article 32 (2)(f) , Article 61 (11) and Article 83 (3)(d) \n3 MDR, Recital (43) \n4 MDR, Article 18 \n5 MDR, Article 2 (71) \n6 MDR, Article 2 (68)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  4(24) IFU instructions for use \nMDR Medical Device Regulation (1) NB notified body\n8 \nPMCF post-market clinical follow-up9 \nPMS post-market surveillance10 \nPSUR periodic safety update report11 \nSRN single registration number for an economic operator12 \nSSCP summary of safety and clinical performance TD technical documentation\n13 \nUDI-DI Unique Device Identification - device identifier14 \nURL Uniform Resource Locator (internet address)  \nGeneral requirements and re commendations for the SSCP \n \nThe information in the SSCP should be sourced entirely from the technical documentation (TD) of the device\n15. Examples of such documents are design \nverification/validation reports, the risk management report/file, the clinical evaluation report, and post-market surveillance (P MS) and post-market clinical follow-up \n(PMCF) plans and reports. The IFU includes information extracted from the same sources as the SSCP, but may itself be used as a source for the SSCP if appropriate.  The SSCP shall be kept updated in Eudamed\n16. When the PMCF evaluation report17 \nand the periodic safety update report (PSUR)18 are updated at least annually19, the \nSSCP shall be reviewed and updated20 if needed to ensure that any clinical and/or \nsafety information in the SSCP remains correct and complete. When updating the SSCP, all sections of the document shall be updated if needed so that they are in alignment with the most current version of the relevant parts of the TD of the device.  This guide outlines the minimum content of the SSCP. The manufacturer may add further information from the TD of the device to enhance the comprehension of the mandatory information providing: \n\u0081 it does not affect the readability of the SSCP and \n\u0081 it excludes any element of a promotional nature. \n                                                                                                                                                           \n7 MDR, Article 2(69) \n8 MDR, Article 2 (42) \n9 MDR, Annex XIV Part B \n10 MDR, Article 2 (60) \n11 MDR, Article 86 Periodic safety update report \n12 MDR, Article 31(2) \n13 MDR, as specified in Annexes II and III. \n14 MDR, Article 2 (15) and Article 27 \n15 MDR, Annex II and III \n16 MDR, Article 29 (4) and Annex VI Part A 2.14 \n17 MDR, Article 61 (11) \n18 MDR, Article 86 (1) \n19 MDR Article 86 (1); PSUR for class IIa devices shall be updated when necessary and at least every two years \n20 MDR, Article 61 (11) and Article 83 (3)(d)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  5(24)  \nThe SSCP shall be objective  and adequately summarise  both favourable and \nunfavourable data21.  \n For further guidance on the contents of the SSCP, please refer to sections 1-8 of this document and to the template in the Appendix. The format and structure of this template is recommended. It addresses all of the SSCP content requirements of the MDR\n22, but the order has been revised to enhance its presentation. \n The IFU shall contain all that is needed to directly find the SSCP in Eudamed. The following applies to the IFU\n23. \n\u0081 It shall state that the SSCP is available in the European database on medical \ndevices (Eudamed), where it is linked to the Basic UDI-DI. \n\u0081 It should provide the URL to the Eudamed public website:  \nhttps://ec.europa.eu/tools/eudamed  \n\u0081 It should state the value of the Basic UDI-DI. Alternatively, another metadata \ncan be stated provided it can be used to unambiguously search and find the intended SSCP in Eudamed.  \n Translations to other EU languages No single language will be understood by all intended users and patients in the EU \u2013 see the European Survey on Language Competences initiated by the European Commission (4). In order to meet the requirement in the MDR that the SSCP shall be written in a way that is clear to the intended user and, if relevant, to the patient\n24, \nthe SSCP should be translated into the languages accepted in the Member States where the device is envisaged to be sold. This is by analogy with the requirement for an IFU\n25. Note that Member States may have different language requirements for an \nIFU depending on whether the information is intended for health care professionals or for patients. The SSCP part intended for patients should be provided in all the languages required for IFUs intended for patients in the Member States concerned.  If the selection of European languages for the SSCP does not include English, then an English translation of the document should also be provided. English is the most common language used in medical scientific publications and is understood by many healthcare professionals in the EU. Always providing an English-language version of the SSCP further enhances access to information\n26 about devices available on the \nEU market.   There should be one SSCP document for each language. Each SSCP document should state in which language the SSCP was validated by the NB. The manufacturer should ensure, through their quality management system, that the translations are correct. \n                                                 \n21 MDR, Annex XIV, Part A Clinical evaluation, (2) \n22 MDR, Article 32 (2) \n23 MDR, Article 32 (1) and Annex I, 23.4 (d) \n24 MDR, Article 32 (1) and Recital (43) \n25 MDR, Annex II (2), Article 10 (11) \n26 MDR, Recital (43)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  6(24)  \nRelevant SSCP information for patients The MDR indicates that patients are also intended recipients of the information in the SSCP, \u201cif relevant\u201d\n27. Devices for which information will be especially relevant for \npatients include: \n\u0081 implantable devices for which patients will be given implant cards28, and \n\u0081 class III devices that are intended to be used directly by patients. \n \nFor these devices, a part of the SSCP specifically intended for patients should be provided.  Note: Devices listed in MDR Annex XVI, and eligible for a SSCP, should always be considered as relevant for patient information.  For devices other than the two groups listed above, including any devices listed in Annex XVI and eligible for a SSCP, the manufacturer may consider whether it is relevant to provide specific information intended for patients. This can be based on the manufacturer\u2019s analysis of the device in question.  Readability The SSCP should always have one part for intended users/healthcare professionals, and when it is relevant (see above) a second part for patients. Both should be clear and provide information at an appropriate depth to reflect the healthcare professionals\u2019 and the patients\u2019 different levels of knowledge\n29. \n For further guidance, see references (5) and (6) in this guide. It should not be assumed that the patient has any formal education in a medical discipline or any prior knowledge of medical terminology or clinical research. It is recommended that the readability of the part of the SSCP intended for patients is assessed for example by a test given to lay persons. The manufacturer may use a method it finds adequate for the readability test to confirm that the SSCP is written in a way that is clear to the patient\n30. \n Medical terminology, relevant for the medical device and the clinical context, should be used consistently throughout the part of the SSCP that is intended for healthcare professionals.  Stylistic recommendations The SSCP should be presented in an organised and unambiguous manner.   Usually, abbreviations and acronyms should not be used; if they are, then in the text, the abbreviation or acronym should follow the full phrase it is intended to replace. It may then be used thereafter throughout the document.  \n                                                 \n27 MDR, Article 32 (1) \n28 MDR, Article 18 \n29 MDR, Article 32 (1) and Recital (43) \n30 MDR, Article 32(1), Article 2 (38)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  7(24) Medical terms should be explained in simple language in the parts intended for \npatients. Consistency should be assured by giving the lay term with a description first, and then the medical term immediately afterwards (in brackets). On a case-by-case basis the lay or medical term (but preferably the lay term) may then be used throughout the part intended for patients.  It is recommended to keep the information for patients/lay persons and for intended users/healthcare professionals in two separate parts of the SSCP, separated by a \u201cpage break\u201d. This enhances their readability and facilitates printing of each part \nseparately. See the template in the Appendix of this document.   The SSCP should be written in a font type and size which allow easy reading. Since the SSCP is intended for the public, it needs to be in a format that everyone can read (and that is not editable) without the need for a license. Therefore the SSCP file uploaded in Eudamed should be in PDF format. When downloaded, the PDF file should be printable and searchable with t he search function in the program used to \nview the file, for example the Adobe Reader. \nValidation and uploading of the SSCP \n \nValidation of the initial SSCP by the NB When the NB has assessed that all the required elements\n31 are included in the draft \nSSCP, accurately presented and in alignment with the most current version of \nrelevant documents in the TD, the SSCP has been validated  by the NB. \n \nIn the circumstance that the conformity assessment is performed according to Annex X and XI in the MDR and there are two NBs involved, it is the NB which assesses the TD according to Annex X that shall validate the SSCP.  The validation of the SSCP by the NB covers only one of the language(s) accepted by the NB and agreed with the manufacturer. The manufacturer should state in the revision history in each SSCP document in which language the SSCP was validated by the NB.  The timing of the SSCP validation may depend on the class of device and the conformity assessment routes: \n\u0081 For class III devices and class IIb im plantable devices, except  sutures and \nstaples etc.\n32, the validation is performed when a draft SSCP as a part of the \napplication documents is submitted to the NB involved in the conformity assessment\n33, prior to issuing the certificate. \n\u0081 For class IIa implantable and some IIb implantable devices such as sutures \nand staples etc34, a draft SSCP as a part of the application documents shall \nbe submitted to the NB involved in the conformity assessment. The draft \n                                                 \n31 MDR, Article 32 (2), Article 61 (11), and Article 83 (3) (d) \n32 MDR, Article 52 (4) 2nd paragraph \n33 MDR, Article 32 (1) \n34 MDR, Article 52 (4) 2nd paragraph  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  8(24) SSCP shall be validated by the NB35.  \n In the circumstance if more than one device is covered by the relevant certificate, at least one draft SSCP shall be validated against relevant documents in the TD during the initial conformity assessment, prior to issuing the certificate.   Draft SSCPs that are not validated at the initial conformity assessment, shall be validated against relevant documents in the TD at least once during the period of validity of the certificate. \n Validation of updates of the SSCP between certifica tion activities \nThe manufacturer has an obligation to keep the SSCP updated; for further details see the section \u201cGeneral requirements and recommendations for the SSCP\u201d in this guide. Furthermore the manufacturer shall prepare a periodic safety update report (PSUR) that includes data gathered as a result of the post-market surveillance plan, description of any preventive and corrective actions taken, conclusions of the benefit-risk determination, and the main findings of the PMCF\n36.  \nIf the PSUR contains information rendering any information in the SSCP incorrect or incomplete, the SSCP shall be updated\n37 to be in line with the information in the \nmost recent PSUR.  The manufacturer shall submit a PSUR to the NB at least annually, or for class IIa implantable devices\n38 at least every two years39.  \nIf the SSCP has been updated with new/changed information, except for strictly editorial modifications, the manufacturer should submit the updated SSCP to the NB when submitting the required PSUR.  \n\u0081 If the SSCP has been previously validated, the NB should validate the updated \nSSCP against the submitted and evaluated PSUR. Both the NB and the \nmanufacturer should make an effort to keep the validation time short in order to meet the MDR requirement of an update of the SSCP at least annually if indicated\n40.  \n\u0081 If the SSCP has not previously been validated41, the NB may defer the \nvalidation until a validation against the relevant documents in the TD is planned during the period of validity of the certificate.  \n In addition, as part of its surveillance activities, the NB shall verify that the manufacturer has appropriately updated the SSCP. The NB should take into consideration its assessment of the PMS plan and PSUR, the PMCF plan and its evaluation report, and/or other relevant information. \n                                                 \n35 MDR, Article 32 (1) \n36 MDR, Article 86 (1) \n37 MDR, Article 29 (4) and Annex VI Part A 2.14, and Article 61 (11) and Article 83 (3)(d) \n38 In this context applicable for implantable devices intend ed to be placed in the teeth, MDR Annex VIII, 5.4. Rule \n8) \n39 MDR, Article 86 (1) \n40 MDR, Article 61 (11) \n41 May only be applicable for class IIa implantable devices and some IIb implantable devices such as sutures, \nstaples etc. as listed in MDR, Article 52 (4) 2nd paragraph  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  9(24)  \nValidation of SSCP at certificate renewal With each certificate renewal application, the manufacturer should: \n\u0081 For class III devices and class IIb impl antable devices, other than sutures and \nstaples etc.\n42, submit a draft SSCP which has been updated within the previous \n12 months, regardless of whether there are new data or conclusions. \n\u0081 For class IIa implantable and IIb implantable devices, such as sutures and \nstaples etc.43, confirm that the SSCP in Eudamed is in alignment with the \ncurrent version of the TD, or provide an updated SSCP where required. \n \nAt certificate renewal, the same principles should apply for the validation of the SSCP documents as at the initial certification.  Uploading of the SSCP in Eudamed The SSCP shall be uploaded in Eudamed by the NB\n44, which is the only actor that \ncan manage the SSCPs in Eudamed. Timelines for uploading of the SSCP documents in Eudamed: \n\u0081 The NB shall upload the SSCP validated in conjunction with an initial \nconformity assessment at the same time that it uploads the issued certificate. \n\u0081 For class IIa implantable and IIb implantable devices, such as sutures and \nstaples etc.\n45, the NB shall upload the SSCPs of all the devices covered by \nthe issued certificate at the same time that it uploads the issued certificate, even if some of the SSCPs have not been validated yet, and are to be validated during the period of validity of the certificate.  The manufacturer should state in a revision history in the SSCP document whether that revision was validated by the NB. It is important and should be transparent to the public\n46 whether the SSCP document has been validated \nyet by the NB. See the example of a revision history in section 9 and in the template in the Appendix of this guide. \n\u0081 The NB shall upload a SSCP whenever it has been validated against relevant \ndocuments in the TD, and thus replacing the SSCP uploaded at the initial \ncertification with the currently validated revision. \n\u0081 The manufacturer is responsible for the translations of the SSCP into other \nlanguages\n47, once the \u201cmaster\u201d SSCP has been uploaded by the NB.  \nIf the \u201cmaster\u201d SSCP is in a language other than English, then an English translation should be provided by the manufacturer within 90 days of the upload of the \u201cmaster\u201d SSCP. The NB should upload the English translation within 15 days of receiving this from the manufacturer. \n\u0081 The manufacturer decides when it translates the initial \u201cmaster\u201d SSCP into \nother languages in the Member States depending on when/if they plan to place the product on that market. \n                                                 \n42 MDR, Article 52 (4) 2nd paragraph \n43 MDR, Article 52 (4) 2nd paragraph \n44 MDR, Article 32 (1) \n45 MDR, Article 52 (4) 2nd paragraph \n46 MDR, Recital (43) \n47 See page 4 in this guide, Translations to other EU languages; The manufacturer should ensure, through their \nquality management system, that the translations are correct.  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  10(24) The NB does not validate the translated SSCP documents. It should upload \nthem in Eudamed within 15 days of receiving them. \n The manufacturer shall verify that the SSCP, and any translations needed for any single Member State, have been uploaded in Eudamed before placing a device on that market\n48. \n \n\u0081 When receiving an updated SSCP document in conjunction with the PSUR, \nthe NB should upload the updated SSCP document within 15 days after it is validated, or within 15 days after deeming the validation to be deferred\n49 until \na validation against the relevant documents in the TD is planned during the period of validity of the certificate.  \n\u0081 At certificate renewal, the NB shall upload any updated SSCPs of all the \ndevices covered by the reissued certificate at the same time that it uploads \nthe reissued certificate. The NB should ensure the revision history indicates whether or not these have been validated by the NB. \n\u0081 The manufacturer should provide updated translations to the NB within 90 \ndays of the upload of the updated \u201cmaster\u201d SSCP.  The NB should upload these translations within 15 days of receiving them from the manufacturer. \n \nGuidance for each of the required sections of the SSCP document \n \n1. The identification of the device and the manufacturer, including the Basic \nUDI-DI and, if already issued, the SRN \n \nThe first section of the SSCP shall ident ify the device and the manufacturer, and \nshould also contain some general information related to the device:  \n1.1. Device trade name(s) (this include all trade names the device may have on \nthe market in different Member States) \n1.2. Manufacturer\u2019s name and address 1.3. Manufacturer\u2019s SRN (single registration number) 1.4. Basic UDI-DI 1.5. Medical device nomenclature\n50 description / text  \n1.6. Class of device51 \n1.7. Year when the first certificate (CE) was issued covering the device 1.8. Authorised representative if applicable; name and the SRN 1.9. NB\u2019s name (the NB that will va lidate the SSCP) and the NB\u2019s single \nidentification number\n52 \n \n                                                 \n48 MDR, Article 29 (4) and Section 2 of Part A of Annex VI (2.14) \n49 May only be applicable for class IIa implantable devices and some IIb implantable devices as listed in MDR, \nArticle 52 (4) 2nd paragraph \n50 MDR, Article 26 \n51 MDR, Annex VIII \n52 MDR, Article 43 (1)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  11(24) 2. The intended purpose of the device and any indications, contraindications \nand target populations \n \n2.1. The device's intended purpose(s) shall be described.  \n \n2.2. The indications shall be described. This includes the stages and/or severities \nof the pathologies, the specific medical conditions, and the specific anatomical locations or confirmation that no anatomical locations are contraindicated, as applicable. The target population(s) shall be specified, for example if the device is intended for adults and/or children and/or infants/neonates. \n \n2.3. Any contraindications or restrictions for use or limitations of the device shall \nbe included. \n The information can be sourced from the IFU, or from the clinical evaluation report. \n3. A description of the device, including a reference to previous generation(s) \nor variants if such exist, and a description of the differences, as well as, where relevant, a description of any accessories, other devices and products, which are intende d to be used in comb ination with the device \n \n3.1. A description of the device shall be presented, including its operating \nprinciples and mode(s) of action. Design characteristics should be included, for example key functional elements and any materials or substances in contact with the patient\u2019s tissues. Include information on whether the device is for single use, and its method of  sterilisation. For absorbable implants the \nstability retention profile, including time  to loss of stability and the absorption \ntime, should be provided.  A picture or drawing can be added accompanied by text.  \n \nInformation about the constituents should be provided, as required for the IFU\n53, if the device incorporates \n\u0081 a medicinal substance (including a human blood or plasma derivative), or  \n\u0081 tissue(s) or cells of human or animal origin, or their derivatives, or \n\u0081 substances or combinations of subs tances that are absorbed by or locally \ndispersed in the human body, or \n\u0081 materials incorporated into the device that contain or consist of CMR \n(carcinogenic, mutagenic or toxic to reproduction) substances or \nendocrine-disrupting substances, or  \n\u0081 materials that could result in sensitisation or an allergic reaction by the \npatient or user. \n \nIn Eudamed, the SSCP is associated to one unique Basic UDI-DI. All UDI-DIs/devices associated to this Basic UDI-DI will be seen as having the same \n                                                 \n53 MDR, Annex I (23.2) (e) and (r), and (23.4) (s)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  12(24) SSCP (a UDI-DI/device must always be associated with one and only one \nBasic UDI-DI).  If the device is a system of several components/devices, each device in the system should have a Basic UDI-DI but also one Basic UDI-DI for the system. It is the Basic UDI-DI for the system that is intended to be provided in section 1.4 in the template, and that will be associated with the SSCP in Eudamed. The device system, and any Basic UDI-DIs of included devices, should be described in section 3.1.  The device description in the SSCP shall therefore include all the device(s)/device system associated  with the same Basic UDI-DI. The \ndescription of the device(s)/device system should be comprehensive and can be presented in different ways to include, if such exist, any configurations / combinations / different sizes / specification of any soft-ware versions that can be related to safety and/or performance and their release dates / etc.  The description should also include any model number or similar designation used to identify the device(s)/device system.  \n \n3.2. A reference to previous generation(s) or variants shall be provided, if such \nexist. This applies both to changes/variants of the device itself (same Basic UDI-DI) and to previous generation(s) or variants associated with other Basic UDI-DIs, if available. A description of the differences shall be provided, highlighting the reasons for the change; for example changes to the intended clinical benefits, changes to reduce iden tified clinical risks, or changes for \nmanufacturing reasons etc.  \n 3.3. If there are any accessories\n54 that are not themselves devices, but are \nintended by the manufacturer to be used in combination with the device, they shall be described or listed. The list of accessories should include all those that are essential for the safe and correct use of the device.  \n \n3.4. If there are any other devices and products intended to be used in \ncombination with the device, they shall be described or listed. However, generic surgical equipment and/or other generic devices do not need to be listed. \n In the part of the SSCP that is intended for patients, section 3 may be limited to the device(s) in question (Basic UDI-DI) including relevant and necessary accessories from a patient\u2019s perspective; see suggested headings for section 3 in the template in the Appendix.  \n4. Information on any residual risks and any undesirable effects, warnings \nand precautions \n \n                                                 \n54 MDR, Article 2 (2)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  13(24) 4.1. Residual risks and undesirable effects \n This section of the SSCP guide and template includes residual risks\n55, other \nthan those contraindications, limitations, warnings and precautions that are included in sections 2.3 and 4.2.   Description of residual risks and undesirable effects Risk is defined in the MDR\n56 as the combination of the probability of \noccurrence of harm and the severity of that harm. Harm is defined in the standard ISO 14971:2012\n57 as physical injury or damage to the health of \npeople, or damage to property or the environment. Thus the term \u2018risk\u2019 includes both clinical and non-clinical harms.   The term \u2018residual risk\u2019 is defined in the standard ISO 14971:2012\n58 as \u201crisk \nremaining after risk control measures have been taken\u201d.  \nThere is a requirement in the MDR that the IFU shall contain information on \nany residual risks and any  undesirable side-effects\n59, i.e. no sort of residual \nrisk or undesirable side-effect related to the device is excluded from \ndisclosure. The SSCP should contain information on at least the same residual risks and undesirable side-e ffects as included in the IFU. \n \nFor the purpose of the SSCP, an undesirable effect\n60 can be understood as \nany undesirable side-effect related to the device and that is experienced by the patient and/or can be diagnosed and/or measured in the patient. \n  For the clarity of the SSCP, undesirable side-effects can be annotated also in other terms as appropriate, to present any undesirable side-effects related to the device in question. There may be device-specific terminology for describing side-effects and risks in device -specific ISO standards or scientific \nliterature that is important to use to allow comparison of clinical data.  For example, some events indicated in the MDR by the terms \u2018adverse events\u2019\n61, \u2018undesirable side-effects\u2019 or \u2018incidents\u201962, may all be annotated as \n\u2018adverse events\u2019 in the scientific literature.  Any further discussion on risks can be included in the SSCP if needed for clarity or comprehension.  \nQuantitative data The definition of risk\n63 includes the probability of occurrence of harm. \nTherefore the information in the SSCP on risks shall also include \n                                                 \n55 MDR, Annex I, (23.1) (g) \n56 MDR, Article 2 (23) \n57 EN ISO 14971:2012 Medical devices \u2013 Application of risk management to medical devices, section 2.2 \n58 EN ISO 14971:2012 Medical devices \u2013 Application of risk management to medical devices, section 2.15 \n59 MDR, Annex I , 23.4 (g) \n60 MDR, Article 32 (2) (h) \n61 MDR, Article 2 (57) \n62 MDR, Article 2 (64)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  14(24) quantifications. This information can be sourced from the clinical evaluation \nreport where an updated examination of qualitative and quantitative aspects of clinical safety is available, with clear reference to the determination of residual risks and side-effects\n64. \n It should also be clarified in the SSCP whether quantitative data on side-effects or residual risks rela te to clinical data that were obtained proactively, \nfor example from a structured prospective follow-up study of the device itself, or if the expected frequencies\n65 come from a systematic review of the \nscientific literature. It should be disclosed in the SSCP if data from spontaneously reported incidents or serious incidents\n66 are used as one of \nthe sources for estimating quantitative data on side-effects or residual risks, in which case significant under-reporting needs to be considered.   A relation to time should also be included when presenting the quantitative data, for example during five or ten years of use from implantation, or adverse events per 100 patient-years for implantable devices with constant hazards, etc. The quantitative data and the relation to time should always be presented together.  \nTo use tabulated lists for the presentation of side-effects and residual risks with quantitative data and a relation to time, may enhance the readability.   In the part of the SSCP that is intended for patients, residual risks and side-effects should be explained and quantified in a way that patients and lay persons can understand. A statement should be included about how potential risks have been controlled or managed, and also a statement on what to do if the patient believes that he/she is experiencing side-effects related to the device or its use. See the example in the template in the Appendix.  \n \n4.2. All warnings and precautions pertaining to the device should be presented. \nHowever warnings and precautions solely related to for example installation/preparation of a device or relating to special procedural steps can be discussed on a general level in the SSCP if a link (URL) to the IFU on the manufacturer\u2019s website is provided.  Always include any warnings, precautions or measures to be taken by the patient or a healthcare professional with regard to reciprocal interference with reasonably foreseeable external influences, medical examinations or environmental conditions.   If any particular clinical follow-up is necessary and mentioned in the IFU, that information should also be included in the SSCP.  \n                                                                                                                                                           \n63 MDR, Article 2 (23) \n64 MDR, Annex XIV, Part A Clinical evaluation, (1) \n65 MDR, Article 88 (1) \n66 MDR, Article 2 (64) and (65)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  15(24) 4.3. Other relevant aspects of safety s hould be described. If the device  has been \nsubject to any field safety corrective action (FSCA including FSN), the date of the FSCA and a summary of the associated circumstances and any actions undertaken should also be included.   \n5. The summary of clinical evaluation as referred to in Annex XIV, and relevant \ninformation on post-market clinical follow-up \n \nThis part of section 5 relates to content intended for the user/healthcare professional.  This section is intended to summarise, in a comprehensive manner, the clinical evaluation results and the clinical data\n67 forming the clinical evidence68 for the \nconfirmation of conformity with relevant general safety and performance requirements\n69, the evaluation of undesirable si de-effects and the acceptability of \nthe benefit-risk ratio70. \n It shall be an objective and balanced summary of the clinical evaluation\n71 results \nof all the available clinical data related to the device in question, whether favourable, unfavourable, and/or inconclusive.  See suggested headings for this section in the Appendix of this document.   \n5.1. The SSCP should include a statement if conformity of the device was \nassessed and endorsed by the NB on the basis of equivalence. If equivalence was used, t hen the device(s) for whic h equivalenc e has been \ndemonstrated should be identified by name and Basic UDI-DI if available, together with the name(s) of its/their manufacturer(s). \n \nThe SSCP should also include a statement whether the equivalent device\u2019s SSCP is available in Eudamed. If not available in Eudamed, the SSCP should include a summary of the clinical data pertaining to the equivalent device, written in accordance with the recommendations of this section 5, with a clear note that it relates to the equivalent device. It should be evident from the summary what the clinical evidence for the equivalent device was based on: whether it was clinical investigations of that device itself, or if any other data were used and then the sources of that data. Also include a summary of how long-term safety and performance of the equivalent device has been confirmed. \n \n5.2. All clinical investigations of the device in question, conducted before the CE-\nmarking, should be summarised. It is recommended to keep the format clear \n                                                 \n67 MDR, Article 61 (11) and Article 2 (48) \n68 MDR, Article 2 (51) \n69 MDR, Annex I \n70 MDR, Article 61 (1) and Annex XIV, Part A (1) \n71 MDR, Annex XIV, Part A (2)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  16(24) by grouping the information for each study. The summary of each \ninvestigation should include the following non-exclusive list: \n\u0081 Identity of the investigation/study: If performed under the Medical Device \nDirectives or the MDR, then give the CIV ID or single identification number.  Add reference details if the clinical investigation report is available in Eudamed\n72. For other studies, the title of the study and a clear \nreference to a clinical trials database or publication where detailed data on the study can be found (7)\n73 should be included. In the circumstance that \nthe investigation/study was conducted outside EU, identify the country/-ies where it was performed. \n\u0081 Identity of the device including any model number/version \n\u0081 Intended use of the device in the investigation \n\u0081 Objectives of the study \n\u0081 Study design: randomised controlled trial, other pivotal trial, short-term \nfeasibility study, other; and the duration of the follow-up \n\u0081 Primary and secondary endpoint(s) \n\u0081 Inclusion/exclusion criteria for subject selection \n\u0081 Number of enrolled subjects, including if applicable in different treatment \narms \n\u0081 Study population: main baseline characteristics of each study group, \nincluding gender and age of enrolled subjects \n\u0081 Summary of study methods  \n\u0081 Summary of results: any clinical benefits\n74; any undesirable side-effects or \nadverse events, and their frequency in relation to time; any results on long-term benefits or risks, for exampl e implant survival rates at 5 or 10 \nyears and/or cumulative experience in patient-years. A statement of percentage completeness of follow-up should be provided. Add a note if the study is still ongoing for long-term follow up. \n\u0081 Any limitations of the study, such as high loss to follow-up, or potential \nconfounding factors that may question the results. \n\u0081 Any device deficiency and any device replacements related to safety \nand/or performance during the study. \n \n5.3. Summary of other clinical data and the main findings pertaining to the device \nitself should be included if available.  This can be sourced\n75 for example from: \n\u0081 A systematic literature review yielding articles in which the device in \nquestion was used. References to these articles should be provided. A bibliography can be added at the end of the SSCP document if there are many references. \n\u0081 Clinically relevant information based on clinical data obtained from the \nimplementation of the manufacturer\u2019s PMCF and PMS plans, such as: \n                                                 \n72 MDR, Article 77 (7) \n73 WMA Declaration of Helsinki, sections 35, 36, MDR Recital (64) \n74 MDR, Article 2 (53) \n75 MDR, Article 2 (48)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  17(24) - Conducted PMCF investigation(s)76; include information on each study \nas outlined in section 5.2 in this guide. \n- New or changed likelihood of an undesirable side-effect(s), or \nsignificant increase in the frequency or severity of incidents, or any \nidentified trends77, or any other main findings from the PMCF \nevaluation report or PSUR78. \n\u0081 Analysis of clinical data from medical device registries. Any known \nlimitations such as incomplete follow-up should be disclosed. \n \n5.4. An overall summary of the clinical performance79 and safety should be \nprovided, and that is supported by clinical evidence80, based on clinical data \nand the clinical evaluation results pertaining to the device in question. It is recommended that the overall summary should include the following: \n\u0081 The clinical performance normally leads to clinical benefits for the patient. \nGive a description of the documented clinical benefits\n81 for patients with \nrelevant and specified clinical outcome measures, and the success rate for achieving the outcome measures. This should be described for all clinical claims the manufacturer presents in the IFU, and in any information, marketing, or promotional material that it distributes. For a non-absorbable implant, there should also be information about the expected lifetime of the device including data on implant survival rates. \n\u0081 Benefit-risk assessment for the various indications including the \nacceptability of the benefit-risk ratio\n82. This includes a summary of the \nevaluation of undesirable side-effects.  \nIn the case of a device without an intended medical purpose\n83, the \nrequirement to demonstrate clinical benefit shall be understood as a requirement to demonstrate the performance of the device. The summary of the clinical evaluation shall be based on relevant data concerning safety and performance\n84. \n \n5.5. The SSCP shall have a section on planned or ongoing PMCF85 that should \ninclude the following (non-exclusive list): \n\u0081 Summary of the latest approved PMCF plan for the device. Include any \nplanned or ongoing studies (brief description), and if there are any unanswered questions relating to the use of the device and how they will be investigated. \n                                                 \n76 MDR, Article 74 (1) \n77 MDR, Article 88 (1) and Annex XIV Part B (6.1) (b) \n78 MDR, Article 61 (11), Article 83 (3) (d) \n79 MDR, Article 2 (52) \n80 MDR, Article 61 (1) and Article 2 (51) \n81 MDR, Article 2 (53) \n82 MDR, Article 61 (1) and Annex I Sections 1 and 8 \n83 MDR, Annex XVI \n84 MDR, Article 61 (9) \n85 MDR, Annex XIV Part B  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  18(24) \u0081 If any emerging risks, complicati ons or unexpected device failures have \nbeen detected, and how these will be followed up. \n  The information on clinical evaluation and PMCF intended for patients, in \nsection 5 The part of the SSCP intended for patients should be provided with a brief summary which enables the patient to understand the basis upon which clinical safety and perform ance has been de monstrated. The su mmary shoul d include \nthe following (non-exclusive list): \n\u0081 Clinical background of the device \nA description of the relative novelty of the device: if the product has a \nproven clinical track record of safety and performance, or if there are one or more novel design features. \n\u0081 The clinical evidence for the CE marking \nA description whether clinical evidence is based on data concerning an equivalent device, on data collected during a clinical investigation of the device itself, or on a combination of the two. A short lay-summary of the clinical investigations performed on the device itself should be given, if such exist. If there are clinical investigation reports on the device itself available in Eudamed, this should be stated and identification numbers should be given\n86 (CIV ID or single identification number). The summary \nshould not make misleading claims regarding the strength of clinical evidence, either by direct reporting or omission. \n\u0081 Safety \n- A description of the benefit-risk a ssessments related to safety and \nperformance for each indication claimed by the manufacturer, including \ninformation to address benefit-risk issues of interest to specific patient populations, if applicable.  \n- A description of how the manufacturer continuously collects information \non safety and performance and in particular if any clinical studies \n(PMCF) are ongoing or planned. A description of the purpose of any such studies, for example to corroborate safety and performance claims based on equivalence data, or to demonstrate long-term safety.  \n \n6. Possible diagnostic or therapeutic alternatives \n \nThis part of the SSCP document should contain a review of how the device relates, in terms of benefit-risk, to diagnostic or therapeutic alternatives and the specific conditions under which the device and its alternatives can be considered\n87. \n \n                                                 \n86 MDR, Article 77 (7) \n87 MDR, Recital 49  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  19(24) If reference is made to the \u201cstate of the art\u201d, that statement should be supported \nfor example by referring to relevant recognised guidance documents generated by specialty medical societies or educational bodies.  In the part of the SSCP intended for patients the text should include a recommendation to discuss any possible diagnostic or therapeutic alternatives with a healthcare professional who can take into consideration the individual patient\u2019s situation. See the proposed text in the template in the Appendix.  \n7. Suggested profile and training for users \n \nThe experience, education and/or training of the intended user(s) shall be described\n88. This includes any specific mandatory training before using the \ndevice, and any update training for continued safe use of the device.  If the device is intended to be handled directly by the patient, section 7 should be included in the SSCP part intended for patients and any required training should be described.  \n8. Reference to any harmonised standards and CS applied \n \nA list with all applied common specifications (CS), international standards harmonised under the Medical Device Directives (2)(3) and/or the MDR, and relevant adopted monographs of the European Pharmacopoeia\n89 shall be \nprovided.   The year/revision of the applied CS, standard or monograph, should be listed together with information whether it was applied in full or in part.  The year/revision of an applied harmonised standard or CS may change in the technical documentation for the device. However, an update of the SSCP concerning this change can wait until the next revision of the SSCP is issued.  This list in section 8 does not need to be included in the part of the SSCP that is intended for patients. \n \n9. Revision history \n \nThe SSCP document should include a revision history. The purpose is to include the following information: \n\u0081 The SSCP revision number \n\u0081 Date when the revision was issued \n                                                 \n88 By analogy with the IFU, see MDR, Annex I, 23.1 (a) \n89 MDR, Article 8 (2)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  20(24) \u0081 Description of the main changes \n\u0081 In which language the SSCP was validated by the NB \n\u0081 In case of a SSCP on class IIa implantable or some90 IIb implantable \ndevices; whether the SSCP revision has been validated yet or not by the NB \n See an example of a table for a Revision history in the Appendix of this guide. \nReferences \n1. Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April \n2017 on medical devices http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=OJ:L:2017:117:TOC \n \n2. Council Directive 93/42/EEC of 14 June 1993 concerning medical devices \nhttp://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:01993L0042-20071011  \n \n3. Council Directive of 20 June 1990 on the approximation of the laws of the Member \nStates relating to active implantable medical devices (90/385/EEC) http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:01990L0385-20071011  \n \n4. The European Survey on Language Competences: measuring foreign language \nstudent proficiency.  Patr\u00edcia Costa and Patr\u00edcia Albergaria-Almeida / Procedia - Social and Behavioral Sciences 191 (2015) 2369 \u2013 2373 https://www.sciencedirect.com/science/article/pii/S187704281502515X \n \n5. Summaries of Clinical Trials Results for Laypersons \nhttps://ec.europa.eu/health/sites/health/files/files/eudralex/vol-\n10/2017_01_26_summaries_of_ct_results_for_laypersons.pdf  \n \n6. Common European Framework of Reference for Languages: Learning, teaching, \nassessment (CEFR) https://www.coe.int/en/web/common-european-framework-reference-\nlanguages/home  \n \n7. WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving \nHuman Subjects https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-\nfor-medical-research-involving-human-subjects/  \n \n                                                 \n90 MDR, Article 52 (4) 2nd paragraph  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  21(24) Appendix: Template for the SSCP \nTexts in italic in the template are general information texts proposed to be included in \nthe SSCP document.  \n Note that there shall always be SSCP information dedicated to users/healthcare professionals for all implantable devices and for all class III devices, other than custom-made or investigational devices. When relevant, a second part dedicated to patients/lay persons should be added. See further recommendations on relevant SSCP information for patients in this guide.  Summary of safety and clinical performance  \nThis Summary of Safety and Clinical Perform ance (SSCP) is intend ed to provide public \naccess to an updated summary of the main aspects of the safety and clinical performance of the device.  The SSCP is not intended to replace the Instructions For Use as the main document to ensure the safe use of the device, nor is it intended to provide diagnostic or therapeutic suggestions to intended users or patients.  The following information is intended for users/healthcare professionals. \n \nIf the SSCP includes a part intended for patients, the following can be added:  \nFollowing this information there is a summary intended for patients . \n \n1. Device identification and general information \n1.1. Device trade name(s) 1.2. Manufacturer\u2019s name and address 1.3. Manufacturer\u2019s single registration number (SRN) 1.4. Basic UDI-DI 1.5. Medical device nomenclature description / text  1.6. Class of device 1.7. Year when the first certificate (CE) was issued covering the device 1.8. Authorised representative if applicable; name and the SRN 1.9. NB\u2019s name (the NB that will validate the SSCP) and the NB\u2019s single \nidentification number  \n 2. Intended use of the device  \n2.1. Intended purpose 2.2. Indication(s) and target population(s)  2.3. Contraindications and/or limitations \n  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  22(24) 3. Device description \n3.1. Description of the device 3.2. A reference to previous generation(s) or variants if such exist, and a \ndescription of the differences \n3.3. Description of any accessories which are intended to be used in combination \nwith the device \n3.4. Description of any other devices and products which are intended to be used \nin combination with the device \n 4. Risks and warnings \n4.1. Residual risks and undesirable effects \n4.2. Warnings and precautions 4.3. Other relevant aspects of safety, including a summary of any field safety \ncorrective action (FSCA including FSN) if applicable \n 5. Summary of clinical evaluation and post-market clinical follow-up (PMCF) \n5.1. Summary of clinical data related to equivalent device, if applicable 5.2. Summary of clinical data from conducted investigations of the device before \nthe CE-marking, if applicable \n5.3. Summary of clinical data from other sources, if applicable 5.4. An overall summary of the clinical performance and safety 5.5. Ongoing or planned post-market clinical follow-up \n 6. Possible diagnostic or therapeutic alternatives  7. Suggested profile and training for users  8. Reference to any harmonised standards and CS applied  9. Revision history  \nSSCP  \nrevision \nnumber Date  \nissued  \n Change description  Revision validated by the Notified \nBody \n      Yes  \n        Validation language: \n  No (only applicable for class IIa or \nsome IIb implantable devices (MDR, Article 52 (4) 2\nnd paragraph) for which \nthe SSCP is not yet validated by the NB) \n \n      Yes  \n        Validation language: \n  No \n \n \nIf the SSCP concerns a device for which it is relevant to provide information to patients in lay man\u2019s language, the following text can be included and then followed by a \u201cpage break\u201d:   \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  23(24) A summary of the safety and clinical performance of the device, intended for patients, \nis given below.  \n \nSummary of safety and clinical performance Document revision: Date issued:  \nThis Summary of Safety and Clinical Perform ance (SSCP) is intend ed to provide public \naccess to an updated summary of the main aspects of the safety and clinical performance of the device. The information presented below is intended for patients or lay persons. A more extensive summary of its safety and clinical performance prepared for healthcare professionals is found in the first part of this document.   The SSCP is not intended to give general advice on the treatment of a medical condition. Please contact your healthcare professional in case you have questions about your medical condition or about the us e of the device in your situation. This \nSSCP is not intended to replace an Implant card or the Instructions For Use to provide information on the safe use of the device. \n \n1. Device identification and general information \no Device trade name \no Manufacturer; name and address \no Basic UDI-DI \no Year when the device was first CE-marked \n 2. Intended use of the device  \no Intended purpose \no Indications and intended patient groups  \no Contraindications \n 3. Device description \no Device description and material/substances in contact with patient tissues \no Information about medicinal substances in the device, if any \no Description of how the device is achieving its intended mode of action  \no Description of accessories, if any \n 4. Risks and warnings \nContact your healthcare professional if you believe that you are experiencing side-\neffects related to the device or its use or  if you are concerned about risks. This \ndocument is not intended to replace a consultation with your healthcare professional if needed. \n \no How potential risks have been controlled or managed \no Remaining risks and undesirable effects \no Warnings and precautions \no Summary of any field safety corrective action, (FSCA including FSN) if \napplicable \n  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  24(24) 5. Summary of clinical evaluation and post-market clinical follow-up \no Clinical background of the device \no The clinical evidence for the CE-marking \no Safety \n 6. Possible diagnostic or therapeutic alternatives \nWhen considering alternative treatments, it is recommended to contact your \nhealthcare professional who can take into account your individual situation.  \no General description of therapeutic alternatives \n 7. Suggested training for users"}, {"title": "emdn_eudamed_nomenclature_en.pdf.txt", "text": "Medical Devices                January 2020  \nDG Health and Food Safety   \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \n \n \nPage 1 of 1 \n The European Medical Device  Nomenclature (EMDN)  \nThe European Medical Device Nomenclature (EMDN) will be the nomenclature of use by \nmanufacturers when registering their medical devices in the EUDAMED  database.  \nFounded on  pre-established criteria and requirements1 and based on orientations provided by \nthe Medical Device Coordination Group  (MDCG) , the European Commission decided in \nfavour of the use of the \u2018Classificazione Nazionale Dispositivi medici  (CND)\u20192 as the basis \nfor the EMDN . \nCurrently, a n extrao rdinary revision of the CND is ongoing so that  to release the first version \nof the EMDN, which will be i ntegrated in EUDAMED  for use by operators. The EMDN will \nbe fully available and accessible to any operators and will be copyright free.  \nTo the extent possible, t he Commission will map the EMDN to the G lobal Medical Device \nNomenclature (GMDN) . This task has been undertaken with th e hopes of  possibly facilitating \nEMDN code search by operators current ly using  GMDN . The correspondence between the \nnomenclatures is intended to be visible to operators and incorporated in the future database in \nthe form of a searching tool. Therefore, and  in cooperation with GMDN, t he mapping \nexercise is currently ongoing . The level of quality and reliability of this mapping is dependent \non the commitment of all relevant parties to work together in ma pping and validating the \nresult s.     \nA sub -group of the  MDCG on nomenclature which includes experts from National \nCompetent Authorities and stakeholders has been established to oversee  regulatory activities \nlinked to nomenclature . The sub -group will aim to define the rules and processes related to \nthe creation, update , maintenance and  use of  the European Medical Device  Nomenclature.  \nAdditionally, t he Commission is currently collaborating  with the World Health Organisation \n(WHO ) in the context of their work  and activities on a future international medic al device \nnomenclature.  \n                                                 \n1 (MDCG 2018 -2) \u2013 Future EU medical device nomenclature: Description of requirements  \n2 CND is currently used in Italy, Portugal and Greece."}, {"title": "FAQ_MDR_180117_V1.0-1.pdf.txt", "text": "Page 1 of 13 \n \nCAMD Transition Sub Group  \nFAQ \u2013 MDR Transitional provisions  \nDisclaimer : \nThe information presented in this document is for the purpose of general information only and is not intended to represent legal advice to any individual \nor entity. It reflects  the outcome of discussions within the Transition Sub Group (TSG) of the CAMD (established in May 2017) to establish \nrecommendations on the interpretation of transition -related provisions. It is not intended to be a guidance document . We recommend that you should \nobtain  your own legal advice before taking any action based on information given here. The content of this FAQ table will be updated cont inuously. While \nwe strive to provide the following information in as timely and accurate a manner as possible , this document does not make any claims or guarantees \nabout the accuracy, completeness or sufficiency of its contents. Participants of the Transit ion Sub Group, authors and reviewers of this document \nexpressly disclaim liability for any errors and omissions in the contents.  \n  \nPage 2 of 13 \n Glossary:  \n\u2022 AIMDD/MDD compliant device = device that is compliant with Directive 90/385/EEC/ Directive 93/42/EEC  \n\u2022 AIMDD/MDD certificates = certificates in accordance with Directive 90/385/EEC/ Directive 93/42/EEC  \n\u2022 DoA = date of application  of the MDR  \n\u2022 MDR = Medical Device Regulation (EU) 2017/745  \n\u2022 MDR compliant de vice = device that is compliant with the MDR  \n\u2022 MDCG = Medical Device Coordination Group  \n\u2022 MFR = manufacturer  \n\u2022 PRRC = person responsible for regulatory compliance  \n\u2022 NB = notified body  \n\u2022 \u201cold\u201d NB = NB that has issued an AIMDD/MDD certificate  \n\u2022 The Directives = Directives 90/385/EEC, 93/42/EEC  \nDocument History  \nVersion  Publication  Note  \nV1.0 17/01/18  Original publication  \n   \n   \n   \nConten ts: \nI - Issue: Transition in general  ................................ ................................ ................................ ................................ ................................ ..............................  3 \nII - Issue: Placing on the market of MDR compliant devices until 26 May 2020 (Art. 120 para 5 -7 MDR)  ................................ ................................ .............  4 \nIII - Issue: Placing on the market of devices in conformity with the Directives after 26 May 2020 (Art. 120 para 2 -3 MDR)  ................................ .................  7 \nIV - Issue: The so called \u201csell off\u201d provision of Art. 120 para 4 MDR  ................................ ................................ ................................ ................................ .. 11 \nV \u2013 Issue: EUDAMED and its relevance for the application of certain provisions of the MDR (Art. 123 para 3 d and e, Art. 120 para  8, Art. 122 MDR)  .... 12 \n \n   \nPage 3 of 13 \n  \nI - Issue: Transition in general  \n1 Question:  When does the Medical Devices Regulation (EU) 2017/745 (= MDR) apply?  \n Answer:  The MDR shall apply from 26 May 2020 (= date of application (DOA)) , see Art. 123 para 2  MDR .  \nThere are however exceptions to  that general rule. Some provisions apply earlier (e.g. regarding notified bodies or the \nMedical Device Coordination Group), some later (e.g. regarding UDI labelling). For the exceptions,  see Art. 123 para 3  \nMDR (earlier application: a -c, i; p ostponed application: d \u2013h). \n \n   \n2 Question:  When do the Directives 90/385/EEC , and 93/42/EEC [= the Directives] cease to apply ? \n Answer:  In general  the Directives 90/385/EEC and 93/42/EEC are repealed  with effect from 26 May 2020 (= DoA), see Art. 122  \nMDR . However there are some exceptions , e.g.  \n\u2022 in order to deal with devices that are compliant with the Directives or  \n\u2022 to serve as a \u201cback up\u201d in case EUDAMED is not fully functional at DoA  \n(see Art. 122 MDR).  \n   \n3 Question:  What is  the applicable legislation until  26 May 2020 (= DoA )? \n Answer:  Laws and regulations adopted by Member States in accordance with the Directives (= Directives regime). There are \nhowever exceptions (see for example Art. 123 para 3 a \u2013 c, i MDR and Art. 120 para 5 and 6  MDR ). \n   \n   \nPage 4 of 13 \n II - Issue: Placing on the market of MDR compliant  devices until 26 May 2020 (Art. 120 \npara 5 -7 MDR)  \n4 Question:  Is it possible to place a device, which is compliant with the MDR (= MDR compliant  \ndevice ), on the market prior to 26 May 2020  (= DoA) ? \n Answer:  Yes, see Art. 120 para 5 MDR.  \nManufacturer s (= MFR ) are \u2013 until 26 May 2020  (= DoA)  normally required to place devices on the market that comply with \nthe Directives  (= AIMDD/MDD compliant devices) , however Art. 120 para 5 MDR offers the option  to place MDR compliant \ndevices on the market before  DoA.  \n \n   \n5 Question:  Is it possible for all types  of devices  (for all different risk classes I \u2013 III) compliant with the MDR (= MDR compliant device) \nto be placed on the market prior to 26 May 2020  (according to Art. 120 para 5 MDR )? \n \n Answer:  Yes, all types  of devices  - regardless of their risk class \u2013 may be placed on the market according to Art. 120 para 5 MDR. \nThis includes for example custom made devices  (Art. 2 para 3  MDR ) and system s and procedure packs  (Art. 2 para 10  and \npara 11  MDR).  \nHowever , devices being subject to the \u201cclinical evaluation consultation procedure\u201d according to Art. 54 MDR (= certain \nclass III and class IIb devices) may not be placed on the market in ac cordance with Article 120 para 5 MDR  before  the \nMedical Device Coordination Group ( MDCG ) and the expert panels have been  established  (see Art. 120 para 7 MDR) . \nDepending on the risk class of the device, conformity assessment may requir e the involvement of a NB designated and \nnotified in accordance with the MDR  (see Art. 120 para 6 MDR). In this c ase, such devices cannot complete a  \nconformity assessment, and therefore may not be placed on the market, before  NBs have been designated and notified \nunder the MDR.  \n    \nPage 5 of 13 \n 6 Question:  As a MFR , which obligations of the MDR  do I need to fulfil in order to place  a MDR compliant  device on the market  \nbefore  the DoA according to Art. 120 para 5 MDR?  \n Answer:  As many obligations as are possible , while taking into account that   \n\u2022 EUDAMED is not fully functional and  \n\u2022 the MDR is not fully applicable  \nat that point in time .  \n \nGenerally speaking, that is to say that:  \n\u2022 first, the device  as such needs to be MDR compliant (see Annex I) and  \n\u2022 second, the  MFR  has to comply with the MDR.  \nIn particular, the MFR shall undertake an assessment of the conformity of that device in accordance with the \napplicable conformity assessment procedures set out in Art. 52 MDR . This may, depending on the risk class of the \ndevic e, necessitate the involvement of a notified body designated and notified in accordance with the MDR  (see Art. 120 \npara 6 MDR).  \n \nThe following requirements of the MDR  need to be fulfilled by t he MFR (non -exhaustive list) : \n\u2022 clinical evaluation  \n\u2022 risk management  \n\u2022 QMS  \n\u2022 Post-market surveillance  \n\u2022 Technical documentation and other reports  \n\u2022 Liability for defective devices  \n  \nPage 6 of 13 \n However, exceptions /adaptations  are possible /necessary , particularly due to the fact that EUDAMED may not  be fully \nfunctional before  the DoA . For example : \n \n\u2022 in the absence of a fully functional EUDAMED some requirements of the Directives  shall \u2013 where necessary - \napply in place of the relevant provisions of the Regulation (e.g. registration of d evices and economic operators).  \n \n\u2022 A person responsi ble for regulatory compliance  (PRRC, Art. 15 MDR) needs to be available  but not \nnecessarily registered until EUDAMED is available . . \n \n\u2022 The assignment of an UDI (Art. 27 para 3 MDR)   \nis not possible as long as there are  \n- no issuing entities  designated by the Commission according to Art. 27 para 2 MDR  or  \n- as long as the legal fiction according to Art. 120 para 12 does not apply (it shall apply from 26 May 2019 , see Art. \n123 para 3 i MDR ).  \nIt is of no significant use as long as there is no UDI database .  \n \n\u2022 An implant card and the information according to Art. 18 MDR  need to be provided, however without the UDI \nrelated content  (as the requirement to place the UDI carrier on the devices will be stepwise  introduced after the \nDoA).  \n   \n7 Question:  Are MDR compliant devices  placed on the market according to Art . 120 para 5 MDR subject to the so called \u201csell off\u201d \nprovision  in Art. 120 para 4 MDR (see below)?  \n Answer  No, the possibility of their being made available/put into service is not time-limited.  \n   \n  \nPage 7 of 13 \n III - Issue: Placing on the market of devices in conformity with the Directives  after 26 \nMay 2020 (Art. 120 para 2 -3 MDR)  \n8 Question:  Do certificates  issued by notified bodies in accordance with the Directives  (= AIMDD/MDD certificates ) prior to 25 May \n2020 remain valid after the DoA?  \n Answer:  Yes, as specified in Art. 120 para 2 MDR.  \nIn general , they remain valid until the end of the period indicated on the certificate. Certain AIMDD/MDD certificates (Annex \n4/IV, refer to Art. 120 para 2 first sentence MDR) become void at the latest on 27 May 2022, others (refer to Art. 120 para 2  \nsecond sentence  MDR) on 27 May 2024 at the latest. In other words, after 27 May 2024 there will be no more valid \nAIMDD/MDD certificates.   \n   \n9 Question:  What  kind of certificates remain valid  according to Art. 120 para 2 MDR?  \n Answer:  All certificates which are commonly issued by Notified Bodies  with reference to the Council Directives MDD and AIMDD.  \nThat is [see for example NBOG BPG 2010 -3, similar NB-MED/2.5. 1Rec 4]:  \n\uf02d EC Design -Examination Certificate  \n(Annex II section 4 MDD, Annex 2, section 4 AIMD)   \n\uf02d Certificate of Conformity  \n(Annex IV MDD, Annex 4 AIMD)  \n\uf02d EC Type Examination Certificate   \n(Annex III MDD; Annex 3 AIMD)  \n\uf02d EC Certificate Full Quality Assurance System  \n(Annex II excluding section 4  MDD; Annex 2 section 2 AIMD)  \n\uf02d EC Certificate Production Qualit y Assurance  \n(Annex V MDD, Annex 5 AIMD)   \nPage 8 of 13 \n \uf02d EC Certificate Product Quality Assurance System  \n(Annex VI MDD)  \n   \n10 Question:  May a \u201c declaration of conformity \u201d be considered as a \u201ccertificate\u201d  according  Art.120 para 2 MDR?  \n Answer:  No, since it is not a certificate issued by a NB.  \n   \n11 Question:  Is it possible for a MFR to have valid MDR and valid AIMDD/MDD certificates in parallel  until the 27 May 2024 expiry \ndate? \n Answer:  Yes.  \n   \n12 Question:  May devices, that are compliant with the Directives  (= MDD/AIMDD compliant devices ), be placed on the market/put into \nservice after 26 May 2020  (= DoA) ? \n Answer:  Yes, under certain conditions  (see answer on question 1 7) as specified in Art. 120 para 3 MDR.  \n \nIn general , after 26 M ay 2020 , devices need to comply with the MDR  in order to be placed on the market/put into service  \n(see Art. 5 MDR) . However , for a limited time (depending on the validity of the MDD/AIMDD  certificates) there is the option  \nto continue to place devices on the market  that are compliant with the Directives. Making use of this option  may postpone \nthe immediate need for a new certificate under the MDR.  \n   \n13 Question:  May MFR s of class I devices , that are compliant with the Directives , make use of the derogation in  Art. 120 para 3 \nMDR (= be placed on the market after the DoA)?  \n Answer:  No, they must comply with the MDR , unless the device  concerned is a class I device with measurement function or in \nsterile condition  covered by a valid  MDD certificate .  \n    \nPage 9 of 13 \n 14 Question:  May devices that are excluded  from the scope of the MDR (e.g. via Art. 1 para 6 lit h) nonetheless benefit from Art. 120 \npara 3 MDR ? \n Answer:  No, these devices do not fall under the MDR, thus Art. 120 para 3 MDR is not applicable.  \n   \n15 Question:  May MDD/AIMDD compliant devices , which  under the MDR will be subject to an \u201cupgrade\u201d in risk class  (\u201cup-\nclassification\u201d) , e.g. formerly class IIa -> then class III , benefit from Art. 120 para 3  MDR ? \n Answer:  Yes, under the conditions specified in Art. 120 para 3 MDR (e.g. valid AIMDD/MDD certificate ). Devices which are in a \ndifferent respectively higher risk class in MDR than under the Directives are not as such excluded from the scope of Art. \n120 para 3  MDR . \n   \n16 Question:  If, according to Art. 120 para 3 MDR, a MFR intend s to place  a MDD/ AIMDD compliant device  on the market after the \nDoA, that , under the MDR , will be subject to an \u201cupgrade\u201d in risk class  (\u201cup-classification\u201d) , what is the relevant risk \nclass  with regard to the applicable MDR requirements  listed in Article 120 para 3  MDR (e.g. PSUR)?  \n Answer:  The risk class under MDD/AIMDD . \n   \n17 Question:  What are the requirements  for the placing on the market/putting into service of MDD/AIMDD compliant devices  \naccording to Art. 120 para 3 MDR  after DoA? \n Answer:  See Art. 120 para 3 MDR.  \nIn short:  \n1. A valid AIMDD/MDD  certificate according to Art. 120 para 2 MDR  \n[All certificates necessary for the placing on the market of the device in question need to be valid , e.g. a class III \ndevice needs to have a valid QMS as well as product specific certificate .] \n2. Continuous compliance of the device  with the Directives    \nPage 10 of 13 \n 3. No signif icant changes  in the design and intended purpose  \n[If there is a significant change in either the design or the intended purpose , Art. 120 para 3  MDR cannot be \nclaimed .  Qualification  of a change as \u201csignificant \u201d according to Art. 120 para 3 MDR shall be determined on a \ncase by case basis. However,  \n- limitations of the intended purpose  \n- design changes related to corrective actions  assessed and accepted by the Competent Authority  \nare not considered \u201c significant \u201d in the sense of Art. 120 para 3 MDR. . \n4. Appl ication of MDR requirements  in place of the corresponding requirements of the Directives with regard to:  \na. Registration of economic operators and of devices   \n(see Art. 31 MDR and Art. 29 MDR)  \nb. Post market surveillance  (PMS)  \n(see Art. 83 -86, 92 MDR including Annex III but without the PMS having to be an integral part of the QMS)  \nc. Market surveillance   \n(see Art. 93 \u2013 100 MDR, but device s tandards to be met = Directives ) \nd. Vigilance   \n(see Art - 87-92 MDR)  \nHowever exceptions are possible in the case that EUDAMED is no t fully functional in time (then see Art. 123 \npara 3 d and e MDR).  \n \nMoreover, the \u201cold\u201d NB which issued the AIMDD/MDD certificate shall continue to be responsible for the appropriate \nsurveillance of all the applicable requirements relating to the devices it has certified. This should be agreed on between the \n\u201cold\u201d NB and the MFR on a contractual basis . \n   \n \n   \nPage 11 of 13 \n IV - Issue: The so called \u201csell off\u201d  provision  of Art. 120 para 4 MDR  \n18 Question:  What is the so called \u201csell off\u201d provision (Art. 120 para 4 MDR) about?  \n Answer:  It is intended to  limit the time  during which AIMDD/MDD compliant devices, that have already been placed on the \nmarket (either before the DoA or by virtue of Art. 120 para 3 after the DoA) , may be made available  e.g. by a \ndistributor . \nAfter May 27, 2025 these devices may not be made available/put into service (= deadline) . If such devices are still within \nthe supply chain by this date - i.e. have not reached the final user as being ready for use (e.g. the hospital) - they are not \n\u201cmarketable\u201d any more.  \n \nThis provision is thus primarily dealing with the \u201cmaking available\u201d  of AIMD/MDD compliant  devices once they have \nbeen placed on the market , e.g. within the supply chain . It does not apply to  the \u201cplacing on the market\u201d  of these \ndevices by the MFR . \n \nPlease  also note, that this provision is not intended to apply to second hand sales  (see recital 3).  This means , once a \ndevice has been made available to the final use r (e.g. the hospital) as being ready for use, the further making available  \nof this device is not subject to/covered by the MDR.  \n   \n19 Question:  Does Art. 120 para 4 MDR enable MFRs to place MDD/AIMDD compliant devices  on the market until May 27, 2025? \n Answer:  No. Art. 120 para 4 MDR is not applicable to  the \u201cplacing on the marke t\u201d of MDD/AIMDD compliant devices (see question \n18). The only way to place MDD/AIMDD compliant devices on the market after DoA is Art. 120 para 3  MDR (see \nquestion s 12-17). Given th at MDD/AIMDD certificate s will no longer be  valid after May 27 2024 , this option ceases to \nexist from that date onwards .  \n   \n   \nPage 12 of 13 \n V \u2013 Issue: EUDAMED  and its relevance for the application of certain provisions of the MDR \n(Art. 123 para 3 d and e, Art. 120 para 8, Art. 122 MDR)  \n20 Question:  Do all devices  have to be registered according to Art. 29 para 4 MDR  by the DoA? \n Answer:  No. Even if EUDAMED is  fully functional at the DoA there will be a n 18-month \u201cinterim  phase \u201d (= EUDAMED fully \nfunctional but Art. 29 para 4 MDR not yet applicable) during which the different devices to be placed on the market may \nbe registered \u201cstep by step\u201d  in EUDAMED  accordin g to Art. 29 para 4 MDR instead of nationally according to the \nDirectives (see Art. 123 para 3 e  and Art. 120 para 8 MDR) . However , at the end  of this \u201cinterim  phase \u201d it must be \nensured that  all devices of a MFR\u2019s portfolio have been registered in EUDAMED.  \n \nIf EUDAMED is not fully functional  until a date after the DoA,  the 18 -month \u201cinterim phase\u201d will be postponed accordingly \n(beginning at the later of the dates referred to in point d) of Art. 123 para 3 MDR).  \n   \n21 Question:  Must  NBs have entered all the certificate related information of all devices  according to Art. 56 para 5 MDR into \nEUDAMED by the DoA ? \n Answer:  No. Even if EUDAMED is fully functional at the DoA there will be an 18-month \u201cinterim phase\u201d  (= EUDAMED fully \nfunctional but Art. 56 para 5 MDR not yet applicable) during which the relevant information according to Art. 56 para 5 \nMDR may be registered in EUDAMED \u201cstep by step = certificate by certificate\u201d instead of nationally acco rding to the \nDirectives (see Art. 123 para 3 e and Art. 120 para 8 MDR). However , at the end of this \u201cinterim phase\u201d it must be \nensured that all the relevant data regarding all certificates  have been  registered in EUDAMED.  \n \nIf EUDAMED is not fully functio nal until a date after the DoA, the 18 -month \u201cinterim phase\u201d will be postponed accordingly \n(beginning at the later of the dates referred to in point d) of Art. 123 para 3 MDR).  \n    \nPage 13 of 13 \n 22 Question:  What happens if EUDAMED  is not fully functional  at the DoA?  How does this affect the application of obligations and \nrequirements of the MDR that relate to EUDAMED ? \n Answer:  The relevant provisions to refer to  are mainly Art. 123 para 3 d and e . \n \nArt. 123 para 3 d MDR:  \nThe different Articles  listed in Art. 123 para 3 d  (= dealing with e.g. the registration of devices and economic operators, \nclinical investigations, notified bodies, vigilance, post -market surveillance, market surveillance) are not fully  postponed \nwith regard to their applicati on but generally  remain applicable  from the DoA. However , their application is postponed as \nfar as  the obligations and requirements within these Articles relate to EUDAMED (which is not fully functional yet). To \nthat extent  they shall apply  from the date c orresponding to 6 months after the date of notice of full functionality . \nMeanwhile ( until EUDAMED is fully functional ) the corresponding provisions of the Directives regarding exchange of \ninformation  continue to apply .  \nThe principle is that the derogation applies to the electronic exchange of information/upload to EUDAMED. If the \nderogation is applicable this does not necessarily mean that the information itself does not need to be \nprepared/exchanged. This exchange of in formation e.g. reports will have to be done by other means in lieu  of exchange \nvia EUDAMED (Directives regime ). The underlying idea behind this paragraph was to ensure  compliance with the new \nobligations and requirements via the \u201cold\u201d systems  as far as pos sible.  \n \nThe actual practical implication of this concept with regard to the different Articles listed in Art. 123 para 3 d MDR needs a \ncloser look and further guidance , which is in progress.  \n \nArt. 123 para 3 e MDR : \nFor the application of Art. 29 para 4 MDR and Art. 56 para 5 MDR  in the case that EUDAMED is not fully functional in \ntime, see question  20 and 2 1."}, {"title": "ivd_mfr_stepbystep.pdf.txt", "text": "MEDICAL DEVICES  CHANGE OF LEGISLATION\nInternal market, \nIndustry,  \nEntrepreneurship  \nand SMEs1STEP  INTENTION / ACTION\nPre-assessmentBrief management to ensure a clear understanding of the importance and  \nbusiness implications of the IVDR\nConsider organisational challenges: management awareness, staffing capability \nand availability, budget implications\nGAP analysis and actions  \nresulting from thisAssess impact on products, internal resources, organisation and budget\nCheck new classification rules (IVDR Classes A\u2013D) and confirm conformity assess -\nment routes for existing and future products. Check the requirement for involving the \nNotified Bodies\nReview the changes needed to existing technical documentation (Technical Files)\nReview and upgrade quality management system (QMS) (point 3 below)\nCheck the adequacy of available clinical evidence and risk management and \nidentify any gaps (Article 56)\nReview product labelling (Annex I Chapter III)\nEnsure post-market surveillance (PMS) arrangements are adequate (Chapter VII \nSection 1)\nPrepare a post-market performance follow-up plan (PMPF, Annex XIII Part B) \nGet ready for the new vigilance requirements (Chapter VII Section 2)\nEnsure the respect of traceability obligations (Chapter III)\nQuality Management  \nSystem (QMS)Review adequacy of QMS to meet standards and processes for IVDs under the \nnew Regulation\nBuild new regulatory requirements into the QMS\nIdentify/hire the person responsible for regulatory compliance within your  \norganisation (Article 15) and be sure it is adequately qualified and trained1\n2\n3What you need to know!Implementation Model for\nIn-Vitro Diagnostic Medical \nDevices Regulation  \nStep by Step Guide\nRef. Ares(2018)3873813 - 20/07/20182Legal entitiesClarify how the company is affected: legal entities, obligation of economic  \noperators, organisational structures and resources\nConsider organisational challenges: management awareness, staffing capability \nand availability, budget implications\nEnsure product liability insurance is adequate\nPortfolioDo a cost/benefit analysis for your product portfolio; bear in mind costs related \nto the new risk classification system and the need of involving a Notified Body \nand costs for post-market surveillance and gaps in the technical documentation, \nand plan your transition to the IVDR accordingly\nReview supply chain provisions, and clarify roles and responsibilities of business \npartners (authorised representatives, importers, distributors)\nMaster implementation \nplanBuild a roadmap for implementation, including definition of sub-projects, re -\nsource requirements and a steering group, and ensure overall responsibility for \nIVDR implementation has been established\nGive special consideration to certificate expiry dates, bearing in mind the transi -\ntional period, transitional provisions and availability of your Notified Bodies\nNotified BodiesContact the selected Notified Bodies and determine their capacity and  \navailability to service the implementation plan \nRegulatory trainingEmpower and train staff through IVDR implementation and transition workshops\nExecute master  \nimplementation planImplement the various sub-projects (performance evaluation, technical  \ndocumentation, relations with other economic operators, Unique Device Identifica -\ntion, labelling, post-market surveillance, vigilance, and reporting IT systems)\nEnsure a cross-functional project management team is in place to cover all \naspects of implementation\nEnsure overall and individual responsibilities for IVDR implementation have been \nestablished\nReview efficiency and  \neffectivenessImplement regular meetings on project status and progress, discrepancy and \ngap analyses, risks, next steps and requirements\nHold regular progress reviews against the IVDR implementation plan and include \nthese in the management review process\nNotified Body submissionDiscuss submission dates to avoid delays in the approval process\nOngoing monitoringActively monitor the still-developing European regulatory environment and \nguidelines expected in the coming months (check DG GROW web pages on  \nmedical devices and subscribe to the newsletter)\nEstablish a procedure for dealing with unannounced inspections from Notified Bodies \nRegularly review the IVDR implementation plan, identifying and addressing key \nareas of risk4\n5\n6\n7\n8\n9\n10\n11\n12\n\u00a9 European Union, [2018]  Reuse is authorised provided the source is acknowledged.\nThe reuse policy of European Commission documents is regulated by Decision 2011/833/EU (OJ L 330, 14.12.2011, p. 39).\nISBN: 978-92-79-89124-3    DOI: 10.2873/41862\nET-04-18-659-EN-N"}, {"title": "scheer_o_015.pdf.txt", "text": "Final Version  \n \nGuidelines on the benefit -risk assessment of the presence of phthalates in certain \nmedical devices  \n  \n \n \n \n \n \nScientific Committee on Health, Environmental and Emerging Risks  \nSCHEER  \n \nGUIDELINES   \non the benefit -risk assessment of the presence of  \nphthalates in certain medical devices  \ncovering phthalates which are carcinogenic, mutagenic, toxic to \nreproduction (CMR) or have endocrine -disrupting (ED) \nproperties  \n \n \n \n \n \nThe SCHEER adopted this document at plenary meeting on 18 June 2019  \n  \nGuidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n2 \n ABSTRACT  \nThe SCHEER was requested to provide Guidelines on the benefit -risk assessment (BRA)  \nof the presence, in the medical devices specified in the regulation , of phthalates , which \nhave one or more of the following properties: carcinogenic, mutagenic, toxic to \nreproduction (CMR) or endocrine -disrupt ing (ED), according to the criteria outlined in the \nlegal obligation section from the mandate.  \n  \nPhthalates are widely used in industry as plastici sers of polymers, in a variety of \napplications such as coated fabrics and roofing membranes, as well as in me dical \ndevices, adhesives, paints, inks and enteric -coated tablets. Di -(2-(ethylhexyl) phthalate \n(DEHP) is the most widely used phthalate in medical devices. Dimethyl phthalate (DMP) \nand diethyl phthalate  (DEP) are not used as plasticis ers but e.g. as addit ives in \ncosmetics, medical devices, and household products.  \nThe interaction of phthalates with the polymers they are embedded in is weak, so they \nmay be released from the plastic product into the environment and into the human body \nif the product is in con tact with it.  \n \nThe Medical Device Regula tion, Regulation (EU) 2017/745 allows the use of CMR 1A/1B \nand/or ED substances in medical devices above a concentration of 0.1% w/w. when a \nproper justification can be provided (Annex I, Chapter II Section  10.4). Fo r such a \njustification several steps need to be considered including  the availability  of alternative \nsubstances, materials, designs, and medical treatments. In addition, the risk associated \nwith such alternatives should be weighed against the risk of the u se of CMR 1A/1B and/or \nED identified phthalates covered under MDR Annex I Chapter II Section  10.4.1 . However, \nthe risk by itself is not the only parameter to consider:  also the impact of the possible \nalternatives on the functionality, performance and the overall benefit -risk ratio of the \nmedical device shall be evaluated.  \n \nThese Guidelines describe the methodology on how to perform a BRA for the justification of \nthe presence of CMR 1A or 1B and/or ED phthalates (CMR/ED phthalates) in medical devices \nand/or or parts or materials used therein  at percentages above 0.1% by weight (w/w).  \nThey also describe  the evaluation of possible alternatives for these phthalates used in \nmedical devices , including  alternative materials, designs or medical treatments .  \nThey are intended to be used by the relevant stakeholders e.g. manufacturers, notified \nbodies and regulatory bodies.  \nThe approach of these Guidelines may also be used for a BRA of other CMR/ED \nsubstances present in medical devices.  \n \nDuring the preparation of these Guidelines for BRA of the use of CMR/ED phthalates in \nmedical devices, SCHEER noticed that a number of BRA methodologies are theoretically \navailable. However , there is a considerable lack of data  needed for the BRA  for potential \nrelevant  alternatives to be used in medical devices. Therefore, SCHEER encourages \nmanufacturers to generate data of high quality on  such alternatives  for CMR/ED \nphthalates in medical devices.  \nPending on new scientific evidence, it is recommended to evaluate the use and \nusefulness of these Guidelines after an application  period of three years.  \n \nKeywords: Guidelines, benefit -risk assessment , CMR/ED phthalates, medical devices, \nSCHEER . \nGuidelines  to be cited as:  SCHEER (Scientific Committee on Health, Environmental and \nEmerging Risks), Guidelines on the benefit -risk assessment of the presence of phthalates \nin certain medical devices  covering phthalates which are ca rcinogenic, mutagenic, toxic \nto reproduction (CMR)  or have endocrine -disrupting (ED) properties, final version \nadopted at  SCHEER plenary on 18 June 2019.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n3 \n  \nACKNOWLEDGMENTS  \n \n \nMembers of the Working Group are acknowledged for their valuable contribution to this \nopinion. The members of the Working Group are:  \n \nSCHEER members:  \nTeresa Borges  \nRodica Mariana Ion  \nWim H. de Jong    (Chair and Rapporteur)  \nDemosthenes Panagiotakos   \nEmanuela Testai  \nTheo Vermeire  \n \n \nSCCS members:  \nUlrike Bernauer  \nChristophe Rousselle  \n \n \nExternal experts:  \nSt\u00e9phane B\u00e9gu\u00e9  (Etablissement Fran\u00e7ais du Sang, EFS, Paris, France)  \nHilde B. M. Kopperud  (Nordic Institute of Dental Materials, Oslo, Norway)  \nMaria Rosaria Milana   (Istituto Superiore di Sanit\u00e0, Dip. Ambiente e Salute, Roma, Italy)  \nTanja Schmidt   (Ansbach University of Applied Science,  Ansbach,  Germany)  \n \n \nExperts from EU Agencies : \nFrancesco Pignatti   (European Medicines  Agency ) \nEvgenia Stoyanova   (European Chemicals Agency ) \nKatarina Volk    (European Food & Safety Authority ) \n  \n \n \n \n \nAll Declarations of Working Group members are available at  the following webpage:  \nhttp://ec.europa.eu/health/scientific_committees/experts/declarations/scheer_wg_en   \n \n \n \n \n \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n__________________________________________________________________________________\n4About the Scientific Committees (2016 -2021)  \nTwo independent non -food Scientific Committees provide the Commission with the \nscientific advice it needs when preparing policy and proposals relating to consumer \nsafety, public health and the environment. The Committees also draw the Commissio n's \nattention to the new or emerging problems which may pose an actual or potential threat . \nThey are: the Scientific Committee on Consumer Safety (SCCS) and the Scientific \nCommittee on Health, Environmental and Emerging Risks (SCHEER). The Scientific \nComm ittees review and evaluate relevant scientific data and assess potential risks. Each \nCommittee has top independent scientists from all over the world who are committed to \nwork in the public interest. \nIn addition, the Commission relies upon the work of other Union bodies, such as the \nEuropean Food Safety Authority (EFSA), the European Medicines Agency (EMA), the \nEuropean Centre for Disease prevention and Control (ECDC) and the European Chemicals \nAgency (ECHA).  \nSCHEER  \nThis Committee, on request of Commission services, provides Opinions on questions \nconcerning health, environmental and emerging risks. The Committees addresses \nquestions on: \n-health and environmental risks related to pollutants in the environmental media  and\nother biological and physical factors in relation to air quality, water, waste and soils.\n-complex or multidisciplinary issues requiring a comprehensive assessment of risks to\nconsumer safety or public health, for example antimicrobial resistance, n anotechnologies,\nmedical devices and physical hazards such as noise and electromagnetic fields.\nSCHEER members  \nRoberto Bertollini, Teresa Borges, Wim de Jong, Pim de Voogt, Raquel Duarte -Davidson, \nPeter Hoet, Rodica Mariana Ion, Renate Kraetke, Demosthen es Panagiotakos, Ana \nProykova, Theo Samaras, Marian Scott , Remy Slama, Emanuela Testai, Theo Vermeire, \nMarco Vighi, Sergey Zacharov  \nContact  \nEuropean Commission  \nDG Health and Food Safety  \nDirectorate C: Public Health, Country Knowledge, Crisis management  \nUnit C2 \u2013 Country Knowledge and Scientific Committees \nOffice: HTC 03/073   L -2920 Luxembourg\nSANTE- C2-SCHEER@ec.europa.eu   \nISBN 978-92-76-15387-0\u00a9 European Union, 2020 \nISSN 2467-4559\ndoi: 10.2875/784367 EW-CA-20-001-EN-N\nThe Opinions of the Scientific Committees present the views of the independent scientists \nwho are members of the committees. They do not necessarily reflect the views of the \nEuropean Commission. The Opinions are published by the European Commission in their \noriginal language only. \nhttp://ec.europa.eu/health/scientific_committees/policy/index_en.htm  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n5 \n  \nTABLE OF CONTENTS  \n \nACKNOWLEDGMENTS  ................................ ................................ ................................ ...........  3 \nA. GUIDELINES on benefit -risk assessment for CMR and/or endocrine -disrupting phthalates \nused in medical devices  ................................ ................................ ..............................  6 \n1. Introduction  ................................ ................................ ................................ ..............  7 \n2. Framework for Benefit -Risk Assessment  ................................ ................................ ..... 10 \n3. Assessment of the presence of phthalates in a medical device  ................................ ....... 15 \n4. Assessment of possible alternative substances, materials, designs or medical treatments  . 18 \n5. Assessment of potential relevant alternative substances, materials, designs or medical \ntreatments versus CMR/ED phthalates  ................................ ................................ ........  23 \n6. Justification for the use of CMR/ED phthalate  ................................ ..............................  25 \n7. Benefit assessment  ................................ ................................ ................................ .. 27 \n7.1 Material benefit  ................................ ................................ ................................ ....... 28 \n7.2 Clinical benefits  ................................ ................................ ................................ ....... 28 \n8. Methodologies for Benefit \u2013Risk Assessment  ................................ ...............................  29 \n9. Uncertainty analysis  ................................ ................................ ................................ . 30 \n10. Conclusions  ................................ ................................ ................................ .............  34 \n11. Consideration of the responses received during the public consultation process  ...............  35 \nB. REFERENCES  ................................ ................................ ................................ ...........  36 \nC. ANNEXES  ................................ ................................ ................................ ................  40 \nAnnex  1: SCHEER mandate on benefit -risk assessment on the use of CMR/ED phthalates  ...........  40 \nAnnex 2: Medical Device Regulation (Regulation 2017/745) on CMR and/or ED substances  .........  44 \nAnnex 3: Definitions/descriptions \u2013 References - Glossary  ................................ .......................  45 \nAnnex 4: CMR and/or ED substances  ................................ ................................ ....................  51 \nAnnex 5: Legislation on CMR and/or ED phthalates  ................................ ................................ . 53 \nAnnex 6: Use of phthalates in medical devices  ................................ ................................ ....... 57 \nAnnex 7: Approaches for Benefit -Risk Assessment  ................................ ................................ .. 60 \n \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n6 \n  \nA. GUIDELINES  on benefit -risk assessment  for CMR and/or endocrine -\ndisrupting phthalates used in medical devices  \n \nScope  \nThe Regulation  (EU) 2017/745 on m edical devices (MDR), Annex I \u201cGeneral Safety and \nPerformance Requirements\u201d, Chapter II \u201cRequirements regarding design and \nmanufacture\u201d, Section  10.4 deals with the presence of substances that may be released \nfrom a medical device. Annex I Chapter II Section  10.4.1 state s that substances that are \ncarcinogenic, mutagenic, or reprotoxic (CMR) of category 1A and 1B, or substances \nhaving endocrine -disrupting (ED) properties for which there is scientific evidence of \nprobable serious effects on humans, shall only be present in device s, or parts thereof or \nthose materials used therein , above 0.1% weight by weight (w/w) when justified \naccording to a set of criteria listed under Section  10.4.2.  \nThese Guidelines1 describe the methodology on how to perform a BRA for the justification \nof the presence of CMR 1A or 1B and/or ED phthalates (CMR/ED phthalates) in medical \ndevices at percentages above 0.1% by weight (w/w). They also describe the evaluation \nof possible alt ernatives for these phthalates used in medical devices , including  alternative \nmaterials, designs or medical treatments . They are intended to be used by the relevant \nstakeholders e.g. manufacturers, notified bodies and regulatory bodies.  \nThese Guidelines apply to those medical devices and components thereof indicated in \nAnnex I section 10.4.1.of the MDR . They do not provide information for the BRA of the \nuse of a medical device itself . However, the BRA as described can be integrated within \nthe risk management system for individual medical devices. For the BRA of medical \ndevices in general, stakeholders are referred to  section A7.2. of MEDDEV 2.7/1, revision \n4. Additional information may be found elsewhere, for example in the following \ndocuments  FDA 2 016, 2018, EN ISO 14971,  ISO/TR 24971. It should be noted that the \nacceptability of any risk is evaluated in relation to the benefit of the use of the medical \ndevice.  \nWhen the word \u201cpatient\u201d is used in these Guidelines, this also covers  professional users  \nand other persons (e.g. donors in case of blood donation) exposed to the medical device \nas well.  \nAnnex 1 to these Guidelines describes the mandate, Annex 2 describes Annex I Chapter \nII Section  10.4. of the MDR regarding the use of substances  that could be  released from \nthe medical device and pose a risk to patients,  and Annex 3 describes the definitions \nused in these Guidelines.  \n \n \n \n                                                           \n1 It should be noted that, in accordance with Regulation (EC) 2017/745, Annex I, Chapter II Section 10.4.3. \nand 10.4.4., updates of these Guidelines might be available in the future.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n7 \n  \n1. Introduction  \n \nPlacing medical devices  on the market,  making them available on the market and putting \nthem into service are all activities governed by Regulation (EU) 2017/745 that replaces \nDirective s 90/385/EEC and  93/42/EEC . Medical devices are defined in the MDR as \npresented in the text box below:  \nFor the purposes of this Regulation, the following definitions apply  \n(1) \u2018medical device\u2019 means any instrument, apparatus, appliance, software, implant, \nreagent, material or other article intended by the manufacturer to be used, alone \nor in combination, for human beings for one or more of the following specific \nmedical purposes :  \n\u2014 diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of \ndisease,  \n\u2014 diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or \ndisability,  \n\u2014 investigation, replacement or modification of the anat omy or of a physiological or \npathological process or state,  \n\u2014 providing information by means of in vitro examination of specimens derived from \nthe human body, including organ, blood and tissue donations, and which does not \nachieve its principal intended a ction by pharmacological, immunological or metabolic \nmeans, in or on the human body, but which may be assisted in its function by such \nmeans.  \nThe following products shall also be deemed to be medical devices:  \n\u2014 devices for the control or support of conce ption;  \n\u2014 products specifically intended for the cleaning, disinfection or sterilisation of \ndevices as referred to in Article 1(4) and of those referred to in the first paragraph of \nthis point.  \nAs a general requirement , the medical device shall perform acc ording to its intended \npurpose and be safe for professional  users and patients , or where applicable other \npersons (e.g. donor s) on which the device is used. The conformity of medical devices \nshall be evaluated against the requirements of the Regulation (EU) 2017/745. They shall \nbe presumed to be in conformity with this Regulation if they are in conformity with EU -\nharmonised standa rds or the relevant parts of those standards, the references of which \nhave been published in the Official Journal  of the European Union. Although not \nmandatory, these standards provide a route to comply with the MDR.  \nFor medical devices the horizontal standards EN ISO 14971 and EN ISO 10993 -1 are \nespecially relevant. EN ISO 14971 describes the application of a risk management \nprocess for medical devices, whereas EN ISO 10993 -1 deals with the biological evaluation \nand t esting of medical devices within a risk management process. According to EN ISO \n10993 -1, evaluation of the biological safety of a medical device should be a strategy Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n8 \n planned on a case -by-case basis to identify the hazards and estimate the risks of known \nhazards. In Annex A of EN ISO 10993 -1, a series of endpoints is indicated from which a \nselection can be made for the biological evaluation of a medical device. The selection is \nbased on the nature of the device's contact with the body (device category: surfa ce \ndevice, external communicating device, or implant device; type of contact: skin, mucosal \nmembrane, compromised surface, blood, tissues, organs; duration of the contact: limited \n\u226424 h, prolonged >24 h to 30 days, permanent >30 days). A systematic literat ure \nreview is part of the biological evaluation of a medical device in order to avoid \nunnecessary testing  (EN ISO 10993 -1). This systemic literature review should also be \nperformed for a CMR/ED phthalate or potential relevant alternatives identified for a given  \nin a medical device.  \nIn addition to EN ISO 10993 -1, a series of EN ISO 10993 standards has been published \ndescribing various assays and approaches for the evaluation of the endpoints identified in \nEN ISO 10993 -1 for the biological evaluation of medic al devices. Assays described in the \nvarious standards include cytotoxicity, sensitisation, irritation, systemic toxicity, \nimplantation, haemocompatibility, genotoxicity, and carcinogenicity endpoints.  \nAdditionally immunotoxicity and organ -specific toxiciti es need to be considered, if \nappropriate.  In addition, reproductive and developmental toxicity should be addressed for \nnovel materials, materials containing substances with a known reproductive or \ndevelopmental toxicity, medical devices with relevant targe t populations (e.g. pregnant \nwomen), and/or medical devices where there is the potential for local presence of device \nmaterials in the reproductive organs (EN ISO 10993 -1:2018). For the risk assessment EN \nISO 10993 -17 describes determination of allowable l imits for leachable substances, \nwhereas EN ISO 10993 -18 describes methods for chemical characterization of materials \nused in medical devices. In addition to the horizontal standards, vertical i.e. device \nspecific standards and standards for clinical investigation are available ( e.g. EN ISO \n14155).  \nFurthermore, the EU also provides guidance in MEDDEV documents (e.g. MEDDEV 2.7/1 \nrev.4 for clinical evaluation of medical devices).  \nThe MDR states that substances that are classified as carcinogenic, muta genic, or toxic to \nreproduction (CMR) of category 1A or 1B, or substances identified at EU level as having \nendocrine -disrupting (ED) properties for which there is scientific evidence of probable \nserious effects on humans  (CMR/ED substances, in this text) , shall only be present in a \ndevice s or parts thereof or those materials used therein  above 0.1% weight  by weight \n(w/w) when justified. Annex 4 provides further information on the classification of CMR \nand on identification of ED substances. The justificatio n for the use of CMR/ED \nsubstances in a medical device above 0.1% w/w, shall be based on an analysis of \npotential patient and user exposure, availability of possible alternatives, an \nargumentation why possible alternatives are appropriate or inappropriate,  and on the \nmost recent Guidelines of this Scientific Committee.  \nPhthalates are a group of substances widely used in medical devices. When  used as  \nplastici sers they may comprise a substantial part of the medical device. A typical \nconcentration of Bis(2 -ethylhexyl) phthalate (DEHP; CAS 117 -81-7) in plastici sed \npolyvinyl chloride (PVC) can be 30% based on weight (ECB 2008, SCENIHR 201 5). For \nmany years the reproductive toxicity and the possible endocrine disrupting activity of \ncertain phthalates has been a source for debate.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n9 \n Phthalates currently classified as reproductive toxicants category 1B under the \nClassification, Labelling and Pa ckaging (CLP) regulation (EC 1272/2008) and identified as \nsubstances of very high concern (SVHC)  under Article 57 (c) of REACH Regulation (EC) \n1907/2006 are listed in Annex 5  of this document . This list may be updated, so it is \nrecommended to consult the An nex VI of the CLP Regulation.  \nIn addition, the Commission Implementing Decision (EU) 2017/1210 and Commission \nImplementing Decision (EU) 2018/636 identified some phthalates as substances of very \nhigh concern (SVHC) according to Article 57(f) of REACH Regu lation (EC) 1907/2006,  \ndue to their endocrine disrupting properties with probabl e serious effects to humans, \nnamely Bis(2 -ethylhexyl) phthalate (DEHP), Benzyl butyl phthalate (BBP), Dibutyl \nphthalate (DBP) , Diisobutyl phthalate (DIBP) , and Dicyclohexylphthalate  (DCHP) . Bis(2-\nethylhexyl) phthalate (DEHP), was also identified in 2014 as a substance of very high \nconcern in  accordance with Article 57(f) of Regulation (EC) 1907/2006 (REACH) because \nit is a substance with endocrine disrupting prop erties for which there is scientific evidence \nof probable serious effects to the environment which give rise to an equivalent level of \nconcern to those of other substances listed in points (a) to (e) of Article 57 REACH. \nhttps://echa.europa.eu/documents/10162/21837b30 -0318-8b45-92db-9e8c39f89dee  \nSCENIHR adopted an Opinion on the safety of medical devices containing DEHP -\nplasticised PVC in 2008, and a revision of this  Opinion in 201 5 (SCENIHR 2008, 201 5). \nThe main source for DEHP exposure of the general population was determined to be food. \nIn addition, the use of medical devices can increase the exposure considerably in the \ncourse of specific medical treatments, for e xample during massive blood transfusions, \nhaemodialysis, and in neonatal intensive care units (NICU) for prematurely born \nneonates (SCENIHR 201 5). Although quite a number of alternative substances were \navailable for DEHP, for some of them serious data gaps were observed regarding hazard \nidentification and exposure estimation (Bui et al., 2016, SCENIHR 201 5). The Danish EPA \nassessed different alternatives and concluded that to various degrees some substances \ncan be considered to be relevant alternatives to DEHP in terms of human health hazards, \nespecially regarding the endpoints reproductive and developmental toxicity (Nielsen et al. \n2014). However, for a number of possible alternatives the data set was limited. Some \nalternatives showed a low  migration rate and some of them are already used as \nsubstitutes in medical devices for traditional DEHP -applications. For example, four \nadditional plasticisers for PVC (BTHC, DEHT, DINCH, and TOTM) used in medical devices \nhave recently been included in th e updated chapters of the European Pharmacopoeia \n(Council of Europe, EDQM 2018).  \nPhthalates classified as CMR of category 1A or 1B according to the procedure described in \nAnnex 4 are listed in Annex VI of the CLP regulation (CLP -Regulation (EC) No 1272/200 8, \nOJ L353). According to  article 57 (f) of REACH (Regulation (EC) 1907/2006) or the \nBiocides Regulation ( Regulation (EC)  528/2012) phthalates can be identified as having \nED-properties when  there is scientific evidence of probable serious effects to human \nhealth .  \nThese Guidelines provide a framework of how to perform a BRA for the presence of such \nCMR and/or ED phthalates in medical devices or parts or materials used therein at \npercentages above 0.1% weight by weight (w/w) , and shall be used by all relevant \nstakeholders, e.g. manufacturers and notified bodies, and regulatory bodies for the \njustification of the presence of CMR/ED phthalates . The evaluation according to the Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n10 \n Guidelines should be performed by a multidisciplinary team including amongst others  e.g. \na material scientist, medical device specialist, toxicologist and clinician.  \nA justification for the use of a CMR/ED phthalate can also be based on an already \navailabl e justification relating to a medical device for which equivalence with the device \nin question can be demonstrated according to the MDR Annex XIV Section 3. The existing \njustification can be used as a reference, and the data used for this justification sho uld be \navailable . \nThe approach of these Guidelines can also be u sed for a BRA of other CMR/ED substances \npresent in medical devices.  \nOther descriptions for BRA may be \u201cbenefit -risk analysis\u201d or \u201cbenefit -risk determination\u201d \nas defined in the MDR. As Annex I Section 10.4.3 indicates a benefit -risk assessment this \nterminology is used in these Guidelines.  \n \n \n2. Framework for Benefit -Risk A ssessment   \n \nThe MDR allows the use of CMR 1A/1B and/or ED substances in medical devices above a \nconcentration of 0.1% w/w when a proper justification can be provided ( MDR Annex I, \nChapter II  Section  10.4). For such a justification several steps need to be considered \nincluding the availability  of alternative substances, materials, designs, and medical \ntreatments. In addition, the r isk associated with such alternatives shall be weighed \nagainst the risk of the use of CMR 1A/1B and/or ED identified phthalates covered  under \nMDR Annex I Chapter II Section  10.4.1. However, the risk is not the only parameter to \nconsider . The impact of the possible alternatives on the functionality, performance and \nthe overall benefit -risk ratio of the medical device should also be evaluated.   \nThe justification for the presence of CMR 1A or 1B and/or ED phthalates for which there \nis scientific evidence of probable  serious effects on humans should be based on a number \nof considerations as described below and in Figure 1 .  \nIn order to perform the BRA as indicated above , it is important to describe the \nterminology to compare the risk s of the presence of the phthalates  to be evaluated (see \ntext box below). Annex 3  provides  a selection of definitions as present in the MDR and/or \nthe OECD Substitution and Alternatives Assessment Toolbox. (http://www.oecdsaatoolbox.org/ ) \nFor the purpose of these Guidelines the following definition for \"alternatives\" is used:  \n\u201calternatives  are defined as substances, materials, designs  and medical treatments  that \ncan be used to replace the use of CMR and/or ED  substances in medical devices\u201d  \nThe alternative therefore is not limited to a possible substitute substance or material but \ncould also be another device design (e.g. coating/production process/ techniques /lower \nconcentration  of substances)  or medical treatment (e.g. procedure, device) or a \ncombination of technical and substance alternatives that can substitute or eliminate the \nuse of the CMR/ED phthalate (modified from the ECHA REACH guidance on the \npreparation of an application for authori sation).  \nThe functionality and performance of the alternative should  be comparable to the extent \nthat there would be no clinical ly relevant  difference foreseen in the performance of the Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n11 \n device or in the outcome of the alternative medical procedure. Conside rations of \nfunctionality and performance shall be based on proper scientific justification. In order to \njustify the use of a CMR 1A or 1B and/or ED phthalate, the manufacturer shall clearly \ndemonstrate that the identified alternative(s) are not appropriate  to maintain the \nfunctionality, performance and benefit -risk ratios of the medical device.  \nA number of aspects need to be considered for the justification of the presence of a \nphthalate classified as CMR category 1A or 1B and/or identified as ED above  content > \n0.1% w/w in a medical device , or parts thereof or those materials used therein, as \nintended to be used.   \nIn summary, these aspects can be considered by a stepwise approach given below and \npresented in Figure 1. Further details and examples on the steps used in the Guidelines \nare given in the following chapters.  \nAssessment of the CMR/ED phthalate  (CMR/ED scenario)  \nStep 1:  \nDescription and characterisation of the composition of the medical device  (or parts \nor materials thereof) . Identif ication  of the  presence and concentration of CMR/ED \nphthalate (s) in weight by weight percentage (% w/w) . \n \nStep 2:  \nDescription of the use and function of the CMR/ED phthalate used in medical \ndevice.  \n2a. Description of functionality/performance provided by the presence of the \nCMR/ED phthalate.  \n2b. Description of the benefit (material and/or clinical) of the presence  of CMR/ED \nphthalate in the medical device.  \n \nStep 3:  \nAssessment of the risks of the CMR/ED phthalate.  \n3a. Determin ation of  the patient exposure based on realistic worst -case2 use \nscenario  in the intended use . \n3b. Identif ication of  biocompatibility, general toxicological and specific CMR/ED \nhazards associated with the phthalate.  \n3c. Determin ation of  the maxim um tolerable/ acceptable exposure for the patient,  \nbased on pre -clinical and clinical information (if available).  \n3d. Determination of the risks for various intended  use scenarios and patient \ngroups.  \n \nAssessment of possible alternative (s) (non CMR/ED  phthalate scenario)  \nStep 4:  \nInventory of possible alternative (s).  \n4a. Substances.  \n4b. Materials.  \n                                                           \n2 Realistic worst case is the situation where the exposure is estimated us ing a range of factors (i.e. duration, \namount, exposure controls), where applicable, the ones that would be expected to lead to maximum amount of \nexposure (e.g. exposure might be assessed under realistic simulated -use scenarios by EN ISO 10993 -12 and \nEN IS O 10993 -18 or a non-volatile  residue test (USP <661>)). The realistic worst case does not include \ndeliberate misuse. (EU Biocides Regulation 528/2012).  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n12 \n 4c. Designs and/or medical treatments3. \n \nStep 5:  \nIdentification of the potential relevant candidates for assessment as alternatives \nto CMR/ED  phthalates and justification for the selection and exclusion of possible \nalternatives.  This also includes assessment of the availability of the potential \nalternative (s). \n \nStep 6:  \nDescription of identified potential relevant alternative(s).  \n6a. Description of functionality and performance  of the potential alternative(s).  \n6b. Description of the benefit (material and/or clinical) of the use o f the potential \nalternative(s).  \n \nStep 7:  \nAssessment of the risk of identified potential relevant alternative (s). \n7a. Determination of patient exposure o f the alternative based on a realistic \nworst -case use scenario in the intended use.  \n7b. Identification, where available, of biocompatibility, toxicological and CMR/ED \nhazards associated with the alternative.  \n7c. Determination of maximum tolerable/acceptabl e exposure of the alternative \nfor patient (if available).  \n7d. Determination of risk of potential alternatives for various use scenarios and \npatient groups.  \n \nAssessment of potential relevant alternative (s) versus CMR/ED phthalate  \nStep 8:  \nComparison of functionality and performance of CMR/ED phthalate as used in the \nmedical device with functionality and performance of identified potential relevant \nalternative (s). \n \nStep 9:  \nComparison of hazard (s) of original CMR/ED phthalate as used in the medical \ndevice with hazard (s) of identified potential relevant alternative (s). \n \nStep 10:  \nComparison of benefit and risk of CMR/ED phthalate used in the medical device \nwith identified potential relevant alternatives.  \n \nIn addition to patients, the same  approach shall be used for the justification of the \npresence of CMR/ED phthalate in medical devices to evaluate the risk for professional \nusers and for other persons (e.g. donors) exposed to the CMR/ED phthalates. When \nalternative designs or medical treat ments were identified as potential alternatives in step \n5, adequately adopted endpoints for risks and benefits shall be chosen.  \nIt should be noted that scientific developments may be available after the initial \nassessment regarding the use of alternatives for CMR/ED phthalates . Therefore, a \n                                                           \n3 It should be noted that for alternative designs and/or medical treatments, appropriate endpoints for r isks and \nbenefits shall be selected.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n13 \n revision of the BRA of the presence of the CMR and/or ED phthalate may be necessary. \nRevisions of the above indicated BRA shall occur as indicated in the relevant sections of \nMDR for the general risk assessment of the me dical device.   \nFigure 1 illustrates the BRA and is based on Eliason and Morose (2011), EMA (2014), FDA \n(2016) and a critical selection from the OECD Substitution and Alternatives Assessment \nToolbox ( http://www.oecdsaatoolbox.org ). It presents the stepwise approach described \nabove including a general description of factors to consider when performing a BRA.  \nFigure 1 presents a use scenario in which the CMR/ED is used in a medical device versus \na non -use scenario in which a proper potential alternative is evaluated.  \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n14 \n Figure 1 . BRA for evaluation of presence  of CMR/ED phthalates and their  \npotential alternatives in medical devices  (relevant sections between brackets) . \nStep 3 (3)\nUse scenario\nAssessment of the risks of phthalate\n3a. Exposure assessment patient\n3b. Biocompatibility, hazard assessment\n3c. Maximum tolerable /acceptable dose\n3d. Risk characterisation Step 4 (4)\nInventory of possible alternatives\n4a. Substitute substances\n4b. Substitute materials\n4c. Alternative designs/treatmentsDefine aim and \nscope\nStep 1 (3)\nDescription and characterisation of \ncomposition of medical device, \nIdentifIcation of presence and \namount of CMR/ED phthalate\nStep 2\nDescription of phthalate \n2a. Use, functionality and performance of \nphthalate (3)\n2b. Benefit (7)Step 5 (4) \nIdentification of  potential candidates for \nalternatives and justification for the \nselection and exclusion\nStep 6\nDescription of identified potential \nrelevant alternatives\n6a. Functionality, performance (4)\n6b. Material and clinical benefit of the \nuse (7)\nStep 7 (4)\nAssessment of the risks of Identified \npotential relevant alternative(s)\n7a. Exposure assessment patient or user\n7b. Biocompatibility, hazard assessment\n7c. Maximum tolerable /acceptable dose\n7d. Risk characterisation\nStep 8 (5)\nComparIson of  functionality,  \nperformance of use and non- \nuse scenario\nOverall summary report\nJustification for continued use of \nCMR/ED phthalate (6)Step 9 (5)\nComparison of hazard(s) of use \nand non-use scenario\nStep 10 (5,7, 8)\nComparison of benefit and risk \nof  use and non-use scenario\nUncertainty analysis (9)Non-CMR/ED \nphthalate \nscenarioCMR/ED \nphthalate \nscenario\n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n15 \n  \n3. Assessment of the presence of phthalates in a medical device4 \n \nIt is already necessary to provide most of the information as indicated for the use of \nCMR/ED phthalates in order to prove compliance with the general safety and \nperformance requirements for the phthalate containing medical device.  \n \nWhen more than one CMR/ED phthalate is used simultaneously in the medical device, a \njustification shall be provided for each of the phthalates and their combination.  Some risk \nassessment data regarding the combinat ion of phthalates are available, as EFSA has \nrecently proposed a Group TDI for some of them, having a similar Mode of Action (MOA) \nin vivo  (EFSA 2019, see Annex 5). Information on assessment of combined exposures to \nphthalates can be found for example at the report by the National Research Council \nCommittee on the Health Risk of Phthalates (2008) and the ECHA website on the  \nrestriction of f our phthalates ( https://echa.europa.eu/registry -of-restriction -intentions/ -\n/dislist/details/0b0236e180d73895 ) and EFSA guidance on cumulative expos ure (EFSA, \n2019 https://doi.org/10.2903/j.efsa.2019.5634 )  \n \nStep 1: Description and characterisation of the composition of the medical device.  \nProvide a description of the medical device and its composition including identification \nand the concentration of each CMR/ED phthalate in the device , and the type of chemical \n/physical binding of the phthalate in the formulation/device, when there is an impact on \nleakage.  Use available chemical information  for identifying target phthalates (e.g. CAS \nN\u00ba; EINECS N\u00ba; IUPAC name).  The chemical composition of a medical device can be \nevaluated by using e.g. EN ISO 10993 -18 (FDIS published in 2019) . \n \nStep 2: Use and function of CMR/ED phthalates in the medical dev ice.  \nCharacterise the function and use of the CMR/ED phthalates in the medical device and \nthe properties it imparts to the device. Provide a description of the intended use, \nfunctionality and performance of the medical device containing the CMR/ED phthala te \nand how the use of the phthalate is critical for its functionality and performance . For \nexample, for PVC consider, with regard to the performance of the medical device, \nmaintenance, flexibility, durability and for the phthalate viscosity and PVC compatibility. \nProvide a description of the patients targeted (e.g. with respect to sex, age, probable \nvulnerable groups5). Provide a description of use types of the medical device for which it \nis intended (e.g. single  vs repeated exposure ). Other aspects that can be relevant include \nthe critical properties (e.g., flexibility), the conditions of use, critical quality criteria, \nprocess/treatment and performance constraints (e.g., sterilization, device/drug \ninteractions), regulatory or clinical or other requi rements that the CMR/ED phthalates \nand the phthalate -containing device need to deliver. Key criteria for the function,  \n                                                           \n4 The analysis presented in section 3 (steps 1 -3) describes the current use scenario of the CMR/ED phthalate, \ni.e., the scenario that would continue in the future if no additional action (other than, e.g., a planned regulatory \naction entering into force) is taken to limit, substitute or eliminate the presence of the CMR/ED phthalate in the \nmedical device. The current scenario can also be referred to as baseline, business as usual or continued use \nscenario.  \n5 Vulnerabl e Groups (in these Guidelines): vulnerable groups of the population such as children and individuals \nwith increased susceptibility due to pre -existing disease, medication, compromised immunity, pregnancy or \nbreastfeeding, women and men in reproductive age.  These vulnerable groups also include infants, elderly \npeople or people with poor health conditions.  \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n16 \n performance and overall use should be outlined and applied as the basis for an \nidentification and screening of possible alternatives and a more detailed assessment of \npotential alternatives. Justification for the selection of these criteria should be provided.  \n \nBenefits of the device with CMR/ED phthalates should also be considered  e.g. treatment \nof specific patients groups due to tuning of  flexibility of the medical device . Present an \ninventory of the benefits of the CMR/ED phthalates in the medical device for the patients \n(separately for vulnerable groups). More detailed information on the benefit assessment \nis presented in section 7.  \n \nStep 3: Assessment of the risks of the CMR/ED phthalate.  \nPerform a risk assessment of the CMR/ED phthalate present in the medical device. The \nrisk assessment should contain a description of the potential phthalate exposure of \nvarious patient groups for which  the medical device is intended (e.g. single  vs repeated \nexposure ). This should separately include vulnerable groups. EN ISO 10993 -1 provides \ninformation on use type in terms of exposure potential (e.g.  limited ( \u226424h), prolonged \n(>24h to 30d) and permanen t (>30d))  that slightly differs from the duration of use as \ndefined in the MDR (Annex VIII, 1, transient <60 minutes, short term 60 minutes to 30 \ndays, long term >30 days).  \n \nExposure estimation  \n \nProvide information , preferably based on data from direct measurement or, when not \navailable, an estimation based on worst -case scenario or from scientific literature , on the \nrelease of the CMR/ED phthalate from the medical device when used in various clinical \nmodalities. For  data generation , analytical contact conditions for the evaluation of \nleaching of substances from medical device s, should consider fo r example temperature, \ncontact duration and frequency, polarity of contact liquids, flow rates, contact surface, \nand volume  of contact liquids (EN ISO 10993 -1, EN ISO 10993 -12, EN ISO 10993 -18,  USP \n661). The contact conditions should be set to represent realistic worst -case conditions \ntaking into account the intended use of the medical device.  \n \nEstimate exposure to the phtha late(s) considering data on the release of the substance \nfrom the device. Consider repeated use scenarios (e.g. dialysis, apheresis donation, \nchronic treatment)  and different population groups. The combined exposure to different  \nCMR/ED  phthalates also needs to be considered  when present in a medical device. More \ndetails on the use of phthalates in medical devices  are presented in Annex 6.  Risk \nmanagement measures in place and their effectiveness should be described and taken \ninto account in the assessme nt (EN ISO 14971, EN ISO 10993 -1). In addition, data from \nbiomonitoring programs may become available that could also provide information on \nexposure levels of phthalates in the general population and more specifically during \nmedical treatment.   \n \nHazard id entification  \n \nDescribe hazards associated with the CMR/ED phthalate by considering all relevant \ntoxicological endpoints for acute as well as for repeated dose toxicity. EN ISO 10993 -1 \nprovides information on hazard endpoints to be considered depending on the exposure \nand use category of a medical device, whereas allowable limits can be determined \naccording to EN ISO 10993 -17.  Possible hazardous effects of combined exposure  should Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n17 \n also be assessed.  Identify  an adequate point of departure (PoD) for risk ass essment. In \ncase of a threshold Mode of Action, such a PoD could be the most sensitive no-observed -\nadverse -effect -level (NOAEL ) or lowest -observ ed-adverse -effect -levels (LOAEL ), or a \ndose that causes a predefined response (Benchmark dose \u2013 BMD) obtained by  \nBenchmark dose modelling. In case of non -threshold effects (e.g. in the case of \ngenotoxic carcinogens or for certain substances acting via an ED -mediated MoA), such a \ndose descriptor could be a T256 value or the benchmark dose associated with a 10% \nresponse (BMD10) (ECHA, 2012).  \n \nWhere a reference DNEL and /or a reference DMEL have already been derived in the \ncontext of other EU legislations, the analysis could refer to these derived figures without \nreferring to detailed assessment how these data have been derived (e.g. under REACH \nlegislation, Food Contact Material legislation). However, as some of these data may have \nbeen derived in the past, relevant up -to-date scientific evidence (based upon a \nsystematic li terature review) and up -to-date risk assessment methodology for all \nrelevant toxicological endpoints needs to be considered . If such DNEL/DMELs are not \nused in the assessment, a justification should be presented (e.g. new \ninformation /studies). Some of thes e other legislations  are defined under Annex 4. In \naddition, information can also be obtained in the SCENIHR 201 5 Opinion on DEHP.  \n \nThe ED property of the phthalate can be described according to the recently published \nEFSA/ECHA guidance document . \nhttps://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2018.5311   \nThis includes impacts on fertility, birth defects (e.g., cryptorchidism, hypospadias), \ndevelopmental effects, and other effects associated with the CMR/ED phthalates.   \n \nDescribe risk (risk characterisation)  \n \nThe risk can be described by comparing exposure levels that are considered safe with the \nexpected exposure (worst -case scenario) to obtain a risk characterisation ratio (RCR). \nStarting points (points of departure, PoD) for exposure levels that are considered safe \ncould be the most sensitive no -observed -adverse -effect -level (NOAEL) or lowest -\nobserved -adverse -effect -levels (LOAEL), or a dose that causes a predefined response \n(Benchmark dose \u2013 BMD) for threshold substances. For non -threshold substances, a T25 \nvalue or the benchmark dose associated with a 10% response (BMD10) could be used. \nFrom these PoDs, acceptable expo sure values can be derived such as \u201cDer ived No -Effect \nLevel \u201d (DNEL), \u201cDerived Minimum Effect Level\u201d (DMEL) or intakes over lifetime without \npresenting an appreciable risk to health (ADI or TDI/TWI or TE).  As such data are often \nobtained in rat studies, th e use of the TDI seems more appropriate in view of the critical \neffect window for androgenic reproductive toxicity in rats has been reported to be a few \ndays (Welsh et al. , 2008). In addition, patients may be exposed to medical devices only \nfor a limited p eriod of time.  EN ISO 10993 -17:2002 7 calculates for medical devices a \nTolerable Exposure (TE), which is based on a product of the tolerable intake, the body \nmass and the utilization factor.  When necessary, acceptable exposure levels  can be \nderived by dividing the point of departure for risk assessment by appropriate assessment \nor uncertainty factors . Specifically for ED effects additional assessment factors might be \nconsidered as proposed recently (Hass et al.,  2019).  \n                                                           \n6 Animal dose -descriptor; chronic dose rate that will give 25% of the animal's tumours at a specific tissue site \nafter correction for spontaneous incidenc e (Dybing et al.,  1997)  \n7 EN ISO 10993 -17:2002 is currently under revision. It is discussed to replace in the updated version TE by TI.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n18 \n  \nThe risks can also be described by calculation of the Margin of Safety (MoS), which is the \nratio between the lowest PoD and the expected exposure (worst case scenario) and \ncomparison with a reference MoS (see SCCS Notes of Guidance \u2013 SCCS/1602/18).  \nPerform this evaluation for e very group (patients/donors) for which the device is \nintended to be used.  \n \nDetermine and describe in which situation the risk can be acceptable for the use of the \nCMR/ED phthalate in the medical device. The benefit -risk assessment for the use of the \nCMR/ED  phthalate can be performed using for example MEDDEV 2.7/1rev4 and EN ISO \n14971 (see also Section 8).  The MDR considers a risk acceptable when outweighed by \nthe benefit of using the device in patients (Chapter I of MDR , Chapter VI Article 62 ). \n \nIn addition to potential CMR/ED effects, discuss any other potential hazards associated \nwith the composition of the device (e.g. by using the EN ISO 10993 series of standards).  \nEvaluate if such effects are associated with the use of the CMR/ED phthalates i n the \ndevice.  \n \nNote: It should be noted that for some genotoxic carcinogens a no effect level is \nassumed not to exist.  Similarly, a scientific debate is ongoing about whether this also \napplies to ED activity.  \n \nThe assessment of the risk should be accompan ied by an estimation of the impact of \nuncertainties in the described outcomes  (see section  9). \n \n \n4. Assessment of possible alternative substances, materials, designs or \nmedical treatments8 \n \nIn general a similar risk assessment as presented in step 3 above has to be performed \nfor the alternative (substance s, material s, designs or medical treatment ). An inventory \nshould be prepared  in order to be able to evaluate possible alternative s. An alternative \ncould be another substance/material or device design modifi cation or it could be a clinical \nprocedure (e.g. a process, technique, treatment or modification) or a combination of \ntechnical and substance alternatives.  \n \nStep 4: Inventory of possible alternatives  \nPrepare a list of possible alternatives ( such as  substances, materials, designs or medical \ntreatments)9.  \nA description of the alternative scenario (CMR/ED phthalate \"non -use scenario\u201d) needs to \nbe presented including identification of alternative substances , materials, designs or \nmedical treatment , e.g.  by includ ing consideration of all available information, such as \nalternative medical devices available on the market, information about independent \nresearch, published peer-reviewed studies, systematic literature reviews, risk assessment \nreports or scient ific opinions from relevant scientific committees and the results of in -\n                                                           \n8 The analysis presented in section 4 constitutes the non -use scenario or the scenario that would transpire if the \nCMR/ED phthalates would no longer be used in the medical device.  \n9 Information source for alternatives might be the European Pharmacopoeia.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n19 \n house research and development.  The identif ication of  possible  alternatives should be \nproperly documented.  \nStep 5: Identification of the candidates for assessment as potential relevant  alternatives \nfor phthalates  \nThe MDR indicates that an analysis of all possible alternatives shall be performed. \nHowever, when many alternatives are available it would not be feasible to do an \nextensive evaluation of all alternatives. It is therefo re recommended to select a number \nof potential relevant  alternatives  based on screening against key criteria for function, \nperformance, toxicity, and overall use in the medical device in question  (see below). In \naddition, analysis of availability and technical feasibility might affect choices for \nalternatives as well.   \nA preliminary analysis of possible alternative substances, materials or designs or medical \ntreatments should be performed . This preliminary analysis  should include a description of \ntheir possible use as alternative substance , material , designs or medical treatment s. \nJustification on how and why alternatives are rejected for further assessment by defining \ninclusion and exclusion criteria should be provided.  \nInformation/data on functionalit y (e.g. level of flexibility in tubes) as well as performance \nand/or chemical safety assessment (e.g. hazard profile) may be used for rejection of the \nless likely alternatives (see below ) and no further risk assessment for the alternative is \nrequired. The rejection of the less likely alternatives requires justification and \ndocumentation.  The chemical safety assessment should be done after assessment of the \nfunctionality and performance.  \nIn addition to the comparison in terms of functionality, technical per formance and risks \nto patients and users, which are critical elements for the benefit -risk assessment, Annex \nI Section 10.4.2 of the MDR states that the justification for the presence of CMR/ED \nsubstances should also be based on an analysis of the availabi lity of possible alternatives. \nAvailability has several aspects, including for example the availability of necessary \nquantity (volumes) of the alternative on the market within a required timeframe and the \nability to gain access to alternatives that may be proprietary (e.g., via licensing).   \nIf potential alternatives can be identified, a shortlist of the potential alternatives can be \nestablished  for further detailed assessment with regard to technical feasibility, health \nbenefits, comparison of risks, exist ing legal requirements, availability (e.g. sufficient \navailability or accessible to the manufacturer), and technical performance.  In the event \nthat no alternative  is identified, i nformation should be presented on the actions \nundertaken  to identify alternat ives. \n \nA compilation of resources and elements in support of chemical substitution and an \nassessment of alternatives can be found on the OECD webpage : \nhttp://www.oecdsaatoolbox.org/  \nStep 6: Description of identified potential relevant  alternative(s)  and conclusion on their \ntechnical feasibility  \nCMR/ED phthalates are present in medical devices for a specific purpose depending on \nthe intended use of the medical device. For example, phthalates offer the possibility for \nfine tuning the flexibility  (e.g. optimal flexibility without kinking)  of a PVC -based medical Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n20 \n device. In addition, DEHP has a stabilising effect on red blood cells in blood bags \n(SCENIHR 201 5). Technical feasibility of an alternative is based on the alternative \nfulfilling the function of the CMR/ED phthalate. Therefore, the assessment of the \nfunctional properties in relation to the intended use of the medical device is essential. \nBesides functionality, performance under intended use conditi ons should also be \nconsidered.  \n \nArgumentation shall be provided for justifying why possible substances and/or material \nsubstitutes, if available, or design or medical treatment changes, if feasible, are \ninappropriate in relation to main taining the functionality and/or performance of the \nmedical device. For example, it might be the case that replacement is possible for one \nspecific functional use whereas for another functionality the use of the CMR/ED phthalate \nremains necessary . Also oth er aspects related to performance of the alternatives need to \nbe considered like material processing conditions (Crespo et al.,  2007), material quality \nafter sterilisation (Burgos and Jim\u00e9nez 2009), and possible interaction with drugs in \ntherapeutic infusi on systems (Treleano et al. , 2009, Salloum et al. , 2015, Tortolano et \nal., 2018).  \n \nThe benefit(s) should also be considered. An inventory of the benefit(s) of the potential \nalternative substances, materials, designs or medical treatments for patient populations \n(separately for vulnerable patient groups) should be presented (see section 7 ).  \n \nThe evaluation of the identified potential relevant alternatives can be done in a tiered \nway to avoid full assessments for each candidate alternative. For example, based on the \noutcome of the functionality evaluation, the choice of the potential relev ant candidates \nmight be reconsidered and some might be discarded before performing the risk \nassessment (see Step 7).  \n \nThe ECHA guidance on the preparation of an application for authorisation  and ECHA \nformats for Analysis of Alternatives  provide more detailed information on how to conduct \nan initial screening of possible alternatives and to assess the technical feasibility of \npotential alternatives. Submitted applications for authorisations contain a number of  \nexamples (https://echa.europa.eu/applying -for-authorisation/preparing -applications -for-\nauthorisation ) of technical feasibility assessment for uses of substances of very high \nconcern. \nStep 7:  Assessment of the risk of identified potential relevant  alternatives  \nThe risk assessment of alternatives is comparative in nature. Its aim is to assist in the \nconclusion in section 5 whether the transition to the alternatives would lead to lower \nbenefit and/or risk to human health for patients when compared to the current u se of the \nCMR/ED phthalates in the medical device. Th e methodology of the assessment in this  \nstep is similar to that in step 3 as performed for the phthalate to be evaluated with \nreference to the alternative.  \n \nIf potential relevant alternative s were identified under Steps 1 -6, a risk  assessment of \nthese potential relevant  alternative substance/material or designs or medical treatments \nshould be performed. The risk assessment should contain a description of the potential \nsubstance/material (alternative  medical procedure) exposure of various person groups \n(e.g. including patients, donors, professional users)  for which the medical device is \nintended to be used (considering single or repeated use). This should include separately Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n21 \n vulnerable groups . For each  subgroup a different level of risk may be accepted based on \nthe potential benefit of the medical device for that particular group . Risk management \nmeasures (EN ISO 14971, EN ISO 10993 -1) and their effectiveness to reduce exposure \nshould be described and t aken into account in the assessment.  \n \nExposure estimation  \n \nEstimate the potential release of the alternative substance(s) when used in various \ntreatment modalities. Consider also the rate of leaching to estimate the potential \nexposure to the alternative substance. Multiple use scenarios (including various types of \npossible contact) should be considered for the exposure estimation of the alternative \nsubstance (e.g. frequent use of dialyzer) and different population groups.  \n \nHazard identification  \n \nIdentify hazards based on literature, supplier documentation and other information (such \nas risk assessments performed by regulatory bodies). Describe hazards associated with \nthe alternative substance/material by considering all relevant toxicological endpoints for  \nacute as well as for repeated dose toxicity including human data. Identify an adequate \npoint of departure (PoD) for risk assessment. In case of a threshold Mode of Action, such \na PoD could be the most sensitive no -observed -adverse -effect -level (NOAEL) or lowest -\nobserved -adverse -effect -levels (LOAEL), or a dose that causes a predefined response \n(Benchmark dose \u2013 BMD) obtained by Benchmark dose modelling. In case of non -\nthreshold effects (e.g. in the case of genotoxic carcinogens or for substances acting via  \nan ED -mediated MoA), such a dose descriptor could be a T25 value or the benchmark \ndose associated with a 10% response (BMD10) (ECHA, 2012).  Hazards should preferably \nbe evaluated by a relevant exposure route for the intended use of the assessed medical \ndevice. \n \nFor the hazard identification  special attention should be on the determination of any \npotential CMR and/or ED property of the alternative substance used . For further \ninformation purposes, a procedure is described in ECHA Guidance on the application of \nthe CLP criteria  \nhttps://echa.europa.eu/documents/10162/23036412/clp_en.pdf/58b5dc6d -ac2a-4910-\n9702-e9e1f5051cc5   \nor by searching Annex VI of  CLP regulation. ED propert ies of the alternative \nsubstance/material can be described according to the recently published EFSA/ECHA \nguidance document . \nhttps://echa.europa.eu/documents/10162/23036412/bpr_guidance_identif_ed_en.pdf/1a\n4d2811 -3faa-fe61-1de2-3cbce8fd4d95   \nThese effects include impacts on fertility, birth defects (e.g., cryptorchidism, \nhypospadias), developmental eff ects, and other potential toxic effects associated with \nphthalates with ED properties and reprotoxic effects category 1A/B.  It needs also to be \nconsidered that the potential alternative (substances, materials, designs or medical \ntreatments) could also have  other hazards than those of the CMR/ED activity. These \nother hazards and their possible associated risks should be discussed for example by \nusing the EN ISO 14971 and the EN ISO 10993 series. See also Table 1.  \n \nDescri ption of  risk (risk characteri sation)  \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n22 \n The risk can be described by comparing exposure levels that are considered safe with the \nexpected exposure (realistic worst case use scenario). Exposure levels that are \nconsidered safe could be \u201cDerived  No Effect-Levels\u201d (DNEL s) for threshold substances, \n\u201cDerived Minim um Effect Levels\u201d (DMEL s) for non -threshold substances or intakes over \nlifetime without presenting an appreciable risk to health (ADI or TDI/TWI or TE ). As such \ndata are often obtained in rat studies, the use of the TDI seems more appropriate in view \nof the critical effect window for androgenic reproductive toxicity in rats has been reported \nto be a few days (Welsh et al. , 2008). In addition, patients may be exposed to medical \ndevices only for a limited period of time. EN ISO 10993 -17:2002 calculates for medical \ndevices a Tolerable Exposure (TE), which is based on a product of the tolerable intake, \nthe body mass and the utilization factor. When necessary, a cceptable exposure levels   \ncan be derived by dividing the point of departure for risk assessment by appropriate \nassessment or uncertainty factors.  For medical devices allowable limits of their chemical \nconstituents can be determined by EN ISO 10993 -17. \n \nThe risks can also be described by calculation of the Margin of Exposure (MoE) or the \nMargin of Safety (MoS)  due to the substances present in a medical device , which  is the \nratio between the lowest PoD and the expected exposure (e.g. realistic worst case  use \nscenario) and comparison with a reference MoS (see SCCS Notes of Guidance \u2013 \nSCCS/1602/18 ). \nPerform this evaluation for every patient group for which the device is intended to be \nused.  \n \nWhere a reference DNEL and /or a reference DMEL have already been derived in the \ncontext of other EU legislations, the assessment  could refer to these derived figures \nwithout referring to a detailed assessment of how these data have been derived (e.g. \nunder REACH legislation, Food Contact Material legislation). Data on the relevant \nexposure route of the medical device application (e.g. intravenously) are preferred (see \nalso Table 1A, EN ISO 10993 -1). The risk can be described by the so -called risk \ncharacterisation ratio (RCR), being a ratio between the exposure and the DNEL /DMEL . If \nsuch DNEL/DMELs are not used in the assessment, a justification should be stated (e.g. \nnew information /studies).  \n \nDetermine and describe acceptability of the risk for the use of the potential alternative s. \nRisks may be acceptable when they are outweighed by the benefits for the patient.   \n \nConsider any known adverse events associated with the operation of the device using the \nphthalate, and whether the potential alternatives might affect these adverse event s. \nThese considerations can be based upon a systematic literature review  (see MEDDEV \n2.7/1rev4) . \n \nThis exercise has to be performed for each potential relevant  alternative substance  \nand/or materials .  \nA large number of phthalates exist and some may be potential relevant alternatives  for \nthe CMR/ED phthalate used in the medical device. However, a number of these  \nphthalates are also classified as CMR and/or designated ED (see above  and Table 1 \nAnnex 5 ). Such phthalates might be identified as alternatives when the CMR/ED risk is \nreduced compared to the phthalate intended to be  used.  In addition, different \nsubstances , have also been proposed as alternative plastici sers. In 201 5 SCENIHR \npublished an updated Opinion of potential alternative plastici sers for DEHP (SCENIHR Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n23 \n 2015). Although many alternatives were potentially available, it was also observed that \nfor many of them the information on potential risks and the necessary risk assessment \nwas rather limited precluding their use as alternative s. For DEHP an extensive amount of \nliterature is available, allowing a very careful evaluation of the risk associated to its use .  \n \nIn the event that the risk assessment of a potential relevant alternative cannot be \nperformed due to lack of information, document ation should be presented on the actions \nundertaken to obtain information to characterise the risk, including the outcome (for \nexample, QSAR /read across could be performed).  \n \nNote shall be taken that alternative designs or medical treatments might lead to  \nadaptation of  endpoints for the benefit -risk assessme nt when compared to the \ntoxicological endpoints of CMR/ED phthalates.  \n \nThe assessment of the risk should be accompanied by an estimation of the uncertainties \nin the described outcomes which might be qua ntitative (e.g. confidence interval, \nstandard deviation) or qualitative (see section 9).  \nConclude the analysis of the potential  relevant alternative(s) with a summary describing \nthe possible  scenario(s) ( see Fig ure 1).  \n \n \n5. Assessment of potential relevant  alternative substances, materials, \ndesigns or medical treatments versus CMR/ED phthalates  \n \nBased on the information obtained above a decision can be made on the appropriateness \nof potential relevant alternative s (substance, material , design or medical treatment ). In \nthis evaluation several factors need to be included such as weighing of technical \nfeasibility, benefits and risks . And, if possible, quantification of benefits and risks. These \nsteps entail a comparison of the CMR/ED phthalate  \u201cuse-scenario\u201d  (summarised in step \n3) with the \u201cNon-use scenario \u201d (summarised in step 4)  as shown in Figure 1.  \n \nStep 8: Comparison of functionality and performance of CMR/ED phthalate as used in the \nmedical device with functionality and performance of identified potential relevant \nalternative (s). \n \nCompare the functionality and performance of CMR/ED phthalate in the medical device \nand the potential relevant alternative substance/material (or designs or medical \ntreatments by choosing adequate endpoints).  \nPerform step 8 for each candidate identified as the potential relevant alternative in \nsection 4.  \nIf several potential relevant alternatives have a similar functionality and hazard profile, \nexposure conditions and possibilities for Risk Management Measures (RMM) res ulting in \nrisk reduction should be considered (see below).  Risk management is described in EN \nISO 14971.  \nIn this comparison also additional issues not directly related to the functionality and \nperformance of the alternative itself, like technical possibili ties, sterilisation effects and Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n24 \n interactions with infusion liquids, are important for the application of the alternative and \nthe comparison with the CMR/ED phthalates, and thus should be considered.  \nStep 9:  Comparison of risk(s) of CMR/ED phthalate as used in the medical device with \nrisk(s) of identified potential relevant alternatives.  \n \nCompare the risk of both CMR/ED phthalate and alternative substance/material (or \ndesigns or medical treatments by choosing adequate endpoints).  \nPerform step 9 for each potential relevant alternative.  \n \nThere may be difficulties in comparing the risks of a substance e.g. a phthalate, and the \nrisks of a technical alternative such as medical design or medical treatment. For example, \nthere may be risks as sociated with alternative technologies but these may not be of the \nsame nature of the risk of the phthalate. However, the potential relevant alternative \nmust represent a reduction in the overall risks to human health  (Step 10) . Therefore, a \ncomparison of risks must be conducted and the applicant will need to consider how these \ndifferent risks might be compared in terms of risks to human health. Note that an \nalternative medical design or medical treatment may also result in expo sure to other \nrisks previously not present  in the treatment modality. Possible risks of these substances \nwill also need to be considered in the assessment. The comparison with technological \nalternatives such as a medical design or medical treatment can nor mally not be fully \nquantitative (i.e. with directly comparable numeric values), as the hazards and \nassociated risks will not be expressed in similar terms, but will in most cases be \nqualitative or semi -quantitative.  Nevertheless, a clear and transparent de scription can \ngive a good basis to conclude whether overall risks are reduced  or not  (Step 10) .  \nStep 10: Comparison of benefit and risk of CMR/ED phthalate used in the medical device \nwith identified potential relevant alternatives.  \n \nPresent summary/overvi ew of comparison of benefit and risk of CMR/ED phthalate used \nin the medical device with the potential relevant alternatives, including uncertainties  \nabout the estimates or reliability of the data, assumptions, etc. for the parameters \npresented. The summary should contain various aspects of functionality, performance, \nrisk and benefit of the use of the original CMR/ED phthalate used in the medical devic e \nand the potential relevant  alternative (s). In section  6 below the justification of the use of \na CMR/ED phthalate is described based on the summary table comparing an alternative \nwith the CMR/ED phthalate.  \nPerform step 10 for every potential relevant alternative.  \n \nEach of the assessments performed in steps 1 to 1 0 is associated with uncertainties. \nCertain uncertainties can be described by the use of measures  like the standard deviation \nor confidence interval. For other uncertainties , a description may be necessary to explain \nthe extent of the uncertainty  and its impact on the final outcome . \n \nBenefit and risks should be described and weighted against each other in the use of the \npotential alternative substance /material  in the medical device (or designs or medical \ntreatments  by choosing adequate endpoints)  similar to the procedure for the CMR/ED \nphthalate (see step 2).  \n \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n25 \n  \n6. Justification for the u se of CMR/ED phthalate  \n \nBased on the comparison of functionality, performance, availability, risk and benefit, an \nargumentation can be built as to why a possible substance and/or material alternative, if \navailable, or changes in designs or medical treatment, if feasible, are inap propriate in \nrelation to maintaining the functionality, performance and the benefit -risk ratio or profile \n(quantitative/semi -quantitative or qualitative) of the medical device containing a CMR/ED \nphthalate.  \n \nExplain the importance of any difference in ter ms of benefits and risks between the \nCMR/ED phthalate to be used in the medical device and potential relevant alternatives \nusing value judg ements and explain how  the use of the CMR/ED phthalate can be \njustified over the alternatives by describing the accep tability of trade -offs in the \nachievement of some criteria against others.  Any advantage in benefits needs to be \nweighed against possible disadvantages in terms of functionality and risks. Both \ndifferences in benefits and risks need to be considered jointly.  \n  \nIn building the argumentation for the use of a CMR/ED phthalate, note can be taken of \nthe Memorandum on weight of evidence and uncertainties of SCHEER (SCHEER 2018). \nThis Memorandum describes a  methodology  that classifies the strength of evidenc e in the \nhuman health risk assessment  based on integration of different lines of evidence  into \nstrong, moderate, weak, uncertain and inconclusive (no suitable evidence available).  Any \nweight of evidence evaluation needs to show the overall confidence in t he assessment.   \n \nThe argumentation should specifically take into account the intended use of such devices. \nThis should include consideration and discussion of possible high risk groups such as \nchildren or pregnant or breastfeeding women, and other patient groups considered \nparticularly vulnerable to such substances and/or materials. In addition, where applicable \nand available, any future update of these Guidelines shall be considered. A Table with the \nmost relevant information and values should be used to p resent an overview of the \nperformed assessment comparing the CMR/ED phthalate with potential alternative(s). A \nnon-exhaustive example of such Table is presented below. The Table should  be extended \ndepending on the number of criteria evaluated and the numbe r of potential alternatives \nidentified.  \n \nTable 1:  Example for a comparison of CMR/ED phthalate with potential relevant \nalternative(s).  \n  \nAssessment criteria  Description \n(examples)  Reference \nphthalate  Alternative I  Alternative \nII etc.  \nIdentification of \nsubstances/material etc  \nName and CAS number  Chemical \ninformation  CAS \n117-81-7  \n   \nFunctionality/performance  Used as \nplasticiser  e.g. DEHP    \nClinical \nbenefit/performance  Treatment \npossibility  e.g. Flexibility \nof tubing / \nred blood   Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n26 \n cells storage  \nMaterial benefit      \nConcentration (% w/w)      \nLeaching  from medical \ndevice for relevant \nconditions e.g. media, \ntemperature, etc  \n(mg per hour/day)      \nExposure estimation \n(realistic worst case use \nscenario ) for relevant \nroute of exposure      \nHazard identification  Local and \nsystemic \nacute and \nrepeat -dose \ntoxicity, ED -\nproperties, \norgan \ntoxicity, CMR \nproperties, \nbiocompatibili\nty, and \nothers     \nIdentification of a point of \ndeparture for risk \nassessment ( LOAEL, \nNOAEL, BMD, T25, \nBMD10)  \n     \nIdentification of dose \nlevels associated with \nminimal or negligible risk  \n(e.g. DNEL, DMEL, TDI , \nTE, TI)     \nRisk characterisation \n(MoE, MoS, RCR)      \nConfidence  estimation \n(see Table 2)      \nTechnical feasibility       \nOther      \n \nThis Table shall be completed for every component of the medical device that contains \nCMR/ED phthalate(s ) above the 0.1% w/w level. For some medical devices used as a \nsystem (e.g. blood bag system) the whole system might be evaluated.  Note that in case \nof alternative designs or medical treatments adequate endpoints for the comparison shall \nbe chosen. These endpoints may represent risks that may be of a different nature than \nthat of the risk of the phthalate.  \nWhen the outcome of the comp arison shows that the alternative fulfils a comparable or \nbetter intended functionality as well as performance and shows a reduced risk, the use of \na CMR/ED phthalate is not possible. The risk assessment should also indicate whether \nthere would be a reduce d hazard concerning CMR and/or ED properties, and/or reduced \nexposure overall resulting in reduced risk. In this evaluation, other toxicities (e.g. for any Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n27 \n other organ  or system ) of the potential relevant alternatives shall also be considered. So, \nthe full  toxicological profile of the potential relevant alternatives shall be taken into \naccount.  \nA balanced weighing of the benefit  versus the risk has to be performed . For example it is \npossible to use a combination of a CMR/ED phthalate and PVC/material with h igh intrinsic \ntoxicological hazards, thus accepting a risk from a toxicological perspective, in case the \nclinical benefit is very high . In contrast, a minor loss in medical  functionality might be \nacceptable if there is a large reduction  or even absence of risk. Each comparison of a \npotential alternative for the use of a phthalate should be based on the combination of \nfunctionality , risk and benefits for patients.  \nIn this final evaluation , the assessment  of uncertainties associated with the alternatives \n(e.g. on the nature of the risks; assumptions made) should also be considered (see Table \n2 below section 9). Therefore, where possible, quantitative results should be collected \nand compared (e.g. NOAEL, estimated exposure in mg/kg) and their uncertainties should \nbe reported. Also a qualitative description of the uncertainties may be useful (see Table 2 \nbelow sec tion 9). Their impact on the conclusions should also be discussed.  \nAlthough not the main subject of these Guidelines, it should be realised that availability \nand accessibility on the market  might be a limitation for the introduction of an alternative \nsubst ance/material. Some chemicals proposed as alternatives are widely available (e.g. \nBTHC, DEHT, DINCH, and TOTM) however, this may not be the case for other alternatives \nidentified . The lack of the availability of a potential alternative for a medical device might \nresult in the conclusion that replacement is not feasible and that the use of a phthalate \nwith CMR and/or ED property continues in order to keep the device available for pat ients. \nSo, besides technical feasibility in terms of functionality and risk reduction (risk \nassessment of the phthalate versus the alternative), also availability and accessibility on \nthe market needs to be considered.  \nThe BRA of the CMR/ED phthalate shoul d be updated when new scientific information \nbecomes available on alternatives for the use of phthalates, when new Guidelines are \nreleased, or as the \"overall\" benefit -risk determination of the medical device is updated.  \nA plan to perform an update of the relevant part of the technical file of the device needs \nto be submitted during the certification process (post -market surveillance plan referred \nto in Article 84, the requirements are set out in  Section 1.1 of Annex III MDR) and this \nshould also cover upd ates needed on the justification for the presence of CMR/ED \nphthalates .  \n \n7. Benefit assessment  \n \nThese Guidelines do not provide information for the benefit -risk assessment of the use of \na medical device itself but are limited to the methodology on how to perform a BRA for \nthe justification of the  presence  of CMR 1A or 1B and/or ED phthalates in a medical \ndevice  above 0.1% (w/w).  \nThe evaluation of the overall benefit -risk assessment of a medical device is  presented in \nother documents (e.g. MEDDEV 2.7/1 rev4, EN ISO 14971).   \nThe benefits of the CMR/ED phthalate use in a medical device need to be compared to \nthe benefits of the potential relevant alternatives, with the focus of the analysis being on Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n28 \n the net or incremental benefits of use of the CMR/ED phthalate in comparison to the \nalternatives. These benefits may include material or clinical benefits. Uncertainties about \nthe estimates or reliability of the data, assumptions, etc. for the parameters need to b e \npresented.  \n \n7.1 Material benefit  \n \nA medical device does not achieve its principal intended action by pharmacological, \nimmunological or metabolic means, in or on the human body, but may be assisted in its \nfunction by such means.  For the use of phthalates in medical devices, additional \nfunctionalit ies need to be considered. One of the functionalit ies is the fine -tuning of the \nflexibility of PVC when  used as plasticiser s e.g. in intubation devices. For blood bag \nmaterials other requirements are , for example,  resistance to heat and chemicals, \nespecially during sterili sation, and permeability of gases to assure that pH and oxygen \nlevels remain stable .  In addition, DEHP has an additional property namely the stabilising \neffect on red blood cells (RBCs) (SCENIHR 2015). A number of alternatives were \nevaluated as alternative for DEHP in blood bags (Simmchen et al., 2012, SCHENIR \n2015).  \nPlatelets are extremely sensitive to changes in the pH of the medium in which they are \nsuspended, so sufficient gas permeability to O2 and CO 2 has to be assured in the \ncontainers devoted to their storage (Simmchen et al. , 2012). For this reason, DEHP has \nbeen almost fully replaced with  BTHC, DINCH, and/or Trioctyltrimellitate (TOTM or  Tri( 2 -\nethyl hexyl)trimellitate (TEHTM) ) (Simmchen et al.  2012, Prowse et al.  2014).  A better \ngas exchange has been found in bags plasticised with these chemicals . Also other \nmaterials, like polyolefins, are currently used for platelet storage bags (Prowse et al.  \n2014).  This potentially will allow  the stor age of platelet concentrates for up to 7 days, if \nmeasures to prevent bacterial contamination can be safely implemented.  \nIt should be noted that the benefit of phthalates in terms of material  functionality and \nperformance may differ from device to device. An alternative may be available  for one \napplication while this may not be available  for another in view of added or specific \ndemands on the functionality  of the p hthalate .  \n \n \n7.2 Clinical benefits  \n \nClinical benefit of medical devices is defined in the MDR as follows:  \n\u2018clinical benefit\u2019 means the positive impact of a device on the health of an individual, \nexpressed in terms of a meaningful, measurable, patient -relevant clinical outcome(s), \nincluding outcome(s) related to diagnos is, or a positive impact on patient management or \npublic health; (Regulation (EU)2017/745: Article 2 Definitions: (53)):  \nThis \u201cclinical benefit\u201d has to  be substantiated by the manufacturers in the \u201cclinical \nevaluation\u201d of the medical device, which includes a number of considerations. These  \ninclude a discussion and overall conclusions covering safety and performance results, \nassessment  of risks and clinic al benefits, discussion of clinical relevance in accordance Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n29 \n with clinical state of the art, any specific precautions for specific patient populations, \nimplications for the investigational device  and limitations of the investigation.  \nA \u201dclinical benefit \u201d could include any meaningful, measurable, patient -relevant outcome \nas presented below. SCHEER identified the following examples  that may be relevant for \nthe use of phthalates (list not exclusive):  \n\uf0b7 Improved survival rates  \n\uf0b7 Improved length of hospital stay  \n\uf0b7 Improved time of intervention  \n\uf0b7 Improved time of placing ( among others  in tubes and catheters)  \n\uf0b7 Improved product quality/ clinical performance ( among others in tubes and \ncatheters) in terms of:  \no Improved leakage rates  \no Improved breakage rates  \no Improved knotting rates  \no Improved blockage rates  \no Improved bending performance rates  \no Improved release rates of toxic substances  \no Improved release rates of (nano -)particles  \n\uf0b7 Improved displacement  rates \n\uf0b7 Improved possibilities for sterili sation \n\uf0b7 Reduction of diameters in relation to performance  \n\uf0b7 Possibility to produce \u201cmultiple -purpose\u201d devices, (e.g. inclusion of additional \nsensors), and therefore reduction of over -all patient -stress and patient -impact  \n\uf0b7 Improved observability (safety) in terms of translucence, printability, radiopaque \nlines included, identifiab ility, traceability, etc. ( among others  in tubes and \ncatheters)  \n\uf0b7 Fewer  adverse events , e.g. r educed mucosal or endothelial irritation or injury \nrates ( among others  in tubes and catheters)  \n\uf0b7 Fewer serious adve rse events  and serious incidents  \nThe benefit of the use of the CMR/ED phthalate should always be judged with respect to \nthe \u201cintended use\u201d of the medical device and the exposed patient -group to the medical \ndevice and weighed in its clinical impact (\u201cclinically relevant difference\u201d). These aspects \nshould be judged by clinical experts.  \nQuantitative information on the benefits should be provided where possible or at a \nminimum qualitative description of their magnitude. Information on the probability of  the \nbenefit to occur and/or the duration of the benefit should also be included.  \n \n \n8. Methodologies for Benefit \u2013Risk A ssessment  \n \nIn general, a Benefit - Risk A ssessment  (BRA) aims to evaluate the desired effects of \ntherapeutic mean s, medicine s or device s, against their undesired effects, i.e., risks for \nhuman health. An appropriate BRA can contribute to a more objective analysis and help  \nconformity verification bodies and  authorities towards a more objective and transparent \ndecision -making process. Weighi ng the benefits and risks can be a complex task. It may \ninvolve the evaluation of a large amount of data that should be as accurate  as possible , Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n30 \n without methodological weaknesses  and biases. There is always some uncertainty around \nthe actual benefits and r isks, because they can only be determined by looking at the \ninformation that is available at a given point in time  which may contain various sources \nof uncertainty.  \nFor the BRA of medical devices in general, guidance is available in section A7.2. of  \nMEDDEV 2.7/1, revision 4   \u201cClinical evaluation: A guide for manufacturers and notified \nbodies under directives 93/42/EEC and 90/385/EEC\u201d . EN ISO 14971  (FDIS published in \n2019)  and the accompanying  ISO/TR 24971 provide information on the risk benefit \nanalys is to be performed within a risk management process. Additional information may \nbe found elsewhere, for example in the documents  of the FDA 2016,  2018,. It should be \nnoted that the acceptability of any risk is weighted against the benefit of the use of the \nmedical device.   \nSeveral methodologies for BRA have been proposed (Guo et al, 2010 , Mt-Isa et al.  \n2014), of which most methodologies  are so far , mainly used for pharmaceutical products. \nHowever, it should be underlined that f or medical devices the quantitative determination \nof a benefit -risk ratio may be rather difficult to be made  and expressed in a figure. In \nsuch cases a qualitative approach of weighing the benefit based on expert judgement \nmight be used.  One methodology, namely the multi criteria decision analysis (MCDA), \ncan be generally applied to various areas of BRA. Therefore, this methodology might also \nbe suitable for performing the BRA of medical devices (see Annex 7).  The MCDA \nmethodology has its origins in decisi on theory aiming to evaluate multiple conflicting \ncriteria in decision making. These criteria can include the benefits and risks of the use of \na medical device on human health.   \nThe final BRA of both the used CMR/ED  phthalate and potential relevant alterna tives \nshould contain all aspects as indicated in the framework above. A quantitative or semi -\nquantitative description of the risks (e.g. MoS, RCR) and of the benefits of a medical \ndevice containing a CMR/ED phthalate or alternative should  be the basis for a BRA. \nHowever, a lthough quantitative approaches for a BRA are preferable, a qualitative \ndescription of the value judgements about the balance of benefits and risks might also be \nan acceptable approach when justified (see step 10).  \n \n \n9. Uncertainty analysis  \n \nUncertainty plays an important role in medical decision making. It is widely accepted \nthat, despite the methodological and technological improvements that were achieved in \nthe past decades, there is never absolute certainty regarding the safety, effective ness, or \nperformance  of a medical treatment or use of a device. Therefore, the degree of certainty \nand thus uncertainty of the benefits and risks of a medical device is a factor that should \nalways be considered when making BRA.  \nThere are various sources of uncertainty in bio -medical studies; a major source of \nuncertainty is the biological differences among individuals. Another source of uncertainty \nis the intra - and inter - variability of the laboratories, with respect to equipmen t, \nreagents, and methods used. It is also accepted that diagnostic tools which evaluate \nbenefit and risk share several limitations , giving false negative and false positive results \nin a variety of cases. Observer variation occurs quite often  and should alw ays be taken Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n31 \n into account. Other factors that may influence the degree of uncertainty include: the type \nof clinical information available (e.g., clinical investigation  data, observational studies, \nevidence derived from registries or use experience), the re presentativeness of the \ninformation (e.g., sample size, relevance  of the sample to the referent population \nexposed to the device), as well as the statistical inferences derived from the information.  \nA number of techniques for uncertainty analysis are descr ibed in t he Guidance for Socio -\nEconomic Analysis of ECHA (ECHA 2011). The aim is to determine whether uncertainties \nin the estimation of impacts could affect the overall conclusions. More accurately , the \ntechniques shown can be used to either reduce the va riability of estimates, or to help \ntest whether uncertainties affect the conclusions drawn. The only way to actually reduce \nuncertainty is through better data, better understanding and knowledge of the \nuncertainties and through further analysis. However, i n most cases residual uncertainties \nwill remain.  \nRecently EFSA published a guidance on uncertainty analysis (EFSA 2018 a) and a \ndescription of the principles and methods behind the guidance for uncertainty analysis \n(EFSA 2018 b). The EFSA Guidance recogni ses that the form and extent of uncertainty \nanalysis, and how the conclusions should be reported, vary widely depending on the \nnature and context of each analysis and the degree of uncertainty that is present. \nTherefore it is important to identify appropriat e options for each BRA. The EFSA \ndocuments provide a flexible framework for uncertainty analysis within which different  \nmethods may be selected, according to the needs of each BRA. It seems likely that also \nfor medical devices a similar flexibility is need ed in view of the broad range of medical \ndevices used.  \nEFSA describes a number of main elements of uncertainty that need to be considered in \nthe uncertainty analysis:  \nEFSA: Main elements of uncertainty analysis  \n\uf0b7 Identifying uncertainties affecting the assessment. This is necessary in every \nassessment and should be done in a structured way to minimise the chance of \noverlooking relevant uncertainties. In assessments that follow standardised \nprocedures, it is only necessary to identify nonstandard uncertai nties.  \n\uf0b7 Prioritising uncertainties within the assessment plays an important role in planning \nthe uncertainty analysis, enabling the assessor to focus detailed analysis on the \nmost important uncertainties and address others collectively when evaluating \novera ll uncertainty. Often prioritisation will be done by expert judgement during \nthe planning process, but in more complex assessments it may be done explicitly \nusing influence analysis or sensitivity analysis.  \n\uf0b7 Dividing the uncertainty analysis into parts. In some assessments, it may be \nsufficient to characterise overall uncertainty for the whole assessment directly, by \nexpert judgement. In other cases, it may be preferable to evaluate uncertainty for \nsome or all parts of the assessment separately and then comb ine them, either by \ncalculation or expert judgement.  \n\uf0b7 Ensuring the questions or quantities of interest are well -defined. Each question or \nquantity of interest must be well -defined so that the true answer or value could be \ndetermined, at least in principle.  This is necessary to make the question or \nquantity a proper subject for scientific assessment, and to make it possible to \nexpress uncertainty about the true answer or value clearly and unambiguously. Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n32 \n Some assessments follow standardised procedures, within  which the questions \nand/or quantities of interest should be predefined. In other assessments, the \nassessors will need to identify and define the questions and/or quantities of \ninterest case by case.  \n\uf0b7 Characterising uncertainty for parts of the uncertainty analysis. This is needed for \nassessments where assessors choose to divide the uncertainty analysis into parts \nbut may only be done for some of the parts, with the other parts being considered \nwhen characterising overall uncertainty.  \n\uf0b7 Combining uncertainty f rom different parts of the uncertainty analysis. This is \nneeded for assessments where the assessors quantify uncertainty separately for \ntwo or more parts of the uncertainty analysis.  \n\uf0b7 Characterising overall uncertainty. Expressing quantitatively the overall  impact of \nas many as possible of the identified uncertainties, and describing qualitatively \nany that remain unquantified. This is necessary in all assessments except those \nstandardised assessments where only standard uncertainties are identified  (e.g. \ninter-and intra -species uncertainty factors).  \n\uf0b7 Prioritising uncertainties for future investigation. This is implicit or explicit in any \nassessment where recommendations are made for future data collection or \nresearch, and may be informed by influence or sensit ivity analysis.  \n\uf0b7 Reporting uncertainty analysis. Required for all assessments, but extremely brief \nin standardised assessments where only standard  uncertainties  are identified.  \nA number of methods that can be used in the uncertainty analysis include:  \n\uf0b7 Sensitivity analysis  \n\uf0b7 Scenario analysis  \n\uf0b7 Expert judgement  \n\uf0b7 Monte Carlo Simulations  \nSome of these techniques can be used in combination (e.g. scenario analysis together \nwith expert judgement to establish ranges for key variables) but also together with less  \ncommonly used techniques such as risk -risk analysis, Delphi techniques and portfolio \nanalysis, which can be used to help reduce the variability of estimates but are not \ndiscussed in these Guidelines.  \nAfter performing the uncertainty analysis , the observed overall confidence associated \nwith a BRA can be expressed as a probability score. This score gives the risk assessor an \nindication what the uncertainty is in the BRA. \nIn situations where sufficient data are available, a quantitative categori sation of \nprobability levels is preferred. If this is not possible, the manufacturer should give a \nqualitative description. A good qualitative description is preferable to an inaccurate \nquantitative description ( EN ISO  14971).  \nEFSA (EFSA, 2018 b) and SCHEER (2018) use a rather detailed probability scale  of 9 and \n7 probab ility levels, respectively. EFSA stresses that this scale may be used as an aid to \nsupport the development of judgements and that other ranges or qualitative descriptions \ncan be used as well. EFSA (2018 b) also argues that presenting the numerical \nprobabilities alongside verbal expressions of probability, e.g. \u2018Likely (> 66% probability)\u2019, \nincreases the consistency of interpretation.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n33 \n A detailed scale does not seem to be applicable for the uncertainties that can be obtained \nduring a  BRA evaluation of medical devices. For medical devices, a probability scale as \nindicated in Table 2  may b e used  EN ISO showing a 5-level scale recommended by ISO \nfor semi -quantitative assessments ( EN ISO  14971, Table D4 ). Table 2 further show s the \nverbal terms and subjective probability ranges that are based on a simplification of the \nEFSA/SCHEER scales.  \n \nTable 2: Probability scale for (semi -)quantitative  description of the overall \nconfidence  \nISO probabil ity term  \n Subjective  probability range  Probability term  \n \nFrequent  \n \nProbable  \n \nOccasional  \n \nRemote  \n \nImprobable  \n  \n> 90% \n \n66-90% \n \n33-66% \n \n10-33% \n \n<10%  \nvery l ikely \n \nlikely \n \nas likely as not  \n \nunlikely  \n \nvery unlikely  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n34 \n  \n10.  Conclusions  \n \nThese G uidelines are intended to be used for  a BRA of the presence of phthalates in \ncertain medical devices  covering phthalates which are carcinogenic, mutagenic, toxic to \nreproduction (CMR) or have endocrine -disrupting (ED) properties . The Guidelines can be \nused for the justification of the use of CMR/ED phthalates in a medical device according \nto the Regulation (EU) 2017/745 on medical devices. They also provide a framework on \nhow to assess  and compare possible alternative substances, materials , designs  or \nmedic al treatments  to the use of CMR/ED phthalates in medical devices. Major aspects \ninclude the functionality of phthalates, the performance  of the medical device using  the \nphthalate or the potential  relevant alternative for the phthalate, as well as the risk \nassessment of the phthalate or the alternative s. In the end , the benefit (s) shall be \nweighed against the possible risk s of the use of the CMR/ED phthalate and of the \nalternative substance, materials , desig ns or medical treatments . This overall analysis  will \ndetermine whether it is justified  or not  to use  a CMR/ED phthalat e in a medical device.  \nIn view of the concern of the CMR/ED properties of phthalates, further research to \npossibilities to replace these p hthalates in medical devices is highly encouraged  by the \nSCHEER .  \nDuring the preparation of these Guidelines for BRA of the use of CMR/ED phthalates in \nmedical devices , SCHEER noticed that a number of BRA methodologies are theoretically \navailable. However , there is a considerable lack of data for the BRA for potential  relevant \nalternatives to be used in medical devices. Therefore, SCHEER encourages manufacturers \nto generate data of high quality on such alternatives for CMR/ED phthalates in medical \ndevices . As the BRA of the presence of phthalates may have an impact on the \nconclusions of the \"overall\" benefit -risk determination of the medical device, a  periodic  \nupdate of the BRA of the medical device may be needed. The BRA of the presence of the \nCMR/ ED phtha late should be updated when new scientific information becomes available \non alternatives for the use of phthalates, when new Guidelines are released, or as the \n\"overall\" benefit -risk determination of the medical device is updated . A plan to perform \nan update of the general BRA for the medical device should be included in the dossier \nbefore marketing the device, and this should also include a plan regarding the necessary \nupdates on the evaluation of alternatives for CMR/ED phthalate s.  \nPending on new scientific evidence, i t is recommended to evaluate the use and \nusefulness of these Guidelines after an application  period of three years.  \n \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n35 \n  \n11.  Consideration of the responses received during the public \nconsultation process   \n \nA public consultation on these Guidelines was opened on the website of the non -food \nscientific committees from 18 March to 29 April 2019 . Information about the public \nconsultation was broadly communicated to national authorities, international \norganisation s and other stakeholders. A to tal of 197 submissions from 19  contributors \n(providing 378 comments  and additional references ) provided input to different chapters \nand subchapters of the document.  The vast majority of comments came from industry  \nand were requesting clarifications .  Each submission was carefully considered by the \nSCHEER and the scientific opinion has been revised to take account of relevant \ncomments. The literature has been accordingly updated with relevant publications. The \nSCHEE R expresses their thanks to all contributors for their comments and for the \nliterature references provided during the public consultation. The text of the comments \nreceived and the response provided by the SCHEER is available at:   \nhttps://ec.europa.eu/health/scientific_committees/consultations/public_consultations/sch\neer_consultation_08_en   \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n36 \n  \nB. REFERENCES  \n \n\uf0b7 Bui TT, Giovanoulis G, Cousins AP, Magn\u00e9r J, Cousins IT, de Wit CA. Human \nexposure, hazard and risk of alternative plasticizers to phthalate esters.  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EFSA Journal 2018;16(1):5123, 39 pp. \n(https://doi.org/10.2903/j.efsa.2018.5123 .) \n \n\uf0b7 EFSA Scientific Committee, Benford D, Halldorsson T, Jeger MJ, Knutsen HK,More \nS, Naegeli H, Noteborn H, Ockleford C, Ricci A, Rychen G, Schlatter JR, Silano V, \nSolecki R, Turck D, Younes M, Craig P, Hart A, Von Goetz N, Koutsoumanis K, \nMortensen A, Ossend orp B, Germini A, Martino L, Merten C, Mosbach -Schulz O, \nSmith A and Hardy A, 2018. Scientific Opinion on the principles and methods Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n37 \n behind EFSA\u2019s Guidance on Uncertainty Analysis in Scientific Assessment. EFSA \nJournal 2018;16(1):5122,235 pp. https://doi.org/10.2903/j.efsa.2018.5122  \n \n\uf0b7 EFSA Scienti\ufb01c Com mittee, More SJ, Bampidis V, Benford D, Bennekou \n-Jerez AF, Koutsoumanis K, Naegeli H, \nSchlatter JR, Silano V,N ielsen SS, Schrenk D, Turck D, Younes M, Benfenati E, \nCastle L, Cedergreen N, Hardy A, Laskowski R,Leblanc JC, Kortenkamp A, Ragas \nA, Posthuma L, Svendsen C, Solecki R, Testai E, Dujardin B, Kass GEN,Manini P, \nJeddi MZ , Dorne J -LCM and Hogstrand C, 2019. Guidance on harmonised method \nologies forhuman health, animal health and ecological risk assessment of \ncombined exposure to multiple chemicals.EFSA Journal 2019;17(3):5634, 77 pp. \nhttps://doi.org/10. 2903/j.efsa.2019.5634  \n \n\uf0b7 Eliason P, Morose G Safer alternatives assessment: the Massachusetts process as \na model for state governments. Journal of Cleaner Production 2011 , 19, 517-526 \n \n\uf0b7 European Commission 2017 COMMISSION IMPLEMENTING DECISION (EU) \n2017/1210 of 4 July 2017 on the identification of bis(2 -ethylhexyl) phthalate \n(DEHP), dibutyl phthalate (DBP), benzyl butyl phthalate (BBP) and diisobutyl \nphthalate (DIBP) as substances of very high concern according to Article 57(f) of \nRegulation (EC) No 1907/2006 of the European Parliament and of the Council. \nOfficial Journal of the European Commission,  L173/35,  6.7.2017.  \n \n\uf0b7 European Directorate for the Quality of Medicines and Healthcare (EDQM), \nEuropean Pharmacopoeia (Ph. Eur.) 9th Edition 2019, Council of Europe, \nStrasbourg, France.   \n \n\uf0b7 European Medicines Agency (2014)  Benefit -risk methodology project \n(https://www.ema.europa.eu/documents/report/benefit -risk-methodology -\nproject -update -work-package -5-effects -table-pilot-phase -i_en.pdf ) \n \n\uf0b7 FDA. US Food and Drug Administration.  Benefit -Risk Factors to Consider When \nDetermining Substantial Equivalence in Premarket Notifications (510(k)) with \nDifferent Technological Characteristics.  Guidance for Industry and Food and Drug \nAdministration Staff. September 25, 2018. Washington , USA. \nhttps://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/G\nuidanceDocuments/UCM404773.pdf  \n \n\uf0b7 FDA. US Food and Drug Administration.  Factors to Consider Regarding Benefit -\nRisk in Medical Device Product Availability, Compliance, and Enforcement \nDecisions.  Guidance for Industry and Food and Drug Administration Staff. \nDecember 27, 2016. Washington, USA.  \nhttps://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/G\nuidanceDocuments/UCM506679.pdf  \n \n\uf0b7 Guo JJ, Pandey S, Doyle J, Bian B, Lis Y, Raisch DW. A review of quantitative risk -\nbenefit methodologies for assessing drug safety and efficacy -report of the ISPOR \nrisk-benefit management working group. Value Health. 2010;13(5):657 -66 \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n38 \n \uf0b7 Hass U, Christiansen S, Andersson A -M, Holbech H, Bjerregaard P. Report on \ninterpretation of knowledge on endocr ine disrupting substances (EDs) \u2013 what is \nthe risk? Danish Centre on Endocrine Disruptors, Denmark . \n(http://www.cend.dk/files/ED_Risk_report -final-2019.pdf)  \n \n\uf0b7 Katsikantami I, Sifakis S, Tzatzarakis MN, Vakonaki E, Kalantzi OI, Tsatsakis AM, \nRizos AK. A global assessment of phthalates burden and related links to health \neffects.  Environ Int. 2016;97:212 -236. doi: 10.1016/j.envint.2016.09.013  \n \n\uf0b7 Mariana M, Feiteiro J, Verde I, Cairrao E. The effects of phthalates in the \ncardiovascular and reproductive systems: A review.  Environ Int. 2016;94:758 -\n776. doi: 10.1016 /j.envint.2016.07.004.  \n \n\uf0b7 Mt-Isa S, Hallgreen C.E., Wang N., Callr\u00e9us T.,  Genov G., Hirsch I., Hobbiger S., \nHockley .S., Luciani D., Phillips L.D., Quartey G., Sarac S.B., Stoeckert I., Tzoulaki \nI., Micaleff A., Ashby D. , IMI-PROTECT benefit -risk participants.  Balancing benefit \nand risk of medicines a systematic review and clas sification of available \nmethodologies, Pharmacoepidemiol Drug Saf. 23(7):667 -78, 2014. doi: \n10.1002/pds.3636.  \n \n\uf0b7 Nielsen BS, Andersen BN, Giovalle E, Bjergstrom M, Larsen PB. Alternatives to \nclassified phthalates in medical devices. The Danish Environmental Protection \nAgency 2014, Copenhagen, Denmark  \n \n\uf0b7 Prowse CV, de Korte D, Hess JR, van der Meer PF; Biomedical Excellence for Safer \nTransfusion (BEST) Collaborative.Commercially available blood storage containers.  \nVox Sang. 106(1):1 -13, 2014. doi: 10.1111/vox.12 084.  \n \n\uf0b7 Salloum HA, Saunier J, Aymes -Chodur C, Barakat H, Yagoubi N. Impact of the \nnature and concentration of plasticizers on the ability of PVC to sorb drug. \nInternational Journal of Pharmaceutics 496, 664 \u2013675, 2015.  \n \n\uf0b7 SCHEER 2018 Memorandum on weight of evidence and  uncertainties. Revision \n2018. \nhttps://ec.europa.eu/health/sites/health/files/scientific_committees/scheer/docs/s\ncheer_o_014.pdf  \n \n\uf0b7 SCENIHR Opinion on The safety of medical devices containing DEHP  plasticized   \nPVC or other plasticizers on neonates and other groups possibly at risk (2015 \nupdate).  2015 \nhttps://ec.europa.eu/health/scientific_committees/emerging/docs/scenihr_o_047.\npdf \n \n\uf0b7 Simmchen J , Ventura R , Segura J . Progress in the removal of di -[2-ethylhexyl] -\nphthalate as plasticizer in blood bags. Transfus Med Rev. 2012; 26(1):27 -37. doi: \n10.1016/j.tmrv.2011.06.001. Epub 2011 Aug 5.  \n \n\uf0b7 Tortolano L, Matmati H, Bourhis M,Manerlax K, Lemare F, Saunier J,Yagoubi N. \nDinCH and ESBO actual migration from PVC infusion tubings used in an \noncopediatric unit. J. Appl. Polym.  Sci. 135, 46649, 2018.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n39 \n  \n\uf0b7 Treleano A,Wolz  G,Brandsch  R, Welle  F. Investigation into the sorption of \nnitroglycerin and diazepam intoPVC tubes and alternative tube materials during \napplication . Intl JPharmac 369, 30 \u201337, 2009.  \n \n\uf0b7 Welsh M, Saunders PT, Fisken M, Scott HM, Hutchison GR, Smith LB, Sharpe RM.  \nIdentification in rats of a programming window for reproductive tract \nmasculinization, disruption of which leads to hypospadias and cryptorchidism. J \nClin Invest. 2008 ; 118(4):1479 -90. doi: 10.1172/JCI34241.  \n \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n40 \n  \nC. ANNEXES  \n \nAnnex   1: SCHEER mandate on benefit -risk assessment on the use of CMR/ED phthalates  \n \n1. Background  \n \nWhat are phthalates?  \nPhthalates are the esters of 1,2 -benzenedicarboxylic acid (o -phthalic acid) and their \nchemical structure consists of one benzene  ring and two ester functional groups linked \nwith two consecutive carbons on the ring10. The hydrocarbon chains of the ester groups \nare either straight or branching; they give each substance its name and they are \nresponsible for the different properties amo ng phthalates. Phthalate esters (PEs) may be \ncategori sed into three distinct groups according to the length of their carbon chain. High \nmolecular weight (HMW) phthalates include those with 7 \u201313 carbon atoms in their carbon \nchain and low molecular weight (L MW) those with 3 \u20136 carbon atoms in their backbone. \nDEHP is classified as a LMW phthalate. A third group includes dimethyl phthalate (DMP) \nand diethyl phthalate (DEP)11. \n \nWhat are they used for?  \nPhthalates are widely used in industry as plastici sers of polym ers such as polyvinyl \nchloride (PVC). HMW phthalates are used in a variety of applications such as coated \nfabrics and roofing membranes.  LMW phthalates are used in medical devices, adhesives, \npaints, inks and enteric -coated tablets. DEHP is the most widel y used phthalate in \nmedical devices. DMP and DEP are not used as plastici sers but e.g. as  additives in \ncosmetics, medical devices, and household products.  \n \nPotential CMR  or endocrine -disrupting properties  \nThe interaction of phthalates with the polymers the y are embedded in is weak, so they \nmay migrate from the plastic product into the environment and into the human body if \nthe product is in contact with it.  \nCorrelation between exposure to a range of phthalates and adverse health effects has \nbeen documented in animals and humans (see for example tables in Mariana et al. 2016 \nand Katsikantami et al.  2016). A number of phthalates are suspected of and/or have \nbeen classified or identified as having CMR or endocrine -disrupting properties.  \n                                                           \n10 A global assessment of phthalates burden and related links to health effects. Katsikantami et al., Environ Int. \n2016 Dec;97:212 -236. https://www.ncbi.nlm.nih.gov/pubmed/?term=katsikantami   \n11 Footnote added by SCHEER. It should be noted that there are hundreds of phthalates of which only a limited \nnumber is used as plasticiser in polymers. Phthalates can be categorised according to the length of the carbon \nchain and one of these categorisations is mentioned in the mandate of DG GROW.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n41 \n  \nPrevious work of Commission Scientific Committees on phthalates  \nPrevious opinions on the most commonly used phthalate DEHP [di -(2-(ethylhexyl) \nphthalate] in medical devices were issued by EU Scientific Committees in 2002 \n(SCMPMD), 2008 and 2015 (SCENIHR). The 2008 Opinion concluded that \"So far, there is \nno conclusive scientific evidence that DEHP exposure via medical treatments has harmful \neffects in humans\",  but noted that \"newborn and pre -term born male infants are of \nspecial concern\" . In the 2015 Opinion, SCENIHR additi onally identified that \"patients \nsubject to haemodialysis procedure may be at risk of DEHP induced effects\" . The \nCommittee noted that \"Food is the primary source of exposure to DEHP for the general \npopulation.\"  \nIn both opinions, the Committee emphasised th at \"the benefit of the medical devices \nmust also be considered\"  and in the 2008 Opinion the Committee states that \"each \nalternative to DEHP, however, must also be evaluated with regard to their functionality in \nrespect to medical devices. The risk and bene fits of using alternative plasti cizers should \nbe evaluated case by case.\"  In the 2015 opinion, the Committee states that \u201cThe \npotential for replacement of DEHP in these products should be considered against their \nefficiency in the treatment, as well as the  toxicological profile and leaching properties of \nthe alternative materials.\u201d  \n \nThe legal obligation  \nArticle 5 paragraph 2 of the Regulation 2017/745 on medical devices stipulates: \"A \ndevice shall meet the general safety and performance requirements set out  in Annex I \nwhich apply to it, taking into account its intended purpose.\"   \nAccordingly, Section 10.4 of Annex I, which deals with substances in medical devices, \nstates that \"Devices shall be designed and manufactured in such a way as to reduce as \nfar as possible the risks posed by substances or particles, including wear debris, \ndegradation products and  processing residues, that may be released from the device.\"  \nParticular substances of concern are those which (a) are carcinogenic, mutagenic or toxic \nto reproduction (CMR),  of category 1A or 1B,12 or (b) have endocrine -disrupting \nproperties (ED)13. The Regulation states that:  \n \n\"Devices, or those parts thereof or those materials used therein that:  \n\uf02d are invasive and come into direct contact with the human body,   \n\uf02d (re)administer medicines, body liquids or other substances, including gases, \nto/from the body, or  \n\uf02d transport or store such medicines, body fluids or substances, including gases, to \nbe (re)administered to the body\"  \n \n                                                           \n12 in accordance with Part 3 of Annex VI to Regulation (EC) No 1272/2008  \n13 identified as such in accordance with the relevant provisions of Regulation (EC) No 1907/2006 or respectively \nof Regulation (EU) No 528/2012  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n42 \n shall only contain any such substance ab ove the concentration of 0.1% weight by weight \nwhere justified pursuant to Section 10.4.2. The justification shall be based on several \nelements, including the latest relevant scientific committee guidelines on benefit -risk \nassessment of the presence of suc h substance in devices.  \nAccording to Section 10.4.3, the Commission shall provide a mandate to the relevant \nscientific committee to prepare such guidelines for phthalates which are subject to these \nprovisions. These guidelines are explicitly requested by t he Regulation to be available at \nthe latest on the date of application of the Regulation, and are to be updated whenever \nappropriate on the basis of the latest scientific evidence, or at least every five years.  \n \n2. Terms of reference  \n \nThe Scientific Committee  is requested to provide guidelines on the benefit -risk \nassessment of the presence, in the medical devices specified below, of phthalates which \nhave one or more of the following properties: carcinogenic, mutagenic, toxic to \nreproduction or endocrine -disrup ting, according to the criteria outlined in the previous \nsection.  \nThe devices covered, or those parts thereof of those materials used therein, are those \nwhich:  \n\uf0b7 are invasive and come into direct contact with the human body,  \n\uf0b7 (re)administer medicines, body l iquids or other substances, including gases, \nto/from the body, or  \n\uf0b7 transport or store such medicines, body fluids or substances, including gases, to \nbe (re)administered  to the body.  \n \nThe guidelines shall include guidance on how, for an individual device, to: \n\uf0b7 analyse and estimate potential patient or user exposure to the substance,  \n\uf0b7 analyse possible alternative substances, materials, designs, or medical \ntreatments,  \n\uf0b7 to justify why possible substance and/or material substitutes, if available, or \ndesign change s, if feasible, are inappropriate in relation to maintaining the \nfunctionality, performance and the benefit -risk ratios of the product, including \ntaking into account if the intended use of such devices includes treatment of \nchildren or treatment of pregnan t or breastfeeding women or treatment of other \npatient groups considered particularly vulnerable to such substances and/or \nmaterials.  \n \nIn addition, the Scientific Committee is requested to : \n\uf0b7 identify any relevant knowledge gap , and \n\uf0b7 to give consideration to what extent of new evidence would be deemed \nappropriate to justify an update of these guidelines before the maximum period of \nfive years.  \n \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n43 \n  \nIn order to ensure the appropriateness of this guidance the Scientific Committee should \ninter alia : \n\uf0b7 involve at the appropriate level the notified bodies active in the field of medical \ndevices, or other relevant stakeholders such as Competent Authorities, \nprofessional and patient associations, industry associations, while maintaining \nscientific independence , \n\uf0b7 involve to the necessary extent the relevant EU Agencies  and Scientific \nCommittees.  \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n44 \n  \nAnnex  2: Medical Device Regulation (Regulation 2017/745) on CMR and/or ED \nsubstances  \n \nThe requirement for justification of the presence  of CMR 1A or 1B and/or ED hazardous \nsubstances is described in Annex I 10.4.2 as presented in the text box below.  \n \n \n \n10.4. Substances  \n \n10.4.1. Design and manufacture of devices  \n \nDevices shall be designed and manufactured in such a way as to reduce as fa r as possible the \nrisks posed by substances or particles, including wear debris, degradation products and \nprocessing residues that  may be released from the device.  \nDevices, or those parts thereof or those materials used therein that:  \n \n\u2014 are invasive and come into direct contact with the human body,  \n \n\u2014 (re)administer medicines, body liquids or other substances, including gases, to/from the \nbody, or  \n \n\u2014 transport or store such medicines, body fluids or substances, including gases, to be \n(re)administered to the body,  \n  \nshall only contain the following substances in a concentration that is above 0,1 % weight by \nweight (w/w) where justified pursuant to Section 10.4.2:  \n  \n(a) substances which are carcinogenic, mutagenic or toxic to reproduction (\u2018CMR\u2019), of category \n1A or 1B, in accordance with Part 3 of Annex VI to Regulation (EC) No 1272/2008 of the \nEuropean Parliament and of the Council (1), or  \n  \n(b) substances having endocrine -disrupting properties for which there is scientific ev idence of \nprobable serious effects to human health and which are identified either in accordance with the \nprocedure set out in Article 59 of Regulation (EC) No 1907/2006 of the European Parliament \nand of the Council (2) or, once a delegated act has been ad opted by the Commission pursuant \nto the first subparagraph of Article 5(3) of Regulation (EU) No 528/2012 of the European \nParliament and the Council (3), in accordance with the criteria that are relevant to human \nhealth amongst the criteria established the rein.  \n \n10.4.2. Justification regarding the presence of CMR and/or endocrine -disrupting substances  \n \nThe justification for the presence of such substances shall be based upon:  \n(a) an analysis and estimation of potential patient or user exposure to the subs tance;  \n(b) an analysis of possible alternative substances, materials or designs, including, where \navailable, information about independent research, peer -reviewed studies, scientific opinions \nfrom relevant scientific committees and an analysis of the avail ability of such alternatives;  \n(c) argumentation as to why possible substance and/ or material substitutes, if available, or \ndesign changes, if feasible, are inappropriate in relation to maintaining the functionality, \nperformance and the benefit -risk ratio s of the product; including taking into account if the \nintended use of such devices includes treatment of children or treatment of pregnant or \nbreastfeeding women or treatment of other patient groups considered particularly vulnerable to \nsuch substances an d/or materials; and  \n(d) where applicable and available, the latest relevant scientific committee guidelines in \naccordance with Sections 10.4.3 and 10.4.4.  \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n45 \n  \nAnnex 3:  Definitions/descriptions \u2013 References - Glossary  \n \nDefinitions ( Regulation  (EU) 2017/745 ) \n \nBenefit -risk determination:  means the analysis of all assessments of benefit and risk \nof possible relevance for the use of the device for the intended purpose, when used in \naccordance with the intended purpose given by the manufacturer.  \n \nPerformance:  means the ability of a device to achieve its intended purpose as stated by \nthe manufacturer.  \n \nClinical performance:  means the ability of a device, resulting from any direct or \nindirect medical effects which stem from its technical or functional characteri stics, \nincluding diagnostic characteristics, to achieve its intended purpose as claimed by the \nmanufacturer, thereby leading to a clinical benefit for patients, when used as intended by \nthe manufacturer.  \n \nClinical benefit:  means the positive impact of a de vice on the health of an individual, \nexpressed in terms of a meaningful, measurable, patient -relevant clinical outcome(s), \nincluding outcome(s) related to diagnosis, or a positive impact on patient management or \npublic health.  \n \nRisk: means the combination of the probability of occurrence of harm and the severity of \nthat harm.  \n \nAdverse event:  means any untoward medical occurrence, unintended disease or injury \nor any untoward clinical signs, including an abnormal laboratory finding, in subjects, \nusers or othe r persons, in the context of a clinical investigation, whether or not related to \nthe investigational device.  \n  \nSerious adverse event:  means any adverse event that led to any of the following: (a) \ndeath, (b) serious deterioration in the health of the subjec t, that resulted in any of the \nfollowing: (i) life -threatening illness or injury, (ii) permanent impairment of a body \nstructure or a body function, (iii) hospitali sation or prolongation of patient hospitali sation, \n(iv) medical or surgical intervention to p revent life -threatening illness or injury or \npermanent impairment to a body structure or a body function, (v) chronic disease, (c) \nfetal distress, fetal death or a congenital physical or mental impairment or birth defect.  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n46 \n   \nIncident:  means any malfunction or deterioration in the characteristics or performance \nof a device made available on the market, including use -error due to ergonomic features, \nas well as any inadequacy in the information supplied by the manufacturer and any \nundesir able side -effect.  \n \nSerious incident:  means any incident that directly or indirectly led, might have led or \nmight lead to any of the following: (a) the death of a patient, user or other person, (b) \nthe temporary or permanent serious deterioration of a pati ent's, user's or other person's \nstate of health, (c) a serious public health threat.  \n \nSerious public health threat : means an event which could result in imminent risk of \ndeath, serious deterioration in a person's state of health, or serious illness, that may \nrequire prompt remedial action, and that may cause significant morbidity or mortality in \nhumans, or that is unusual or unexpected for the given place and time.  \n \nDevice deficiency:  means any inadequacy in the identity, quality, durability, reliability,  \nsafety or performance of an investigational device, including malfunction, use errors or \ninadequacy in information supplied by the manufacturer.  \n \nRegulation (EU) 2017/745 Annex XIV Clinical evaluation and post -market \nclinical follow -up. Part A \u201cClinical evaluation\u201d Section 3 describes the \ncharacteristics that shall be considered for demonstration of equivalence .  \n\u201cA clinical evaluation may be based on clinical data relating to a device for which \nequivalence to the device in question can be demonstrated. T he following technical, \nbiological and clinical characteristics shall be taken into consideration for the \ndemonstration of equivalence:  \n \nTechnical : the device is of similar design; is used under similar conditions of use; has \nsimilar specifications and pr operties including physicochemical properties such as \nintensity of energy, tensile strength, viscosity, surface characteristics, wavelength and \nsoftware algorithms; uses similar deployment methods, where relevant; has similar \nprinciples of operation and cr itical performance requirements;  \n  \nBiological : the device uses the same materials or substances in contact with the same \nhuman tissues or body fluids for a similar kind and duration of contact and similar release \ncharacteristics of substances, including de gradation products and leachables;  \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n47 \n  \nClinical : the device is used for the same clinical condition or purpose, including similar \nseverity and stage of disease, at the same site in the body, in a similar population, \nincluding as regards age, anatomy and physiology; has the same kind of user; has \nsimila r relevant critical performance in view of the expected clinical effect for a specific \nintended purpose.  \nThe characteristics shall be similar to the extent that there would be no clinically \nsignificant  difference in the safety and clinical performance of the device. Considerations \nof equivalence shall be based on proper scientific justification. It shall be clearly \ndemonstrated that manufacturers have sufficient levels of access to the data relating  to \ndevices with which they are claiming equivalence in or der to justify their claims of \nequivalence. \u201d \n \nDefinitions on assessment of alternatives (OECD Toolbox Glossary)  \nNote: The term \"chemical\" is used synonymously with \"substance\"  \n \nAlternativ es assessment : A process for identifying and comparing potential chem ical \nand non -chemical alternatives that can be used as substitutes to replace chemicals or \ntechnologies of high concern1 \n \nChemical substitution : The process of replacing a chemical of concern with a safer \nchemical, material or product, or technology/process that eliminates the need to use that \nchemical  \n \nCost/benefits and availability : The negative (cost) and positive (benefit) implications, \ndirect and indirect, resulting from some actio n. This includes both financial and non -\nfinancial information. Availability refers to the production of an alternative and its market \naccessibility3 \n \nFunctional use approach : This approach starts with identifying the function that is \ndesired. The concept is applied in two ways: \ufb01rst and foremost, to characteri se the \npurpose a chemical or mixture serves, or the properties it imparts in a product or process \n(functional use), and second, to eva luate the function of the product and how its use may \nin\ufb02uence the assessment of alternatives4, 5 \n \nMaterial substitution : The process of replacing a material containing a chemical of \nconcern with a safer chemical, material, product or technology/process that eliminates \nthe need to use that chemical  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n48 \n  \nMixture : A composition of at least two chemicals in which they do not react6 \n \nTechnical feasibility : The determination as to whether the performance or functional \nrequirements of a chemical, material or product could be fulfilled or replaced by \neliminating or using an alternative chemical, material, product, process or technology, \nwhile considering any need for process adaptations and changes3 \n \nProcess modification : Changes in manufacturing processes to eliminate, reduce or \nsubstitute chemicals of concern. Such changes may include synthesis pathways, waste \nreduction, and manufacturing procedures where chemicals are used.  \n \nProduct performance : The ability of a product to meet identified performance \nrequirements. The boundaries of performance characteristics are defined by the user3 \n \nProduct substitution : The process of replacing a product containing a chemical of \nconcern with a chemical, material or product or technology/process that eliminates, \nreduces or substitutes the need to use that chemical.  \n \n1 Adapted from Alternatives Assessment Guide, version 1.0 . 2013. Interstate Chemicals \nClearinghouse.  \n2 REACH. Title I, Chapter 2, Article 3.  \n3 Current Landscape of Alternatives Assessment Practice: A Meta -Review. Organisation \nfor Economic Cooperation and Development. 2013.  \n4 U.S. EPA. 2006. National Pollution Prevention and Toxics Advisory Committee (NPPTAC) \nRecommendation to the EPA Administrat or and Deputy Administrator on Incorporating \nthe Functional Use Approach into OPPT Activities.  \n5 Lavoie, E. T., et al.  2010. \"Chemical Alternatives Assessment: Enabling Substitution to \nSafer Chemicals.\" Environmental Science & Technology 44(24): 9244 -9249.  \n6 Adapted from U.N. Global Harmonized System of Classification and Labelling  of \nChemicals . 2003.  \n7 ECHA, 2008. Guidance on Socio -Economic Analysis - Restrictions.  \n8 Adverse event means pre -clinical and clinical occurrences of an effect whereas incident \nindicates a clinical effect occurring during post -market surveillance.  \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n49 \n  \nReference s \n\uf0b7 ECHA (2011) Guidance on the preparation of socio -economic analysis as part of \nan application for authorisation, European Chemicals Agency 2011 . \n\uf0b7 EFSA (2019)  Draft update of the risk assessment of di -butylphthalate 1 (DBP), \nbutyl-benzyl -phthalate (BBP), bis(2 -2 ethylhexyl)phthalate (DEHP), di -\nisononylphthalate (DINP) 3 and di -isodecylphthalate (DIDP) for use in food \ncontact 4 materials  http://www.efsa.europa.eu/en/consultations/call/190221 .  \n\uf0b7 Guo JJ, Pandey S, Doyle J, Bian B, Lis Y, Raisch DW. A review of quantitative risk -\nbenefit methodologies for assessing drug safety and efficacy -report o f the ISPOR \nrisk-benefit management working group. Value Health. 2010;13(5):657 -66. \n \nGlossary  \nBBP   Benzylbutylphthalate  \nBMD  Bench Mark Dose  \nBRA  Benefit -Risk Analysis  \nBTHC   Butyryl -tri-n-hexylcitrate  \nCAS  Chemical Abstracts Service  \nCEN  European Committee for Standardization  \nCLP  Classification Labelling and Packaging regulation (EC No 1272/2008)  \nCMR  Carcinogenic, Mutagenic, toxic to Reproduction (Reprotoxic)  \nDBP   DiButylphthalate,  \nDCHP   Dicyclohexylphthalate  \nDEHP   Diethylhexylphthalate  \nDIBP   Diisobutylphthalate  \nDIDP   Di isodecyl phthalate)  \nDINCH  1,2- cyclohexan edicarboxylic acid, di isononyl ester)  \nDINP   Di isononyl phthalate)  \nDIPP  Diisopentylphthalate  \nDMEP   Bis(2-methoxyethyl)phthalate  \nDNHP   Dihexylphthalate  \nDHNUP  1,2-Benzenedicarboxylic acid, di -C7-11-branched and linear alkyl esters  \nDPP   Dipentyl phthalate  \nDMEL   Derived Minimum Effect Level  \nDNEL   Derived No Effect Level  \nEC  European Commission  \nECB  European Chemicals Bureau (now ECHA)  \nECHA   European Chemicals Ag ency (formerly ECB)  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n50 \n ED  Endocrine Disruptor  \nEEC  European Economic Community  \nEMA  European Medicines Agency  \nEFSA  European Food Safety Authority  \nEN-ISO CEN and ISO combined published document  \nFDA  Food and Drug Administration (USA)  \nFDIS  Final Draft International Standard  \nISO  International Organization  for Standardization  \nLOAEL   Lowest Observed Adverse Effect Level  \nMCDA   Multi Criteria Decision Analysis  \nMDD  Medical Device Directive (Council Directive 93/42/EEC)  \nMDR  Medical Device Regulation (EU 20 17/745)  \nMoA  Mode of Action \nMoE  Margin of Exposure  \nMoS  Margin of Safety  \nNICU  Neonatal Intensive Care Unit  \nNOAEL   No Observed Adverse Effect Level  \nOECD   Organization for Economic Cooperation and Development  \nPoD  Point of departure  \nPVC  Polyvinyl chloride  \nRBC  Red Blood Cell  \nRCR  Risk Characterisation Ratio  \nREACH   Registration, Evaluation, Authorisation and restriction of CHemicals.  \nSCHEER  Scientific Committee on Health, Environmental and Emerging Risks  \nSCENIHR  Scientific Committee on Emerging and Newly Identified Health Risks  \nT25   25 % increase of the tumour rate over controls  \nTDI  Tolerable Daily Intake  \nTE  Tolerable Exposure (EN ISO 10993 -17:2002 in mg/day)  \nTEHTM   Tri( 2 -ethyl hexyl)trimellitate also TOTM Trioctyltrimellitate  \nTI  Tolerable Intake  \nTOTM   Trioctyltrimellitate also TEHTM Tri( 2 -ethyl hexyl)trimellitate  \nTWI    Tolerable Weekly Intake   Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n51 \n  \nAnnex 4:  CMR and/or ED substances  \n \nCMR substances are substances identified and classified as carcinogenic, mutagenic or \ntoxic for reproduction of different categories based on the intrinsic toxic properties of a \nsubstance for which categories 1A and 1B apply to these Guidelines. In Europe, \nclassification for  these endpoints is harmonised through harmonised classification and \nlabelling (CLH). Details  can be found at  \nhttps://echa.europa.eu/regulations/clp/understanding -clp. For a specific substance to be \nclassified as CMR 1A, 1B or 2 a dossier needs to be prepared and if the Commission finds \nthat the proposed classification is appropriate, it submits a draft decision concerning the \ninclusion of that substance in Part 3 of Annex VI to the CL P Regulation (Regulation (EC) \n1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures).  \n\uf0b7 Category 1A means that the substance is a known human carcinogen, mutagen or \nreproductive toxicant based on human evidence.  \n\uf0b7 Category 1B means that the substance is a presumed human carcinogen, \nmutagen or reproductive toxicant based on animal studies.  \n\uf0b7 Category 2 means that a substance is considered as suspected carcinogen, \nmutagen or reproductive toxicant based on limited evidence from ani mal studies \nor humans  (not part of these Guidelines) .  \nDocuments on the classification are publicly available , and  a tutorial to search entries is \ngiven here:  \nhttp://www.chemsafetypro.com/Topics/EU/Annex_VI_to_CLP:_List_of_Harmonised_Class\nification_and_Labelling_for_Certain_Hazardous_Substances.html  \nGuidance for the identification of endocrine disrupto rs (ED) in the context of Regulations \n(EU) No 528/2012 and (EC) No 1107/2009 has been published on 7th June 2018 by \nECHA and EFSA (doi: 10.2903/j.efsa.2018.5311; EFSA Journal 2018;16(6):5311) which \ncan be accessed via:   \nhttps://efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2018.5311  \nThis EFSA/ECHA Guidance describes when a substance shall be considered as having \nendocrine disrupting  properties.  \n\u201cA  substance shall be considered as having endocrine disrupting properties  if it meets all \nof the following criteria:  \na) it shows an adverse effect in [an intact organism or its progeny]/[non -target \norganisms], which is a change in the morphology, physiology , growth, \ndevelopment, reproduction or life span of an organism, system or \n(sub)population6 that results in an impairment of functional capacity, an \nimpairment of the capacity to compensate for additional stress or an increase in \nsusceptibility to other in fluences;  \nb) it has an endocrine mode of action, i.e. it alters the function(s) of the endocrine \nsystem;  \nc) the adverse effect is a consequence of the endocrine mode of action.  \nIt should be highlighted that the \u2018endocrine mode of action \u2019 as stated in point  (b) \nshould be interpreted  as \u2018endocrine activity \u2019 while the term \u2018endocrine mode of Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n52 \n action\u2019 in point (c) covers the link between the adverse effect and the endocrine activity \nidentified in points a) and b), respectively.  \nKeeping this in mind point (b) abo ve should be understood as (differences from above in \nitalics ): \nit shows endocrine  activity, i.e. it has the potential to alter the function(s) of the \nendocrine system;  \nConsequently point (c) above should be understood as (differences from above in italics ): \nthe substance has an endocrine disrupting mode of action, i.e. there is a \nbiologically plausible link between the adverse effect and the endocrine activity. \u201d \nEDs identified with the procedure set out in Article 59 of Regulation (EC) No 1907/2006 \nconcern ing the Registration, Evaluation, Authorisation and Restriction of Chemicals \n(REACH),   will finally enter the REACH candidate list of substances of very high concern \nfor potential inclusion in REACH Annex XIV.  The information can be found in the \nrespecti ve decision document accessible via : https://echa.europa.eu/candidate -list-table. \nFor substances having endocrine -disrupting properties as indicated above, there is \ncurrently no information concer ning whether it is foreseen to publish them in central lists \nor annexed to a Regulation.  \nEDs identified by the delegated act pursuant to the first subparagraph of Article 5(3) of \nRegulation (EU) No 528/2012 concerning the making available on the market and  use of \nbiocidal products, can be accessed through the Biocidal Products Committee opinions on \nactive substance approval which can be accessed via ECHA\u2019s website \n(https://echa.europa.eu/regulations/biocidal -products -regulation/approval -of-active -\nsubstances/bpc -opinions -on-active -substance -approval ).  \nSubstances undergoing an ED assessment under the REACH or Biocidal Products \nregulations that have been brought for discussion to ECHA\u2019s ED Expert Group are \nincluded in ECHA\u2019s endocrine disruptor (ED) assessment list: https://echa.europa.eu/ed -\nassessment . For each substance, the table shows the assessing or evaluating Member \nState (submitter), the outcome and the suggested follow -up for the assessment, and the \ndate of the latest update to the list entry.  \nRecently the Commission Implementing Decision (EU) 2017/1210 was published that \nidentified some phthalates (Bis(2 -ethylhexyl) phthalate (DEHP), Benzyl butyl phthalate \n(BBP), Dibutyl phthalate (DBP) and Diisobutyl phthalate (DIBP)) as substances of very \nhigh concern due to their endocrine disrupting properties with probable serious effects to \nhumans (European Commission 2017).  \nhttps://publications.europa.eu/en/publication -detail/ -/publication/357b3d45 -620f-11e7-\n9dbe-01aa75ed71a1/language -en/format -PDF \nFor completeness, even if not relevant for the purpose of this guidelines, Bis(2 -\nethylhexyl) phthalate (DEHP) was also  identified in 2014 as a substance of very high \nconcern due to its endocrine disrupting properties with probable serious effects to the \nenvironment.  \nIn addition, Commission Implementing Decision (EU) 2018/636 identified \nDicyclohexylphthalate (DCHP) as subs tance of very high concern (SVHC) according to \nArticle 57(f) of REACH Regulation (EC) 1907/2006, due to its endocrine disrupting Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n53 \n properties with probable serious effects to humans.  https://eur -lex.europa.eu/legal -\ncontent/EN/TXT/PDF/?uri=CELEX:32018D0636&fr om=EN     Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n54 \n  \nAnnex 5:  Legislation on CMR and/or ED phthalates  \n \nDue to their reprotoxic properties and additionally since 2014 for DEHP due to their \nendocrine disrupting properties for the environment and since 2017 for DEHP, BBP, DBP, \nand DIBP  due to their endocrine disrupting properties  for human health , a considerable \nnumber of phthalates have been identified as substances of very high concern (SVHC) \nand therefore included in the candidate list for the inclusion in Annex XIV of the REACH \nregulation (Annex XIV of REACH EC 1907/2006 , see \nhttps://echa.europa.eu/de/candidate -list-table for the most recent update of the \ncandidate list).  \nEight phthalates are also listed on the Authorisation list (Annex XIV of REACH), namely \nDEHP, BBP, DIBP, DBP, DIPP (diisopentylphthalate), Bis(2 -methoxyethyl) phthalate, \ndipentyl phthalate, and N -pentyl -isopentylphthalate. Since February 2015 DEHP, BBP, \nDIBP, and DBP cannot be used within the European Union withou t authorisation. The \nsame provision would apply to the remaining four phthalates on Annex XIV from July \n2020. To date, applications for authorisation have been submitted for DEHP and DBP \nonly. However, imported articles do not come under the authorisation requirement. For \nthe purpose of evaluating applications for authorisation, the ECHA Committee for Risk \nAssessment (RAC) has developed reference DNELs for several substances, including \nDEHP, BBP, DBP, and DIPP. (See Evaluating Applications table/Ref erence D NELs on \nECHA\u2019s website:  \nhttps://echa.europa.eu/applying -for-authorisation/evaluating -applications .) \nRisks to human health arising from the use of an Annex XIV substan ce in medical devices \nregulated by Directives 90/385/EEC, 93/42/EEC or 98/79/EC are exempted from \nauthorisation requirements under Title VII of the REACH Regulation14. ECHA is currently \npreparing a recommendation on the inclusion of the ED properties for environment for \nDEHP in Annex XIV to REACH .15 If DEHP is included on Annex XIV for environmental \nhazards , applications for authorisations may need to be prepared for uses of the \nsubstance in medical devices in the future.  \nREACH Annex XVII (entry 51) also restricts the placing on the market of articles \ncontaining DEHP, BBP, DBP, and DIBP in concentration greater than 0.1% weight by \nweight of the plasticised material, individually or in combination in a range of articles. \nThese articles include toys16 and childcare articles, as well as other primarily consumer \nand professional use articles whic h lead to dermal or inhalation exposure. (For risk \nassessment conclusions, including derivation of a DNEL for DIBP, see Compiled RAC & \nSEAC opinion and background document on ECHA\u2019s website:  \nhttps://echa.europa.eu/previous -consultations -on-restriction -proposals/ -/substance -\nrev/13919/term .)   \n                                                           \n14 These Regulations will be replaced by:  \n\uf0b7 Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical \ndevices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No \n1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC  \n\u2022Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro  \ndiagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU  \n15 https://echa.europa.eu/draft -recommendation -for-amendment -of-authorisation -list-entries -previous -\nconsultation   \n16 The Toy Safety Directive (2009/48/EC) stipulates that chemicals that are susceptible to cause cancer, change \ngenetic information, harm fertility or harm an unborn child (CMR substances) are no longer allowed in \naccessible parts of toys beyond the concentration limits set in the CLP Regulation ((EC) No 1272/2008).  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n55 \n REACH Annex XVII (entry 52) restricts the placing on the market and the use of DINP, \nDIDP, and DNOP, as a  substance or in mixture, in concentrations greater than 0.1% \nweight by weight of the plasticised material in toys and childcare articles which can be \nplaced in the mouth of children. In 2010, the European Commission requested ECHA to \nreview the scientific  evidence on the risks posed by articles containing these phthalates \nwith the view to conclude on the need or not for further actions under REACH. The report \nand RAC risk assessment conclusions (including information on the derivation of DNELs) \ncan be foun d on ECHA\u2019s website: https://echa.europa.eu/consultations -draft-review -\nreport -previous -consultations/ -/substance -rev/1108/term .  \nEFSA recently launched a consultation on its updated 2005 risk assessments of DBP, \nBBP, DEHP, DINP and DIDP which are authorised for use in plastic FCM, by using the \nsame database as ECHA for its 2017 assessment of certain phthalates. The draft update \nof the ri sk assessment can be found here:  \nhttp://www.efsa.europa.eu/en/consultations/call/190221  \nIn addition to the REACH legislation, there is also product -specific legislation which \nregulates certain phthalates, i.e. the Cosmetic Products\u2019 Regulation (EC/1223/2009) and \nthe Regulation on materials and articles intended to come into contact with food ( Food \nContact Materials,  Regulation EC 1935/2004 , as general framework regulation and \nRegulation EU 10/2011 specific for plastic materials and articles destined to be in contact \nwith foodstuffs , recently amended by Regulation 2018/831 ). Both in the MDD \n(93/42/EEC) and the more recent MDR (2017/745), phthalates are specifically mentioned \nfor their use in medical devices.  \nFor a number of phthalates there is legislation available that might contain information \nrelevant for the use of phthalates in medical devices. Of specific relevance for medical \ndevices may be the Regulation EU 10/ 2011, which also incl udes provisions for the use of \nphthalates in food contact materials and articles with respect to migration limits. This \nmay be a parallel with migration (and thus potential internal exposure) of phthalates as \npresent in polymers used for medical device man ufacturing. In Annex I of the Regulation \nEU 10/2011 all substances are listed, which are authorised for the use as starting \nmaterial or additive for plastic layers in plastic materials and articles. Each substance \nmust not exceed its specific migration lim it (SML). The following phthalates and other \nplastici sers17 are authorised for use as additives:  \n \nDBP (SML) = 0.3 mg/kg food  \nonly to be used as:  \n(a) plasticiser in repeated use materials and articles in contact with  non -fatty foods;   \n(b) technical supp ort agent in polyolefins in concentrations up to 0.05% in the final  \nproduct  \n \nBBP, SML = 30 mg/kg food  \nOnly to be used as:  \n(a) plasticiser in repeated use materials and articles;  \n                                                           \n17 Not exhausti ve examples for other than phthalates  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n56 \n (b) plasticiser in single -use materials and articles in contact with  non -fatty foods, not for \ncontact with infant formulae and follow -on formulae (Directive 2006/141/EC) and \nprocessed cereal -based foods and baby foods for infants and young children (Direc tive \n2006/125/EC);  \n(c) technical support agent in concentrations up to 0.1% in the final product.  \n \nDEHP, SML = 1.5 mg/kg food   \nOnly to be used as:  \n(a) plasticiser in repeated use materials and articles in contact with non -fatty foods;  \n(b) technical su pport agent in concentrations up to 0.1% in the final product.  \n \nDINP SML = 9 mg/kg food (cumulative with DIDP)  \nonly to be used as  \n(a) plasticiser in repeated use materials and articles;  \n(b) plasticiser in single -use materials and articles in contact with  non -fatty foods , not \nfor contact with  infant formulae and follow -on formulae ( Directive 2006/141/EC) and \nprocessed cereal -based foods and baby foods for infants and young children (Di rective \n2006/125/EC)  \n(c) technical support agent in concentrations up to 0.1% in the final product.   \n \nDIDP, SML = 9 mg/kg food ( cumulative with DINP)  \nOnly to be used as  \n(a) plasticiser in repeated use materials and articles;  \n(b) plasticiser in single -use materials and articles in contact with  non -fatty foods , not \nfor contact with infant formulae and follow -on formulae ( Directive 2006/141/EC) and \nprocessed cereal -based foods and baby foods for infants and young children (Directive \n2006/125/EC)  \n(c) te chnical support agent in concentrations up to 0.1% in the final product.   \n \nFurthermore, for certain plasticizers listed in Regulation (EU) 10/2011, including a \nnumber of phthalates, applies a group restriction  (Group restriction number 32),  that is, \nthe sum of these substances must not exceed an SML of 60 mg/kg foodstuff.  \nDEHP, BBP, DBP and DIBP must not be contained in homogenous materials above the \nconcentration of 0.1% w/w from July 2019 on according to the Restriction of Hazardous \nSubstances Directive  in electrical and electronic equipment RoHS2 (2011/65/EC). For \nmedical devices and  in vitro  diagnostic products this restriction takes effect in July 2021.  \n \n \n Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n57 \n  \nTable 1  CMR Classification*) and ED designation**) of phthalates (status Jan 2019)  \nPhthalate  Abbreviation  CAS \nnumber  CMR \nClassification*  ED \nidentification**  \nbis(2-\nmethoxyethyl)phthalate  DMEP  117-82-\n8 Repr 1B  - \nbis  \n(2-ethylhexyl)phthalate  DEHP  117-81-\n7 Repr 1B  ED \ndibutyl phthalate  DBP 84-74-2 Repr 1B  ED \n1,2-\nbenzenedicarboxylic \nacid, dipentylester, \nbranched and linear   84777 -\n06-0 Repr 1B  - \nn-pentyl -\nisopentylphthalate  PIPP No CAS  \n776297 -\n69-9? Repr 1B  - \ndi-n-pentyl phthalate  DnPP 131-18-\n0 Repr 1B  - \ndiisopentylphthalate  DiPeP  605-50-\n5 Repr 1B  - \nbenzyl butyl phthalate  BBP 85-68-7 Repr 1B - ED \ndiisobutylphthalate  DIBP 85-69-5 Repr 1B  ED \ndihexylphthalate  DHP 84-75-3 Repr 1B   \ndicyclohexylphthalate  DCHP  84-61-7 Repr 1B  ED \n*) as indicated in Annex VI to CLP_ATP10 (in force from 1 December 2018).  \n**) according to the ECHA Candidate List of substances of very high concern for Authorisation  published in \naccordance with Article 59(10) of the REACH Regulation  https://echa.europa.eu/candidate -list-table  \n \nAs substances of concern, knowledge on the exposure to phthalates is important and \nbiomonitoring of populations provides important information.  For some of the phthalates \nalready human biomonitoring assessment values, namely Biomonitoring equi valents (BE) \nor human biomonitoring (HBM) values, have been derived \u2013 these are concentrations of \nbiomarkers (metabolites) in urine, which reflect an acceptable chronic exposure, since \nthe basic assumption is an equilibrium between external exposure and in ternal burden \n(Angerer et al.  2011, Apel et al.  2017). In the course of the work done within the \nHBM4EU project, Human Biomonitoring Guidance Values (HBM -GVs) could be derived for \nDEHP and DINCH (see HBM4EU Deliverable D5.2, https://www.hbm4eu.eu ). In addition, \nHBM-GVs for the following SVHC phthal ates are finalised in September 2019 (Deliverable \nD5.6) and will also be published on the website: BBzP, DiBP, and DnBP.   Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n58 \n  \nAnnex 6:  Use of phthal ates in medical devices  \n \nPhthalates are abundantly used in polyvinyl chloride (PVC) medical devices such as blood \nbags, intravenous bags, nutrition pockets, tubing, catheters, respiratory masks or \ndisposable gloves. More than 40% of all plastic -based disposable medical devices are  \nmade from PVC. Di -2-ethylhexyl phthalate (DEHP) has been for many years the most \ncommonly used phthalate ester plasticiser in medical devices. A survey among the \nDanish Medical Device Industry found that 95% of the products contained DEHP [Huntley \nP, edit or The classified phthalates should be phased out of medical devices. Alternatives \nto Classified Phthalates in PVC Medical Devices Conference; 2014 Mar 27; Copenhagen, \nDenmark].  \n \nSafety concerns have been expressed for several high -risk patients groups, s uch as \nneonates, infants, pregnant and breast -feeding women exposed to DEHP. The SCENIHR \nin its Opinion of 201 5 indicated that \u201ca lack of evidence of causation between DEHP -PVC \nand any disease or adverse effect does not mean that there are no risks\u201d. This lack of \nevidence applies to all phthalates classified as CMR and/or identified as ED. Therefore the \nrequirement of patient subgroup analysis for the target patient groups as defined in the \n\u201cIntended Use\u201d of a medical device is now included in the Regulatio n (EU) 2017/745.  \n \nFor the use of DEHP, high risk groups were identified including patients undergoing \nhaemodialysis, extracorporeal membrane oxygenation (ECMO), and prematurely born \ninfants in Neonatal Intensive Care Units (NICU), (SCENIHR 201 5). The actua l exposure of \nsuch patient groups relative to the toxicity including CMR/ED property needs to be \ndetermined. However, even if the remaining risk is high, the benefit of the treatment \nshould be considered as well. It might be useful to evaluate the patient subgroups \nseparately:  \n \n\uf0b7 Paediatric Population (see subgroups)  \n\uf0b7 Peripubertal males  \n\uf0b7 Pregnant women  \n\uf0b7 Breast -feeding women  \n\uf0b7 any other patient group considered particularly vulnerable or exposed to high \nlevels of phthalates.  \n \nFor purposes of this Guideline, the following ranges of paediatric subpopulations are \nproposed to be used as a guide for manufacturers in medical devices (ref. SCCS Notes of \nGuidance \u2013 SCCS/1602/18, section 3 -6.9.1, page 7818) \n \n \n \n \n \n \n \n \n                                                           \n18 https://ec.europa.eu/health/sites/health/files/scientific_committees/consumer_safety/docs/sccs _o_224.pdf   Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n59 \n  \nDefinition of Paediatric Population Subgroups  \n \nPaediatri c Subgroup  Approximate Age Range  \nFull-term neonate  <1 week  \nNewborn  1 week\u20132 months  \nEarly infant  2\u20136 months   \nCrawlers/toddler  6 months \u20132 years  \nPreadolescent  2\u201312 years   \nAdolescent  12\u201318 years   \n \nIn view of ED activity, a dditional (paediatric ) subpopulations may need to be considered \ninclud ing:  \n \n\uf0b7 very low birth weight describes newborns less than 1.5 Kg  \n\uf0b7 low birth weight describes newborns less than 2.5 Kg  \n\uf0b7 preadolescent age group typically ranges from 11 to 13 years.  \n\uf0b7 peripubertal males  or females  \n \nIt should be realised that the benefit of medical devices including the use of phthalates \nmust also be considered: The survival of prematurely born infants often depends on the \navailability of the same medical devices that result in a relative ly high phthalate content \nexposure due to treatment. Whenever possible, material with low release potential \nshould be used (see SCENIHR opinion 201 5). \n \nBesides the direct patient benefits of the treatment with a medical device containing \nphthalates, other functionalities may also need to be considered.  For example, DEHP has \na stabilising effect on red blood cells (RBCs). RBCs have increased survival rates when \nstored in DEHP containing blood bags. DEHP is incorporated into the cell walls of RBCs \nand stabil ises the membrane integrity of the RBCs. This results in a prolonged shelf life \nand thus patient availability of blood stored in DEHP containing blood bags (SCENIHR \n2015). A maximum limit of extractable DEHP of 15 mg/100 mL for flexible PVC \ncontaining DEHP  is indicated in EN ISO 3826 -1 on containers for the collection of human \nblood and blood components.   \n \nThe plasticiser industry has been investing and developing alternatives to DEHP in \nmedical devices. Today, other plasticisers such as Di -isononyl cyclohe xanoate (DINCH, \nCAS 166412 -78-8), Tri -2-ethylhexyl trimellitate (TEHTM, CAS 3319 -31-1), butyryl tri -n-\nhexyl citrate (BTHC, CAS 102818 -95-1) and Dioctyl Terephthalate (DOTP, CAS \u200e6422-86-\n2) are being proposed in medical applications such as medical tubing and blood bags.  \nhttps://www.plasticisers.org/applications/medical -applications/   \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n60 \n In conclusion, for any BRA on the use of phthalates and the development of alternatives \nin me dical devices, careful consideration should be used to appropriate patient subgroup \nanalysis regarding medical device use and the resulting potential exposure.  \n \nReference  \nHuntley P, Editor . The classified phthalates  should be phased out of medical devices. \nProgram Meeting on Alternatives to Classified Phthalates in PVC Medical Devices \nConference; 2014 Mar 27; Copenhagen, Denmark.  \nhttps://pvc.dk/wp -content/uploads/2016/02/pvc -alternativer -til-klassificerede -ftalater -\nprogram.pdf  \n \n \n   Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n61 \n  \nAnnex 7:  Approaches for Benefit -Risk Assessment  \n \nSeveral approaches for BRA have been proposed especially in the context of medicinal \nproducts. The Innovative Medicines Initiative PROTECT Project (www.imiprotect.eu), \npresented a detailed review of approaches used for BRA (Mt -Isa et al.  2014). In this \nreview, a large number of approaches were identified and classified as descriptive \n(qualitative or semi -qualitative) or quantitative frameworks (relying on quantitative \nmethods of trading risks and benefits following mathematical principles), metrics \n(measure s for benefits and risks that are usually endpoint specific), estimation \ntechniques (i.e., simulation techniques and meta -analysis) , and utility survey techniques \n(to elicit stakeholders\u2019 preferences).  \nConcerning quantitative frameworks, according to the European Medicines Agency (EMA) \nProject Report (EMA/227124/2011), there is no agreement on any one approach to be \nused in regulatory submission on the benefits and risks of medicines. However, EMA has \nencouraged the use of quantitative frameworks in regulatory submissions of applications \nfor marketing authorisation of medicinal products.  \nAlthough there is little experience with quantitative frameworks in the area of medical \ndevices, some of the BRA appro aches used for pharmaceuticals may also be relevant for \nmedical devices and particularly regarding the use of CMR/ED phthalates. In particular, \napproaches based on multicriteria decision analysis ( MCDA) have attracted much \nattention during the past years in the field of medical decisions. For an introduction to \nMCDA see Dodgson et al. (2009).  \nIn brief, MCDA is based on decision theory and belongs to the general class of multi -\ncriteria analysis mode ls that accommodate decision making with multiple objectives. The \nmain purpose of MCDA is to bring together evaluations of options on different criteria into \none overall evaluation.  The starting point for MCDA approaches include s identification of \nthe alte rnatives and the criteria against which the alternatives are appraised.  MCDA \nincludes weighting, which ensures that the units of value on all the criteria are \ncomparable so that benefits and risks can be compared by using a common unit of value. \nIn this wa y, the added value of benefits can be compared to the loss of value from the \nrisks. A number of different weighting methods can be used, ranging from precise \nelicitation of weights, to weights based on qualitative judgements or including \nuncertainty.  \nA generic framework for conducting an MCDA can be based on the steps of the PROACT -\nURL framework (Hammond et al. , 1999), as presented below. A detailed description of \nthe different implementations of MCDA techniques is beyond the scope of this guideline. \nThe c hosen techniques and analyses should be presented and justified among others on \nthe basis of internal consistency, logical soundness and transparency.  \n  Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n62 \n  \nSTEP Description and relation to framework for Benefit -Risk \nAssessment described in section A of the  Guidelines  \nProblem  Describe the medical device, its intended use, and the \ntherapeutic context; frame the decision problem in terms \nof potential alternatives to CMR/ED phthalate. See Step 1: \nDescription and characterisation of the composition of the \nmedic al device; and Step 2: Use and function of the \nphthalates in the medical device.  \nObjectives  Identify the full set of criteria to evaluate different \nalternatives. See Step 2: Use and function of the \nphthalates in the medical device; and Step 3: Assessment  \nof the risks of the CMR/ED phthalate. See 7 Benefit \nassessment . \nAlternatives  Identify alternatives that are being evaluated against each \nother. See Step 4: Inventory of possible alternatives; and \nStep 5: Identification of the candidates for assessment as  \npotential relevant alternatives for phthalates . \nConsequences  Describe how the alternatives perform for each of the \ncriteria, i.e., the magnitudes of all effects in terms of the \ndifferent benefits and risks. See Step 2: Use and function \nof the phthalates in the medical device; Step 3: \nAssessment of the risks of the C MR/ED phthalate; Step 6: \nDescription of identified relevant potential alternative(s); \nStep 7: Assessment of the risk of identified potential \nrelevant alternatives. For a summary table see Table 1. \nExample for a comparison of CMR/ED phthalate with \npotential  alternative(s).  \nTrade -offs Assess the balance between benefits and risks using \njudgements of weights associated with the criteria and the \nvalue associated with the benefits and risks of every \nalternative. MCDA techniques commonly achieve this \nthrough num erical analysis. A number of different \nweighting methods can be used. Conduct sensitivity \nanalyses to explore uncertainties using different scenarios, \nand assess how different weights affect the overall \nordering of the alternatives.  \nSee also Step 8: Compar ison of functionality and \nperformance of CMR/ED phthalate as used in the medical \ndevice with functionality and performance of identified \npotential relevant alternatives; Step 9: Comparison of \nrisk(s) of original CMR/ED phthalate as used in the medical \ndevice with risk(s) of identified potential relevant \nalternatives; and Step 10: Comparison of benefit and risk \nof CMR/ED phthalate used in the medical device with \nidentified potential relevant alternatives.  \nUncertainty  Report the uncertainty associated with the benefits and  \nRisks. Consider how the balance between benefits and \nrisks is affected by uncertainty. A quantitative model will Guidelines o n the benefit -risk assessment of the presence of CMR/ED phthalates in certain medical devices  \n(final version)  \n_________________________________________________________________________________________  \n \n \n__________________________________________________________________________________\n63 \n explore in sensitivity analyses and scenario analyses (or by \nexplicitly incorporating probability distributions in the \nmodel) the effects on the overall benefit -risk balance of all \nsources of uncertainty. See 1.9 Uncertainty analysis.  \nRisk tolerance  Describe any considerations that could or should affect the \ndecision maker\u2019s attitude toward risks (e.g., special \npopulation, unmet  medical need).  \nLinked -decisions  Discuss how the value judgements and data are consistent \nwith similar decisions on medical devices.  \n  \n \nReferences  \n\uf0b7 Dodgson J, Spackman M, Pearman A, Phillips LD. Multi -criteria analysis: A \nmanual. London: Department for Communities and Local Government, First \npublished in 2000 by the Department for Environment, Transport and the \nRegions; 2009.  \n \n\uf0b7 ECHA 2011 Guidance on the preparation of socio -economic analysis as part of an \napplication for authorisation, European Chemicals Agency 2011 . \n \n\uf0b7 Hammond JS, Keeney RL, Raiffa H, Smart Choices: A Practical Guide to making \nBetter Decisions, Boston, MA: Harvard Business School Press; 1999.  \n \n\uf0b7 Mt-Isa S, Hallgreen C.E., Wang N., Callr\u00e9us T., Genov G., Hirsch I., Hobbiger S., \nHockley .S., Luciani D., Phillips L.D., Quartey G., Sarac S.B., Stoeckert I., Tzoulaki \nI., Micaleff A., Ashby D. - Balancing benefit and risk of medicines a systematic \nreview and classification of available methodologies, Pharmacoepidemiology and \nDrug Safety, May 2014 ."}, {"title": "md_transitional-provisions-art-3-and-4_en.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document                          MDCG 2020 -2 rev.1  \n \n \n \n \n     MDCG  2020 -2 rev. 1  \n       Class I Transitional provisions under  Article      \n      120 (3 and 4) \u2013 (MDR)             \n \n             March 2020  \n         July 2020 rev.1  \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group  (MDCG) established by \nArticle 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member \nStates and it is chaired by a representative of the European Commission.  \nThe document is not a European Commission document and it cannot be regarded as reflecting the \nofficial position of the European Commission. Any views expressed in this document are not legally \nbinding and only the Court of Justice of the European Union can give binding interpretations of Union \nlaw. \n \n \n \n  Medical Device       \nMedical Device Coordination Group Document                          MDCG 2020 -2 rev.1  \n \nMDCG 2020 -2 revision 1 changes  \nMDR postponement dates  : from 2020 to 2021  \nHow can a ffected manufacturers of some class I devices1 make efficient \nuse of the transitional provisions in A rticle 120 (3 ) and (4) of Regulation \n(EU) 2017/745 \u2013 Medical Devices Regulation ( MDR )? \nBackground:  \nThe corrected MDR2 Article 120 (3) allows  under certain condition s, some class I devices pursuant to \nDirective 93/42/EEC  \u2013 Medical Devices Directive (MDD) , for which the Declaration of C onformity \nwas drawn up prior to 26 May 2021 and for which the conformity assessment procedure pursuant to \nthe MDR would require the involvement of a notified body,  to be placed on the market3 until 2 6 May \n20244.  \nIn order  to make use of this article , the following conditions must be met:  \n1. The device continues to comply with Directive 93/42/EEC,  \n2. A notified body will need to be involved under the MDR (e.g. re -usable surgical instruments \nor up -classified devices)  \n3. A valid Declaration of C onformity , according to Annex VII  of the MDD , must be drawn up \nbefor e 26 May 2021,  \n4. No significant changes to the design or intended purpose of the device  after 26 May 202 15, \n5. The requirements of the MDR relating to post -market surveillance, market surveillance, \nvigilance, registration of economic operators and of devices shall apply in place of the \ncorresponding  requirements in Directive 93/42/EEC .6 This shall be in place on the 26 May \n2021. \n \nScope  \nThe scope of this document is to provide guidance related to the information to be provided in the \nform of a  Declaration of Conformity by manufacturers of Class I devices  (devices which are non -\n                                                           \n1 Class I devices for which the conformity assessment procedure pursuant to the MDR would require the involvement of a \nnotified body.  \n2 Corrigendum to Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical \ndevices, amending Directive 2001/83/EC, Regulation (EC) No\u202f178/2002 and Regulation (EC) No\u202f1223/2009 and repealing \nCouncil Directives 90/385/E EC and 93/42/EEC (OJ L 117, 5.5.2017), of 27.12.2019.  \n3 Devices which are not placed on the market but put into service may also make use of the transitional provisions .  \n4 Article 120(4) \u2018and may continue to be made available on the market \u2026until 26  May 2025\u2019 . \n5 Guidance on significant changes under Article 120 of the MDR with regard to devices covered by certificates according to \nMDD or AIMDD . \n6 Upcoming guidance on harmonised practices and technical solutions  to facilitate exchange of information in absence of \nEUDAMED .  Medical Device       \nMedical Device Coordination Group Document                          MDCG 2020 -2 rev.1  \n \nsterile or do not have a measuring function) that are required to have certificates after 26 May 2024 \naccording to the MDR.  \nContent of a val id Declaration of Conformity  \nThe manufacturer or his authorised representative established in the European Union is  obliged to \nissue a  Declaration of Conformity  that the  product has undergone  a conformity assessment  procedure \nrequired by the MDD  before being placed on the market.   \n \nWith the Declaration of Conformity, the manufacturer declares that the products concerned meet the \nrelevant provisions of the MDD.  \nMDD Annex II, Annex V, Annex VI set out that a Declaration of Conformity must cover one or more \nmedical devices manufactured  7 clearly identified by means of product name, product code or other \nunambiguous reference for class IIa, IIb and III devices, and also class Im and class Is devices. This is \nhowever not necessary for  other  Class I devices, as it is not required by the MD D (Annex VII) and as \nthere is no certificate from a notified body to which the issued Declaration of Conformity is related.  \nGuidance on  the content of the Declaration of C onformity can be found, inter alia, in the \u201cThe \u2018Blue \nGuide\u2019 on the implementa tion of EU products rules 2016 (2016/C272/01) \u201d8 and the  standard EN \nISO/IEC 17050 -1.9 According to this standard , the declaration may take the form of a document or any \nother suitable medium , and should contain sufficient information to enable all products  covered to be \ntraced back to it.  The model declaration in Annex III of Decision No 768/2008/EC  and the \u2018Blue \nGuide\u2019  on the implementation of EU products rules 2016 (2016/C272/0 1) describe the content of the \nDeclaration of C onformity to be as follows:   \n1.  A number identifying the product. This number does not need to be unique to each product. It \ncould refer to a product, batch, type or a serial number .10 This is left to the discretion of the \nmanufacturer .11   \n2.  The name and address of the manufacturer or  the authorised representative issuing the \ndeclaration.  \n3.  A statement that the declaration is issued under the sole responsibility of the manufacturer.  \n                                                           \n7 MDD Annex II, paragraph 2  \u2018This declaration must cover one or more medical devices manufactured, clearly identified by \nmeans of product name, product code or other unambiguous reference and must be kept by the manufacturer.\u2019  \n8 https://eur -lex.europa.eu/legal -content/GA/TXT/?uri=CELEX:52016XC0726(02) . \n9 EN ISO/IEC 17050 -1 : 2004 Conf ormity assessment \u2013 Supplier\u2019s D eclaration of Conformity \u2013 Part 1: General requirements \n/EN ISO/IEC 17050 -2 : 200 4 Conformity assessment \u2013 Supplier\u2019s Declaration of C onformity \u2013 Part 2: Supporting \ndocumentation . \n10 The \u2018number\u2019 may be an alpha -numerical code  or could also refer to a software version .  \n11 In addition, whether this is expressly envisaged or not by the Union harmonisation legislation,  manufacturers are free to \nadd a number identifying the Declaration of Conformity itself in line with EN ISO/IEC 17050 -2. Medical Device       \nMedical Device Coordination Group Document                          MDCG 2020 -2 rev.1  \n \n4.  The identification of the product allowing traceability. This is any relevant information \nsuppleme ntary to point 1 describing the product and allowing for its traceability . Where relevant \nfor the identification of the product , it may  contain an image, but unless specified as a \nrequirement in the Union harmonisation legislation this is left to the discr etion of the \nmanufacturer.  \n5.  All relevant Union harmonisation legislation complied with; the referenced standards or other \ntechnical specifications (such as national technical standards and specifications) in a precise,  \ncomplete and clearly defined way;  this implies that the version and/or date of the relevant \nstandard is specified.12  \n6.  If applicable, t he name and identification number of the notified body ,13 when it has been \ninvolved in the conformity assessment procedure ,14 15 and the reference to the relevant \ncertificate.  \n7.  If applicable, a ll supplementary information that may be required (for example category) . \n8.  The date of issue of the declaration; signature and title or an equivalent marking of the \nauthorised person16 17 \n\uf0fc This could be any date after the complet ion of the conformity assessment , but must be before \n26 May 202 1 if the manufacturer wants to make use of the transitional period in Article \n120(3) and (4)  of the MDR . \nEvery Declaration of C onformity must be based on proper technical documentation according to \nAnnex VII para graph  3 of the MDD.  The technical documentation and the D eclaration of Conformity \nshould be subject to appropriate  measures of document and record control. The Declaration  of \nConformity is to be kept by the manufacturer and shall be at the  disposal of the competent  authorities \nfor a period ending at least five years after the last product  has been manufactured.  \nNecessary amendm ents/updates to the t echnical documentation should be done in a transparent \nmanner. Both t he changes and the dates of when the changes were  made should be recorded. On the \nbasis of the Declaration of Conformity and the corresponding technical documentation, the \nmanufacturer should be able to demonstrate that the Declaration of Conformity was lawfully18 issued \nbefore 26 May 202 1 and that, subsequently, there are no significant changes  in the design or intended \n                                                           \n12 According to the MDD , referencing st andards or technical specifications complied with is voluntary .  \n13 For class I devices in scope of this guidance document, the involvement of a notified body is not required.  \n14 Not all Union harmonisation legislation requires the intervention of a notified  body (e.g. the Low Voltage Directive and the \nToys D irective . \n15 The name and address of the person who keeps the technical documentation may also be required by some pieces of Union \nharmonisation legislation since according to those, not only the manufactu rer shall keep the technical documentation.  \n16 This could be the m anaging director of the company or another representative of the company to whom this responsibility \nhas been delegated.  \n17 It is not necessary for the signatory to be domiciled in the Europea n Union. A manufacturer established outside the Union \nis entitled to carry out all the conformity assessment procedures at his premises and, to sign the Declaration of Conformity . \n18 Lawfully according to the Directive and to any relevant national provisions which apply.  Medical Device       \nMedical Device Coordination Group Document                          MDCG 2020 -2 rev.1  \n \npurpose19 in the meaning of Article 120(3) MDR. Taking into account Article 123(3) and 123 (3)(d), \nand a s EUDAMED will not be fully functional in May 202 1, it is required that the manufacturer keep \nthe Declaration of Conformity together with the  technical documentation available to the Competent \nAuthorities . This would also include details o f all device registrations and economic operator \nregistrations completed pursuant to national provisions implementing the requirements of Articles 14 \n(1) and (2) of Directive 93/42/EEC.  \n \n \n                                                           \n19 Guidance on significant changes under Article 120 of the MDR with regard to devices covered by certificates according to \nMDD or AIMDD ."}, {"title": "09 MDCG 2020-9 Regulatory Requirements for Ventilators and Reated Accessories.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document   MDCG  2020-9  \n \n  \n  \n \n \n \nMDCG 2020-9 \n  \n         REGULATORY REQUIREMENTS    \n      FOR VENTILATORS AND \n      RELATED ACCESSORIES    \n           \n \n April 2020 \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.The document is not a European \nCommission document and it cannot be regarded as reflecting the official \nposition of the European Commission. Any views expressed in this document are \nnot legally binding and only the Court of Justice of the European Union can give \nbinding interpretations of Union law. \n \n   \n2 REGULATORY REQUIREMENTS FOR VENTILATORS AND \nRELATED ACCESSORIES  \nOptions for supporting production and/or placing on the market of \nventilators in the context of COVID-19 pandemic \n1. INTRODUCTION AND SCOPE  \nThe World Health Organization (WHO) declared the COVID-19 outbreak a pandemic on \nMarch the 12th 2020. Patients infected by SARS-CoV-2 virus and developing the \nCOVID-19 disease with acute and severe respiratory symptoms have to be treated with \nmechanical ventilators to assure possibilities of survival.  \nThis guidance document focuses on ventilators and related accessories that are currently \nregulated under the Council Directive 93/42/EEC (MDD)1. According to the MDD, \ndevices may be placed on the market and/or put into service only if they comply with the \nrequirements laid down in this Directive when duly supplied and properly installed, \nmaintained and used in accordance with their intended purpose2. \nThe devices must meet the essential requirements set out in Annex I of the MDD, which \napply to them, taking account of the intended purpose of the devices concerned. In \naddition, devices may be placed and circulate on the European single market if they have \nbeen subject to a conformity assessment in accordance with the provisions of Article 11 \nof the MDD.  \nUnder the current COVID-19 context, the demand for ventilators and related accessories \nhas rapidly increased. Therefore, this document intends to outline the different regulatory \noptions for placing these devices on the EU market indicating their feasibility to allow \nshort-term supply. \n2. TYPES OF MEDICAL DEVICES AND THEIR PARTS /COMPONENTS  \n2.1. Ventilators \nVentilators are breathing support devices and can fall into different types according to \ntheir intended use and characteristics3: \n                                                \n1 However, placing on the market of devices which comply with MDD is limited to 27 May 2024. After \nthis date every device placed on the market has to comply with the requirements of Regulation (EU) \n2017/745 (MDR). According to the Article 120 section 5 and 6 of the MDR devices which comply \nwith MDR may be placed on the market before its application and notified bodies which are \ndesignated and notified in accordance with MDR may carry out the conformity assessment procedures \nlaid down in MDR and issue certificates in accordance with MDR. \n2 According to Article 1(g) of the MDD, intended purpose is the use for which the device is intended \naccording to the data supplied by the manufacturer on the labelling, in the instructions and/or in \npromotional materials. \n3 This list of ventilators includes some standards applicable to the specific ventilator. However, it should be \nnoted that this is not an exhaustive list and other standards also apply to these devices and should be \ntaken into account (e.g. EN 60601-1-2, EN 60601-1-6, EN 60601-1-8, EN 60601-1-11, EN 62304, EN \n62366). In addition, the current state of the art should be considered. This applies also to accessories.   \n3 - Ventilator for critical care:   automatic equipment that is intended to augment or \nprovide ventilation of the lungs of the patient when connected to the airway of the \npatient: \no intended for use in an environment that provides specialized care for \npatients whose conditions can be life threatening and who can require \ncomprehensive care and constant monitoring in a professional healthcare \nfacility; \no intended to be operated by a healthcare professional operator; and \no intended for those patients who need differing levels of support from \nartificial ventilation including for ventilator-dependent patients. \n(See e.g. EN ISO/IEC 80601-2-12:2011 + Cor.:2011).   \n- Home healthcare environment ventilators for ventilator-dependent patients: \nintended for use in the home healthcare environment; intended for use by a lay \noperator; intended for use with patients who are dependent on mechanical \nventilation for their life support. Depending on the intended purpose can be also \nused in the clinical setting (See e.g. EN ISO 80601-2-72:2015). \n- Ventilators for emergency and transport : these ventilators are used in \nEmergency Medical Service environment, e.g. in ambulances, transport of \npatients to the hospital, patient transport from hospital to hospital or transport \nwithin the hospital. The alarm and safety concept of emergency and transport \nventilators in general is designed for a permanent presence of the user. This \nfacilitates fast recognition and response in the event of an alarm or in the event of \nany malfunction (See e.g. EN 794-3:1998+A2:2009).  \n- Anaesthetic ventilator:  are designed for use during anaesthesia with an \nanaesthetic breathing system (See e.g. EN ISO 80601-2-13:2012). \nVentilators for critical care are usually invasive, which enables the ventilator machine to \nprovide lung support for inspiration and expiration through tracheal intubation. However, \nmost critical care ventilators allow non-invasive ventilation modes for critical care \npatients as well. Ventilators for non-critical care are usually non-invasive and therefore \nprovide air pressure support to natural breathing through e.g. a facemask. \nVentilators may offer different types of additional complementary functions that include: \n\uf0b7 High flow oxygen supply (nasal high flow therapy); \n\uf0b7 Monitoring systems; \n\uf0b7 Nebulisation systems. \n \n2.2. Accessories \nVentilators need to be \u201cconnected\u201d to the patients through dedicated accessories4 to the \nventilator that allow the machine to support the patient\u2019s breathing; therefore, it is \nimportant to proof compatibility with the ventilator(s). These accessories can be placed \non the market individually and usually fall into one of the following categories: \n                                                \n4 See MEDDEV 2.1/1  Definitions of 'medical devices', 'accessory' and 'manufacturer' \n(https://ec.europa.eu/docsroom/documents/10278/attachments/1/translations ).  \n4 \uf0b7 Breathing systems and circuits, such as: \no Circuits; \no Connections/Adapters; \no Tubes; \no Nasal cannulas for O 2; \no Masks or helmets for non-invasive ventilation; \no Air compressors; \n\uf0b7 Nebulizers; \n\uf0b7 Humidifiers and filters; \n\uf0b7 Monitoring accessories, including alarms, in-built safety features. \nAccessories are provided either disposable or reusable and are treated as medical devices \nin their own right5. \n2.3. Parts or components \nParts or components of medical devices that do not qualify as accessories are generally \nnot considered medical devices and thus not requiring themselves to be CE marked \naccording to the MDD (e.g. expiratory valves or flow sensors).  \n3. CLASSIFICATION  \n3.1. Ventilators \nThere are different types of ventilators depending on the degree of invasiveness and the \nsetting in which they are used in (e.g. Intensive Care Unit - ICU). Ventilators fall under \ntwo different classes in accordance with rule 11 (or rule 9) of Annex IX6,7 to the MDD: \n- Class IIa: only applicable to non-invasive devices, e.g. continuous positive airway \npressure \u2013 CPAP non-intended for critical care, or devices that only support \nspontaneous breathing. \n- Class IIb: applicable to most ventilators.  \nThe classification depends on the intended purpose of the ventilator and has important \nimplications in the selection of appropriate conformity assessment procedure(s) for the \ndevice including timing and complexity (see section 4 for details).  \n3.2. Accessories \nAccessories are classified in their own right usually in accordance with rule 2 or 5 of \nAnnex IX to the MDD, under Class I, IIa or IIb.  \n                                                \n5 Art. 1(1) of the MDD \n6 See MEDDEV 2.4/1 rev.9 Classification of Medical Devices -  \n(https://ec.europa.eu/docsroom/documents/10337/attachments/1/translations).  \n7 Please note that if a conformity assessment under the MDR is followed, the rules of classification \nspecified in Annex VIII to the MDR apply. Breathing support devices may be classified to class IIa or \nIIb (rule 12) or class III (rule 22) if they integrate or incorporate diagnostic functions which \nsignificantly determine the patient management by the device, such as closed loop systems.  \n5 3.3. Impact of classification on conformity assessment \nGiven that ventilators are classified as Class IIa or Class IIb, and accessories (except for \nClass I non-sterile and without measuring function), will in principle need the \ninvolvement of a notified body prior to their placing on the market.  Other options for the \nplacing on the market are provided in section 4 for both ventilators and accessories. \n4. REGULATORY OPTIONS FOR PLACING VENTILATORS ON THE MARKET  \nIn the context of the COVID-19 outbreak, several industries have expressed their \nwillingness to support and scale up the production of ventilators8. There are different \nregulatory options9 available for supporting production or placing on the market of \nventilators. These options are presented below, ordered by feasibility, to allow a swift \nsupply in the current context. \n4.1. Supplying parts, components or the finished devices to medical devices \nmanufacturers currently placing on the market ventilators  \nWhen the legal manufacturer10 has already undergone a conformity assessment for the \nventilator, has obtained a certificate and is lawfully placing ventilators on the market \nunder its own name, other producers (e.g. not currently working in the medical devices \nfield) can support its production. Such producers can provide parts or components, or the \nfinished device, therefore becoming suppliers or subcontractors of this manufacturer. \nGiven that the medical devices sector is highly regulated and complex, leveraging the \nknowledge and responsibilities of an already established manufacturer of ventilators \ncould be the least burdensome and fastest option to scale up the production of \nventilators.   \n4.1.1. Producers supplying parts or components to medical devices manufacturers \ncurrently placing on the market ventilators \nManufacturers of medical devices can have many suppliers, which in case of quality \nsystem certification are qualified, approved and controlled by the manufacturer. These \nsuppliers may need to be assessed by a notified body as part of the conformity \nassessment procedure on the basis of their criticality and the manufacturer\u2019s process in \nplace to control suppliers and the verification of purchased products11. When the \nmanufacturer wishes to use an additional supplier, this might need to be communicated in \nadvance to the notified body.  \n                                                \n8 Scaling up of production might also be needed for accessories. These medical devices can follow the \nsame options explained in section 4 but small differences can be applicable in case they have a \ndifferent classification (e.g. class Is).   \n9 This document mainly focuses on regulatory options provided by the MDD. If a conformity assessment \nunder the MDR is followed, similar procedures will apply under Annex IX, X or XI of the MDR \ndepending on the classification of the product.  \n10 Legal manufacturer refers to the definition of manufacturer established in Art. 1(f) of the MDD.  \n11 See Guidance for Notified Bodies auditing suppliers to medical device manufacturers \u2013 \n(http://www.doks.nbog.eu/Doks/NBOG_BPG_2010_1.pdf)   \n6 4.1.2. Producers manufacturing the ventilator itself for the medical device \nmanufacturer currently placing on the market ventilators \nManufacturers of medical devices producing ventilators may provide the specifications \nof a ventilator (e.g. current or older/simpler design) including parts of the technical \ndocumentation to a producer that becomes its subcontractor. The producer will \nmanufacture the ventilator but the medical device manufacturer will keep its role of legal \nmanufacturer according to the MDD.  \nThe legal manufacturer of the ventilator, which holds a quality system certification, \nqualifies, approves and controls the subcontractor that will need to be assessed by a \nnotified body as part of the conformity assessment procedure. When the manufacturer \nwishes to use an additional subcontractor, this will need to be communicated in advance \nto the notified body (i.e. as the subcontractor is considered critical11) that will assess the \navailable information and will decide the actions to be put in place e.g. whether or not it \nis necessary to carry out an (on-site12) audit. \nAlternatively, the manufacturer of medical devices could also follow other conformity \nassessment routes such as the EC type-examination, as established in Annex III to the \nMDD, and/or EC verification, as established in Annex IV to the MDD (these routes are \nelaborated in 4.3.2).     \n4.2. Derogation procedure \u2013 placing on the market authorised by the \nrelevant authorities of one Member State in the interest of public health \nThe relevant authority of one Member State may decide to authorise the placing on the \nmarket of devices in the interest of protection of health, even if the applicable conformity \nassessment procedures have not been finalised or initiated ('national derogation'). \nIn view of the epidemiological context as well as the exponential growth in demand for \nmedical devices, the Commission has published a Guidance on medical devices, active \nimplantable medical devices and in vitro diagnostic medical devices in the Covid-19 \ncontext.  \nQuestion 5 of this guidance provides information on the derogation procedures for \nmedical devices which is established in Article 11(13) of the MDD. In particular, the \nguidance specifies that the Covid-19 context warrants the application of such \nderogations.  \nBy amendment of 23 April 202013, Article 59(1) of Medical Devices Regulation (EU) \n2017/745 (MDR) empowers Member States to adopt national derogations under both the \nMDD and the MDR from the date of entry into force of that amendment. \nThe relevant competent authority of the Member State in this case authorises the placing \non the market within its territory and can also organise the purchase.  \n                                                \n12 See MDCG 2020-4 Guidance on temporary extraordinary measures related to medical device Notified \nBody audits during COVID-19 quarantine orders and travel restrictions \n(https://ec.europa.eu/docsroom/documents/40705).   \n13 Regulation 2020/561  amending Regulation (EU) 2017/745 on medical devices as regards the dates of \napplication of certain of its provisions.  \n7 In practice, this implies that each competent authority would need to assess whether the \nproducts produced by the manufacture provides an adequate level of safety in respect to \nthe applicable legal requirements. The assessment procedures can vary among Member \nStates and in some cases will involve the support of third parties (e.g. testing \nlaboratories).   \nIn the exceptional COVID-19 context, the assessment procedures will ensure a short-\nterm supply while guaranteeing patient safety14. The Member State will evaluate the \navailable technical documentation to find evidence that essential performance and safety \nrequirements are guaranteed in the context of use. In particular, the role of healthcare \nteams and health facilities is essential to allow a rational use and a continuous assessment \nof these crisis solutions. \nOnce this assessment is performed, the authority has to take a decision, whether or not \nthe respective device produced by the manufacturer may enter the national territory of the \nMember State. Competent authorities should inform the Commission and their \ncounterparts in other Member States of any temporary agreement they have granted to \nspecific devices.  \nIn addition, Article 59(3) of the MDR empowers the Commission to extend, in \nexceptional cases relating to public health or patient safety or health, by means of \nimplementing acts, for a limited period of time the validity of a national derogation, \ngranted by a Member State under the MDD or the MDR, to the territory of the Union and \nset the conditions under which a device may be placed on the market or put into service. \nThis allows the Commission and the Member States to address potential shortages Union \nwide of vitally important medical devices in an effective manner. \nTiming to obtain a national derogation by a competent authority will greatly depend on \nthe quality and adequacy of the evidence provided by the manufacturer.  When technical \ndocumentation and evidence of safety of performance is adequate, this can be a feasible \noption to ensure short-term supply.  \n \n4.3. Manufacturing of the finished device by a producer that was not \npreviously placing on the market ventilators  \nIf the ventilator is entirely manufactured by a producer that decides to place it on the \nmarket under its name, such producer will become the legal manufacturer in its own \nright. This means that the manufacturer will need to fulfil all requirements of the MDD \n(e.g. including the need to draw up the technical documentation and clinical evaluation \nrelated to the ventilator, and to establish and keep up to date a systematic procedure to \nreview experience gained from devices in the post-production phase).  \nThe manufacturer who places the finished CE marked ventilator on the market under its \nown name needs to ensure that the device complies with the essential requirements \n(established in Annex I of the MDD) and provide relevant evidence. A notified body will \nbe involved in the conformity assessment in all cases.  \n                                                \n14 Some Member States have published guidance on their respective websites to support this assessment \ne.g. in case of implementation of innovative manufacturing processes such as 3D printing.   \n8 Given that the medical devices sector is highly regulated and complex, the scenarios \npresented below will be the most burdensome and therefore only applicable to increase \nsupply in the medium-long term.  \n4.3.1. Medical devices manufacturers\u2019 not currently producing ventilators request \nan extension of their product range. \nThis option is available for medical devices manufacturers currently certified. It includes, \nfor instance, medical devices manufacturers already holding a full quality management \nsystem certificate under Annex II to the MDD for other devices and wishing to add \nventilators to their certification. They could seek the support from (non-medical devices) \nproducers to act as subcontractors and extend the scope of their certificate.   \nFrom a procedural point of view, the medical devices manufacturer may produce the \nventilator itself or may utilise a subcontractor (i.e. producer linked or not to the medical \ndevices field). In the latter case, the manufacturer will qualify, approve and control the \nsubcontractor that will be assessed by the notified body as part of the conformity \nassessment procedure. When the manufacturer wishes to use an additional subcontractor, \nthis will need to be communicated in advance to the notified body (i.e. as the \nsubcontractor is considered critical11) that will assess the available information and will \ndecide the actions to be put in place e.g. whether or not it is necessary to carry out an (on-\nsite12) audit. \nMost importantly, the manufacturer will need to request an extension of the product \nrange from its notified body. The notified body will assess the available information in \nrelation to the new product (that include an assessment of the technical documentation \nand clinical evaluation) and update the certificate. \nThe manufacturer of medical devices could also use other conformity assessment routes \nsuch as the EC Type-Examination and EC Verification and testing of every product \nunder Annex III and IV respectively (these routes are elaborated in section 4.3.2).   \n \n4.3.2. Ventilator manufactured entirely by a producer that is not currently a legal \nmanufacturer under the MDD \nProducers that do not currently qualify as legal manufacturers under the MDD and decide \nto place ventilators on the market under their own name need to be aware of all the legal \nrequirements for manufactures under the MDD. It is important to mention that in the field \nof medical devices some Member States could have additional requirements, for instance, \nthe need to authorise the facility of the medical device manufacturer prior to starting \nproduction.  \nIn addition to this, the involvement of a notified body will depend on the classification. \nIn particular: \n1. Class IIa ventilators can follow the following routes established in the relevant \nAnnexes of the MDD: \na. Annex II (excluding point 4) \u2013 which involves the assessment of the full \nmanufacturer\u2019s quality management system. This will require an on-site \naudit (which may be performed remotely in the current context) and  \n9 regular surveillance audits at least annually. In addition, the notified body \nwill assess the technical documentation and the clinical evaluation of the \nproduct to be certified prior to certification on a sampling basis15.   \nb. Declaration of conformity (Annex VII) combined with either an \nassessment of the quality assurance of the production or of the product \n(Annex V or VI) or a EC verification (set out in Annex IV): \n\uf0a7 The assessment of the quality system performed by the notified \nbody will be similar to the one outlined in section 1.a above. \n\uf0a7 The verification by testing of products by the notified body will be \nperformed by examination and testing of every product.   \n \n2. Class IIb ventilators can follow the following routes: \na. Annex II (excluding point 4) \u2013 which involves the assessment of the full \nmanufacturer\u2019s quality management system. This will require an on-site \naudit (which may be performed remotely in the current context) and \nregular surveillance audits at least annually. In addition, the notified body \nwill assess the technical documentation and the clinical evaluation of the \nproducts to be certified prior to certification on a sampling basis15.   \nb. EC type-examination (Annex III) combined with either an assessment of \nthe quality assurance either of the production or of the product (Annex V \nor VI) or EC verification by testing of products (set out in Annex IV). EC \nType-examination consists in the assessment of the technical \ndocumentation and testing of a number of features of the device type to \nensure it conforms to the requirements. The additional procedures (Annex \nIV, V or VI) are the same as the ones described in 1.b above. \nThe assessment of the quality management system of the manufacturer (Annex II, V and \nVI) can be partly fulfilled by compliance with a harmonised standard (EN ISO 13485) \nbut this route will unlikely be fast enough to ensure short-term supply. This is due to the \ntimelines and experience required to get a certificate under these annexes of the MDD \nand taking into account the current circumstances where auditing capacity is restricted by \nthe Covid19 situation. \nA faster route but also time-consuming route will probably be the performance of tests on \nthe products that might be combined with the assessment of the technical documentation, \nnamely:  \n- declaration of conformity (Annex VII) + verification of products (Annex IV) for \nClass IIa; or \n- EC type-examination (Annex III) + verification of products (Annex IV) for \nClass IIb. \nThrough this route, the device type or device samples are tested and there is no obligation \nto have a certified quality management system in place and subject to regular \nsurveillance audits. However, quality management processes are important and critical to \nthe production of safe and functional medical devices. The conformity assessment will be \n                                                \n15 See Annex II, section 3.3 to the MDD  \n10 based on the manufacturers testing strategy that must ensure compliance with the safety \nand performance requirements.  \nIt should be noted that this option is burdensome and will take several months, especially \nto draw up an adequate technical documentation. In addition, there is only a limited \nnumber of notified bodies designated to perform EC type-examination and/or EC \nverification in ventilators (according to NANDO16 18 notified bodies out of 56 are \nauthorised to perform these tests at the moment).  \n                                                \n16 This information can be found in NANDO, by searching notified bodies under the MDD that are \ndesignated under Annex III and IV for code MD 1102 - Respiratory devices, devices including \nhyperbaric chambers for oxygen therapy, inhalation anaesthesia -   \nhttps://ec.europa.eu/growth/tools-databases/nando/index.cfm?fuseaction=directive.notifiedbody&dir_id=13"}, {"title": "Mdr.Html.txt", "text": "L_2017117EN.01000101.xml\n\n\n\n\n\n\n\n\n\n\n\n5.5.2017\u00a0\u00a0\u00a0\n\n\nEN\n\n\nOfficial Journal of the European Union\n\n\nL 117/1\n\n\n\n\n\n\n\n\n            REGULATION (EU) 2017/745 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL\n         \nof 5 April 2017\n         \non medical devices, amending Directive\u00a02001/83/EC, Regulation\u00a0(EC)\u00a0No\u00a0178/2002 and Regulation\u00a0(EC)\u00a0No\u00a01223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC\n(Text with EEA relevance)\n\n\nTHE EUROPEAN PARLIAMENT AND THE COUNCIL OF THE EUROPEAN UNION,\n\nHaving regard to the Treaty on the Functioning of the European Union, and in particular Article\u00a0114 and Article\u00a0168(4)(c) thereof,\n\n\nHaving regard to the proposal from the European Commission,\n\n\nAfter transmission of the draft legislative act to the national parliaments,\n\n\nHaving regard to the opinion of the European Economic and Social Committee\u00a0(1),\n\n\nAfter consulting the Committee of the Regions,\n\n\nActing in accordance with the ordinary legislative procedure\u00a0(2),\n\nWhereas:\n\n\n\n\n\n\n\n(1)\n\n\nCouncil Directive\u00a090/385/EEC\u00a0(3) and Council Directive\u00a093/42/EEC\u00a0(4) constitute the Union regulatory framework for medical devices, other than in vitro diagnostic medical devices. However, a fundamental revision of those Directives is needed to establish a robust, transparent, predictable and sustainable regulatory framework for medical devices which ensures a high level of safety and health whilst supporting innovation.\n\n\n\n\n\n\n\n\n\n\n\n\n(2)\n\n\nThis Regulation aims to ensure the smooth functioning of the internal market as regards medical devices, taking as a base a high level of protection of health for patients and users, and taking into account the small- and medium-sized enterprises that are active in this sector. At the same time, this Regulation sets high standards of quality and safety for medical devices in order to meet common safety concerns as regards such products. Both objectives are being pursued simultaneously and are inseparably linked whilst one not being secondary to the other. As regards Article\u00a0114 of the Treaty on the Functioning of the European Union (TFEU), this Regulation harmonises the rules for the placing on the market and putting into service of medical devices and their accessories on the Union market thus allowing them to benefit from the principle of free movement of goods. As regards Article\u00a0168(4)(c)\u00a0TFEU, this Regulation sets high standards of quality and safety for medical devices by ensuring, among other things, that data generated in clinical investigations are reliable and robust and that the safety of the subjects participating in a clinical investigation is protected.\n\n\n\n\n\n\n\n\n\n\n\n\n(3)\n\n\nThis Regulation does not seek to harmonise rules relating to the further making available on the market of medical devices after they have already been put into service such as in the context of second-hand sales.\n\n\n\n\n\n\n\n\n\n\n\n\n(4)\n\n\nKey elements of the existing regulatory approach, such as the supervision of notified bodies, conformity assessment procedures, clinical investigations and clinical evaluation, vigilance and market surveillance should be significantly reinforced, whilst provisions ensuring transparency and traceability regarding medical devices should be introduced, to improve health and safety.\n\n\n\n\n\n\n\n\n\n\n\n\n(5)\n\n\nTo the extent possible, guidance developed for medical devices at international level, in particular in the context of the Global Harmonization Task Force (GHTF) and its follow-up initiative, the International Medical Devices Regulators Forum (IMDRF), should be taken into account to promote the global convergence of regulations which contributes to a high level of safety protection worldwide, and to facilitate trade, in particular in the provisions on Unique Device Identification, general safety and performance requirements, technical documentation, classification rules, conformity assessment procedures and clinical investigations.\n\n\n\n\n\n\n\n\n\n\n\n\n(6)\n\n\nFor historical reasons, active implantable medical devices, covered by Directive\u00a090/385/EEC, and other medical devices, covered by Directive\u00a093/42/EEC, were regulated in two separate legal instruments. In the interest of simplification, both directives, which have been amended several times, should be replaced by a single legislative act applicable to all medical devices other than in vitro diagnostic medical devices.\n\n\n\n\n\n\n\n\n\n\n\n\n(7)\n\n\nThe scope of application of this Regulation should be clearly delimited from other Union harmonisation legislation concerning products, such as in vitro diagnostic medical devices, medicinal products, cosmetics and food. Therefore, Regulation\u00a0(EC)\u00a0No\u00a0178/2002 of the European Parliament and of the Council\u00a0(5) should be amended to exclude medical devices from its scope.\n\n\n\n\n\n\n\n\n\n\n\n\n(8)\n\n\nIt should be the responsibility of the Member\u00a0States to decide on a case-by-case basis whether or not a product falls within the scope of this Regulation. In order to ensure consistent qualification decisions in that regard across all Member\u00a0States, particularly with regard to borderline cases, the Commission should be allowed to, on its own initiative or at the duly substantiated request of a Member\u00a0State, having consulted the Medical Device Coordination Group (\u2018MDCG\u2019), decide on a case-by-case basis whether or not a specific product, category or group of products falls within the scope of this Regulation. When deliberating on the regulatory status of products in borderline cases involving medicinal products, human tissues and cells, biocidal products or food products, the Commission should ensure an appropriate level of consultation of the European Medicines Agency\u00a0(EMA), the European Chemicals Agency and the European Food Safety Authority, as relevant.\n\n\n\n\n\n\n\n\n\n\n\n\n(9)\n\n\nSince in some cases it is difficult to distinguish between medical devices and cosmetic products, the possibility of taking a Union-wide decision regarding the regulatory status of a product should also be introduced in Regulation\u00a0(EC)\u00a0No\u00a01223/2009 of the European Parliament and of the Council\u00a0(6).\n\n\n\n\n\n\n\n\n\n\n\n\n(10)\n\n\nProducts which combine a medicinal product or substance and a medical device are regulated either under this Regulation or under Directive\u00a02001/83/EC of the European Parliament and of the Council.\u00a0(7) The two legislative acts should ensure appropriate interaction in terms of consultations during pre-market assessment, and of exchange of information in the context of vigilance activities involving such combination products. For medicinal products that integrate a medical device part, compliance with the general safety and performance requirements laid down in this Regulation for the device part should be adequately assessed in the context of the marketing authorisation for such medicinal products. Directive\u00a02001/83/EC should therefore be amended.\n\n\n\n\n\n\n\n\n\n\n\n\n(11)\n\n\nUnion legislation, in particular Regulation\u00a0(EC)\u00a0No\u00a01394/2007 of the European Parliament and of the Council\u00a0(8) and Directive\u00a02004/23/EC of the European Parliament and of the Council\u00a0(9), is incomplete in respect of certain products manufactured utilising derivatives of tissues or cells of human origin that are non-viable or are rendered non-viable. Such products should come under the scope of this Regulation, provided they comply with the definition of a medical device or are covered by this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(12)\n\n\nCertain groups of products for which a manufacturer claims only an aesthetic or another non-medical purpose but which are similar to medical devices in terms of functioning and risks profile should be covered by this Regulation. In order for manufacturers to be able to demonstrate the conformity of such products, the Commission should adopt common specifications at least with regard to application of risk management and, where necessary, clinical evaluation regarding safety. Such common specifications should be developed specifically for a group of products without an intended medical purpose and should not be used for conformity assessment of the analogous devices with a medical purpose. Devices with both a medical and a non-medical intended purpose should fulfil both the requirements applicable to devices with, and to devices without, an intended medical purpose.\n\n\n\n\n\n\n\n\n\n\n\n\n(13)\n\n\nAs is the case for products that contain viable tissues or cells of human or animal origin, that are explicitly excluded from Directives\u00a090/385/EEC and 93/42/EEC and hence from this Regulation, it should be clarified that products that contain or consist of viable biological materials or viable organisms of another origin in order to achieve or support the intended purpose of those products are not covered by this Regulation either.\n\n\n\n\n\n\n\n\n\n\n\n\n(14)\n\n\nThe requirements laid down in Directive\u00a02002/98/EC of the European Parliament and of the Council\u00a0(10) should continue to apply.\n\n\n\n\n\n\n\n\n\n\n\n\n(15)\n\n\nThere is scientific uncertainty about the risks and benefits of nanomaterials used for devices. In order to ensure a high level of health protection, free movement of goods and legal certainty for manufacturers, it is necessary to introduce a uniform definition for nanomaterials based on Commission Recommendation\u00a02011/696/EU\u00a0(11), with the necessary flexibility to adapt that definition to scientific and technical progress and subsequent regulatory development at Union and international level. In the design and manufacture of devices, manufacturers should take special care when using nanoparticles for which there is a high or medium potential for internal exposure. Such devices should be subject to the most stringent conformity assessment procedures. In preparation of implementing acts regulating the practical and uniform application of the corresponding requirements laid down in this Regulation, the relevant scientific opinions of the relevant scientific committees should be taken into account.\n\n\n\n\n\n\n\n\n\n\n\n\n(16)\n\n\nSafety aspects addressed by Directive\u00a02014/30/EU of the European Parliament and of the Council\u00a0(12) are an integral part of the general safety and performance requirements laid down in this Regulation for devices. Consequently, this Regulation should be considered a lex\u00a0specialis in relation to that Directive.\n\n\n\n\n\n\n\n\n\n\n\n\n(17)\n\n\nThis Regulation should include requirements regarding the design and manufacture of devices emitting ionizing radiation without affecting the application of Council Directive\u00a02013/59/Euratom\u00a0(13) which pursues other objectives.\n\n\n\n\n\n\n\n\n\n\n\n\n(18)\n\n\nThis Regulation should include requirements for devices' design, safety and performance characteristics which are developed in such a way as to prevent occupational injuries, including protection from radiation.\n\n\n\n\n\n\n\n\n\n\n\n\n(19)\n\n\nIt is necessary to clarify that software in its own right, when specifically intended by the manufacturer to be used for one or more of the medical purposes set out in the definition of a medical device, qualifies as a medical device, while software for general purposes, even when used in a healthcare setting, or software intended for life-style and well-being purposes is not a medical device. The qualification of software, either as a device or an accessory, is independent of the software's location or the type of interconnection between the software and a device.\n\n\n\n\n\n\n\n\n\n\n\n\n(20)\n\n\nThe definitions in this Regulation, regarding devices themselves, the making available of devices, economic operators, users and specific processes, the conformity assessment, clinical investigations and clinical evaluations, post-market surveillance, vigilance and market surveillance, standards and other technical specifications, should be aligned with well-established practice in the field at Union and international level in order to enhance legal certainty.\n\n\n\n\n\n\n\n\n\n\n\n\n(21)\n\n\nIt should be made clear that it is essential that devices offered to persons in the Union by means of information society services within the meaning of Directive\u00a0(EU)\u00a02015/1535 of the European Parliament and of the Council\u00a0(14) and devices used in the context of a commercial activity to provide a diagnostic or therapeutic service to persons within the Union comply with the requirements of this Regulation, where the product in question is placed on the market or the service is provided in the Union.\n\n\n\n\n\n\n\n\n\n\n\n\n(22)\n\n\nTo recognise the important role of standardisation in the field of medical devices, compliance with harmonised standards as defined in Regulation (EU)\u00a0No\u00a01025/2012 of the European Parliament and of the Council\u00a0(15) should be a means for manufacturers to demonstrate conformity with the general safety and performance requirements and other legal requirements, such as those relating to quality and risk management, laid down in this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(23)\n\n\nDirective\u00a098/79/EC of the European Parliament and of the Council\u00a0(16) allows the Commission to adopt common technical specifications for specific categories of in vitro diagnostic medical devices. In areas where no harmonised standards exist or where they are insufficient, the Commission should be empowered to lay down common specifications which provide a means of complying with the general safety and performance requirements, and the requirements for clinical investigations and clinical evaluation and/or post-market clinical follow-up, laid down in this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(24)\n\n\nCommon specifications (\u2018CS\u2019) should be developed after consulting the relevant stakeholders and taking account of European and international standards.\n\n\n\n\n\n\n\n\n\n\n\n\n(25)\n\n\nThe rules applicable to devices should be aligned, where appropriate, with the New Legislative Framework for the Marketing of Products, which consists of Regulation\u00a0(EC)\u00a0No\u00a0765/2008 of the European Parliament and of the Council\u00a0(17) and Decision\u00a0No\u00a0768/2008/EC of the European Parliament and of the Council\u00a0(18).\n\n\n\n\n\n\n\n\n\n\n\n\n(26)\n\n\nThe rules on Union market surveillance and control of products entering the Union market laid down in Regulation\u00a0(EC)\u00a0No\u00a0765/2008 apply to devices covered by this Regulation which does not prevent Member\u00a0States from choosing the competent authorities to carry out those tasks.\n\n\n\n\n\n\n\n\n\n\n\n\n(27)\n\n\nIt is appropriate to set out clearly the general obligations of the different economic operators, including importers and distributors, building on the New Legislative Framework for the Marketing of Products, without prejudice to the specific obligations laid down in the various parts of this Regulation, to enhance understanding of the requirements laid down in this Regulation and thus to improve regulatory compliance by the relevant operators.\n\n\n\n\n\n\n\n\n\n\n\n\n(28)\n\n\nFor the purpose of this Regulation, the activities of distributors should be deemed to include acquisition, holding and supplying of devices.\n\n\n\n\n\n\n\n\n\n\n\n\n(29)\n\n\nSeveral of the obligations on manufacturers, such as clinical evaluation or vigilance reporting, that were set out only in the Annexes\u00a0to Directives\u00a090/385/EEC and\u00a093/42/EEC, should be incorporated into the enacting provisions of this Regulation to facilitate its application.\n\n\n\n\n\n\n\n\n\n\n\n\n(30)\n\n\nHealth institutions should have the possibility of manufacturing, modifying and using devices in-house and thereby address, on a non-industrial scale, the specific needs of target patient groups which cannot be met at the appropriate level of performance by an equivalent device available on the market. In that context, it is appropriate to provide that certain rules of this Regulation, as regards medical devices manufactured and used only within health institutions, including hospitals as well as institutions, such as laboratories and public health institutes that support the healthcare system and/or address patient needs, but which do not treat or care for patients directly, should not apply, since the aims of this Regulation would still be met in a proportionate manner. It should be noted that the concept of \u2018health institution\u2019 does not cover establishments primarily claiming to pursue health interests or healthy lifestyles, such as gyms, spas, wellness and fitness centres. As a result, the exemption applicable to health institutions does not apply to such establishments.\n\n\n\n\n\n\n\n\n\n\n\n\n(31)\n\n\nIn view of the fact that natural or legal persons can claim compensation for damage caused by a defective device in accordance with applicable Union and national law, it is appropriate to require manufacturers to have measures in place to provide sufficient financial coverage in respect of their potential liability under Council Directive\u00a085/374/EEC\u00a0(19). Such measures should be proportionate to the risk class, type of device and the size of the enterprise. In this context, it is also appropriate to lay down rules concerning the facilitation, by a competent authority, of the provision of information to persons who may have been injured by a defective device.\n\n\n\n\n\n\n\n\n\n\n\n\n(32)\n\n\nTo ensure that devices manufactured in series production continue to be in conformity with the requirements of this Regulation and that experience from the use of the devices they manufacture is taken into account for the production process, all manufacturers should have a quality management system and a post-market surveillance system in place which should be proportionate to the risk class and the type of the device in question. In addition, in order to minimize risks or prevent incidents related to devices, manufacturers should establish a system for risk management and a system for reporting of incidents and field safety corrective actions.\n\n\n\n\n\n\n\n\n\n\n\n\n(33)\n\n\nThe risk management system should be carefully aligned with and reflected in the clinical evaluation for the device, including the clinical risks to be addressed as part of clinical investigations, clinical evaluation and post-market clinical follow up. The risk management and clinical evaluation processes should be inter-dependent and should be regularly updated.\n\n\n\n\n\n\n\n\n\n\n\n\n(34)\n\n\nIt should be ensured that supervision and control of the manufacture of devices, and the post-market surveillance and vigilance activities concerning them, are carried out within the manufacturer's organisation by a person responsible for regulatory compliance who fulfils minimum conditions of qualification.\n\n\n\n\n\n\n\n\n\n\n\n\n(35)\n\n\nFor manufacturers who are not established in the Union, the authorised representative plays a pivotal role in ensuring the compliance of the devices produced by those manufacturers and in serving as their contact person established in the Union. Given that pivotal role, for the purposes of enforcement it is appropriate to make the authorised representative legally liable for defective devices in the event that a manufacturer established outside the Union has not complied with its general obligations. The liability of the authorised representative provided for in this Regulation is without prejudice to the provisions of Directive\u00a085/374/EEC, and accordingly the authorised representative should be jointly and severally liable with the importer and the manufacturer. The tasks of an authorised representative should be defined in a written mandate. Considering the role of authorised representatives, the minimum requirements they should meet should be clearly defined, including the requirement of having available a person who fulfils minimum conditions of qualification which should be similar to those for a manufacturer's person responsible for regulatory compliance.\n\n\n\n\n\n\n\n\n\n\n\n\n(36)\n\n\nTo ensure legal certainty in respect of the obligations incumbent on economic operators, it is necessary to clarify when a distributor, importer or other person is to be considered the manufacturer of a device.\n\n\n\n\n\n\n\n\n\n\n\n\n(37)\n\n\nParallel trade in products already placed on the market is a lawful form of trade within the internal market on the basis of Article\u00a034 TFEU subject to the limitations arising from the need for protection of health and safety and from the need for protection of intellectual property rights provided for under Article\u00a036 TFEU. Application of the principle of parallel trade is, however, subject to different interpretations in the Member\u00a0States. The conditions, in particular the requirements for relabelling and repackaging, should therefore be specified in this Regulation, taking into account the case-law of the Court of Justice\u00a0(20) in other relevant sectors and existing good practice in the field of medical devices.\n\n\n\n\n\n\n\n\n\n\n\n\n(38)\n\n\nThe reprocessing and further use of single-use devices should only take place where permitted by national law and while complying with the requirements laid down in this Regulation. The reprocessor of a single-use device should be considered to be the manufacturer of the reprocessed device and should assume the obligations incumbent on manufacturers under this Regulation. Nevertheless, Member\u00a0States should have the possibility of deciding that the obligations relating to reprocessing and re-use of single-use devices within a health institution or by an external reprocessor acting on its behalf may differ from the obligations on a manufacturer described in this Regulation. In principle, such divergence should only be permitted where reprocessing and reuse of single-use devices within a health institution or by an external reprocessor are compliant with CS that have been adopted, or, in the absence of such CS, with relevant harmonised standards and national provisions. The reprocessing of such devices should ensure an equivalent level of safety and performance to that of the corresponding initial single-use device.\n\n\n\n\n\n\n\n\n\n\n\n\n(39)\n\n\nPatients who are implanted with a device should be given clear and easily accessible essential information allowing the implanted device to be identified and other relevant information about the device, including any necessary health risk warnings or precautions to be taken, for example indications as to whether or not it is compatible with certain diagnostic devices or with scanners used for security controls.\n\n\n\n\n\n\n\n\n\n\n\n\n(40)\n\n\nDevices should, as a general rule, bear the CE marking to indicate their conformity with this Regulation so that they can move freely within the Union and be put into service in accordance with their intended purpose. Member\u00a0States should not create obstacles to the placing on the market or putting into service of devices that comply with the requirements laid down in this Regulation. However, Member\u00a0States should be allowed to decide whether to restrict the use of any specific type of device in relation to aspects that are not covered by this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(41)\n\n\nThe traceability of devices by means of a Unique Device Identification system\u00a0(UDI\u00a0system) based on international guidance should significantly enhance the effectiveness of the post-market safety-related activities for devices, which is owing to improved incident reporting, targeted field safety corrective actions and better monitoring by competent authorities. It should also help to reduce medical errors and to fight against falsified devices. Use of the UDI system should also improve purchasing and waste disposal policies and stock-management by health institutions and other economic operators and, where possible, be compatible with other authentication systems already in place in those settings.\n\n\n\n\n\n\n\n\n\n\n\n\n(42)\n\n\nThe UDI system should apply to all devices placed on the market except custom-made devices, and be based on internationally recognised principles including definitions that are compatible with those used by major trade partners. In order for the UDI system to become functional in time for the application of this Regulation, detailed rules should be laid down in this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(43)\n\n\nTransparency and adequate access to information, appropriately presented for the intended user, are essential in the public interest, to protect public health, to empower patients and healthcare professionals and to enable them to make informed decisions, to provide a sound basis for regulatory decision-making and to build confidence in the regulatory system.\n\n\n\n\n\n\n\n\n\n\n\n\n(44)\n\n\nOne key aspect in fulfilling the objectives of this Regulation is the creation of a European database on medical devices (Eudamed) that should integrate different electronic systems to collate and process information regarding devices on the market and the relevant economic operators, certain aspects of conformity assessment, notified bodies, certificates, clinical investigations, vigilance and market surveillance. The objectives of the database are to enhance overall transparency, including through better access to information for the public and healthcare professionals, to avoid multiple reporting requirements, to enhance coordination between Member\u00a0States and to streamline and facilitate the flow of information between economic operators, notified bodies or sponsors and Member\u00a0States as well as between Member\u00a0States among themselves and with the Commission. Within the internal market, this can be ensured effectively only at Union level and the Commission should therefore further\u00a0develop and manage the European databank on medical devices set up by Commission Decision\u00a02010/227/EU\u00a0(21).\n\n\n\n\n\n\n\n\n\n\n\n\n(45)\n\n\nTo facilitate the functioning of Eudamed, an internationally recognised medical device nomenclature should be available free of charge to manufacturers and other natural or legal persons required by this Regulation to use that nomenclature. Furthermore, that nomenclature should be available, where reasonably practicable, free of charge also to other stakeholders.\n\n\n\n\n\n\n\n\n\n\n\n\n(46)\n\n\nEudamed's electronic systems regarding devices on the market, the relevant economic operators and certificates should enable the public to be adequately informed about devices on the Union market. The electronic system on clinical investigations should serve as a tool for the cooperation between Member\u00a0States and for enabling sponsors to submit, on a voluntary basis, a single application for several Member\u00a0States and to report serious adverse events, device deficiencies and related updates. The electronic system on vigilance should enable manufacturers to report serious incidents and other reportable events and to support the coordination of the evaluation of such incidents and events by competent authorities. The electronic system regarding market surveillance should be a tool for the exchange of information between competent authorities.\n\n\n\n\n\n\n\n\n\n\n\n\n(47)\n\n\nIn respect of data collated and processed through the electronic systems of Eudamed, Directive\u00a095/46/EC of the European Parliament and of the Council\u00a0(22) applies to the processing of personal data carried out in the Member\u00a0States, under the supervision of the Member\u00a0States' competent authorities, in particular the public independent authorities designated by the Member\u00a0States. Regulation\u00a0(EC)\u00a0No\u00a045/2001 of the European Parliament and of the Council\u00a0(23) applies to the processing of personal data carried out by the Commission within the framework of this Regulation, under the supervision of the European Data Protection Supervisor. In accordance with Regulation\u00a0(EC)\u00a0No\u00a045/2001, the Commission should be designated as the controller of Eudamed and its electronic systems.\n\n\n\n\n\n\n\n\n\n\n\n\n(48)\n\n\nFor implantable devices and for class III devices, manufacturers should summarise the main safety and performance aspects of the device and the outcome of the clinical evaluation in a document that should be publicly available.\n\n\n\n\n\n\n\n\n\n\n\n\n(49)\n\n\nThe summary of safety and clinical performance for a device should include in particular the place of the device in the context of diagnostic or therapeutic options taking into account the clinical evaluation of that device when compared to the diagnostic or therapeutic alternatives and the specific conditions under which that device and its alternatives can be considered.\n\n\n\n\n\n\n\n\n\n\n\n\n(50)\n\n\nThe proper functioning of notified bodies is crucial for ensuring a high level of health and safety protection and citizens' confidence in the system. Designation and monitoring of notified bodies by the Member\u00a0States, in accordance with detailed and strict criteria, should therefore be subject to controls at Union level.\n\n\n\n\n\n\n\n\n\n\n\n\n(51)\n\n\nNotified bodies' assessments of manufacturers' technical documentation, in particular documentation on clinical evaluation, should be critically evaluated by the authority responsible for notified bodies. That evaluation should be part of the risk-based approach to the oversight and monitoring activities of notified bodies and should be based on sampling of the relevant documentation.\n\n\n\n\n\n\n\n\n\n\n\n\n(52)\n\n\nThe position of notified bodies vis-\u00e0-vis manufacturers should be strengthened, including with regard to their right and duty to carry out unannounced on-site audits and to conduct physical or laboratory tests on devices to ensure continuous compliance by manufacturers after receipt of the original certification.\n\n\n\n\n\n\n\n\n\n\n\n\n(53)\n\n\nTo increase transparency with regard to the oversight of notified bodies by national authorities, the authorities responsible for notified bodies should publish information on the national measures governing the assessment, designation and monitoring of notified bodies. In accordance with good administrative practice, this information should be kept up to date by those authorities in particular to reflect relevant, significant or substantive changes to the procedures in question.\n\n\n\n\n\n\n\n\n\n\n\n\n(54)\n\n\nThe Member\u00a0State in which a notified body is established should be responsible for enforcing the requirements of this Regulation with regard to that notified body.\n\n\n\n\n\n\n\n\n\n\n\n\n(55)\n\n\nIn view, in particular, of the responsibility of Member\u00a0States for the organisation and delivery of health services and medical care, they should be allowed to lay down additional requirements on notified bodies designated for the conformity assessment of devices and established on their territory as far as issues that are not regulated in this Regulation are concerned. Any such additional requirements laid down should not affect more specific horizontal Union legislation on notified bodies and equal treatment of notified bodies.\n\n\n\n\n\n\n\n\n\n\n\n\n(56)\n\n\nFor class III implantable devices and class IIb active devices intended to administer and/or remove a medicinal product, notified bodies should, except in certain cases, be obliged to request expert panels to scrutinise their clinical evaluation assessment report. Competent authorities should be informed about devices that have been granted a certificate following a conformity assessment procedure involving an expert panel. The consultation of expert panels in relation to the clinical evaluation should lead to a harmonised evaluation of high-risk medical devices by sharing expertise on clinical aspects and developing CS on categories of devices that have undergone that consultation process.\n\n\n\n\n\n\n\n\n\n\n\n\n(57)\n\n\nFor class\u00a0III devices and for certain class\u00a0IIb devices, a manufacturer should be able to consult voluntarily an expert panel, prior to that manufacturer's clinical evaluation and/or investigation, on its clinical development strategy and on proposals for clinical investigations.\n\n\n\n\n\n\n\n\n\n\n\n\n(58)\n\n\nIt is necessary, in particular for the purpose of the conformity assessment procedures, to maintain the division of devices into four product classes in line with international practice. The classification rules, which are based on the vulnerability of the human body, should take into account the potential risks associated with the technical design and manufacture of the devices. To maintain the same level of safety as provided by Directive\u00a090/385/EEC, active implantable devices should be in the highest risk class.\n\n\n\n\n\n\n\n\n\n\n\n\n(59)\n\n\nRules under the old regime applied to invasive devices do not sufficiently take account of the level of invasiveness and potential toxicity of certain devices which are introduced into the human body. In order to obtain a suitable risk-based classification of devices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body, it is necessary to introduce specific classification rules for such devices. The classification rules should take into account the place where the device performs its action in or on the human body, where it is introduced or applied, and whether a systemic absorption of the substances of which the device is composed, or of the products of metabolism in the human body of those substances occurs.\n\n\n\n\n\n\n\n\n\n\n\n\n(60)\n\n\nThe conformity assessment procedure for class I devices should be carried out, as a general rule, under the sole responsibility of manufacturers in view of the low level of vulnerability associated with such devices. For class\u00a0IIa, class\u00a0IIb and class\u00a0III devices, an appropriate level of involvement of a notified body should be compulsory.\n\n\n\n\n\n\n\n\n\n\n\n\n(61)\n\n\nThe conformity assessment procedures for devices should be further strengthened and streamlined whilst the requirements for notified bodies as regards the performance of their assessments should be clearly specified to ensure a level playing field.\n\n\n\n\n\n\n\n\n\n\n\n\n(62)\n\n\nIt is appropriate that certificates of free sale contain information that makes it possible to use Eudamed in order to obtain information on the device, in particular with regard to whether it is on the market, withdrawn from the market or recalled, and on any certificate on its conformity.\n\n\n\n\n\n\n\n\n\n\n\n\n(63)\n\n\nTo ensure a high level of safety and performance, demonstration of compliance with the general safety and performance requirements laid down in this Regulation should be based on clinical data that, for class\u00a0III\u00a0devices and implantable devices should, as a general rule, be sourced from clinical investigations that have been carried out under the responsibility of a sponsor. It should be possible both for the manufacturer and for another natural or legal person to be the sponsor taking responsibility for the clinical investigation.\n\n\n\n\n\n\n\n\n\n\n\n\n(64)\n\n\nThe rules on clinical investigations should be in line with well-established international guidance in this field, such as the international standard ISO\u00a014155:2011 on good clinical practice for clinical investigations of medical devices for human subjects, so as to make it easier for the results of clinical investigations conducted in the Union to be accepted as documentation outside the Union and to make it easier for the results of clinical investigations conducted outside the Union in accordance with international guidelines to be accepted within the Union. In addition, the rules should be in line with the most recent version of the World Medical Association Declaration of Helsinki on Ethical Principles for Medical Research Involving Human Subjects.\n\n\n\n\n\n\n\n\n\n\n\n\n(65)\n\n\nIt should be left to the Member\u00a0State where a clinical investigation is to be conducted to determine the appropriate authority to be involved in the assessment of the application to conduct a clinical investigation and to organise the involvement of ethics committees within the timelines for the authorisation of that clinical investigation as set out in this Regulation. Such decisions are a matter of internal organisation for each Member\u00a0State. In that context, Member\u00a0States should ensure the involvement of laypersons, in particular patients or patients' organisations. They should also ensure that the necessary expertise is available.\n\n\n\n\n\n\n\n\n\n\n\n\n(66)\n\n\nWhere, in the course of a clinical investigation, harm caused to a subject leads to the civil or criminal liability of the investigator or the sponsor being invoked, the conditions for liability in such cases, including issues of causality and the level of damages and sanctions, should remain governed by national law.\n\n\n\n\n\n\n\n\n\n\n\n\n(67)\n\n\nAn electronic system should be set up at Union level to ensure that every clinical investigation is recorded and reported in a publicly accessible database. To protect the right to the protection of personal data, recognised by Article\u00a08 of the Charter of Fundamental Rights of the European Union (\u2018the Charter\u2019), no personal data of subjects participating in a clinical investigation should be recorded in the electronic system. To ensure synergies with the area of clinical trials on medicinal products, the electronic system on clinical investigations should be interoperable with the EU database to be set up for clinical trials on medicinal products for human use.\n\n\n\n\n\n\n\n\n\n\n\n\n(68)\n\n\nWhere a clinical investigation is to be conducted in more than one Member\u00a0State, the sponsor should have the possibility of submitting a single application in order to reduce administrative burden. In order to allow for resource-sharing and to ensure consistency regarding the assessment of the health and safety-related aspects of the investigational device and of the scientific design of that clinical investigation, the procedure for the assessment of such single application should be coordinated between the Member\u00a0States under the direction of a coordinating Member\u00a0State. Such coordinated assessment should not include the assessment of intrinsically national, local and ethical aspects of a clinical investigation, including informed consent. For an initial period of seven years from the date of application of this Regulation, Member\u00a0States should be able to participate on a voluntary basis in the coordinated assessment. After that period, all Member\u00a0States should be obliged to participate in the coordinated assessment. The Commission, based on the experience gained from the voluntary coordination between Member\u00a0States, should draw up a report on the application of the relevant provisions regarding the coordinated assessment procedure. In the event that the findings of the report are negative, the Commission should submit a proposal to extend the period of participation on a voluntary basis in the coordinated assessment procedure.\n\n\n\n\n\n\n\n\n\n\n\n\n(69)\n\n\nSponsors should report certain adverse events and device deficiencies that occur during clinical investigations to the Member\u00a0States in which those clinical investigations are being conducted. Member\u00a0States should have the possibility of terminating or suspending the investigations or revoking the authorisation for those investigations, if considered necessary to ensure a high level of protection of the subjects participating in a clinical investigation. Such information should be communicated to the other Member\u00a0States.\n\n\n\n\n\n\n\n\n\n\n\n\n(70)\n\n\nThe sponsor of a clinical investigation should submit a summary of results of the clinical investigation that is easily understandable for the intended user together with the clinical investigation report, where applicable, within the timelines laid down in this Regulation. Where it is not possible to submit the summary of the results within the defined timelines for scientific reasons, the sponsor should justify this and specify when the results will be submitted.\n\n\n\n\n\n\n\n\n\n\n\n\n(71)\n\n\nThis Regulation should cover clinical investigations intended to gather clinical evidence for the purpose of demonstrating conformity of devices and should also lay down basic requirements regarding ethical and scientific assessments for other types of clinical investigations of medical devices.\n\n\n\n\n\n\n\n\n\n\n\n\n(72)\n\n\nIncapacitated subjects, minors, pregnant women and breastfeeding women require specific protection measures. However, it should be left to Member\u00a0States to determine the legally designated representatives of incapacitated subjects and minors.\n\n\n\n\n\n\n\n\n\n\n\n\n(73)\n\n\nThe principles of replacement, reduction and refinement in the area of animal experimentation laid down in the Directive\u00a02010/63/EU of the European Parliament and of the Council\u00a0(24) should be observed. In particular, the unnecessary duplication of tests and studies should be avoided.\n\n\n\n\n\n\n\n\n\n\n\n\n(74)\n\n\nManufacturers should play an active role during the post-market phase by systematically and actively gathering information from post-market experience with their devices in order to update their technical documentation and cooperate with the national competent authorities in charge of vigilance and market surveillance activities. To this end, manufacturers should establish a comprehensive post-market surveillance system, set up under their quality management system and based on a post-market surveillance plan. Relevant data and information gathered through post-market surveillance, as well as lessons learned from any implemented preventive and/or corrective actions, should be used to update any relevant part of technical documentation, such as those relating to risk assessment and clinical evaluation, and should also serve the purpose of transparency.\n\n\n\n\n\n\n\n\n\n\n\n\n(75)\n\n\nIn order to better protect health and safety regarding devices on the market, the electronic system on vigilance for devices should be made more effective by creating a central portal at Union level for reporting serious incidents and field safety corrective actions.\n\n\n\n\n\n\n\n\n\n\n\n\n(76)\n\n\nMember\u00a0States should take appropriate measures to raise awareness among healthcare professionals, users and patients about the importance of reporting incidents. Healthcare professionals, users and patients should be encouraged and enabled to report suspected serious incidents at national level using harmonised formats. The national competent authorities should inform manufacturers of any suspected serious incidents and, where a manufacturer confirms that such an incident has occurred, the authorities concerned should ensure that appropriate follow-up action is taken in order to minimise recurrence of such incidents.\n\n\n\n\n\n\n\n\n\n\n\n\n(77)\n\n\nThe evaluation of reported serious incidents and field safety corrective actions should be conducted at national level but coordination should be ensured where similar incidents have occurred or field safety corrective actions have to be carried out in more than one Member\u00a0State, with the objective of sharing resources and ensuring consistency regarding the corrective action.\n\n\n\n\n\n\n\n\n\n\n\n\n(78)\n\n\nIn the context of the investigation of incidents, the competent authorities should take into account, where appropriate, the information provided by and views of relevant stakeholders, including patient and healthcare professionals' organisations and manufacturers' associations.\n\n\n\n\n\n\n\n\n\n\n\n\n(79)\n\n\nThe reporting of serious adverse events or device deficiencies during clinical investigations and the reporting of serious incidents occurring after a device has been placed on the market should be clearly distinguished to avoid double reporting.\n\n\n\n\n\n\n\n\n\n\n\n\n(80)\n\n\nRules on market surveillance should be included in this Regulation to reinforce the rights and obligations of the national competent authorities, to ensure effective coordination of their market surveillance activities and to clarify the applicable procedures.\n\n\n\n\n\n\n\n\n\n\n\n\n(81)\n\n\nAny statistically significant increase in the number or severity of incidents that are not serious or in expected side-effects that could have a significant impact on the benefit-risk analysis and which could lead to unacceptable risks should be reported to the competent authorities in order to permit their assessment and the adoption of appropriate measures.\n\n\n\n\n\n\n\n\n\n\n\n\n(82)\n\n\nAn expert committee, the Medical Device Coordination Group (MDCG), composed of persons designated by the Member\u00a0States based on their role and expertise in the field of medical devices including in vitro diagnostic medical devices, should be established to fulfil the tasks conferred on it by this Regulation and by Regulation\u00a0(EU)\u00a02017/746 of the European Parliament and of the Council\u00a0(25), to provide advice to the Commission and to assist the Commission and the Member\u00a0States in ensuring a harmonised implementation of this Regulation. The MDCG should be able to establish subgroups in order to have access to necessary in-depth technical expertise in the field of medical devices including in vitro diagnostic medical devices. When establishing subgroups, appropriate consideration should be given to the possibility of involving existing groups at Union level in the field of medical devices.\n\n\n\n\n\n\n\n\n\n\n\n\n(83)\n\n\nExpert panels and expert laboratories should be designated by the Commission on the basis of their up-to-date clinical, scientific or technical expertise, with the aim of providing scientific, technical and clinical assistance to the Commission, the MDCG, manufacturers and notified bodies in relation to the implementation of this Regulation. Moreover, expert panels should fulfil the tasks of providing an opinion on clinical evaluation assessment reports of notified bodies in the case of certain high-risk devices.\n\n\n\n\n\n\n\n\n\n\n\n\n(84)\n\n\nCloser coordination between national competent authorities through information exchange and coordinated assessments under the direction of a coordinating authority is essential for ensuring a consistently high level of health and safety protection within the internal market, in particular in the areas of clinical investigations and vigilance. The principle of coordinated exchange and assessment should also apply across other authority activities described in this Regulation, such as the designation of notified bodies and should be encouraged in the area of market surveillance of devices. Joint working, coordination and communication of activities should also lead to more efficient use of resources and expertise at national level.\n\n\n\n\n\n\n\n\n\n\n\n\n(85)\n\n\nThe Commission should provide scientific, technical and corresponding logistical support to coordinating national authorities and ensure that the regulatory system for devices is effectively and uniformly implemented at Union level based on sound scientific evidence.\n\n\n\n\n\n\n\n\n\n\n\n\n(86)\n\n\nThe Union and, where appropriate, the Member\u00a0States should actively participate in international regulatory cooperation in the field of medical devices to facilitate the exchange of safety-related information regarding medical devices and to foster the further development of international regulatory guidelines that promote the adoption in other jurisdictions of regulations that lead to a level of health and safety protection equivalent to that set by this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(87)\n\n\nMember\u00a0States should take all necessary measures to ensure that the provisions of this Regulation are implemented, including by laying down effective, proportionate and dissuasive penalties for their infringement.\n\n\n\n\n\n\n\n\n\n\n\n\n(88)\n\n\nWhilst this Regulation should not affect the right of Member\u00a0States to levy fees for activities at national level, Member\u00a0States should, in order to ensure transparency, inform the Commission and the other Member\u00a0States before they decide on the level and structure of such fees. In order to further ensure transparency, the structure and level of the fees should be publicly available on request.\n\n\n\n\n\n\n\n\n\n\n\n\n(89)\n\n\nThis Regulation respects the fundamental rights and observes the principles recognised in particular by the Charter and in particular human dignity, the integrity of the person, the protection of personal data, the freedom of art and science, the freedom to conduct business and the right to property. This Regulation should be applied by the Member\u00a0States in accordance with those rights and principles.\n\n\n\n\n\n\n\n\n\n\n\n\n(90)\n\n\nThe power to adopt delegated acts in accordance with Article\u00a0290 TFEU should be delegated to the Commission in order to amend certain non-essential provisions of this Regulation. It is of particular importance that the Commission carry out appropriate consultations during its preparatory work, including at expert level, and that those consultations be conducted in accordance with the principles laid down in the Interinstitutional Agreement of 13\u00a0April\u00a02016 on Better Law-Making\u00a0(26). In particular, to ensure equal participation in the preparation of delegated acts, the European Parliament and the Council receive all documents at the same time as Member\u00a0States' experts, and their experts systematically have access to meetings of Commission expert groups dealing with preparation of delegated acts.\n\n\n\n\n\n\n\n\n\n\n\n\n(91)\n\n\nIn order to ensure uniform conditions for the implementation of this Regulation, implementing powers should\u00a0be conferred on the Commission. Those powers should be exercised in accordance with Regulation\u00a0(EU)\u00a0No\u00a0182/2011 of the European Parliament and of the Council\u00a0(27).\n\n\n\n\n\n\n\n\n\n\n\n\n(92)\n\n\nThe advisory procedure should be used for implementing acts that set out the form and presentation of the data elements of manufacturers' summaries of safety and clinical performance, and that establish the model for certificates of free sale, given that such implementing acts are of a procedural nature and do not directly have an impact on health and safety at Union level.\n\n\n\n\n\n\n\n\n\n\n\n\n(93)\n\n\nThe Commission should adopt immediately applicable implementing acts where, in duly justified cases relating to the extension to the territory of the Union of a national derogation from the applicable conformity assessment procedures, imperative grounds of urgency so require.\n\n\n\n\n\n\n\n\n\n\n\n\n(94)\n\n\nIn order to enable it to designate issuing entities, expert panels and expert laboratories, implementing powers should be conferred on the Commission.\n\n\n\n\n\n\n\n\n\n\n\n\n(95)\n\n\nTo allow economic operators, especially SMEs, notified bodies, Member\u00a0States and the Commission to adapt to the changes introduced by this Regulation and to ensure its proper application, it is appropriate to provide for a sufficient transitional period for that adaptation and for the organisational arrangements that are to be made. However, certain parts of the Regulation that directly affect Member\u00a0States and the Commission should be implemented as soon as possible. It is also particularly important that, by the date of application of this Regulation, a sufficient number of notified bodies be designated in accordance with the new requirements so as to avoid any shortage of medical devices on the market. Nonetheless, it is necessary that any designation of a notified body in accordance with the requirements of this Regulation prior to the date of its application be without prejudice to the validity of the designation of those notified bodies under Directives\u00a090/385/EEC and 93/42/EEC and to their capacity to continue issuing valid certificates under those two Directives until the date of application of this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n(96)\n\n\nIn order to ensure a smooth transition to the new rules for registration of devices and of certificates, the obligation to submit the relevant information to the electronic systems set up at Union level pursuant to this Regulation should, in the event that the corresponding IT\u00a0systems are developed according to plan, only become fully effective from 18\u00a0months after the date of application of this Regulation. During this transitional period, certain provisions of Directives\u00a090/385/EEC and 93/42/EEC should remain in force. However, in order to avoid multiple registrations, economic operators and notified bodies who register in the relevant electronic systems set up at Union level pursuant to this Regulation should be considered to be in compliance with the registration requirements adopted by the Member\u00a0States pursuant to those provisions.\n\n\n\n\n\n\n\n\n\n\n\n\n(97)\n\n\nIn order to provide for a smooth introduction of the UDI system, the moment of application of the obligation to place the UDI carrier on the label of the device should vary from one to five years after the date of application of this Regulation depending upon the class of the device concerned.\n\n\n\n\n\n\n\n\n\n\n\n\n(98)\n\n\nDirectives\u00a090/385/EEC and 93/42/EEC should be repealed to ensure that only one set of rules applies to the placing of medical devices on the market and the related aspects covered by this Regulation. Manufacturers' obligations as regards the making available of documentation regarding devices they placed on the market and manufacturers' and Member\u00a0States' obligations as regards vigilance activities for devices placed on the market pursuant to those Directives should however continue to apply. While it should be left to Member\u00a0States to decide how to organise vigilance activities, it is desirable for them to have the possibility of reporting incidents related to devices placed on the market pursuant to the Directives using the same tools as those for reporting on devices placed on the market pursuant to this Regulation. It is furthermore appropriate, in order to ensure a smooth transition from the old regime to the new regime, to provide that Commission Regulation\u00a0(EU)\u00a0No\u00a0207/2012\u00a0(28) and Commission Regulation\u00a0(EU)\u00a0No\u00a0722/2012\u00a0(29) should remain in force and continue to apply unless and until repealed by implementing acts adopted by the Commission pursuant to this Regulation.\nDecision\u00a02010/227/EU adopted in implementation of those Directives and Directive\u00a098/79/EC should also remain in force and continue to apply until the date when Eudamed becomes fully functional. Conversely, no such maintenance in force is required for Commission Directives\u00a02003/12/EC\u00a0(30) and 2005/50/EC\u00a0(31) and Commission Implementing Regulation (EU)\u00a0No\u00a0920/2013\u00a0(32).\n\n\n\n\n\n\n\n\n\n\n\n\n(99)\n\n\nThe requirements of this Regulation should be applicable to all devices placed on the market or put into service from the date of application of this Regulation. However, in order to provide for a smooth transition it should be possible, for a limited period of time from that date, for devices to be placed on the market or put into service by virtue of a valid certificate issued pursuant to Directive\u00a090/385/EEC or pursuant to Directive\u00a093/42/EEC.\n\n\n\n\n\n\n\n\n\n\n\n\n(100)\n\n\nThe European Data Protection Supervisor has given an opinion\u00a0(33) pursuant to Article\u00a028(2) of\u00a0Regulation\u00a0(EC)\u00a0No\u00a045/2001.\n\n\n\n\n\n\n\n\n\n\n\n\n(101)\n\n\nSince the objectives of this Regulation, namely to ensure the smooth functioning of the internal market as regards medical devices and to ensure high standards of quality and safety for medical devices, thus ensuring a high level of protection of health and safety of patients, users and other persons, cannot be sufficiently achieved by the Member\u00a0States but can rather, by reason of its scale and effects, be better achieved at Union level, the Union may adopt measures, in accordance with the principle of subsidiarity as set out in Article\u00a05 of the Treaty on European Union. In accordance with the principle of proportionality, as set out in that Article, this Regulation does not go beyond what is necessary in order to achieve those objectives,\n\n\n\n\n\nHAVE ADOPTED THIS REGULATION:\n\n\n\nCHAPTER I\n\n\nSCOPE AND DEFINITIONS\n\n\n\nArticle\u00a01\n\nSubject matter and scope\n\n\n1.\u00a0\u00a0\u00a0This Regulation lays down rules concerning the placing on the market, making available on the market or putting into service of medical devices for human use and accessories for such devices in the Union. This Regulation also applies to clinical investigations concerning such medical devices and accessories conducted in the Union.\n\n\n2.\u00a0\u00a0\u00a0This Regulation shall also apply, as from the date of application of common specifications adopted pursuant to Article\u00a09, to the groups of products without an intended medical purpose that are listed in Annex\u00a0XVI, taking into account the state of the art, and in particular existing harmonised standards for analogous devices with a medical purpose, based on similar technology. The common specifications for each of the groups of products listed in Annex\u00a0XVI shall address, at least, application of risk management as set out in Annex\u00a0I for the group of products in question and, where necessary, clinical evaluation regarding safety.\nThe necessary common specifications shall be adopted by 26 May 2020. They shall apply as from six months after the date of their entry into force or from 26 May 2020, whichever is the latest.\nNotwithstanding Article\u00a0122, Member\u00a0States' measures regarding the qualification of the products covered by Annex\u00a0XVI as medical devices pursuant to Directive\u00a093/42/EEC shall remain valid until the date of application, as referred to in the first subparagraph, of the relevant common specifications for that group of products.\nThis Regulation also applies to clinical investigations conducted in the Union concerning the products referred to in the first subparagraph.\n\n\n3.\u00a0\u00a0\u00a0Devices with both a medical and a non-medical intended purpose shall fulfil cumulatively the requirements applicable to devices with an intended medical purpose and those applicable to devices without an intended medical purpose.\n\n\n4.\u00a0\u00a0\u00a0For the purposes of this Regulation, medical devices, accessories for medical devices, and products listed in Annex\u00a0XVI to which this Regulation applies pursuant to paragraph\u00a02 shall hereinafter be referred to as \u2018devices\u2019.\n\n\n5.\u00a0\u00a0\u00a0Where justified on account of the similarity between a device with an intended medical purpose placed on the market and a product without an intended medical purpose in respect of their characteristics and risks, the Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 to amend the list in Annex\u00a0XVI, by adding new groups of products, in order to protect the health and safety of users or other persons or other aspects of public health.\n\n\n6.\u00a0\u00a0\u00a0This Regulation does not apply to:\n\n\n\n\n\n\n(a)\n\n\n\nin vitro diagnostic medical devices covered by Regulation\u00a0(EU)\u00a02017/746;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nmedicinal products as defined in point\u00a02 of Article\u00a01 of Directive\u00a02001/83/EC. In deciding whether a product falls under Directive\u00a02001/83/EC or under this Regulation, particular account shall be taken of the principal mode of action of the product;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nadvanced therapy medicinal products covered by Regulation\u00a0(EC)\u00a0No\u00a01394/2007;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nhuman blood, blood products, plasma or blood cells of human origin or devices which incorporate, when placed on the market or put into service, such blood products, plasma or cells, except for devices referred to in paragraph\u00a08 of this Article;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\ncosmetic products covered by Regulation\u00a0(EC)\u00a0No\u00a01223/2009;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\ntransplants, tissues or cells of animal origin, or their derivatives, or products containing or consisting of them; however this Regulation does apply to devices manufactured utilising tissues or cells of animal origin, or their derivatives, which are non-viable or are rendered non-viable;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\ntransplants, tissues or cells of human origin, or their derivatives, covered by Directive\u00a02004/23/EC, or products containing or consisting of them; however this Regulation does apply to devices manufactured utilising derivatives of tissues or cells of human origin which are non-viable or are rendered non-viable;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nproducts, other than those referred to in points (d), (f) and (g), that contain or consist of viable biological material or viable organisms, including living micro-organisms, bacteria, fungi or viruses in order to achieve or support the intended purpose of the product;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nfood covered by Regulation (EC)\u00a0No\u00a0178/2002.\n\n\n\n\n\n\n7.\u00a0\u00a0\u00a0Any device which, when placed on the market or put into service, incorporates as an integral part an in vitro diagnostic medical device as defined in point\u00a02 of Article\u00a02 of Regulation\u00a0(EU)\u00a02017/746, shall be governed by this Regulation. The requirements of Regulation\u00a0(EU)\u00a02017/746 shall apply to the in vitro diagnostic medical device part of the device.\n\n\n8.\u00a0\u00a0\u00a0Any device which, when placed on the market or put into service, incorporates, as an integral part, a substance which, if used separately, would be considered to be a medicinal product as defined in point\u00a02 of Article\u00a01 of Directive\u00a02001/83/EC, including a medicinal product derived from human blood or human plasma as defined in point\u00a010 of Article\u00a01 of that Directive, and that has an action ancillary to that of the device, shall be assessed and authorised in accordance with this Regulation.\nHowever, if the action of that substance is principal and not ancillary to that of the device, the integral product shall be governed by Directive\u00a02001/83/EC or Regulation\u00a0(EC)\u00a0No\u00a0726/2004 of the European Parliament and of the Council\u00a0(34), as applicable. In that case, the relevant general safety and performance requirements set out in Annex\u00a0I to this Regulation shall apply as far as the safety and performance of the device part are concerned.\n\n\n9.\u00a0\u00a0\u00a0Any device which is intended to administer a medicinal product as defined in point\u00a02 of Article\u00a01 of Directive\u00a02001/83/EC shall be governed by this Regulation, without prejudice to the provisions of that Directive\u00a0and of Regulation\u00a0(EC)\u00a0No\u00a0726/2004 with regard to the medicinal product.\nHowever, if the device intended to administer a medicinal product and the medicinal product are placed on the market in such a way that they form a single integral product which is intended exclusively for use in the given combination and which is not reusable, that single integral product shall be governed by Directive\u00a02001/83/EC or Regulation\u00a0(EC)\u00a0No\u00a0726/2004, as applicable. In that case, the relevant general safety and performance requirements set out in Annex\u00a0I to this Regulation shall apply as far as the safety and performance of the device part of the single integral product are concerned.\n\n\n10.\u00a0\u00a0\u00a0Any device which, when placed on the market or put into service, incorporates, as an integral part, non-viable tissues or cells of human origin or their derivatives that have an action ancillary to that of the device shall be assessed and authorised in accordance with this Regulation. In that case, the provisions for donation, procurement and testing laid down in Directive\u00a02004/23/EC shall apply.\nHowever, if the action of those tissues or cells or their derivatives is principal and not ancillary to that of the device and the product is not governed by Regulation\u00a0(EC)\u00a0No\u00a01394/2007, the product shall be governed by Directive\u00a02004/23/EC. In that case, the relevant general safety and performance requirements set out in Annex\u00a0I to this Regulation shall apply as far as the safety and performance of the device part are concerned.\n\n\n11.\u00a0\u00a0\u00a0This Regulation is specific Union legislation within the meaning of Article\u00a02(3) of Directive\u00a02014/30/EU.\n\n\n12.\u00a0\u00a0\u00a0Devices that are also machinery within the meaning of point\u00a0(a) of the second paragraph\u00a0of Article\u00a02 of Directive\u00a02006/42/EC of the European Parliament and of the Council\u00a0(35) shall, where a hazard relevant under that Directive\u00a0exists, also meet the essential health and safety requirements set out in Annex\u00a0I to that Directive\u00a0to the extent to which those requirements are more specific than the general safety and performance requirements set out in Chapter\u00a0II of Annex\u00a0I to this Regulation.\n\n\n13.\u00a0\u00a0\u00a0This Regulation shall not affect the application of Directive\u00a02013/59/Euratom.\n\n\n14.\u00a0\u00a0\u00a0This Regulation shall not affect the right of a Member\u00a0State to restrict the use of any specific type of device in relation to aspects not covered by this Regulation.\n\n\n15.\u00a0\u00a0\u00a0This Regulation shall not affect national law concerning the organisation, delivery or financing of health services and medical care, such as the requirement that certain devices may only be supplied on a medical prescription, the requirement that only certain health professionals or healthcare institutions may dispense or use certain devices or that their use be accompanied by specific professional counselling.\n\n\n16.\u00a0\u00a0\u00a0Nothing in this Regulation shall restrict the freedom of the press or the freedom of expression in the media in so far as those freedoms are guaranteed in the Union and in the Member\u00a0States, in particular under Article\u00a011 of the Charter of Fundamental Rights of the European Union.\n\n\n\nArticle\u00a02\n\nDefinitions\n\nFor the purposes of this Regulation, the following definitions apply:\n\n\n\n\n\n\n(1)\n\n\n\u2018medical device\u2019 means any instrument, apparatus, appliance, software, implant, reagent, material or other article intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the following specific medical purposes:\n\n\n\n\n\n\n\u2014\n\n\ndiagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndiagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninvestigation, replacement or modification of the anatomy or of a physiological or pathological process or state,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nproviding information by means of in vitro examination of specimens derived from the human body, including organ, blood and tissue donations,\n\n\n\n\nand which does not achieve its principal intended action by pharmacological, immunological or metabolic means, in or on the human body, but which may be assisted in its function by such means.\nThe following products shall also be deemed to be medical devices:\n\n\n\n\n\n\n\u2014\n\n\ndevices for the control or support of conception;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nproducts specifically intended for the cleaning, disinfection or sterilisation of devices as referred to in Article\u00a01(4) and of those referred to in the first paragraph\u00a0of this point.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(2)\n\n\n\u2018accessory for a medical device\u2019 means an article which, whilst not being itself a medical device, is intended by its manufacturer to be used together with one or several particular medical device(s) to specifically enable the medical device(s) to be used in accordance with its/their intended purpose(s) or to specifically and directly assist the medical functionality of the medical device(s) in terms of its/their intended purpose(s);\n\n\n\n\n\n\n\n\n\n\n(3)\n\n\n\u2018custom-made device\u2019 means any device specifically made in accordance with a written prescription of any person authorised by national law by virtue of that person's professional qualifications which gives, under that person's responsibility, specific design characteristics, and is intended for the sole use of a particular patient exclusively to meet their individual conditions and needs.\nHowever, mass-produced devices which need to be adapted to meet the specific requirements of any professional user and devices which are mass-produced by means of industrial manufacturing processes in accordance with the written prescriptions of any authorised person shall not be considered to be custom-made devices;\n\n\n\n\n\n\n\n\n\n\n(4)\n\n\n\u2018active device\u2019 means any device, the operation of which depends on a source of energy other than that generated by the human body for that purpose, or by gravity, and which acts by changing the density of or converting that energy. Devices intended to transmit energy, substances or other elements between an active device and the patient, without any significant change, shall not be deemed to be active devices.\nSoftware shall also be deemed to be an active device;\n\n\n\n\n\n\n\n\n\n\n(5)\n\n\n\u2018implantable device\u2019 means any device, including those that are partially or wholly absorbed, which is intended:\n\n\n\n\n\n\n\u2014\n\n\nto be totally introduced into the human body, or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nto replace an epithelial surface or the surface of the eye,\n\n\n\n\nby clinical intervention and which is intended to remain in place after the procedure.\nAny device intended to be partially introduced into the human body by clinical intervention and intended to remain in place after the procedure for at least 30\u00a0days shall also be deemed to be an implantable device;\n\n\n\n\n\n\n\n\n\n\n(6)\n\n\n\u2018invasive device\u2019 means any device which, in whole or in part, penetrates inside the body, either through a body orifice or through the surface of the body;\n\n\n\n\n\n\n\n\n\n\n(7)\n\n\n\u2018generic device group\u2019 means a set of devices having the same or similar intended purposes or a commonality of technology allowing them to be classified in a generic manner not reflecting specific characteristics;\n\n\n\n\n\n\n\n\n\n\n(8)\n\n\n\u2018single-use device\u2019 means a device that is intended to be used on one individual during a single procedure;\n\n\n\n\n\n\n\n\n\n\n(9)\n\n\n\u2018falsified device\u2019 means any device with a false presentation of its identity and/or of its source and/or its CE\u00a0marking certificates or documents relating to CE\u00a0marking procedures. This definition does not include unintentional non-compliance and is without prejudice to infringements of intellectual property rights;\n\n\n\n\n\n\n\n\n\n\n(10)\n\n\n\u2018procedure pack\u2019 means a combination of products packaged together and placed on the market with the purpose of being used for a specific medical purpose;\n\n\n\n\n\n\n\n\n\n\n(11)\n\n\n\u2018system\u2019 means a combination of products, either packaged together or not, which are intended to be inter-connected or combined to achieve a specific medical purpose;\n\n\n\n\n\n\n\n\n\n\n(12)\n\n\n\u2018intended purpose\u2019 means the use for which a device is intended according to the data supplied by the manufacturer on the label, in the instructions for use or in promotional or sales materials or statements and as specified by the manufacturer in the clinical evaluation;\n\n\n\n\n\n\n\n\n\n\n(13)\n\n\n\u2018label\u2019 means the written, printed or graphic information appearing either on the device itself, or on the packaging of each unit or on the packaging of multiple devices;\n\n\n\n\n\n\n\n\n\n\n(14)\n\n\n\u2018instructions for use\u2019 means the information provided by the manufacturer to inform the user of a device's intended purpose and proper use and of any precautions to be taken;\n\n\n\n\n\n\n\n\n\n\n(15)\n\n\n\u2018Unique Device Identifier\u2019 (\u2018UDI\u2019) means a series of numeric or alphanumeric characters that is created through internationally accepted device identification and coding standards and that allows unambiguous identification of specific devices on the market;\n\n\n\n\n\n\n\n\n\n\n(16)\n\n\n\u2018non-viable\u2019 means having no potential for metabolism or multiplication;\n\n\n\n\n\n\n\n\n\n\n(17)\n\n\n\u2018derivative\u2019 means a \u2018non-cellular substance\u2019 extracted from human or animal tissue or cells through a manufacturing process. The final substance used for manufacturing of the device in this case does not contain any cells or tissues;\n\n\n\n\n\n\n\n\n\n\n(18)\n\n\n\u2018nanomaterial\u2019 means a natural, incidental or manufactured material containing particles in an unbound state or as an aggregate or as an agglomerate and where, for\u00a050 % or more of the particles in the number size distribution, one or more external dimensions is in the size range 1-100\u00a0nm;\nFullerenes, graphene flakes and single-wall carbon nanotubes with one or more external dimensions below 1\u00a0nm shall also be deemed to be nanomaterials;\n\n\n\n\n\n\n\n\n\n\n(19)\n\n\n\u2018particle\u2019, for the purposes of the definition of nanomaterial in point\u00a0(18), means a minute piece of matter with defined physical boundaries;\n\n\n\n\n\n\n\n\n\n\n(20)\n\n\n\u2018agglomerate\u2019, for the purposes of the definition of nanomaterial in point\u00a0(18), means a collection of weakly bound particles or aggregates where the resulting external surface area is similar to the sum of the surface areas of the individual components;\n\n\n\n\n\n\n\n\n\n\n(21)\n\n\n\u2018aggregate\u2019, for the purposes of the definition of nanomaterial in point\u00a0(18), means a particle comprising of strongly bound or fused particles;\n\n\n\n\n\n\n\n\n\n\n(22)\n\n\n\u2018performance\u2019 means the ability of a device to achieve its intended purpose as stated by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(23)\n\n\n\u2018risk\u2019 means the combination of the probability of occurrence of harm and the severity of that harm;\n\n\n\n\n\n\n\n\n\n\n(24)\n\n\n\u2018benefit-risk determination\u2019 means the analysis of all assessments of benefit and risk of possible relevance for the use of the device for the intended purpose, when used in accordance with the intended purpose given by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(25)\n\n\n\u2018compatibility\u2019 is the ability of a device, including software, when used together with one or more other devices in accordance with its intended purpose, to:\n\n\n\n\n\n\n(a)\n\n\nperform without losing or compromising the ability to perform as intended, and/or\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nintegrate and/or operate without the need for modification or adaption of any part of the combined devices, and/or\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nbe used together without conflict/interference or adverse reaction.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(26)\n\n\n\u2018interoperability\u2019 is the ability of two or more devices, including software, from the same manufacturer or from different manufacturers, to:\n\n\n\n\n\n\n(a)\n\n\nexchange information and use the information that has been exchanged for the correct execution of a specified function without changing the content of the data, and/or\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ncommunicate with each other, and/or\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nwork together as intended.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(27)\n\n\n\u2018making available on the market\u2019 means any supply of a device, other than an investigational device, for distribution, consumption or use on the Union market in the course of a commercial activity, whether in return for payment or free of charge;\n\n\n\n\n\n\n\n\n\n\n(28)\n\n\n\u2018placing on the market\u2019 means the first making available of a device, other than an investigational device, on the Union market;\n\n\n\n\n\n\n\n\n\n\n(29)\n\n\n\u2018putting into service\u2019 means the stage at which a device, other than an investigational device, has been made available to the final user as being ready for use on the Union market for the first time for its intended purpose;\n\n\n\n\n\n\n\n\n\n\n(30)\n\n\n\u2018manufacturer\u2019 means a natural or legal person who manufactures or fully refurbishes a device or has a device designed, manufactured or fully refurbished, and markets that device under its name or trademark;\n\n\n\n\n\n\n\n\n\n\n(31)\n\n\n\u2018fully refurbishing\u2019, for the purposes of the definition of manufacturer, means the complete rebuilding of a device already placed on the market or put into service, or the making of a new device from used devices, to bring it into conformity with this Regulation, combined with the assignment of a new lifetime to the refurbished device;\n\n\n\n\n\n\n\n\n\n\n(32)\n\n\n\u2018authorised representative\u2019 means any natural or legal person established within the Union who has received and accepted a written mandate from a manufacturer, located outside the Union, to act on the manufacturer's behalf in relation to specified tasks with regard to the latter's obligations under this Regulation;\n\n\n\n\n\n\n\n\n\n\n(33)\n\n\n\u2018importer\u2019 means any natural or legal person established within the Union that places a device from a third country on the Union market;\n\n\n\n\n\n\n\n\n\n\n(34)\n\n\n\u2018distributor\u2019 means any natural or legal person in the supply chain, other than the manufacturer or the importer, that makes a device available on the market, up until the point of putting into service;\n\n\n\n\n\n\n\n\n\n\n(35)\n\n\n\u2018economic operator\u2019 means a manufacturer, an authorised representative, an importer, a distributor or the person referred to in Article\u00a022(1) and 22(3);\n\n\n\n\n\n\n\n\n\n\n(36)\n\n\n\u2018health institution\u2019 means an organisation the primary purpose of which is the care or treatment of patients or the promotion of public health;\n\n\n\n\n\n\n\n\n\n\n(37)\n\n\n\u2018user\u2019 means any healthcare professional or lay person who uses a device;\n\n\n\n\n\n\n\n\n\n\n(38)\n\n\n\u2018lay person\u2019 means an individual who does not have formal education in a relevant field of healthcare or medical discipline;\n\n\n\n\n\n\n\n\n\n\n(39)\n\n\n\u2018reprocessing\u2019 means a process carried out on a used device in order to allow its safe reuse including cleaning, disinfection, sterilisation and related procedures, as well as testing and restoring the technical and functional safety of the used device;\n\n\n\n\n\n\n\n\n\n\n(40)\n\n\n\u2018conformity assessment\u2019 means the process demonstrating whether the requirements of this Regulation relating to a device have been fulfilled;\n\n\n\n\n\n\n\n\n\n\n(41)\n\n\n\u2018conformity assessment body\u2019 means a body that performs third-party conformity assessment activities including calibration, testing, certification and inspection;\n\n\n\n\n\n\n\n\n\n\n(42)\n\n\n\u2018notified body\u2019 means a conformity assessment body designated in accordance with this Regulation;\n\n\n\n\n\n\n\n\n\n\n(43)\n\n\n\u2018CE marking of conformity\u2019 or \u2018CE marking\u2019 means a marking by which a manufacturer indicates that a device is in conformity with the applicable requirements set out in this Regulation and other applicable Union harmonisation legislation providing for its affixing;\n\n\n\n\n\n\n\n\n\n\n(44)\n\n\n\u2018clinical evaluation\u2019 means a systematic and planned process to continuously generate, collect, analyse and assess the clinical data pertaining to a device in order to verify the safety and performance, including clinical benefits, of the device when used as intended by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(45)\n\n\n\u2018clinical investigation\u2019 means any systematic investigation involving one or more human subjects, undertaken to assess the safety or performance of a device;\n\n\n\n\n\n\n\n\n\n\n(46)\n\n\n\u2018investigational device\u2019 means a device that is assessed in a clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(47)\n\n\n\u2018clinical investigation plan\u2019 means a document that describes the rationale, objectives, design, methodology, monitoring, statistical considerations, organisation and conduct of a clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(48)\n\n\n\u2018clinical data\u2019 means information concerning safety or performance that is generated from the use of a device and is sourced from the following:\n\n\n\n\n\n\n\u2014\n\n\nclinical investigation(s) of the device concerned,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclinical investigation(s) or other studies reported in scientific literature, of a device for which equivalence to the device in question can be demonstrated,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreports published in peer reviewed scientific literature on other clinical experience of either the device in question or a device for which equivalence to the device in question can be demonstrated,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclinically relevant information coming from post-market surveillance, in particular the post-market clinical follow-up;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(49)\n\n\n\u2018sponsor\u2019 means any individual, company, institution or organisation which takes responsibility for the initiation, for the management and setting up of the financing of the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(50)\n\n\n\u2018subject\u2019 means an individual who participates in a clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(51)\n\n\n\u2018clinical evidence\u2019 means clinical data and clinical evaluation results pertaining to a device of a sufficient amount and quality to allow a qualified assessment of whether the device is safe and achieves the intended clinical benefit(s), when used as intended by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(52)\n\n\n\u2018clinical performance\u2019 means the ability of a device, resulting from any direct or indirect medical effects which stem from its technical or functional characteristics, including diagnostic characteristics, to achieve its intended purpose as claimed by the manufacturer, thereby leading to a clinical benefit for patients, when used as intended by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(53)\n\n\n\u2018clinical benefit\u2019 means the positive impact of a device on the health of an individual, expressed in terms of a meaningful, measurable, patient-relevant clinical outcome(s), including outcome(s) related to diagnosis, or a positive impact on patient management or public health;\n\n\n\n\n\n\n\n\n\n\n(54)\n\n\n\u2018investigator\u2019 means an individual responsible for the conduct of a clinical investigation at a clinical investigation site;\n\n\n\n\n\n\n\n\n\n\n(55)\n\n\n\u2018informed consent\u2019 means a subject's free and voluntary expression of his or her willingness to participate in a particular clinical investigation, after having been informed of all aspects of the clinical investigation that are relevant to the subject's decision to participate or, in the case of minors and of incapacitated subjects, an authorisation or agreement from their legally designated representative to include them in the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(56)\n\n\n\u2018ethics committee\u2019 means an independent body established in a Member\u00a0State in accordance with the law of that Member\u00a0State and empowered to give opinions for the purposes of this Regulation, taking into account the views of laypersons, in particular patients or patients' organisations;\n\n\n\n\n\n\n\n\n\n\n(57)\n\n\n\u2018adverse event\u2019 means any untoward medical occurrence, unintended disease or injury or any untoward clinical signs, including an abnormal laboratory finding, in subjects, users or other persons, in the context of a clinical investigation, whether or not related to the investigational device;\n\n\n\n\n\n\n\n\n\n\n(58)\n\n\n\u2018serious adverse event\u2019 means any adverse event that led to any of the following:\n\n\n\n\n\n\n(a)\n\n\ndeath,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nserious deterioration in the health of the subject, that resulted in any of the following:\n\n\n\n\n\n\n(i)\n\n\nlife-threatening illness or injury,\n\n\n\n\n\n\n\n\n\n\n(ii)\n\n\npermanent impairment of a body structure or a body function,\n\n\n\n\n\n\n\n\n\n\n(iii)\n\n\nhospitalisation or prolongation of patient hospitalisation,\n\n\n\n\n\n\n\n\n\n\n(iv)\n\n\nmedical or surgical intervention to prevent life-threatening illness or injury or permanent impairment to a body structure or a body function,\n\n\n\n\n\n\n\n\n\n\n(v)\n\n\nchronic disease,\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nfoetal distress, foetal death or a congenital physical or mental impairment or birth defect;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(59)\n\n\n\u2018device deficiency\u2019 means any inadequacy in the identity, quality, durability, reliability, safety or performance of an\u00a0investigational device, including malfunction, use errors or inadequacy in information supplied by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(60)\n\n\n\u2018post-market surveillance\u2019 means all activities carried out by manufacturers in cooperation with other economic operators to institute and keep up to date a systematic procedure to proactively collect and review experience gained from devices they place on the market, make available on the market or put into service for the purpose of identifying any need to immediately apply any necessary corrective or preventive actions;\n\n\n\n\n\n\n\n\n\n\n(61)\n\n\n\u2018market surveillance\u2019 means the activities carried out and measures taken by competent authorities to check and ensure that devices comply with the requirements set out in the relevant Union harmonisation legislation and do not endanger health, safety or any other aspect of public interest protection;\n\n\n\n\n\n\n\n\n\n\n(62)\n\n\n\u2018recall\u2019 means any measure aimed at achieving the return of a device that has already been made available to the end user;\n\n\n\n\n\n\n\n\n\n\n(63)\n\n\n\u2018withdrawal\u2019 means any measure aimed at preventing a device in the supply chain from being further made available on the market;\n\n\n\n\n\n\n\n\n\n\n(64)\n\n\n\u2018incident\u2019 means any malfunction or deterioration in the characteristics or performance of a device made available on the market, including use-error due to ergonomic features, as well as any inadequacy in the information supplied by the manufacturer and any undesirable side-effect;\n\n\n\n\n\n\n\n\n\n\n(65)\n\n\n\u2018serious incident\u2019 means any incident that directly or indirectly led, might have led or might lead to any of the following:\n\n\n\n\n\n\n(a)\n\n\nthe death of a patient, user or other person,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe temporary or permanent serious deterioration of a patient's, user's or other person's state of health,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\na serious public health threat;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(66)\n\n\n\u2018serious public health threat\u2019 means an event which could result in imminent risk of death, serious deterioration in a person's state of health, or serious illness, that may require prompt remedial action, and that may cause significant morbidity or mortality in humans, or that is unusual or unexpected for the given place and time;\n\n\n\n\n\n\n\n\n\n\n(67)\n\n\n\u2018corrective action\u2019 means action taken to eliminate the cause of a potential or actual non-conformity or other undesirable situation;\n\n\n\n\n\n\n\n\n\n\n(68)\n\n\n\u2018field safety corrective action\u2019 means corrective action taken by a manufacturer for technical or medical reasons to prevent or reduce the risk of a serious incident in relation to a device made available on the market;\n\n\n\n\n\n\n\n\n\n\n(69)\n\n\n\u2018field safety notice\u2019 means a communication sent by a manufacturer to users or customers in relation to a field safety corrective action;\n\n\n\n\n\n\n\n\n\n\n(70)\n\n\n\u2018harmonised standard\u2019 means a European standard as defined in point\u00a0(1)(c) of Article\u00a02 of Regulation\u00a0(EU)\u00a0No\u00a01025/2012;\n\n\n\n\n\n\n\n\n\n\n(71)\n\n\n\u2018common specifications\u2019 (CS) means a set of technical and/or clinical requirements, other than a standard, that provides a means of complying with the legal obligations applicable to a device, process or system.\n\n\n\n\n\n\nArticle\u00a03\n\nAmendment of certain definitions\n\nThe Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 in order to amend the definition of nanomaterial set out in point\u00a0(18) and the related definitions in points\u00a0(19), (20) and (21) of Article\u00a02 in the light of technical and scientific progress and taking into account definitions agreed at Union and international level.\n\n\nArticle\u00a04\n\nRegulatory status of products\n\n\n1.\u00a0\u00a0\u00a0Without prejudice to Article\u00a02(2) of Directive\u00a02001/83/EC, upon a duly substantiated request of a Member\u00a0State, the Commission shall, after consulting the Medical Device Coordination Group established under Article\u00a0103 of this Regulation\u00a0(\u2018MDCG\u2019), by means of implementing acts, determine whether or not a specific product, or category or group of products, falls within the definitions of \u2018medical device\u2019 or \u2018accessory for a medical device\u2019. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3) of this Regulation.\n\n\n2.\u00a0\u00a0\u00a0The Commission may also, on its own initiative, after consulting the MDCG, decide, by means of implementing acts, on the issues referred to in paragraph\u00a01 of this Article. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n3.\u00a0\u00a0\u00a0The Commission shall ensure that Member\u00a0States share expertise in the fields of medical devices, in vitro diagnostic medical devices, medicinal products, human tissues and cells, cosmetics, biocides, food and, if necessary, other products, in order to determine the appropriate regulatory status of a product, or category or group of products.\n\n\n4.\u00a0\u00a0\u00a0When deliberating on the possible regulatory status as a device of products involving medicinal products, human tissues and cells, biocides or food products, the Commission shall ensure an appropriate level of consultation of the European Medicines Agency\u00a0(EMA), the European Chemicals Agency\u00a0(ECHA) and the European Food Safety Authority\u00a0(EFSA), as relevant.\n\n\n\n\nCHAPTER II\n\n\nMAKING AVAILABLE ON THE MARKET AND PUTTING INTO SERVICE OF DEVICES, OBLIGATIONS OF ECONOMIC OPERATORS, REPROCESSING, CE MARKING, FREE MOVEMENT\n\n\n\nArticle\u00a05\n\nPlacing on the market and putting into service\n\n\n1.\u00a0\u00a0\u00a0A device may be placed on the market or put into service only if it complies with this Regulation when duly supplied and properly installed, maintained and used in accordance with its intended purpose.\n\n\n2.\u00a0\u00a0\u00a0A device shall meet the general safety and performance requirements set out in Annex\u00a0I which apply to it, taking into account its intended purpose.\n\n\n3.\u00a0\u00a0\u00a0Demonstration of conformity with the general safety and performance requirements shall include a clinical evaluation in accordance with Article\u00a061.\n\n\n4.\u00a0\u00a0\u00a0Devices that are manufactured and used within health institutions shall be considered as having been put into service.\n\n\n5.\u00a0\u00a0\u00a0With the exception of the relevant general safety and performance requirements set out in Annex\u00a0I, the requirements of this Regulation shall not apply to devices, manufactured and used only within health institutions established in the Union, provided that all of the following conditions are met:\n\n\n\n\n\n\n(a)\n\n\nthe devices are not transferred to another legal entity,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nmanufacture and use of the devices occur under appropriate quality management systems,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe health institution justifies in its documentation that the target patient group's specific needs cannot be met, or cannot be met at the appropriate level of performance by an equivalent device available on the market,\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe health institution provides information upon request on the use of such devices to its competent authority, which shall include a justification of their manufacturing, modification and use;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe health institution draws up a declaration which it shall make publicly available, including:\n\n\n\n\n\n\n(i)\n\n\nthe name and address of the manufacturing health institution;\n\n\n\n\n\n\n\n\n\n\n(ii)\n\n\nthe details necessary to identify the devices;\n\n\n\n\n\n\n\n\n\n\n(iii)\n\n\na declaration that the devices meet the general safety and performance requirements set out in Annex\u00a0I to this Regulation and, where applicable, information on which requirements are not fully met with a reasoned justification therefor,\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe health institution draws up documentation that makes it possible to have an understanding of the manufacturing facility, the manufacturing process, the design and performance data of the devices, including the intended purpose, and that is sufficiently detailed to enable the competent authority to ascertain that the general safety and performance requirements set out in Annex\u00a0I to this Regulation are met;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthe health institution takes all necessary measures to ensure that all devices are manufactured in accordance with the documentation referred to in point\u00a0(f), and\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe health institution reviews experience gained from clinical use of the devices and takes all necessary corrective actions.\n\n\n\n\nMember\u00a0States may require that such health institutions submit to the competent authority any further relevant information about such devices which have been manufactured and used on their territory. Member\u00a0States shall retain the right to restrict the manufacture and the use of any specific type of such devices and shall be permitted access to inspect the activities of the health institutions.\nThis paragraph\u00a0shall not apply to devices that are manufactured on an industrial scale.\n\n\n6.\u00a0\u00a0\u00a0In order to ensure the uniform application of Annex\u00a0I, the Commission may adopt implementing acts to the extent necessary to resolve issues of divergent interpretation and of practical application. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a06\n\nDistance sales\n\n\n1.\u00a0\u00a0\u00a0A device offered by means of information society services, as defined in point\u00a0(b) of Article\u00a01(1) of Directive\u00a0(EU)\u00a02015/1535, to a natural or legal person established in the Union shall comply with this Regulation.\n\n\n2.\u00a0\u00a0\u00a0Without prejudice to national law regarding the exercise of the medical profession, a device that is not placed on the market but used in the context of a commercial activity, whether in return for payment or free of charge, for the provision of a diagnostic or therapeutic service offered by means of information society services as defined in point\u00a0(b) of Article\u00a01(1) of Directive\u00a0(EU)\u00a02015/1535 or by other means of communication, directly or through intermediaries, to a natural or legal person established in the Union shall comply with this Regulation.\n\n\n3.\u00a0\u00a0\u00a0Upon request by a competent authority, any natural or legal person offering a device in accordance with paragraph\u00a01 or providing a service in accordance with paragraph\u00a02 shall make available a copy of the EU\u00a0declaration of conformity of the device concerned.\n\n\n4.\u00a0\u00a0\u00a0A Member\u00a0State may, on grounds of protection of public health, require a provider of information society services, as defined in point\u00a0(b) of Article\u00a01(1) of Directive\u00a0(EU)\u00a02015/1535, to cease its activity.\n\n\n\nArticle\u00a07\n\nClaims\n\nIn the labelling, instructions for use, making available, putting into service and advertising of devices, it shall be prohibited to use text, names, trademarks, pictures and figurative or other signs that may mislead the user or the patient with regard to the device's intended purpose, safety and performance by:\n\n\n\n\n\n\n(a)\n\n\nascribing functions and properties to the device which the device does not have;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ncreating a false impression regarding treatment or diagnosis, functions or properties which the device does not have;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nfailing to inform the user or the patient of a likely risk associated with the use of the device in line with its intended purpose;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nsuggesting uses for the device other than those stated to form part of the intended purpose for which the conformity assessment was carried out.\n\n\n\n\n\n\nArticle\u00a08\n\nUse of harmonised standards\n\n\n1.\u00a0\u00a0\u00a0Devices that are in conformity with the relevant harmonised standards, or the relevant parts of those standards, the references of which have been published in the Official Journal of the European Union, shall be presumed to be in conformity with the requirements of this Regulation covered by those standards or parts thereof.\nThe first subparagraph\u00a0shall also apply to system or process requirements to be fulfilled in accordance with this Regulation by economic operators or sponsors, including those relating to quality management systems, risk management, post-market surveillance systems, clinical investigations, clinical evaluation or post-market clinical follow-up\u00a0(\u2018PMCF\u2019).\nReferences in this Regulation to harmonised standards shall be understood as meaning harmonised standards the references of which have been published in the Official Journal of the European Union.\n\n\n2.\u00a0\u00a0\u00a0References in this Regulation to harmonised standards shall also include the monographs of the European Pharmacopoeia adopted in accordance with the Convention on the Elaboration of a European Pharmacopoeia, in particular on surgical sutures and on interaction between medicinal products and materials used in devices containing such medicinal products, provided that references to those monographs have been published in the Official Journal of the European Union.\n\n\n\nArticle\u00a09\n\nCommon specifications\n\n\n1.\u00a0\u00a0\u00a0Without prejudice to Article\u00a01(2) and 17(5) and the deadline laid down in those provisions, where no harmonised standards exist or where relevant harmonised standards are not sufficient, or where there is a need to address public health concerns, the Commission, after having consulted the MDCG, may, by means of implementing acts, adopt common specifications (CS) in respect of the general safety and performance requirements set out in Annex\u00a0I, the technical documentation set out in Annexes\u00a0II and III, the clinical evaluation and post-market clinical follow-up set out in Annex\u00a0XIV or the requirements regarding clinical investigation set out in Annex\u00a0XV. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n2.\u00a0\u00a0\u00a0Devices that are in conformity with the CS referred to in paragraph\u00a01 shall be presumed to be in conformity with the requirements of this Regulation covered by those CS or the relevant parts of those CS.\n\n\n3.\u00a0\u00a0\u00a0Manufacturers shall comply with the CS referred to in paragraph\u00a01 unless they can duly justify that they have adopted solutions that ensure a level of safety and performance that is at least equivalent thereto.\n\n\n4.\u00a0\u00a0\u00a0Notwithstanding paragraph\u00a03, manufacturers of products listed in Annex\u00a0XVI shall comply with the relevant CS for those products.\n\n\n\nArticle\u00a010\n\nGeneral obligations of manufacturers\n\n\n1.\u00a0\u00a0\u00a0When placing their devices on the market or putting them into service, manufacturers shall ensure that they have been designed and manufactured in accordance with the requirements of this Regulation.\n\n\n2.\u00a0\u00a0\u00a0Manufacturers shall establish, document, implement and maintain a system for risk management as described in Section\u00a03 of Annex\u00a0I.\n\n\n3.\u00a0\u00a0\u00a0Manufacturers shall conduct a clinical evaluation in accordance with the requirements set out in Article\u00a061 and Annex\u00a0XIV, including a PMCF.\n\n\n4.\u00a0\u00a0\u00a0Manufacturers of devices other than custom-made devices shall draw up and keep up to date technical documentation for those devices. The technical documentation shall be such as to allow the conformity of the device with the requirements of this Regulation to be assessed. The technical documentation shall include the elements set out in Annexes\u00a0II and\u00a0III.\nThe Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 amending, in the light of technical progress, the Annexes\u00a0II and III.\n\n\n5.\u00a0\u00a0\u00a0Manufacturers of custom-made devices shall draw up, keep up to date and keep available for competent authorities documentation in accordance with Section\u00a02 of Annex\u00a0XIII.\n\n\n6.\u00a0\u00a0\u00a0Where compliance with the applicable requirements has been demonstrated following the applicable conformity assessment procedure, manufacturers of devices, other than custom-made or investigational devices, shall draw up an EU declaration of conformity in accordance with Article\u00a019, and affix the CE marking of conformity in accordance with Article\u00a020.\n\n\n7.\u00a0\u00a0\u00a0Manufacturers shall comply with the obligations relating to the UDI system referred to in Article\u00a027 and with the registration obligations referred to in Articles\u00a029 and 31.\n\n\n8.\u00a0\u00a0\u00a0Manufacturers shall keep the technical documentation, the EU declaration of conformity and, if applicable, a copy of any relevant certificate, including any amendments and supplements, issued in accordance with Article\u00a056, available for the competent authorities for a period of at least 10 years after the last device covered by the EU\u00a0declaration of conformity has been placed on the market. In the case of implantable devices, the period shall be at least 15 years after the last device has been placed on the market.\nUpon request by a competent authority, the manufacturer shall, as indicated therein, provide that technical documentation in its entirety or a summary thereof.\nA manufacturer with a registered place of business outside the Union shall, in order to allow its authorised representative to fulfil the tasks mentioned in Article\u00a011(3), ensure that the authorised representative has the necessary documentation permanently available.\n\n\n9.\u00a0\u00a0\u00a0Manufacturers shall ensure that procedures are in place to keep series production in conformity with the requirements of this Regulation. Changes in device design or characteristics and changes in the harmonised standards or CS by reference to which the conformity of a device is declared shall be adequately taken into account in a timely manner. Manufacturers of devices, other than investigational devices, shall establish, document, implement, maintain, keep up to date and continually improve a quality management system that shall ensure compliance with this Regulation in the most effective manner and in a manner that is proportionate to the risk class and the type of device.\nThe quality management system shall cover all parts and elements of a manufacturer's organisation dealing with the quality of processes, procedures and devices. It shall govern the structure, responsibilities, procedures, processes and management resources required to implement the principles and actions necessary to achieve compliance with the provisions of this Regulation.\nThe quality management system shall address at least the following aspects:\n\n\n\n\n\n\n(a)\n\n\na strategy for regulatory compliance, including compliance with conformity assessment procedures and procedures for management of modifications to the devices covered by the system;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nidentification of applicable general safety and performance requirements and exploration of options to address those requirements;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nresponsibility of the management;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nresource management, including selection and control of suppliers and sub-contractors;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nrisk management as set out in in Section\u00a03 of Annex\u00a0I;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nclinical evaluation in accordance with Article\u00a061 and Annex\u00a0XIV, including PMCF;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nproduct realisation, including planning, design, development, production and service provision;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nverification of the UDI assignments made in accordance with Article\u00a027(3) to all relevant devices and ensuring consistency and validity of information provided in accordance with Article\u00a029;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nsetting-up, implementation and maintenance of a post-market surveillance system, in accordance with Article\u00a083;\n\n\n\n\n\n\n\n\n\n\n(j)\n\n\nhandling communication with competent authorities, notified bodies, other economic operators, customers and/or other stakeholders;\n\n\n\n\n\n\n\n\n\n\n(k)\n\n\nprocesses for reporting of serious incidents and field safety corrective actions in the context of vigilance;\n\n\n\n\n\n\n\n\n\n\n(l)\n\n\nmanagement of corrective and preventive actions and verification of their effectiveness;\n\n\n\n\n\n\n\n\n\n\n(m)\n\n\nprocesses for monitoring and measurement of output, data analysis and product improvement.\n\n\n\n\n\n\n10.\u00a0\u00a0\u00a0Manufacturers of devices shall implement and keep up to date the post-market surveillance system in accordance with Article\u00a083.\n\n\n11.\u00a0\u00a0\u00a0Manufacturers shall ensure that the device is accompanied by the information set out in Section\u00a023 of Annex\u00a0I in an official Union language(s) determined by the Member\u00a0State in which the device is made available to the user or patient. The particulars on the label shall be indelible, easily legible and clearly comprehensible to the intended user or patient.\n\n\n12.\u00a0\u00a0\u00a0Manufacturers who consider or have reason to believe that a device which they have placed on the market or put into service is not in conformity with this Regulation shall immediately take the necessary corrective action to bring that device into conformity, to withdraw it or to recall it, as appropriate. They shall inform the distributors of the device in question and, where applicable, the authorised representative and importers accordingly.\nWhere the device presents a serious risk, manufacturers shall immediately inform the competent authorities of the Member\u00a0States in which they made the device available and, where applicable, the notified body that issued a certificate for the device in accordance with Article\u00a056, in particular, of the non-compliance and of any corrective action taken.\n\n\n13.\u00a0\u00a0\u00a0Manufacturers shall have a system for recording and reporting of incidents and field safety corrective actions as described in Articles\u00a087 and 88.\n\n\n14.\u00a0\u00a0\u00a0Manufacturers shall, upon request by a competent authority, provide it with all the information and documentation necessary to demonstrate the conformity of the device, in an official Union language determined by the Member\u00a0State concerned. The competent authority of the Member\u00a0State in which the manufacturer has its registered place of business may require that the manufacturer provide samples of the device free of charge or, where that is impracticable, grant access to the device. Manufacturers shall cooperate with a competent authority, at its request, on any corrective action taken to eliminate or, if that is not possible, mitigate the risks posed by devices which they have placed on the market or put into service.\nIf the manufacturer fails to cooperate or the information and documentation provided is incomplete or incorrect, the competent authority may, in order to ensure the protection of public health and patient safety, take all appropriate measures to prohibit or restrict the device's being made available on its national market, to withdraw the device from that market or to recall it until the manufacturer cooperates or provides complete and correct information.\nIf a competent authority considers or has reason to believe that a device has caused damage, it shall, upon request, facilitate the provision of the information and documentation referred to in the first subparagraph\u00a0to the potentially injured patient or user and, as appropriate, the patient's or user's successor in title, the patient's or user's health insurance company or other third parties affected by the damage caused to the patient or user, without prejudice to data protection rules and, unless there is an overriding public interest in disclosure, without prejudice to the protection of intellectual property rights.\nThe competent authority need not comply with the obligation laid down in the third subparagraph\u00a0where disclosure of the information and documentation referred to in the first subparagraph\u00a0is ordinarily dealt with in the context of legal proceedings.\n\n\n15.\u00a0\u00a0\u00a0Where manufacturers have their devices designed or manufactured by another legal or natural person the information on the identity of that person shall be part of the information to be submitted in accordance with Article\u00a030(1).\n\n\n16.\u00a0\u00a0\u00a0Natural or legal persons may claim compensation for damage caused by a defective device in accordance with applicable Union and national law.\nManufacturers shall, in a manner that is proportionate to the risk class, type of device and the size of the enterprise, have measures in place to provide sufficient financial coverage in respect of their potential liability under Directive\u00a085/374/EEC, without prejudice to more protective measures under national law.\n\n\n\nArticle\u00a011\n\nAuthorised representative\n\n\n1.\u00a0\u00a0\u00a0Where the manufacturer of a device is not established in a Member\u00a0State, the device may only be placed on the Union market if the manufacturer designates a sole authorised representative.\n\n\n2.\u00a0\u00a0\u00a0The designation shall constitute the authorised representative's mandate, it shall be valid only when accepted in writing by the authorised representative and shall be effective at least for all devices of the same generic device group.\n\n\n3.\u00a0\u00a0\u00a0The authorised representative shall perform the tasks specified in the mandate agreed between it and the manufacturer. The authorised representative shall provide a copy of the mandate to the competent authority, upon request.\nThe mandate shall require, and the manufacturer shall enable, the authorised representative to perform at least the following tasks in relation to the devices that it covers:\n\n\n\n\n\n\n(a)\n\n\nverify that the EU declaration of conformity and technical documentation have been drawn up and, where applicable, that an appropriate conformity assessment procedure has been carried out by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nkeep available a copy of the technical documentation, the EU declaration of conformity and, if applicable, a copy of the relevant certificate, including any amendments and supplements, issued in accordance with Article\u00a056, at the disposal of competent authorities for the period referred to in Article\u00a010(8);\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\ncomply with the registration obligations laid down in Article\u00a031 and verify that the manufacturer has complied with the registration obligations laid down in Articles\u00a027 and 29;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nin response to a request from a competent authority, provide that competent authority with all the information and documentation necessary to demonstrate the conformity of a device, in an official Union language determined by the Member\u00a0State concerned;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nforward to the manufacturer any request by a competent authority of the Member\u00a0State in which the authorised representative has its registered place of business for samples, or access to a device and verify that the competent authority receives the samples or is given access to the device;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\ncooperate with the competent authorities on any preventive or corrective action taken to eliminate or, if that is not possible, mitigate the risks posed by devices;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nimmediately inform the manufacturer about complaints and reports from healthcare professionals, patients and users about suspected incidents related to a device for which they have been designated;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nterminate the mandate if the manufacturer acts contrary to its obligations under this Regulation.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0The mandate referred to in paragraph\u00a03 of this Article\u00a0shall not delegate the manufacturer's obligations laid down in Article\u00a010(1), (2), (3), (4), (6), (7), (9), (10), (11) and (12).\n\n\n5.\u00a0\u00a0\u00a0Without prejudice to paragraph\u00a04 of this Article, where the manufacturer is not established in a Member\u00a0State and has not complied with the obligations laid down in Article\u00a010, the authorised representative shall be legally liable for defective devices on the same basis as, and jointly and severally with, the manufacturer.\n\n\n6.\u00a0\u00a0\u00a0An authorised representative who terminates its mandate on the ground referred to in point\u00a0(h) of paragraph\u00a03 shall immediately inform the competent authority of the Member\u00a0State in which it is established and, where applicable, the notified body that was involved in the conformity assessment for the device of the termination of the mandate and the reasons therefor.\n\n\n7.\u00a0\u00a0\u00a0Any reference in this Regulation to the competent authority of the Member\u00a0State in which the manufacturer has its registered place of business shall be understood as a reference to the competent authority of the Member\u00a0State in which the authorised representative, designated by a manufacturer referred to in paragraph\u00a01, has its registered place of business.\n\n\n\nArticle\u00a012\n\nChange of authorised representative\n\nThe detailed arrangements for a change of authorised representative shall be clearly defined in an agreement between the manufacturer, where practicable the outgoing authorised representative, and the incoming authorised representative. That agreement shall address at least the following aspects:\n\n\n\n\n\n\n(a)\n\n\nthe date of termination of the mandate of the outgoing authorised representative and date of beginning of the mandate of the incoming authorised representative;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe date until which the outgoing authorised representative may be indicated in the information supplied by the manufacturer, including any promotional material;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe transfer of documents, including confidentiality aspects and property rights;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe obligation of the outgoing authorised representative after the end of the mandate to forward to the manufacturer or incoming authorised representative any complaints or reports from healthcare professionals, patients or users about suspected incidents related to a device for which it had been designated as authorised representative.\n\n\n\n\n\n\nArticle\u00a013\n\nGeneral obligations of importers\n\n\n1.\u00a0\u00a0\u00a0Importers shall place on the Union market only devices that are in conformity with this Regulation.\n\n\n2.\u00a0\u00a0\u00a0In order to place a device on the market, importers shall verify that:\n\n\n\n\n\n\n(a)\n\n\nthe device has been CE marked and that the EU declaration of conformity of the device has been drawn up;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\na manufacturer is identified and that an authorised representative in accordance with Article\u00a011 has been designated by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe device is labelled in accordance with this Regulation and accompanied by the required instructions for use;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nwhere applicable, a UDI has been assigned by the manufacturer in accordance with Article\u00a027.\n\n\n\n\nWhere an importer considers or has reason to believe that a device is not in conformity with the requirements of this Regulation, it shall not place the device on the market until it has been brought into conformity and shall inform the manufacturer and the manufacturer's authorised representative. Where the importer considers or has reason to believe that the device presents a serious risk or is a falsified device, it shall also inform the competent authority of the Member\u00a0State in which the importer is established.\n\n\n3.\u00a0\u00a0\u00a0Importers shall indicate on the device or on its packaging or in a document accompanying the device their name, registered trade name or registered trade mark, their registered place of business and the address at which they can be contacted, so that their location can be established. They shall ensure that any additional label does not obscure any information on the label provided by the manufacturer.\n\n\n4.\u00a0\u00a0\u00a0Importers shall verify that the device is registered in the electronic system in accordance with Article\u00a029. Importers shall add their details to the registration in accordance with Article\u00a031.\n\n\n5.\u00a0\u00a0\u00a0Importers shall ensure that, while a device is under their responsibility, storage or transport conditions do not jeopardise its compliance with the general safety and performance requirements set out in Annex\u00a0I and shall comply with the conditions set by the manufacturer, where available.\n\n\n6.\u00a0\u00a0\u00a0Importers shall keep a register of complaints, of non-conforming devices and of recalls and withdrawals, and provide the manufacturer, authorised representative and distributors with any information requested by them, in order to allow them to investigate complaints.\n\n\n7.\u00a0\u00a0\u00a0Importers who consider or have reason to believe that a device which they have placed on the market is not in conformity with this Regulation shall immediately inform the manufacturer and its authorised representative. Importers shall co-operate with the manufacturer, the manufacturer's authorised representative and the competent authorities to ensure that the necessary corrective action to bring that device into conformity, to withdraw or recall it is taken. Where the device presents a serious risk, they shall also immediately inform the competent authorities of the Member\u00a0States in which they made the device available and, if applicable, the notified body that issued a certificate in accordance with Article\u00a056 for the device in question, giving details, in particular, of the non-compliance and of any corrective action taken.\n\n\n8.\u00a0\u00a0\u00a0Importers who have received complaints or reports from healthcare professionals, patients or users about suspected incidents related to a device which they have placed on the market shall immediately forward this information to the manufacturer and its authorised representative.\n\n\n9.\u00a0\u00a0\u00a0Importers shall, for the period referred to in Article\u00a010(8), keep a copy of the EU\u00a0declaration of conformity and, if applicable, a copy of any relevant certificate, including any amendments and supplements, issued in accordance with Article\u00a056.\n\n\n10.\u00a0\u00a0\u00a0Importers shall cooperate with competent authorities, at the latters' request, on any action taken to eliminate or, if that is not possible, mitigate the risks posed by devices which they have placed on the market. Importers, upon request by a competent authority of the Member\u00a0State in which the importer has its registered place of business, shall provide samples of the device free of charge or, where that is impracticable, grant access to the device.\n\n\n\nArticle\u00a014\n\nGeneral obligations of distributors\n\n\n1.\u00a0\u00a0\u00a0When making a device available on the market, distributors shall, in the context of their activities, act with due care in relation to the requirements applicable.\n\n\n2.\u00a0\u00a0\u00a0Before making a device available on the market, distributors shall verify that all of the following requirements are met:\n\n\n\n\n\n\n(a)\n\n\nthe device has been CE marked and that the EU declaration of conformity of the device has been drawn up;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe device is accompanied by the information to be supplied by the manufacturer in accordance with Article\u00a010(11);\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nfor imported devices, the importer has complied with the requirements set out in Article\u00a013(3);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthat, where applicable, a UDI has been assigned by the manufacturer.\n\n\n\n\nIn order to meet the requirements referred to in points (a), (b) and (d) of the first subparagraph\u00a0the distributor may apply a sampling method that is representative of the devices supplied by that distributor.\nWhere a distributor considers or has reason to believe that a device is not in conformity with the requirements of this Regulation, it shall not make the device available on the market until it has been brought into conformity, and shall inform the manufacturer and, where applicable, the manufacturer's authorised representative, and the importer. Where the distributor considers or has reason to believe that the device presents a serious risk or is a falsified device, it shall also inform the competent authority of the Member\u00a0State in which it is established.\n\n\n3.\u00a0\u00a0\u00a0Distributors shall ensure that, while the device is under their responsibility, storage or transport conditions comply with the conditions set by the manufacturer.\n\n\n4.\u00a0\u00a0\u00a0Distributors that consider or have reason to believe that a device which they have made available on the market is not in conformity with this Regulation shall immediately inform the manufacturer and, where applicable, the manufacturer's authorised representative and the importer. Distributors shall co-operate with the manufacturer and, where applicable, the manufacturer's authorised representative, and the importer, and with competent authorities to ensure that the necessary corrective action to bring that device into conformity, to withdraw or to recall it, as appropriate, is taken. Where the distributor considers or has reason to believe that the device presents a serious risk, it shall also immediately inform the competent authorities of the Member\u00a0States in which it made the device available, giving details, in particular, of the non-compliance and of any corrective action taken.\n\n\n5.\u00a0\u00a0\u00a0Distributors that have received complaints or reports from healthcare professionals, patients or users about suspected incidents related to a device they have made available, shall immediately forward this information to the manufacturer and, where applicable, the manufacturer's authorised representative, and the importer. They shall keep a register of complaints, of non-conforming devices and of recalls and withdrawals, and keep the manufacturer and, where available, the authorised representative and the importer informed of such monitoring and provide them with any information upon their request.\n\n\n6.\u00a0\u00a0\u00a0Distributors shall, upon request by a competent authority, provide it with all the information and documentation that is at their disposal and is necessary to demonstrate the conformity of a device.\nDistributors shall be considered to have fulfilled the obligation referred to in the first subparagraph\u00a0when the manufacturer or, where applicable, the authorised representative for the device in question provides the required information. Distributors shall cooperate with competent authorities, at their request, on any action taken to eliminate the risks posed by devices which they have made available on the market. Distributors, upon request by a competent authority, shall provide free samples of the device or, where that is impracticable, grant access to the device.\n\n\n\nArticle\u00a015\n\nPerson responsible for regulatory compliance\n\n\n1.\u00a0\u00a0\u00a0Manufacturers shall have available within their organisation at least one person responsible for regulatory compliance who possesses the requisite expertise in the field of medical devices. The requisite expertise shall be demonstrated by either of the following qualifications:\n\n\n\n\n\n\n(a)\n\n\na diploma, certificate or other evidence of formal qualification, awarded on completion of a university degree or of a course of study recognised as equivalent by the Member\u00a0State concerned, in law, medicine, pharmacy, engineering or another relevant scientific discipline, and at least one year of professional experience in regulatory affairs or in quality management systems relating to medical devices;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nfour years of professional experience in regulatory affairs or in quality management systems relating to medical devices.\n\n\n\n\nWithout prejudice to national provisions regarding professional qualifications, manufacturers of custom-made devices may demonstrate the requisite expertise referred to in the first subparagraph\u00a0by having at least two years of professional experience within a relevant field of manufacturing.\n\n\n2.\u00a0\u00a0\u00a0Micro and small enterprises within the meaning of Commission Recommendation\u00a02003/361/EC\u00a0(36) shall not be required to have the person responsible for regulatory compliance within their organisation but shall have such person permanently and continuously at their disposal.\n\n\n3.\u00a0\u00a0\u00a0The person responsible for regulatory compliance shall at least be responsible for ensuring that:\n\n\n\n\n\n\n(a)\n\n\nthe conformity of the devices is appropriately checked, in accordance with the quality management system under which the devices are manufactured, before a device is released;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe technical documentation and the EU declaration of conformity are drawn up and kept up-to-date;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe post-market surveillance obligations are complied with in accordance with Article\u00a010(10);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe reporting obligations referred to in Articles\u00a087 to 91 are fulfilled;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nin the case of investigational devices, the statement referred to in Section\u00a04.1 of Chapter II of Annex\u00a0XV is issued.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0If a number of persons are jointly responsible for regulatory compliance in accordance with paragraphs 1, 2 and 3, their respective areas of responsibility shall be stipulated in writing.\n\n\n5.\u00a0\u00a0\u00a0The person responsible for regulatory compliance shall suffer no disadvantage within the manufacturer's organisation in relation to the proper fulfilment of his or her duties, regardless of whether or not they are employees of the organisation.\n\n\n6.\u00a0\u00a0\u00a0Authorised representatives shall have permanently and continuously at their disposal at least one person responsible for regulatory compliance who possesses the requisite expertise regarding the regulatory requirements for medical devices in the Union. The requisite expertise shall be demonstrated by either of the following qualifications:\n\n\n\n\n\n\n(a)\n\n\na diploma, certificate or other evidence of formal qualification, awarded on completion of a university degree or of a course of study recognised as equivalent by the Member\u00a0State concerned, in law, medicine, pharmacy, engineering or another relevant scientific discipline, and at least one year of professional experience in regulatory affairs or in quality management systems relating to medical devices;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nfour years of professional experience in regulatory affairs or in quality management systems relating to medical devices.\n\n\n\n\n\n\n\nArticle\u00a016\n\nCases in which obligations of manufacturers apply to importers, distributors or other persons\n\n\n1.\u00a0\u00a0\u00a0A distributor, importer or other natural or legal person shall assume the obligations incumbent on manufacturers if it does any of the following:\n\n\n\n\n\n\n(a)\n\n\nmakes available on the market a device under its name, registered trade name or registered trade mark, except in cases where a distributor or importer enters into an agreement with a manufacturer whereby the manufacturer is identified as such on the label and is responsible for meeting the requirements placed on manufacturers in this Regulation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nchanges the intended purpose of a device already placed on the market or put into service;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nmodifies a device already placed on the market or put into service in such a way that compliance with the applicable requirements may be affected.\n\n\n\n\nThe first subparagraph\u00a0shall not apply to any person who, while not considered a manufacturer as defined in point\u00a0(30) of Article\u00a02, assembles or adapts for an individual patient a device already on the market without changing its intended purpose.\n\n\n2.\u00a0\u00a0\u00a0For the purposes of point\u00a0(c) of paragraph\u00a01, the following shall not be considered to be a modification of a device that could affect its compliance with the applicable requirements:\n\n\n\n\n\n\n(a)\n\n\nprovision, including translation, of the information supplied by the manufacturer, in accordance with Section\u00a023 of Annex\u00a0I, relating to a device already placed on the market and of further information which is necessary in order to market the device in the relevant Member\u00a0State;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nchanges to the outer packaging of a device already placed on the market, including a change of pack size, if the repackaging is necessary in order to market the device in the relevant Member\u00a0State and if it is carried out in such conditions that the original condition of the device cannot be affected by it. In the case of devices placed on the market in sterile condition, it shall be presumed that the original condition of the device is adversely affected if the packaging that is necessary for maintaining the sterile condition is opened, damaged or otherwise negatively affected by the repackaging.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0A distributor or importer that carries out any of the activities mentioned in points\u00a0(a) and\u00a0(b) of paragraph\u00a02 shall indicate on the device or, where that is impracticable, on its packaging or in a document accompanying the device, the activity carried out together with its name, registered trade name or registered trade mark, registered place of business and the address at which it can be contacted, so that its location can be established.\nDistributors and importers shall ensure that they have in place a quality management system that includes procedures which ensure that the translation of information is accurate and up-to-date, and that the activities mentioned in points\u00a0(a) and\u00a0(b) of paragraph\u00a02 are performed by a means and under conditions that preserve the original condition of the device and that the packaging of the repackaged device is not defective, of poor quality or untidy. The quality management system shall cover, inter\u00a0alia, procedures ensuring that the distributor or importer is informed of any corrective action taken by the manufacturer in relation to the device in question in order to respond to safety issues or to bring it into conformity with this Regulation.\n\n\n4.\u00a0\u00a0\u00a0At least 28 days prior to making the relabelled or repackaged device available on the market, distributors or importers carrying out any of the activities mentioned in points\u00a0(a) and (b) of paragraph\u00a02 shall inform the manufacturer and the competent authority of the Member\u00a0State in which they plan to make the device available of the intention to make the relabelled or repackaged device available and, upon request, shall provide the manufacturer and the competent authority with a sample or mock-up of the relabelled or repackaged device, including any translated label and instructions for use. Within the same period of 28\u00a0days, the distributor or importer shall submit to the competent authority a certificate, issued by a notified body designated for the type of devices that are subject to activities mentioned in points\u00a0(a) and\u00a0(b) of paragraph\u00a02, attesting that the quality management system of the distributer or importer complies with the requirements laid down in paragraph\u00a03.\n\n\n\nArticle\u00a017\n\nSingle-use devices and their reprocessing\n\n\n1.\u00a0\u00a0\u00a0Reprocessing and further use of single-use devices may only take place where permitted by national law and only in accordance with this Article.\n\n\n2.\u00a0\u00a0\u00a0Any natural or legal person who reprocesses a single-use device to make it suitable for further use within the Union shall be considered to be the manufacturer of the reprocessed device and shall assume the obligations incumbent on manufacturers laid down in this Regulation, which include obligations relating to the traceability of the reprocessed device in accordance with Chapter III of this Regulation. The reprocessor of the device shall be considered to be a producer for the purpose of Article\u00a03(1) of Directive\u00a085/374/EEC.\n\n\n3.\u00a0\u00a0\u00a0By way of derogation from paragraph\u00a02, as regards single-use devices that are reprocessed and used within a health institution, Member\u00a0States may decide not to apply all of the rules relating to manufacturers' obligations laid down in this Regulation provided that they ensure that:\n\n\n\n\n\n\n(a)\n\n\nthe safety and performance of the reprocessed device is equivalent to that of the original device and the requirements in points (a), (b), (d), (e), (f), (g) and (h) of Article\u00a05(5) are complied with;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe reprocessing is performed in accordance with CS detailing the requirements concerning:\n\n\n\n\n\n\n\u2014\n\n\nrisk management, including the analysis of the construction and material, related properties of the device (reverse engineering) and procedures to detect changes in the design of the original device as well as of its planned application after reprocessing,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe validation of procedures for the entire process, including cleaning steps,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe product release and performance testing,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe quality management system,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe reporting of incidents involving devices that have been reprocessed, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe traceability of reprocessed devices.\n\n\n\n\n\n\n\n\nMember\u00a0States shall encourage, and may require, health institutions to provide information to patients on the use of reprocessed devices within the health institution and, where appropriate, any other relevant information on the reprocessed devices that patients are treated with.\nMember\u00a0States shall notify the Commission and the other Member\u00a0States of the national provisions introduced pursuant to this paragraph\u00a0and the grounds for introducing them. The Commission shall keep the information publicly available.\n\n\n4.\u00a0\u00a0\u00a0Member\u00a0States may choose to apply the provisions referred to in paragraph\u00a03 also as regards single-use devices that are reprocessed by an external reprocessor at the request of a health institution, provided that the reprocessed device in its entirety is returned to that health institution and the external reprocessor complies with the requirements referred to in points (a) and (b) of paragraph\u00a03.\n\n\n5.\u00a0\u00a0\u00a0The Commission shall adopt, in accordance with Article\u00a09(1), the necessary CS referred to in point\u00a0(b) of paragraph\u00a03 by 26 May 2020. Those CS shall be consistent with the latest scientific evidence and shall address the application of the general requirements on safety and performance laid down in in this Regulation. In the event that those CS are not adopted by 26 May 2020, reprocessing shall be performed in accordance with any relevant harmonised standards and national provisions that cover the aspects outlined in point\u00a0(b) of paragraph\u00a03. Compliance with CS or, in the absence of CS, with any relevant harmonised standards and national provisions, shall be certified by a notified body.\n\n\n6.\u00a0\u00a0\u00a0Only single-use devices that have been placed on the market in accordance with this Regulation, or prior to 26\u00a0May 2020 in accordance with Directive\u00a093/42/EEC, may be reprocessed.\n\n\n7.\u00a0\u00a0\u00a0Only reprocessing of single-use devices that is considered safe according to the latest scientific evidence may be carried out.\n\n\n8.\u00a0\u00a0\u00a0The name and address of the legal or natural person referred to in paragraph\u00a02 and the other relevant information referred to in Section\u00a023 of Annex\u00a0I shall be indicated on the label and, where applicable, in the instructions for use of the reprocessed device.\nThe name and address of the manufacturer of the original single-use device shall no longer appear on the label, but shall be mentioned in the instructions for use of the reprocessed device.\n\n\n9.\u00a0\u00a0\u00a0A Member\u00a0State that permits reprocessing of single-use devices may maintain or introduce national provisions that are stricter than those laid down in this Regulation and which restrict or prohibit, within its territory, the following:\n\n\n\n\n\n\n(a)\n\n\nthe reprocessing of single-use devices and the transfer of single-use devices to another Member\u00a0State or to a third country with a view to their reprocessing;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe making available or further use of reprocessed single-use devices.\n\n\n\n\nMember\u00a0States shall notify the Commission and the other Member\u00a0States of those national provisions. The Commission shall make such information publicly available.\n\n\n10.\u00a0\u00a0\u00a0The Commission shall by 27 May 2024 draw up a report on the operation of this Article\u00a0and submit it to the European Parliament and to the Council. On the basis of that report, the Commission shall, if appropriate, make proposals for amendments to this Regulation.\n\n\n\nArticle\u00a018\n\nImplant card and information to be supplied to the patient with an implanted device\n\n\n1.\u00a0\u00a0\u00a0The manufacturer of an implantable device shall provide together with the device the following:\n\n\n\n\n\n\n(a)\n\n\ninformation allowing the identification of the device, including the device name, serial number, lot number, the UDI, the device model, as well as the name, address and the website of the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nany warnings, precautions or measures to be taken by the patient or a healthcare professional with regard to reciprocal interference with reasonably foreseeable external influences, medical examinations or environmental conditions;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nany information about the expected lifetime of the device and any necessary follow-up;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nany other information to ensure safe use of the device by the patient, including the information in point\u00a0(u) of Section\u00a023.4 of Annex\u00a0I.\n\n\n\n\nThe information referred to in the first subparagraph\u00a0shall be provided, for the purpose of making it available to the particular patient who has been implanted with the device, by any means that allow rapid access to that information and shall be stated in the language(s) determined by the concerned Member\u00a0State. The information shall be written in a way that is readily understood by a lay person and shall be updated where appropriate. Updates of the information shall be made available to the patient via the website mentioned in point\u00a0(a) of the first subparagraph.\nIn addition, the manufacturer shall provide the information referred to in point\u00a0(a) of the first subparagraph\u00a0on an implant card delivered with the device.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States shall require health institutions to make the information referred to in paragraph\u00a01 available, by any means that allow rapid access to that information, to any patients who have been implanted with the device, together with the implant card, which shall bear their identity.\n\n\n3.\u00a0\u00a0\u00a0The following implants shall be exempted from the obligations laid down in this Article: sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips and connectors. The Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 to amend this list by adding other types of implants to it or by removing implants therefrom.\n\n\n\nArticle\u00a019\n\nEU declaration of conformity\n\n\n1.\u00a0\u00a0\u00a0The EU\u00a0declaration of conformity shall state that the requirements specified in this Regulation have been fulfilled in relation to the device that is covered. The manufacturer shall continuously update the EU\u00a0declaration of conformity. The EU\u00a0declaration of conformity shall, as a minimum, contain the information set out in Annex\u00a0IV and shall be translated into an official Union language or languages required by the Member\u00a0State(s) in which the device is made available.\n\n\n2.\u00a0\u00a0\u00a0Where, concerning aspects not covered by this Regulation, devices are subject to other Union legislation which also requires an EU declaration of conformity by the manufacturer that fulfilment of the requirements of that legislation has been demonstrated, a single EU\u00a0declaration of conformity shall be drawn up in respect of all Union acts applicable to the device. The declaration shall contain all the information required for identification of the Union legislation to which the declaration relates.\n\n\n3.\u00a0\u00a0\u00a0By drawing up the EU\u00a0declaration of conformity, the manufacturer shall assume responsibility for compliance with the requirements of this Regulation and all other Union legislation applicable to the device.\n\n\n4.\u00a0\u00a0\u00a0The Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 amending the minimum content of the EU declaration of conformity set out in Annex\u00a0IV in the light of technical progress.\n\n\n\nArticle\u00a020\n\nCE marking of conformity\n\n\n1.\u00a0\u00a0\u00a0Devices, other than custom-made or investigational devices, considered to be in conformity with the requirements of this Regulation shall bear the CE marking of conformity, as presented in Annex\u00a0V.\n\n\n2.\u00a0\u00a0\u00a0The CE marking shall be subject to the general principles set out in Article\u00a030 of Regulation\u00a0(EC)\u00a0No\u00a0765/2008.\n\n\n3.\u00a0\u00a0\u00a0The CE marking shall be affixed visibly, legibly and indelibly to the device or its sterile packaging. Where such affixing is not possible or not warranted on account of the nature of the device, the CE marking shall be affixed to the packaging. The CE marking shall also appear in any instructions for use and on any sales packaging.\n\n\n4.\u00a0\u00a0\u00a0The CE marking shall be affixed before the device is placed on the market. It may be followed by a pictogram or any other mark indicating a special risk or use.\n\n\n5.\u00a0\u00a0\u00a0Where applicable, the CE marking shall be followed by the identification number of the notified body responsible for the conformity assessment procedures set out in Article\u00a052. The identification number shall also be indicated in any promotional material which mentions that a device fulfils the requirements for CE marking.\n\n\n6.\u00a0\u00a0\u00a0Where devices are subject to other Union legislation which also provides for the affixing of the CE marking, the CE marking shall indicate that the devices also fulfil the requirements of that other legislation.\n\n\n\nArticle\u00a021\n\nDevices for special purposes\n\n\n1.\u00a0\u00a0\u00a0Member\u00a0States shall not create obstacles to:\n\n\n\n\n\n\n(a)\n\n\ninvestigational devices being supplied to an investigator for the purpose of a clinical investigation if they meet the conditions laid down in Articles\u00a062 to 80 and Article\u00a082, in the implementing acts adopted pursuant to Article\u00a081 and in Annex\u00a0XV;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ncustom-made devices being made available on the market if Article\u00a052(8) and Annex\u00a0XIII have been complied with.\n\n\n\n\nThe devices referred to in the first subparagraph\u00a0shall not bear the CE marking, with the exception of the devices referred to in Article\u00a074.\n\n\n2.\u00a0\u00a0\u00a0Custom-made devices shall be accompanied by the statement referred to in Section\u00a01 of Annex\u00a0XIII, which shall be made available to the particular patient or user identified by name, an acronym or a numerical code.\nMember\u00a0States may require that the manufacturer of a custom-made device submit to the competent authority a list of such devices which have been made available in their territory.\n\n\n3.\u00a0\u00a0\u00a0At trade fairs, exhibitions, demonstrations or similar events, Member\u00a0States shall not create obstacles to the showing of devices which do not comply with this Regulation, provided a visible sign clearly indicates that such devices are intended for presentation or demonstration purposes only and cannot be made available until they have been brought into compliance with this Regulation.\n\n\n\nArticle\u00a022\n\nSystems and procedure packs\n\n\n1.\u00a0\u00a0\u00a0Natural or legal persons shall draw up a statement if they combine devices bearing a CE\u00a0marking with the following other devices or products, in a manner that is compatible with the intended purpose of the devices or other products and within the limits of use specified by their manufacturers, in order to place them on the market as a system or procedure pack:\n\n\n\n\n\n\n(a)\n\n\nother devices bearing the CE marking;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\n\nin vitro diagnostic medical devices bearing the CE marking in conformity with Regulation\u00a0(EU)\u00a02017/746;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nother products which are in conformity with legislation that applies to those products only where they are used within a medical procedure or their presence in the system or procedure pack is otherwise justified.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0In the statement made pursuant to paragraph\u00a01, the natural or legal person concerned shall declare that:\n\n\n\n\n\n\n(a)\n\n\nthey verified the mutual compatibility of the devices and, if applicable other products, in accordance with the manufacturers' instructions and have carried out their activities in accordance with those instructions;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthey packaged the system or procedure pack and supplied relevant information to users incorporating the information to be supplied by the manufacturers of the devices or other products which have been put together;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe activity of combining devices and, if applicable, other products as a system or procedure pack was subject to appropriate methods of internal monitoring, verification and validation.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0Any natural or legal person who sterilises systems or procedure packs referred to in paragraph\u00a01 for the purpose of placing them on the market shall, at their choice, apply one of the procedures set out in Annex\u00a0IX or the procedure set out in Part A of Annex\u00a0XI. The application of those procedures and the involvement of the notified body shall be limited to the aspects of the procedure relating to ensuring sterility until the sterile packaging is opened or damaged. The natural or legal person shall draw up a statement declaring that sterilisation has been carried out in accordance with the manufacturer's instructions.\n\n\n4.\u00a0\u00a0\u00a0Where the system or procedure pack incorporates devices which do not bear the CE\u00a0marking or where the chosen combination of devices is not compatible in view of their original intended purpose, or where the sterilisation has not been carried out in accordance with the manufacturer's instructions, the system or procedure pack shall be treated as a device in its own right and shall be subject to the relevant conformity assessment procedure pursuant to Article\u00a052. The natural or legal person shall assume the obligations incumbent on manufacturers.\n\n\n5.\u00a0\u00a0\u00a0The systems or procedure packs referred to in paragraph\u00a01 of this Article\u00a0shall not themselves bear an additional CE marking but they shall bear the name, registered trade name or registered trade mark of the person referred to in paragraphs 1 and 3 of this Article\u00a0as well as the address at which that person can be contacted, so that the person's location can be established. Systems or procedure packs shall be accompanied by the information referred to in Section\u00a023 of Annex\u00a0I. The statement referred to in paragraph\u00a02 of this Article\u00a0shall be kept at the disposal of the competent authorities, after the system or procedure pack has been put together, for the period that is applicable under Article\u00a010(8) to the devices that have been combined. Where those periods differ, the longest period shall apply.\n\n\n\nArticle\u00a023\n\nParts and components\n\n\n1.\u00a0\u00a0\u00a0Any natural or legal person who makes available on the market an item specifically intended to replace an identical or similar integral part or component of a device that is defective or worn in order to maintain or restore the function of the device without changing its performance or safety characteristics or its intended purpose, shall ensure that the item does not adversely affect the safety and performance of the device. Supporting evidence shall be kept available for the competent authorities of the Member\u00a0States.\n\n\n2.\u00a0\u00a0\u00a0An item that is intended specifically to replace a part or component of a device and that significantly changes the performance or safety characteristics or the intended purpose of the device shall be considered to be a device and shall meet the requirements laid down in this Regulation.\n\n\n\nArticle\u00a024\n\nFree movement\n\nExcept where otherwise provided for in this Regulation, Member\u00a0States shall not refuse, prohibit or restrict the making available on the market or putting into service within their territory of devices which comply with the requirements of this Regulation.\n\n\n\nCHAPTER III\n\n\nIDENTIFICATION AND TRACEABILITY OF DEVICES, REGISTRATION OF DEVICES AND OF ECONOMIC OPERATORS, SUMMARY OF SAFETY AND CLINICAL PERFORMANCE, EUROPEAN DATABASE ON MEDICAL DEVICES\n\n\n\nArticle\u00a025\n\nIdentification within the supply chain\n\n\n1.\u00a0\u00a0\u00a0Distributors and importers shall co-operate with manufacturers or authorised representatives to achieve an appropriate level of traceability of devices.\n\n\n2.\u00a0\u00a0\u00a0Economic operators shall be able to identify the following to the competent authority, for the period referred to in Article\u00a010(8):\n\n\n\n\n\n\n(a)\n\n\nany economic operator to whom they have directly supplied a device;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nany economic operator who has directly supplied them with a device;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nany health institution or healthcare professional to which they have directly supplied a device.\n\n\n\n\n\n\n\nArticle\u00a026\n\nMedical devices nomenclature\n\nTo facilitate the functioning of the European database on medical devices (\u2018Eudamed\u2019) as referred to in Article\u00a033, the Commission shall ensure that an internationally recognised medical devices nomenclature is available free of charge to manufacturers and other natural or legal persons required by this Regulation to use that nomenclature. The Commission shall also endeavour to ensure that that nomenclature is available to other stakeholders free of charge, where reasonably practicable.\n\n\nArticle\u00a027\n\nUnique Device Identification system\n\n\n1.\u00a0\u00a0\u00a0The Unique Device Identification system (\u2018UDI system\u2019) described in Part C of Annex\u00a0VI shall allow the identification and facilitate the traceability of devices, other than custom-made and investigational devices, and shall consist of the following:\n\n\n\n\n\n\n(a)\n\n\nproduction of a UDI that comprises the following:\n\n\n\n\n\n\n(i)\n\n\na UDI device identifier (\u2018UDI-DI\u2019) specific to a manufacturer and a device, providing access to the information laid down in Part B of Annex\u00a0VI;\n\n\n\n\n\n\n\n\n\n\n(ii)\n\n\na UDI production identifier (\u2018UDI-PI\u2019) that identifies the unit of device production and if applicable the packaged devices, as specified in Part\u00a0C of Annex\u00a0VI;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nplacing of the UDI on the label of the device or on its packaging;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nstorage of the UDI by economic operators, health institutions and healthcare professionals, in accordance with the conditions laid down in paragraphs 8 and 9 of this Article\u00a0respectively;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nestablishment of an electronic system for Unique Device Identification\u00a0(\u2018UDI database\u2019) in accordance with Article\u00a028.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The Commission shall, by means of implementing acts, designate one or several entities to operate a system for assignment of UDIs pursuant to this Regulation (\u2018issuing entity\u2019). That entity or those entities shall satisfy all of the following criteria:\n\n\n\n\n\n\n(a)\n\n\nthe entity is an organisation with legal personality;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nits system for the assignment of UDIs is adequate to identify a device throughout its distribution and use in accordance with the requirements of this Regulation;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nits system for the assignment of UDIs conforms to the relevant international standards;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe entity gives access to its system for the assignment of UDIs to all interested users in accordance with a set of predetermined and transparent terms and conditions;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe entity undertakes to do the following:\n\n\n\n\n\n\n(i)\n\n\noperate its system for the assignment of UDIs for at least 10 years after its designation;\n\n\n\n\n\n\n\n\n\n\n(ii)\n\n\nmake available to the Commission and to the Member\u00a0States, upon request, information concerning its system for the assignment of UDIs;\n\n\n\n\n\n\n\n\n\n\n(iii)\n\n\nremain in compliance with the criteria for designation and the terms of designation.\n\n\n\n\n\n\n\n\nWhen designating issuing entities, the Commission shall endeavour to ensure that UDI\u00a0carriers, as defined in Part C of Annex\u00a0VI, are universally readable regardless of the system used by the issuing entity, with a view to minimising financial and administrative burdens for economic operators and health institutions.\n\n\n3.\u00a0\u00a0\u00a0Before placing a device, other than a custom-made device, on the market, the manufacturer shall assign to the device and, if applicable, to all higher levels of packaging, a UDI created in compliance with the rules of the issuing entity designated by the Commission in accordance with paragraph\u00a02.\nBefore a device, other than a custom-made or investigational device, is placed on the market the manufacturer shall ensure that the information referred to in Part B of Annex\u00a0VI of the device in question are correctly submitted and transferred to the UDI database referred to in Article\u00a028.\n\n\n4.\u00a0\u00a0\u00a0UDI carriers shall be placed on the label of the device and on all higher levels of packaging. Higher levels of packaging shall not be understood to include shipping containers.\n\n\n5.\u00a0\u00a0\u00a0The UDI shall be used for reporting serious incidents and field safety corrective actions in accordance with Article\u00a087.\n\n\n6.\u00a0\u00a0\u00a0The Basic UDI-DI, as defined in Part C of Annex\u00a0VI, of the device shall appear on the EU\u00a0declaration of conformity referred to in Article\u00a019.\n\n\n7.\u00a0\u00a0\u00a0As part of the technical documentation referred to in Annex\u00a0II, the manufacturer shall keep up-to-date a list of all UDIs that it has assigned.\n\n\n8.\u00a0\u00a0\u00a0Economic operators shall store and keep, preferably by electronic means, the UDI of the devices which they have supplied or with which they have been supplied, if those devices belong to:\n\n\n\n\n\n\n\u2014\n\n\nclass III implantable devices;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe devices, categories or groups of devices determined by a measure referred to in point\u00a0(a) of paragraph\u00a011.\n\n\n\n\n\n\n9.\u00a0\u00a0\u00a0Health institutions shall store and keep preferably by electronic means the UDI of the devices which they have supplied or with which they have been supplied, if those devices belong to class III implantable devices.\nFor devices other than class III implantable devices, Member\u00a0States shall encourage, and may require, health institutions to store and keep, preferably by electronic means, the UDI of the devices with which they have been supplied.\nMember\u00a0States shall encourage, and may require, healthcare professionals to store and keep preferably by electronic means, the UDI of the devices with which they have been supplied with.\n\n\n10.\u00a0\u00a0\u00a0The Commission is empowered to adopt delegated acts in accordance with Article\u00a0115:\n\n\n\n\n\n\n(a)\n\n\namending the list of information set out in Part B of Annex\u00a0VI in the light of technical progress; and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\namending Annex\u00a0VI in the light of international developments and technical progress in the field of Unique Device Identification.\n\n\n\n\n\n\n11.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, specify the detailed arrangements and the procedural aspects for the UDI system with a view to ensuring its harmonised application in relation to any of the following:\n\n\n\n\n\n\n(a)\n\n\ndetermining the devices, categories or groups of devices to which the obligation laid down in paragraph\u00a08 is to apply;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nspecifying the data to be included in the UDI-PI of specific devices or device groups;\n\n\n\n\nThe implementing acts referred to in the first subparagraph\u00a0shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n12.\u00a0\u00a0\u00a0When adopting the measures referred to in paragraph\u00a011, the Commission shall take into account all of the following:\n\n\n\n\n\n\n(a)\n\n\nconfidentiality and data protection as referred to in Articles\u00a0109 and 110\u00a0respectively;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe risk-based approach;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe cost-effectiveness of the measures;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe convergence of UDI systems developed at international level;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe need to avoid duplications in the UDI system;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe needs of the healthcare systems of the Member\u00a0States, and where possible, compatibility with other medical device identification systems that are used by stakeholders.\n\n\n\n\n\n\n\nArticle\u00a028\n\nUDI database\n\n\n1.\u00a0\u00a0\u00a0The Commission, after consulting the MDCG shall set up and manage a UDI database to validate, collate, process and make available to the public the information mentioned in Part B of Annex\u00a0VI.\n\n\n2.\u00a0\u00a0\u00a0When designing the UDI database, the Commission shall take into account the general principles set out in Section\u00a05 of Part C of Annex\u00a0VI. The UDI database shall be designed in particular such that no UDI-PIs and no commercially confidential product information can be included therein.\n\n\n3.\u00a0\u00a0\u00a0The core data elements to be provided to the UDI database, referred to in Part\u00a0B of Annex\u00a0VI, shall be accessible to the public free of charge.\n\n\n4.\u00a0\u00a0\u00a0The technical design of the UDI database shall ensure maximum accessibility to information stored therein, including multi-user access and automatic uploads and downloads of that information. The Commission shall provide for technical and administrative support to manufacturers and other users of the UDI database.\n\n\n\nArticle\u00a029\n\nRegistration of devices\n\n\n1.\u00a0\u00a0\u00a0Before placing a device, other than a custom-made device, on the market, the manufacturer shall, in accordance with the rules of the issuing entity referred to in Article\u00a027(2), assign a Basic UDI-DI as defined in Part C of Annex\u00a0VI to the device and shall provide it to the UDI database together with the other core data elements referred to in Part B of Annex\u00a0VI related to that device.\n\n\n2.\u00a0\u00a0\u00a0Before placing on the market a system or procedure pack pursuant to Article\u00a022(1) and (3), that is not a custom-made device, the natural or legal person responsible shall assign to the system or procedure pack, in compliance with the rules of the issuing entity, a Basic UDI-DI and shall provide it to the UDI database together with the other core data elements referred to in Part B of Annex\u00a0VI related to that system or procedure pack.\n\n\n3.\u00a0\u00a0\u00a0For devices that are the subject of a conformity assessment as referred to in Article\u00a052(3) and in the second and third subparagraphs\u00a0of Article\u00a052(4), the assignment of a Basic UDI-DI referred to in paragraph\u00a01 of this Article\u00a0shall be done before the manufacturer applies to a notified body for that assessment.\nFor the devices referred to in the first subparagraph, the notified body shall include a reference to the Basic UDI-DI on the certificate issued in accordance with point\u00a0(a) of Section\u00a04 of Chapter I of Annex\u00a0XII and confirm in Eudamed that the information referred to in Section\u00a02.2 of Part A of Annex\u00a0VI is correct. After the issuing of the relevant certificate and before placing the device on the market, the manufacturer shall provide the Basic UDI-DI to the UDI database together with the other core data elements referred to in Part B of Annex\u00a0VI related to that device.\n\n\n4.\u00a0\u00a0\u00a0Before placing a device on the market, other than a custom-made device, the manufacturer shall enter or if, already provided, verify in Eudamed the information referred to in Section\u00a02 of Part A of Annex\u00a0VI, with the exception of Section\u00a02.2 thereof, and shall thereafter keep the information updated.\n\n\n\nArticle\u00a030\n\nElectronic system for registration of economic operators\n\n\n1.\u00a0\u00a0\u00a0The Commission, after consulting the MDCG, shall set up and manage an electronic system to create the single registration number referred to in Article\u00a031(2) and to collate and process information that is necessary and proportionate to identify the manufacturer and, where applicable, the authorised representative and the importer. The details regarding the information to be provided to that electronic system by the economic operators are laid down in Section\u00a01 of Part A of Annex\u00a0VI.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States may maintain or introduce national provisions on registration of distributors of devices which have been made available on their territory.\n\n\n3.\u00a0\u00a0\u00a0Within two weeks of placing a device, other than a custom-made device, on the market, importers shall verify that the manufacturer or authorised representative has provided to the electronic system the information referred to in paragraph\u00a01.\nWhere applicable, importers shall inform the relevant authorised representative or manufacturer if the information referred to in paragraph\u00a01 is not included or is incorrect. Importers shall add their details to the relevant entry/entries.\n\n\n\nArticle\u00a031\n\nRegistration of manufacturers, authorised representatives and importers\n\n\n1.\u00a0\u00a0\u00a0Before placing a device, other than a custom-made device, on the market, manufacturers, authorised representatives and importers shall, in order to register, submit to the electronic system referred to in Article\u00a030 the information referred to in Section\u00a01 of Part A of Annex\u00a0VI, provided that they have not already registered in accordance with this Article. In cases where the conformity assessment procedure requires the involvement of a notified body pursuant to Article\u00a052, the information referred to in Section\u00a01 of Part\u00a0A of Annex\u00a0VI shall be provided to that electronic system before applying to the notified body.\n\n\n2.\u00a0\u00a0\u00a0After having verified the data entered pursuant to paragraph\u00a01, the competent authority shall obtain a single registration number (\u2018SRN\u2019) from the electronic system referred to in Article\u00a030 and issue it to the manufacturer, the authorised representative or the importer.\n\n\n3.\u00a0\u00a0\u00a0The manufacturer shall use the SRN when applying to a notified body for conformity assessment and for accessing Eudamed in order to fulfil its obligations under Article\u00a029.\n\n\n4.\u00a0\u00a0\u00a0Within one week of any change occurring in relation to the information referred to in paragraph\u00a01 of this Article, the economic operator shall update the data in the electronic system referred to in Article\u00a030.\n\n\n5.\u00a0\u00a0\u00a0Not later than one year after submission of the information in accordance with paragraph\u00a01, and every second year thereafter, the economic operator shall confirm the accuracy of the data. In the event of a failure to do so within six months of those deadlines, any Member\u00a0State may take appropriate corrective measures within its territory until that economic operator complies with that obligation.\n\n\n6.\u00a0\u00a0\u00a0Without prejudice to the economic operator's responsibility for the data, the competent authority shall verify the confirmed data referred to in Section\u00a01 of Part A of Annex\u00a0VI.\n\n\n7.\u00a0\u00a0\u00a0The data entered pursuant to paragraph\u00a01 of this Article\u00a0in the electronic system referred to in Article\u00a030 shall be accessible to the public.\n\n\n8.\u00a0\u00a0\u00a0The competent authority may use the data to charge the manufacturer, the authorised representative or the importer a fee pursuant to Article\u00a0111.\n\n\n\nArticle\u00a032\n\nSummary of safety and clinical performance\n\n\n1.\u00a0\u00a0\u00a0For implantable devices and for class III devices, other than custom-made or investigational devices, the manufacturer shall draw up a summary of safety and clinical performance.\nThe summary of safety and clinical performance shall be written in a way that is clear to the intended user and, if relevant, to the patient and shall be made available to the public via Eudamed.\nThe draft of the summary of safety and clinical performance shall be part of the documentation to be submitted to the notified body involved in the conformity assessment pursuant to Article\u00a052 and shall be validated by that body. After its validation, the notified body shall upload the summary to Eudamed. The manufacturer shall mention on the label or instructions for use where the summary is available.\n\n\n2.\u00a0\u00a0\u00a0The summary of safety and clinical performance shall include at least the following aspects:\n\n\n\n\n\n\n(a)\n\n\nthe identification of the device and the manufacturer, including the Basic UDI-DI and, if already issued, the SRN;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe intended purpose of the device and any indications, contraindications and target populations;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\na description of the device, including a reference to previous generation(s) or variants if such exist, and a description of the differences, as well as, where relevant, a description of any accessories, other devices and products, which are intended to be used in combination with the device;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\npossible diagnostic or therapeutic alternatives;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nreference to any harmonised standards and CS applied;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe summary of clinical evaluation as referred to in Annex\u00a0XIV, and relevant information on post-market clinical follow-up;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nsuggested profile and training for users;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\ninformation on any residual risks and any undesirable effects, warnings and precautions.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, set out the form and the presentation of the data elements to be included in the summary of safety and clinical performance. Those implementing acts shall be adopted in accordance with the advisory procedure referred to in Article\u00a0114(2).\n\n\n\nArticle\u00a033\n\nEuropean database on medical devices\n\n\n1.\u00a0\u00a0\u00a0The Commission, after consulting the MDCG, shall set up, maintain and manage the European database on medical devices (\u2018Eudamed\u2019) for the following purposes:\n\n\n\n\n\n\n(a)\n\n\nto enable the public to be adequately informed about devices placed on the market, the corresponding certificates issued by notified bodies and about the relevant economic operators;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nto enable unique identification of devices within the internal market and to facilitate their traceability;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nto enable the public to be adequately informed about clinical investigations and to enable sponsors of clinical investigations to comply with obligations under Articles\u00a062 to 80, Article\u00a082, and any acts adopted pursuant to Article\u00a081;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nto enable manufacturers to comply with the information obligations laid down in Articles\u00a087 to 90 or in any acts adopted pursuant to Article\u00a091;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nto enable the competent authorities of the Member\u00a0States and the Commission to carry out their tasks relating to this Regulation on a well-informed basis and to enhance the cooperation between them.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0Eudamed shall include the following electronic systems:\n\n\n\n\n\n\n(a)\n\n\nthe electronic system for registration of devices referred to in Article\u00a029(4);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe UDI-database referred to in Article\u00a028;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe electronic system on registration of economic operators referred to in Article\u00a030;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe electronic system on notified bodies and on certificates referred to in Article\u00a057;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe electronic system on clinical investigations referred to in Article\u00a073;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe electronic system on vigilance and post-market surveillance referred to in Article\u00a092;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthe electronic system on market surveillance referred to in Article\u00a0100.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0When designing Eudamed the Commission shall give due consideration to compatibility with national databases and national web-interfaces to allow for import and export of data.\n\n\n4.\u00a0\u00a0\u00a0The data shall be entered into Eudamed by the Member\u00a0States, notified bodies, economic operators and sponsors as specified in the provisions on the electronic systems referred to in paragraph\u00a02. The Commission shall provide for technical and administrative support to users of Eudamed.\n\n\n5.\u00a0\u00a0\u00a0All the information collated and processed by Eudamed shall be accessible to the Member\u00a0States and to the Commission. The information shall be accessible to notified bodies, economic operators, sponsors and the public to the extent specified in the provisions on the electronic systems referred to in paragraph\u00a02.\nThe Commission shall ensure that public parts of Eudamed are presented in a user-friendly and easily-searchable format.\n\n\n6.\u00a0\u00a0\u00a0Eudamed shall contain personal data only insofar as necessary for the electronic systems referred to in paragraph\u00a02 of this Article\u00a0to collate and process information in accordance with this Regulation. Personal data shall be kept in a form which permits identification of data subjects for periods no longer than those referred to in Article\u00a010(8).\n\n\n7.\u00a0\u00a0\u00a0The Commission and the Member\u00a0States shall ensure that data subjects may effectively exercise their rights to information, of access, to rectification and to object in accordance with Regulation\u00a0(EC)\u00a0No\u00a045/2001 and Directive\u00a095/46/EC, respectively. They shall also ensure that data subjects may effectively exercise the right of access to data relating to them, and the right to have inaccurate or incomplete data corrected and erased. Within their respective responsibilities, the Commission and the Member\u00a0States shall ensure that inaccurate and unlawfully processed data are deleted, in accordance with the applicable legislation. Corrections and deletions shall be carried out as soon as possible, but no later than 60\u00a0days after a request is made by a data subject.\n\n\n8.\u00a0\u00a0\u00a0The Commission shall, by means of implementing acts, lay down the detailed arrangements necessary for the setting up and maintenance of Eudamed. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3). When adopting those implementing acts, the Commission shall ensure that, as far as possible, the system is developed in such a way as to avoid having to enter the same information twice within the same module or in different modules of the system.\n\n\n9.\u00a0\u00a0\u00a0In relation to its responsibilities under this Article\u00a0and the processing of personal data involved therein, the Commission shall be considered to be the controller of Eudamed and its electronic systems.\n\n\n\nArticle\u00a034\n\nFunctionality of Eudamed\n\n\n1.\u00a0\u00a0\u00a0The Commission shall, in collaboration with the MDCG, draw up the functional specifications for Eudamed. The Commission shall draw up a plan for the implementation of those specifications by 26 May 2018. That plan shall seek to ensure that Eudamed is fully functional at a date that allows the Commission to publish the notice referred to in paragraph\u00a03 of this Article\u00a0by 25 March 2020 and that all other relevant deadlines laid down in Article\u00a0123 of this Regulation and in Article\u00a0113 of Regulation\u00a0(EU)\u00a02017/746 are met.\n\n\n2.\u00a0\u00a0\u00a0The Commission shall, on the basis of an independent audit report, inform the MDCG when it has verified that Eudamed has achieved full functionality and Eudamed meets the functional specifications drawn up pursuant to paragraph\u00a01.\n\n\n3.\u00a0\u00a0\u00a0The Commission shall, after consultation with the MDCG and when it is satisfied that the conditions referred to in paragraph\u00a02 have been fulfilled, publish a notice to that effect in the Official Journal of the European Union.\n\n\n\n\nCHAPTER IV\n\n\nNOTIFIED BODIES\n\n\n\nArticle\u00a035\n\nAuthorities responsible for notified bodies\n\n\n1.\u00a0\u00a0\u00a0Any Member\u00a0State that intends to designate a conformity assessment body as a notified body, or has designated a notified body, to carry out conformity assessment activities under this Regulation shall appoint an authority (\u2018authority responsible for notified bodies\u2019), which may consist of separate constituent entities under national law and shall be responsible for setting up and carrying out the necessary procedures for the assessment, designation and notification of conformity assessment bodies and for the monitoring of notified bodies, including subcontractors and subsidiaries of those bodies.\n\n\n2.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall be established, organised and operated so as to safeguard the objectivity and impartiality of its activities and to avoid any conflicts of interests with conformity assessment bodies.\n\n\n3.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall be organised in a manner such that each decision relating to designation or notification is taken by personnel different from those who carried out the assessment.\n\n\n4.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall not perform any activities that notified bodies perform on a commercial or competitive basis.\n\n\n5.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall safeguard the confidential aspects of the information it obtains. However, it shall exchange information on notified bodies with other Member\u00a0States, the Commission and, when required, with other regulatory authorities.\n\n\n6.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall have a sufficient number of competent personnel permanently available for the proper performance of its tasks.\nWhere the authority responsible for notified bodies is a different authority from the national competent authority for medical devices, it shall ensure that the national authority responsible for medical devices is consulted on relevant matters.\n\n\n7.\u00a0\u00a0\u00a0Member\u00a0States shall make publicly available general information on their measures governing the assessment, designation and notification of conformity assessment bodies and for the monitoring of notified bodies, and on changes which have a significant impact on such tasks.\n\n\n8.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall participate in the peer-review activities provided for in Article\u00a048.\n\n\n\nArticle\u00a036\n\nRequirements relating to notified bodies\n\n\n1.\u00a0\u00a0\u00a0Notified bodies shall fulfil the tasks for which they are designated in accordance with this Regulation. They shall satisfy the organisational and general requirements and the quality management, resource and process requirements that are necessary to fulfil those tasks. In particular, notified bodies shall comply with Annex\u00a0VII.\nIn order to meet the requirements referred to in the first subparagraph, notified bodies shall have permanent availability of sufficient administrative, technical and scientific personnel in accordance with Section\u00a03.1.1 of Annex\u00a0VII and personnel with relevant clinical expertise in accordance with Section\u00a03.2.4 of Annex\u00a0VII, where possible employed by the notified body itself.\nThe personnel referred to in Sections 3.2.3 and 3.2.7 of Annex\u00a0VII shall be employed by the notified body itself and shall not be external experts or subcontractors.\n\n\n2.\u00a0\u00a0\u00a0Notified bodies shall make available and submit upon request all relevant documentation, including the manufacturer's documentation, to the authority responsible for notified bodies to allow it to conduct its assessment, designation, notification, monitoring and surveillance activities and to facilitate the assessment outlined in this Chapter.\n\n\n3.\u00a0\u00a0\u00a0In order to ensure the uniform application of the requirements set out in Annex\u00a0VII, the Commission may adopt implementing acts, to the extent necessary to resolve issues of divergent interpretation and of practical application. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a037\n\nSubsidiaries and subcontracting\n\n\n1.\u00a0\u00a0\u00a0Where a notified body subcontracts specific tasks connected with conformity assessment or has recourse to a subsidiary for specific tasks connected with conformity assessment, it shall verify that the subcontractor or the subsidiary meets the applicable requirements set out in Annex\u00a0VII and shall inform the authority responsible for notified bodies accordingly.\n\n\n2.\u00a0\u00a0\u00a0Notified bodies shall take full responsibility for the tasks performed on their behalf by subcontractors or subsidiaries.\n\n\n3.\u00a0\u00a0\u00a0Notified bodies shall make publicly available a list of their subsidiaries.\n\n\n4.\u00a0\u00a0\u00a0Conformity assessment activities may be subcontracted or carried out by a subsidiary provided that the legal or natural person that applied for conformity assessment has been informed accordingly.\n\n\n5.\u00a0\u00a0\u00a0Notified bodies shall keep at the disposal of the authority responsible for notified bodies all relevant documents concerning the verification of the qualifications of the subcontractor or the subsidiary and the work carried out by them under this Regulation.\n\n\n\nArticle\u00a038\n\nApplication by conformity assessment bodies for designation\n\n\n1.\u00a0\u00a0\u00a0Conformity assessment bodies shall submit an application for designation to the authority responsible for notified bodies.\n\n\n2.\u00a0\u00a0\u00a0The application shall specify the conformity assessment activities as defined in this Regulation, and the types of devices for which the body is applying to be designated, and shall be supported by documentation demonstrating compliance with Annex\u00a0VII.\nIn respect of the organisational and general requirements and the quality management requirements set out in Sections\u00a01 and 2 of Annex\u00a0VII, a valid accreditation certificate and the corresponding evaluation report delivered by a national accreditation body in accordance with Regulation\u00a0(EC)\u00a0No\u00a0765/2008 may be submitted and shall be taken into consideration during the assessment described in Article\u00a039. However, the applicant shall make available all the documentation referred to in the first subparagraph\u00a0to demonstrate compliance with those requirements upon request.\n\n\n3.\u00a0\u00a0\u00a0The notified body shall update the documentation referred to in paragraph\u00a02 whenever relevant changes occur, in order to enable the authority responsible for notified bodies to monitor and verify continuous compliance with all the requirements set out in Annex\u00a0VII.\n\n\n\nArticle\u00a039\n\nAssessment of the application\n\n\n1.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall within 30 days check that the application referred to in Article\u00a038 is complete and shall request the applicant to provide any missing information. Once the application is complete that authority shall send it to the Commission.\nThe authority responsible for notified bodies shall review the application and supporting documentation in accordance with its own procedures and shall draw up a preliminary assessment report.\n\n\n2.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall submit the preliminary assessment report to the Commission which shall immediately transmit it to the MDCG.\n\n\n3.\u00a0\u00a0\u00a0Within 14 days of the submission referred to in paragraph\u00a02 of this Article, the Commission, in conjunction with the MDCG, shall appoint a joint assessment team made up of three experts, unless the specific circumstances require a different number of experts, chosen from the list referred to in Article\u00a040(2). One of the experts shall be a representative of the Commission who shall coordinate the activities of the joint assessment team. The other two experts shall come from Member\u00a0States other than the one in which the applicant conformity assessment body is established.\nThe joint assessment team shall be comprised of experts who are competent to assess the conformity assessment activities and the types of devices which are the subject of the application or, in particular when the assessment procedure is initiated in accordance with Article\u00a047(3), to ensure that the specific concern can be appropriately assessed.\n\n\n4.\u00a0\u00a0\u00a0Within 90 days of its appointment, the joint assessment team shall review the documentation submitted with the application in accordance with Article\u00a038. The joint assessment team may provide feedback to, or require clarification from, the authority responsible for notified bodies on the application and on the planned on-site assessment.\nThe authority responsible for notified bodies together with the joint assessment team shall plan and conduct an on-site assessment of the applicant conformity assessment body and, where relevant, of any subsidiary or subcontractor, located inside or outside the Union, to be involved in the conformity assessment process.\nThe on-site assessment of the applicant body shall be led by the authority responsible for notified bodies.\n\n\n5.\u00a0\u00a0\u00a0Findings regarding non-compliance of an applicant conformity assessment body with the requirements set out in Annex\u00a0VII shall be raised during the assessment process and discussed between the authority responsible for notified bodies and the joint assessment team with a view to reaching consensus and resolving any diverging opinions, with respect to the assessment of the application.\nAt the end of the on-site assessment, the authority responsible for notified bodies shall list for the applicant conformity assessment body the non-compliances resulting from the assessment and summarise the assessment by the joint assessment team.\nWithin a specified timeframe, the applicant conformity assessment body shall submit to the national authority a corrective and preventive action plan to address the non-compliances.\n\n\n6.\u00a0\u00a0\u00a0The joint assessment team shall document any remaining diverging opinions with respect to the assessment within 30 days of completion of the on-site assessment and send them to the authority responsible for notified bodies.\n\n\n7.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall following receipt of a corrective and preventive action plan from the applicant body assess whether non-compliances identified during the assessment have been appropriately addressed. This plan shall indicate the root cause of the identified non-compliances and shall include a timeframe for implementation of the actions therein.\nThe authority responsible for notified bodies shall having confirmed the corrective and preventive action plan forward it and its opinion thereon to the joint assessment team. The joint assessment team may request of the authority responsible for notified bodies further clarification and modifications.\nThe authority responsible for notified bodies shall draw up its final assessment report which shall include:\n\n\n\n\n\n\n\u2014\n\n\nthe result of the assessment,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nconfirmation that the corrective and preventive actions have been appropriately addressed and, where required, implemented,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nany remaining diverging opinion with the joint assessment team, and, where applicable,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe recommended scope of designation.\n\n\n\n\n\n\n8.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall submit its final assessment report and, if applicable, the draft designation to the Commission, the MDCG and the joint assessment team.\n\n\n9.\u00a0\u00a0\u00a0The joint assessment team shall provide a final opinion regarding the assessment report prepared by the authority responsible for notified bodies and, if applicable, the draft designation within 21 days of receipt of those documents to the Commission, which shall immediately submit that final opinion to the MDCG. Within 42 days of receipt of the opinion of the joint assessment team, the MDCG shall issue a recommendation with regard to the draft designation, which the authority responsible for notified bodies shall duly take into consideration for its decision on the designation of the notified body.\n\n\n10.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, adopt measures setting out the detailed arrangements specifying procedures and reports for the application for designation referred to in Article\u00a038 and the assessment of the application set out in this Article. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a040\n\nNomination of experts for joint assessment of applications for notification\n\n\n1.\u00a0\u00a0\u00a0The Member\u00a0States and the Commission shall nominate experts qualified in the assessment of conformity assessment bodies in the field of medical devices to participate in the activities referred to in Articles\u00a039 and 48.\n\n\n2.\u00a0\u00a0\u00a0The Commission shall maintain a list of the experts nominated pursuant to paragraph\u00a01 of this Article, together with information on their specific field of competence and expertise. That list shall be made available to Member\u00a0States competent authorities through the electronic system referred to in Article\u00a057.\n\n\n\nArticle\u00a041\n\nLanguage requirements\n\nAll documents required pursuant to Articles\u00a038 and 39 shall be drawn up in a language or languages which shall be determined by the Member\u00a0State concerned.\nMember\u00a0States, in applying the first paragraph, shall consider accepting and using a commonly understood language in the medical field, for all or part of the documentation concerned.\nThe Commission shall provide translations of the documentation pursuant to Articles\u00a038 and 39, or parts thereof into an official Union language, such as is necessary for that documentation to be readily understood by the joint assessment team appointed in accordance with Article\u00a039(3).\n\n\nArticle\u00a042\n\nDesignation and notification procedure\n\n\n1.\u00a0\u00a0\u00a0Member\u00a0States may only designate conformity assessment bodies for which the assessment pursuant to Article\u00a039 was completed and which comply with Annex\u00a0VII.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States shall notify the Commission and the other Member\u00a0States of the conformity assessment bodies they have designated, using the electronic notification tool within the database of notified bodies developed and managed by the Commission\u00a0(NANDO).\n\n\n3.\u00a0\u00a0\u00a0The notification shall clearly specify, using the codes referred to in paragraph\u00a013 of this Article, the scope of the designation indicating the conformity assessment activities as defined in this Regulation and the types of devices which the notified body is authorised to assess and, without prejudice to Article\u00a044, any conditions associated with the designation.\n\n\n4.\u00a0\u00a0\u00a0The notification shall be accompanied by the final assessment report of the authority responsible for notified bodies, the final opinion of the joint assessment team referred to in Article\u00a039(9) and the recommendation of the MDCG. Where the notifying Member\u00a0State does not follow the recommendation of the MDCG, it shall provide a duly substantiated justification.\n\n\n5.\u00a0\u00a0\u00a0The notifying Member\u00a0State shall, without prejudice to Article\u00a044, inform the Commission and the other Member\u00a0States of any conditions associated with the designation and provide documentary evidence regarding the arrangements in place to ensure that the notified body will be monitored regularly and will continue to satisfy the requirements set out in Annex\u00a0VII.\n\n\n6.\u00a0\u00a0\u00a0Within 28 days of the notification referred to in paragraph\u00a02, a Member\u00a0State or the Commission may raise written objections, setting out its arguments, with regard either to the notified body or to its monitoring by the authority responsible for notified bodies. Where no objection is raised, the Commission shall publish in NANDO the notification within 42 days of its having been notified as referred to in paragraph\u00a02.\n\n\n7.\u00a0\u00a0\u00a0When a Member\u00a0State or the Commission raises objections in accordance with paragraph\u00a06, the Commission shall bring the matter before the MDCG within 10 days of the expiry of the period referred to in paragraph\u00a06. After consulting the parties involved, the MDCG shall give its opinion at the latest within 40 days of the matter having been brought before it. Where the MDCG is of the opinion that the notification can be accepted, the Commission shall publish in NANDO the notification within 14 days.\n\n\n8.\u00a0\u00a0\u00a0Where the MDCG, after having been consulted in accordance with paragraph\u00a07, confirms the existing objection or raises another objection, the notifying Member\u00a0State shall provide a written response to the MDCG opinion within 40\u00a0days of its receipt. The response shall address the objections raised in the opinion, and set out the reasons for the notifying Member\u00a0State's decision to designate or not designate the conformity assessment body.\n\n\n9.\u00a0\u00a0\u00a0Where the notifying Member\u00a0State decides to uphold its decision to designate the conformity assessment body, having given its reasons in accordance with paragraph\u00a08, the Commission shall publish in NANDO the notification within 14 days of being informed thereof.\n\n\n10.\u00a0\u00a0\u00a0When publishing the notification in NANDO, the Commission shall also add to the electronic system referred to in Article\u00a057 the information relating to the notification of the notified body along with the documents mentioned in paragraph\u00a04 of this Article\u00a0and the opinion and responses referred to in paragraphs 7 and 8 of this Article.\n\n\n11.\u00a0\u00a0\u00a0The designation shall become valid the day after the notification is published in NANDO. The published notification shall state the scope of lawful conformity assessment activity of the notified body.\n\n\n12.\u00a0\u00a0\u00a0The conformity assessment body concerned may perform the activities of a notified body only after the designation has become valid in accordance with paragraph\u00a011.\n\n\n13.\u00a0\u00a0\u00a0The Commission shall by 26 November 2017, by means of implementing acts, draw up a list of codes and corresponding types of devices for the purpose of specifying the scope of the designation of notified bodies. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3). The Commission, after consulting the MDCG, may update this list based, inter\u00a0alia, on information arising from the coordination activities described in Article\u00a048.\n\n\n\nArticle\u00a043\n\nIdentification number and list of notified bodies\n\n\n1.\u00a0\u00a0\u00a0The Commission shall assign an identification number to each notified body for which the notification becomes valid in accordance with Article\u00a042(11). It shall assign a single identification number even when the body is notified under several Union acts. If they are successfully designated in accordance with this Regulation, bodies notified pursuant to Directives\u00a090/385/EEC and 93/42/EEC shall retain the identification number assigned to them pursuant to those Directives.\n\n\n2.\u00a0\u00a0\u00a0The Commission shall make the list of the bodies notified under this Regulation, including the identification numbers that have been assigned to them and the conformity assessment activities as defined in this Regulation and the types of devices for which they have been notified, accessible to the public in NANDO. It shall also make this list available on the electronic system referred to in Article\u00a057. The Commission shall ensure that the list is kept up to date.\n\n\n\nArticle\u00a044\n\nMonitoring and re-assessment of notified bodies\n\n\n1.\u00a0\u00a0\u00a0Notified bodies shall, without delay, and at the latest within 15 days, inform the authority responsible for notified bodies of relevant changes which may affect their compliance with the requirements set out in Annex\u00a0VII or their ability to conduct the conformity assessment activities relating to the devices for which they have been designated.\n\n\n2.\u00a0\u00a0\u00a0The authorities responsible for notified bodies shall monitor the notified bodies established on their territory and their subsidiaries and subcontractors to ensure ongoing compliance with the requirements and the fulfilment of its obligations set out in this Regulation. Notified bodies shall, upon request by their authority responsible for notified bodies, supply all relevant information and documents, required to enable the authority, the Commission and other Member\u00a0States to verify compliance.\n\n\n3.\u00a0\u00a0\u00a0Where the Commission or the authority of a Member\u00a0State submits a request to a notified body established on the territory of another Member\u00a0State relating to a conformity assessment carried out by that notified body, it shall send a copy of that request to the authority responsible for notified bodies of that other Member\u00a0State. The notified body concerned shall respond without delay and within 15 days at the latest to the request. The authority responsible for notified bodies of the Member\u00a0State in which the body is established shall ensure that requests submitted by authorities of any other Member\u00a0State or by the Commission are resolved by the notified body unless there is a legitimate reason for not doing so in which case the matter may be referred to the MDCG.\n\n\n4.\u00a0\u00a0\u00a0At least once a year, the authorities responsible for notified bodies shall re-assess whether the notified bodies established on their respective territory and, where appropriate, the subsidiaries and subcontractors under the responsibility of those notified bodies still satisfy the requirements and fulfil their obligations set out in Annex\u00a0VII. That review shall include an on-site audit of each notified body and, where necessary, of its subsidiaries and subcontractors.\nThe authority responsible for notified bodies shall conduct its monitoring and assessment activities according to an annual assessment plan to ensure that it can effectively monitor the continued compliance of the notified body with the requirements of this Regulation. That plan shall provide a reasoned schedule for the frequency of assessment of the notified body and, in particular, associated subsidiaries and subcontractors. The authority shall submit its annual plan for monitoring or assessment for each notified body for which it is responsible to the MDCG and to the Commission.\n\n\n5.\u00a0\u00a0\u00a0The monitoring of notified bodies by the authority responsible for notified bodies shall include observed audits of notified body personnel, including where necessary any personnel from subsidiaries and subcontractors, as that personnel is in the process of conducting quality management system assessments at a manufacturer's facility.\n\n\n6.\u00a0\u00a0\u00a0The monitoring of notified bodies conducted by the authority responsible for notified bodies shall consider data arising from market surveillance, vigilance and post-market surveillance to help guide its activities.\nThe authority responsible for notified bodies shall provide for a systematic follow-up of complaints and other information, including from other Member\u00a0States, which may indicate non-fulfilment of the obligations by a notified body or its deviation from common or best practice.\n\n\n7.\u00a0\u00a0\u00a0The authority responsible for notified bodies may in addition to regular monitoring or on-site assessments conduct short-notice, unannounced or \u2018for-cause\u2019 reviews if needed to address a particular issue or to verify compliance.\n\n\n8.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall review the assessments by notified bodies of manufacturers' technical documentation, in particular the clinical evaluation documentation as further outlined in Article\u00a045.\n\n\n9.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall document and record any findings regarding non-compliance of the notified body with the requirements set out in Annex\u00a0VII and shall monitor the timely implementation of corrective and preventive actions.\n\n\n10.\u00a0\u00a0\u00a0Three years after notification of a notified body, and again every fourth year thereafter, a complete re-assessment to determine whether the notified body still satisfies the requirements set out in Annex\u00a0VII shall be conducted by the authority responsible for notified bodies of the Member\u00a0State in which the body is established and by a joint assessment team appointed for the purpose of the procedure described in Articles\u00a038 and\u00a039.\n\n\n11.\u00a0\u00a0\u00a0The Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 in order to amend paragraph\u00a010 to modify the frequency at which the complete re-assessment referred to in that paragraph\u00a0is to be carried out.\n\n\n12.\u00a0\u00a0\u00a0The Member\u00a0States shall report to the Commission and to the MDCG, at least once a year, on their monitoring and on-site assessment activities regarding notified bodies and, where applicable, subsidiaries and subcontractors. The report shall provide details of the outcome of those activities, including activities pursuant to paragraph\u00a07, and shall be treated as confidential by the MDCG and the Commission; however it shall contain a summary which shall be made publicly available.\nThe summary of the report shall be uploaded to the electronic system referred to in Article\u00a057.\n\n\n\nArticle\u00a045\n\nReview of notified body assessment of technical documentation and clinical evaluation documentation\n\n\n1.\u00a0\u00a0\u00a0The authority responsible for notified bodies, as part of its ongoing monitoring of notified bodies, shall review an appropriate number of notified body assessments of manufacturers' technical documentation, in particular the clinical evaluation documentation as referred to in points (c) and (d) of Section\u00a06.1 of Annex\u00a0II to verify the conclusions drawn by the notified body based on the information presented by the manufacturer. The reviews by the authority responsible for notified bodies shall be conducted both off-site and on-site.\n\n\n2.\u00a0\u00a0\u00a0The sampling of files to be reviewed in accordance with paragraph\u00a01 shall be planned and representative of the types and risk of devices certified by the notified body, in particular high-risk devices, and be appropriately justified and documented in a sampling plan, which shall be made available by the authority responsible for notified bodies to the MDCG upon request.\n\n\n3.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall review whether the assessment by the notified body was conducted appropriately and shall check the procedures used, associated documentation and the conclusions drawn by the notified body. Such checking shall include the technical documentation and clinical evaluation documentation of the manufacturer upon which the notified body has based its assessment. Such reviews shall be conducted utilising CS.\n\n\n4.\u00a0\u00a0\u00a0Those reviews shall also form part of the re-assessment of notified bodies in accordance with Article\u00a044(10) and the joint assessment activities referred to in Article\u00a047(3). The reviews shall be conducted utilising appropriate expertise.\n\n\n5.\u00a0\u00a0\u00a0Based on the reports of the reviews and assessments by the authority responsible for notified bodies or joint assessment teams, on input from the market surveillance, vigilance and post-market surveillance activities described in Chapter\u00a0VII, on the continuous monitoring of technical progress, or on the identification of concerns and emerging issues concerning the safety and performance of devices, the MDCG may recommend that the sampling, carried out under this Article, cover a greater or lesser proportion of the technical documentation and clinical evaluation documentation assessed by a notified body.\n\n\n6.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, adopt measures setting out the detailed arrangements, associated documents for, and coordination of, the review of assessments of technical documentation and clinical evaluation documentation, as referred to in this Article. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a046\n\nChanges to designations and notifications\n\n\n1.\u00a0\u00a0\u00a0The authority responsible for notified bodies shall notify the Commission and the other Member\u00a0States of any relevant changes to the designation of a notified body.\nThe procedures described in Article\u00a039 and in Article\u00a042 shall apply to extensions of the scope of the designation.\nFor changes to the designation other than extensions of its scope, the procedures laid down in the following paragraphs shall apply.\n\n\n2.\u00a0\u00a0\u00a0The Commission shall immediately publish the amended notification in NANDO. The Commission shall immediately enter information on the changes to the designation of the notified body in the electronic system referred to in Article\u00a057.\n\n\n3.\u00a0\u00a0\u00a0Where a notified body decides to cease its conformity assessment activities it shall inform the authority responsible for notified bodies and the manufacturers concerned as soon as possible and in the case of a planned cessation one year before ceasing its activities. The certificates may remain valid for a temporary period of nine months after cessation of the notified body's activities on condition that another notified body has confirmed in writing that it will assume responsibilities for the devices covered by those certificates. The new notified body shall complete a full assessment of the devices affected by the end of that period before issuing new certificates for those devices. Where the notified body has ceased its activity, the authority responsible for notified bodies shall withdraw the designation.\n\n\n4.\u00a0\u00a0\u00a0Where a authority responsible for notified bodies has ascertained that a notified body no longer meets the requirements set out in Annex\u00a0VII, or that it is failing to fulfil its obligations or has not implemented the necessary corrective measures, the authority shall suspend, restrict, or fully or partially withdraw the designation, depending on the seriousness of the failure to meet those requirements or fulfil those obligations. A\u00a0suspension shall not exceed a period of one year, renewable once for the same period.\nThe authority responsible for notified bodies shall immediately inform the Commission and the other Member\u00a0States of any suspension, restriction or withdrawal of a designation.\n\n\n5.\u00a0\u00a0\u00a0Where its designation has been suspended, restricted, or fully or partially withdrawn, the notified body shall inform the manufacturers concerned at the latest within 10 days.\n\n\n6.\u00a0\u00a0\u00a0In the event of restriction, suspension or withdrawal of a designation, the authority responsible for notified bodies shall take appropriate steps to ensure that the files of the notified body concerned are kept and make them available to authorities in other Member\u00a0States responsible for notified bodies and to authorities responsible for market surveillance at their request.\n\n\n7.\u00a0\u00a0\u00a0In the event of restriction, suspension or withdrawal of a designation, the authority responsible for notified bodies shall:\n\n\n\n\n\n\n(a)\n\n\nassess the impact on the certificates issued by the notified body;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nsubmit a report on its findings to the Commission and the other Member\u00a0States within three months of having notified the changes to the designation;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nrequire the notified body to suspend or withdraw, within a reasonable period of time determined by the authority, any certificates which were unduly issued to ensure the safety of devices on the market;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nenter into the electronic system referred to in Article\u00a057 information in relation to certificates of which it has required their suspension or withdrawal;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\ninform the competent authority for medical devices of the Member\u00a0State in which the manufacturer has its registered place of business through the electronic system referred to in Article\u00a057 of the certificates for which it has required suspension or withdrawal. That competent authority shall take the appropriate measures, where necessary to avoid a potential risk to the health or safety of patients, users or others.\n\n\n\n\n\n\n8.\u00a0\u00a0\u00a0With the exception of certificates unduly issued, and where a designation has been suspended or restricted, the certificates shall remain valid in the following circumstances:\n\n\n\n\n\n\n(a)\n\n\nthe authority responsible for notified bodies has confirmed, within one month of the suspension or restriction, that there is no safety issue in relation to certificates affected by the suspension or restriction, and the authority responsible for notified bodies has outlined a timeline and actions anticipated to remedy the suspension or restriction; or\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe authority responsible for notified bodies has confirmed that no certificates relevant to the suspension will be issued, amended or re-issued during the course of the suspension or restriction, and states whether the notified body has the capability of continuing to monitor and remain responsible for existing certificates issued for the period of the suspension or restriction. In the event that the authority responsible for notified bodies determines that the notified body does not have the capability to support existing certificates issued, the manufacturer shall provide, to the competent authority for medical devices of the Member\u00a0State in which the manufacturer of the device covered by the certificate has its registered place of business, within three months of the suspension or restriction, a written confirmation that another qualified notified body is temporarily assuming the functions of the notified body to monitor and remain responsible for the certificates during the period of suspension or restriction.\n\n\n\n\n\n\n9.\u00a0\u00a0\u00a0With the exception of certificates unduly issued, and where a designation has been withdrawn, the certificates shall remain valid for a period of nine months in the following circumstances:\n\n\n\n\n\n\n(a)\n\n\nwhere the competent authority for medical devices of the Member\u00a0State in which the manufacturer of the device covered by the certificate has its registered place of business has confirmed that there is no safety issue associated with the devices in question; and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nanother notified body has confirmed in writing that it will assume immediate responsibilities for those devices and will have completed assessment of them within twelve months of the withdrawal of the designation.\n\n\n\n\nIn the circumstances referred to in the first subparagraph, the competent authority for medical devices of the Member\u00a0State in which the manufacturer of the device covered by the certificate has its place of business may extend the provisional validity of the certificates for further periods of three months, which altogether shall not exceed twelve\u00a0months.\nThe authority or the notified body assuming the functions of the notified body affected by the change of designation shall immediately inform the Commission, the other Member\u00a0States and the other notified bodies thereof.\n\n\n\nArticle\u00a047\n\nChallenge to the competence of notified bodies\n\n\n1.\u00a0\u00a0\u00a0The Commission, in conjunction with the MDCG, shall investigate all cases where concerns have been brought to its attention regarding the continued fulfilment by a notified body, or of one or more of its subsidiaries or subcontractors, of the requirements set out in Annex\u00a0VII or the obligations to which they are subject. It shall ensure that the relevant authority responsible for notified bodies is informed and is given an opportunity to investigate those concerns.\n\n\n2.\u00a0\u00a0\u00a0The notifying Member\u00a0State shall provide the Commission, on request, with all information regarding the designation of the notified body concerned.\n\n\n3.\u00a0\u00a0\u00a0The Commission, in conjunction with the MDCG, may initiate, as applicable, the assessment procedure described in Article\u00a039(3) and (4), where there is reasonable concern about the ongoing compliance of a notified body or a subsidiary or subcontractor of the notified body with the requirements set out in Annex\u00a0VII and where the investigation by the authority responsible for notified bodies is not deemed to have fully addressed the concerns or upon request of the authority responsible for notified bodies. The reporting and outcome of that assessment shall follow the principles of Article\u00a039. Alternatively, depending on the severity of the issue, the Commission, in conjunction with the MDCG, may request that the authority responsible for notified bodies allow the participation of up to two experts from the list established pursuant to Article\u00a040 in an on-site assessment as part of the planned monitoring and assessment activities in accordance with Article\u00a044 and as outlined in the annual assessment plan described in Article\u00a044(4).\n\n\n4.\u00a0\u00a0\u00a0Where the Commission ascertains that a notified body no longer meets the requirements for its designation, it shall inform the notifying Member\u00a0State accordingly and request it to take the necessary corrective measures, including the suspension, restriction or withdrawal of the designation if necessary.\nWhere the Member\u00a0State fails to take the necessary corrective measures, the Commission may, by means of implementing acts, suspend, restrict or withdraw the designation. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3). It shall notify the Member\u00a0State concerned of its decision and update NANDO and the electronic system referred to in Article\u00a057.\n\n\n5.\u00a0\u00a0\u00a0The Commission shall ensure that all confidential information obtained in the course of its investigations is treated accordingly.\n\n\n\nArticle\u00a048\n\nPeer review and exchange of experience between authorities responsible for notified bodies\n\n\n1.\u00a0\u00a0\u00a0The Commission shall provide for the organisation of exchange of experience and coordination of administrative practice between the authorities responsible for notified bodies. Such exchange shall cover elements including:\n\n\n\n\n\n\n(a)\n\n\ndevelopment of best practice documents relating to the activities of the authorities responsible for notified bodies;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ndevelopment of guidance documents for notified bodies in relation to the implementation of this Regulation;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\ntraining and qualification of the experts referred to in Article\u00a040;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nmonitoring of trends relating to changes to notified body designations and notifications and trends in certificate withdrawals and transfers between notified bodies;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nmonitoring of the application and applicability of scope codes referred to in Article\u00a042(13);\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\ndevelopment of a mechanism for peer reviews between authorities and the Commission;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nmethods of communication to the public on the monitoring and surveillance activities of authorities and the Commission on notified bodies.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The authorities responsible for notified bodies shall participate in a peer review every third year through the mechanism developed pursuant to paragraph\u00a01 of this\u00a0Article. Such reviews shall normally be conducted in parallel with the on-site joint assessments described in Article\u00a039. Alternatively, an authority may make the choice of having such reviews take place as part of its monitoring activities referred to in Article\u00a044.\n\n\n3.\u00a0\u00a0\u00a0The Commission shall participate in the organisation and provide support to the implementation of the peer review mechanism.\n\n\n4.\u00a0\u00a0\u00a0The Commission shall compile an annual summary report of the peer review activities, which shall be made publicly available.\n\n\n5.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, adopt measures setting out the detailed arrangements and related documents for the peer review mechanism and training and qualification as referred to in paragraph\u00a01 of this Article. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a049\n\nCoordination of notified bodies\n\nThe Commission shall ensure that appropriate coordination and cooperation between notified bodies is put in place and operated in the form of a coordination group of notified bodies in the field of medical devices, including in vitro diagnostic medical devices. This group shall meet on a regular basis and at least annually.\nThe bodies notified under this Regulation shall participate in the work of that group.\nThe Commission may establish the specific arrangements for the functioning of the coordination group of notified bodies.\n\n\nArticle\u00a050\n\nList of standard fees\n\nNotified bodies shall establish lists of their standard fees for the conformity assessment activities that they carry out and shall make those lists publicly available.\n\n\n\nCHAPTER V\n\n\nCLASSIFICATION AND CONFORMITY ASSESSMENT\n\n\n\n\nSECTION\u00a01\n\n\n\n\nClassification\n\n\n\n\nArticle\u00a051\n\nClassification of devices\n\n\n1.\u00a0\u00a0\u00a0Devices shall be divided into classes I, IIa, IIb and III, taking into account the intended purpose of the devices and their inherent risks. Classification shall be carried out in accordance with Annex\u00a0VIII.\n\n\n2.\u00a0\u00a0\u00a0Any dispute between the manufacturer and the notified body concerned, arising from the application of Annex\u00a0VIII, shall be referred for a decision to the competent authority of the Member\u00a0State in which the manufacturer has its registered place of business. In cases where the manufacturer has no registered place of business in the Union and has not yet designated an authorised representative, the matter shall be referred to the competent authority of the Member\u00a0State in which the authorised representative referred to in the last indent of point\u00a0(b) of the second paragraph\u00a0of Section\u00a02.2 of Annex\u00a0IX has its registered place of business. Where the notified body concerned is established in a Member\u00a0State other than that of the manufacturer, the competent authority shall adopt its decision after consultation with the competent authority of the Member\u00a0State that designated the notified body.\nThe competent authority of the Member\u00a0State in which the manufacturer has its registered place of business shall notify the MDCG and the Commission of its decision. The decision shall be made available upon request.\n\n\n3.\u00a0\u00a0\u00a0At the request of a Member\u00a0State the Commission shall after consulting the MDCG, decide, by means of implementing acts, on the following:\n\n\n\n\n\n\n(a)\n\n\napplication of Annex\u00a0VIII to a given device, or category or group of devices, with a view to determining the classification of such devices;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthat a device, or category or group of devices, shall for reasons of public health based on new scientific evidence, or based on any information which becomes available in the course of the vigilance and market surveillance activities be reclassified, by way of derogation from Annex\u00a0VIII.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0The Commission may also, on its own initiative and after consulting the MDCG, decide, by means of implementing acts, on the issues referred to in points (a) and (b) of paragraph\u00a03.\n\n\n5.\u00a0\u00a0\u00a0In order to ensure the uniform application of Annex\u00a0VIII, and taking account of the relevant scientific opinions of the relevant scientific committees, the Commission may adopt implementing acts to the extent necessary to resolve issues of divergent interpretation and of practical application.\n\n\n6.\u00a0\u00a0\u00a0The implementing acts referred to in paragraphs 3, 4 and 5 of this Article\u00a0shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\n\n\nSECTION\u00a02\n\n\n\n\nConformity assessment\n\n\n\n\nArticle\u00a052\n\nConformity assessment procedures\n\n\n1.\u00a0\u00a0\u00a0Prior to placing a device on the market, manufacturers shall undertake an assessment of the conformity of that device, in accordance with the applicable conformity assessment procedures set out in Annexes\u00a0IX to XI.\n\n\n2.\u00a0\u00a0\u00a0Prior to putting into service a device that is not placed on the market, manufacturers shall undertake an assessment of the conformity of that device, in accordance with the applicable conformity assessment procedures set out in Annexes\u00a0IX to XI.\n\n\n3.\u00a0\u00a0\u00a0Manufacturers of class\u00a0III devices, other than custom-made or investigational devices, shall be subject to a conformity assessment as specified in Annex\u00a0IX. Alternatively, the manufacturer may choose to apply a conformity assessment as specified in Annex\u00a0X coupled with a conformity assessment as specified in Annex\u00a0XI.\n\n\n4.\u00a0\u00a0\u00a0Manufacturers of class IIb devices, other than custom-made or investigational devices, shall be subject to a conformity assessment as specified in Chapters\u00a0I and III of Annex\u00a0IX, and including an assessment of the technical documentation as specified in Section\u00a04 of that Annex\u00a0of at least one representative device per generic device group.\nHowever, for class\u00a0IIb implantable devices, except sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips and connectors, the assessment of the technical documentation as specified in Section 4 of Annex IX shall apply for every device.\nAlternatively, the manufacturer may choose to apply a conformity assessment based on type examination as specified in Annex\u00a0X coupled with a conformity assessment based on product conformity verification as specified in Annex\u00a0XI.\n\n\n5.\u00a0\u00a0\u00a0Where justified in view of well-established technologies, similar to those used in the exempted devices listed in the second subparagraph\u00a0of paragraph\u00a04 of this Article, being used in other class IIb implantable devices, or where justified in order to protect the health and safety of patients, users or other persons or other aspects of public health, the Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 to amend that list by adding other types of class IIb implantable devices to that list or removing devices therefrom.\n\n\n6.\u00a0\u00a0\u00a0Manufacturers of class IIa devices, other than custom-made or investigational devices, shall be subject to a conformity assessment as specified in Chapters\u00a0I and III of Annex\u00a0IX, and including an assessment of the technical documentation as specified in Section\u00a04 of that Annex\u00a0of at least one representative device for each category of devices.\nAlternatively, the manufacturer may choose to draw up the technical documentation set out in Annexes\u00a0II and III coupled with a conformity assessment as specified in Section\u00a010 or Section\u00a018 of Annex\u00a0XI. The assessment of the technical documentation shall apply for at least one representative device for each category of devices.\n\n\n7.\u00a0\u00a0\u00a0Manufacturers of class I devices, other than custom-made or investigational devices, shall declare the conformity of their products by issuing the EU\u00a0declaration of conformity referred to in Article\u00a019 after drawing up the technical documentation set out in Annexes\u00a0II and III. If those devices are placed on the market in sterile condition, have a measuring function or are reusable surgical instruments, the manufacturer shall apply the procedures set out in Chapters\u00a0I and III of Annex\u00a0IX, or in Part\u00a0A of Annex\u00a0XI. However, the involvement of the notified body in those procedures shall be limited:\n\n\n\n\n\n\n(a)\n\n\nin the case of devices placed on the market in sterile condition, to the aspects relating to establishing, securing and maintaining sterile conditions;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nin the case of devices with a measuring function, to the aspects relating to the conformity of the devices with the metrological requirements;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nin the case of reusable surgical instruments, to the aspects relating to the reuse of the device, in particular cleaning, disinfection, sterilization, maintenance and functional testing and the related instructions for use.\n\n\n\n\n\n\n8.\u00a0\u00a0\u00a0Manufacturers of custom-made devices shall follow the procedure set out in Annex\u00a0XIII and draw up the statement set out in Section\u00a01 of that Annex\u00a0before placing such devices on the market.\nIn addition to the procedure applicable pursuant to the first subparagraph, manufacturers of class III custom-made implantable devices shall be subject to the conformity assessment as specified in Chapter\u00a0I of Annex\u00a0IX. Alternatively, the manufacturer may choose to apply a conformity assessment as specified in Part A of Annex\u00a0XI.\n\n\n9.\u00a0\u00a0\u00a0In addition to the procedures applicable pursuant to paragraph\u00a03, 4, 6, or 7 of this Article, in the case of devices referred to in the first subparagraph\u00a0of Article\u00a01(8), the procedure specified in Section\u00a05.2 of Annex\u00a0IX or Section\u00a06 of Annex\u00a0X, as applicable, shall also apply.\n\n\n10.\u00a0\u00a0\u00a0In addition to the procedures applicable pursuant to paragraph\u00a03, 4, 6, or 7 of this Article, in the case of devices that are covered by this Regulation in accordance with point\u00a0(f) or (g) of Article\u00a01(6) and with the first subparagraph\u00a0of Article\u00a01(10), the procedure specified in Section\u00a05.3 of Annex\u00a0IX or Section\u00a06 of Annex\u00a0X, as applicable, shall also apply.\n\n\n11.\u00a0\u00a0\u00a0In addition to the procedures applicable pursuant to paragraph\u00a03, 4, 6, or 7, in the case of devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed by or locally dispersed in the human body, the procedure specified in Section\u00a05.4 of Annex\u00a0IX or Section\u00a06 of Annex\u00a0X, as applicable, shall also apply.\n\n\n12.\u00a0\u00a0\u00a0The Member\u00a0State in which the notified body is established may require that all or certain documents, including the technical documentation, audit, assessment and inspection reports, relating to the procedures referred to in paragraphs 1 to 7 and 9 to 11 be made available in an official Union language(s) determined by that Member\u00a0State. In the absence of such requirement, those documents shall be available in any official Union language acceptable to the notified body.\n\n\n13.\u00a0\u00a0\u00a0Investigational devices shall be subject to the requirements set out in Articles\u00a062 to\u00a081.\n\n\n14.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, specify detailed arrangements and procedural aspects with a view to ensuring the harmonised application of the conformity assessment procedures by the notified bodies for any of the following aspects:\n\n\n\n\n\n\n(a)\n\n\nthe frequency and the sampling basis of the assessment of the technical documentation on a representative basis as set out in the third paragraph\u00a0of Section\u00a02.3 and in Section\u00a03.5 of Annex\u00a0IX in the case of class\u00a0IIa and class\u00a0IIb devices, and in Section\u00a010.2 of Annex\u00a0XI in the case of class\u00a0IIa devices;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe minimum frequency of unannounced on-site audits and sample tests to be conducted by notified bodies in accordance with Section\u00a03.4 of Annex\u00a0IX, taking into account the risk-class and the type of device;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe physical, laboratory or other tests to be carried out by notified bodies in the context of sample tests, assessment of the technical documentation and type examination in accordance with Sections 3.4 and 4.3 of Annex\u00a0IX, Section\u00a03 of Annex\u00a0X and Section\u00a015 of Annex\u00a0XI.\n\n\n\n\nThe implementing acts referred to in the first subparagraph\u00a0shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a053\n\nInvolvement of notified bodies in conformity assessment procedures\n\n\n1.\u00a0\u00a0\u00a0Where the conformity assessment procedure requires the involvement of a notified body, the manufacturer may apply to a notified body of its choice, provided that the chosen notified body is designated for conformity assessment activities related to the types of devices concerned. The manufacturer may not lodge an application in parallel with another notified body for the same conformity assessment procedure.\n\n\n2.\u00a0\u00a0\u00a0The notified body concerned shall, by means of the electronic system referred to in Article\u00a057, inform the other notified bodies of any manufacturer that withdraws its application prior to the notified body's decision regarding the conformity assessment.\n\n\n3.\u00a0\u00a0\u00a0When applying to a notified body under paragraph\u00a01, manufacturers shall declare whether they have withdrawn an application with another notified body prior to the decision of that notified body and provide information about any previous application for the same conformity assessment that has been refused by another notified body.\n\n\n4.\u00a0\u00a0\u00a0The notified body may require any information or data from the manufacturer, which is necessary in order to properly conduct the chosen conformity assessment procedure.\n\n\n5.\u00a0\u00a0\u00a0Notified bodies and the personnel of notified bodies shall carry out their conformity assessment activities with the highest degree of professional integrity and the requisite technical and scientific competence in the specific field and shall be free from all pressures and inducements, particularly financial, which might influence their judgement or the results of their conformity assessment activities, especially as regards persons or groups with an interest in the results of those activities.\n\n\n\nArticle\u00a054\n\nClinical evaluation consultation procedure for certain class III and class IIb devices\n\n\n1.\u00a0\u00a0\u00a0In addition to the procedures applicable pursuant to Article\u00a052, a notified body shall also follow the procedure regarding clinical evaluation consultation as specified in Section\u00a05.1 of Annex\u00a0IX or as referred to in Section\u00a06 of Annex\u00a0X, as applicable, when performing a conformity assessment of the following devices:\n\n\n\n\n\n\n(a)\n\n\nclass III implantable devices, and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nclass IIb active devices intended to administer and/or remove a medicinal product, as referred to in Section\u00a06.4 of Annex\u00a0VIII (Rule 12).\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The procedure referred to in paragraph\u00a01 shall not be required for the devices referred to therein:\n\n\n\n\n\n\n(a)\n\n\nin the case of renewal of a certificate issued under this Regulation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nwhere the device has been designed by modifying a device already marketed by the same manufacturer for the same intended purpose, provided that the manufacturer has demonstrated to the satisfaction of the notified body that the modifications do not adversely affect the benefit-risk ratio of the device; or\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nwhere the principles of the clinical evaluation of the device type or category have been addressed in a CS referred to in Article\u00a09 and the notified body confirms that the clinical evaluation of the manufacturer for this device is in compliance with the relevant CS for clinical evaluation of that kind of device.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0The notified body shall notify the competent authorities, the authority responsible for notified bodies and the Commission through the electronic system referred to in Article\u00a057 of whether or not the procedure referred to in paragraph\u00a01 of this Article\u00a0is to be applied. That notification shall be accompanied by the clinical evaluation assessment report.\n\n\n4.\u00a0\u00a0\u00a0The Commission shall draw up an annual overview of devices which have been subject to the procedure specified in Section\u00a05.1 of Annex\u00a0IX and referred to in Section\u00a06 of Annex\u00a0X. The annual overview shall include the notifications in accordance with paragraph\u00a03 of this Article\u00a0and point\u00a0(e) of Section\u00a05.1 of Annex\u00a0IX and a listing of the cases where the notified body did not follow the advice from the expert panel. The Commission shall submit this overview to the European Parliament, to the Council and to the MDCG.\n\n\n5.\u00a0\u00a0\u00a0The Commission shall by 27 May 2025 draw up a report on the operation of this Article\u00a0and submit it to the European Parliament and to the Council. The report shall take into account the annual overviews and any available relevant recommendations from the MDCG. On the basis of that report the Commission shall, if appropriate, make proposals for amendments to this Regulation.\n\n\n\nArticle\u00a055\n\nMechanism for scrutiny of conformity assessments of certain class III and class IIb devices\n\n\n1.\u00a0\u00a0\u00a0A notified body shall notify the competent authorities of certificates it has granted to devices for which the conformity assessment has been performed pursuant to Article\u00a054(1). Such notification shall take place through the electronic system referred to in Article\u00a057 and shall include the summary of safety and clinical performance pursuant to Article\u00a032, the assessment report by the notified body, the instructions for use referred to in Section\u00a023.4 of Annex\u00a0I, and, where applicable, the scientific opinion of the expert panels referred to in Section\u00a05.1 of Annex\u00a0IX or Section\u00a06 of Annex\u00a0X, as applicable. In the case of divergent views between the notified body and the expert panels, a full justification shall also be included.\n\n\n2.\u00a0\u00a0\u00a0A competent authority and, where applicable, the Commission may, based on reasonable concerns apply further procedures in accordance with Article\u00a044, 45, 46, 47 or 94 and, where deemed necessary, take appropriate measures in accordance with Articles\u00a095 and\u00a097.\n\n\n3.\u00a0\u00a0\u00a0The MDCG and, where applicable, the Commission, may, based on reasonable concerns, request scientific advice from the expert panels in relation to the safety and performance of any device.\n\n\n\nArticle\u00a056\n\nCertificates of conformity\n\n\n1.\u00a0\u00a0\u00a0The certificates issued by the notified bodies in accordance with Annexes\u00a0IX, X and XI shall be in an official Union language determined by the Member\u00a0State in which the notified body is established or otherwise in an official Union language acceptable to the notified body. The minimum content of the certificates shall be as set out in Annex\u00a0XII.\n\n\n2.\u00a0\u00a0\u00a0The certificates shall be valid for the period they indicate, which shall not exceed five years. On application by the manufacturer, the validity of the certificate may be extended for further periods, each not exceeding five years, based on a re-assessment in accordance with the applicable conformity assessment procedures. Any supplement to a certificate shall remain valid as long as the certificate which it supplements is valid.\n\n\n3.\u00a0\u00a0\u00a0Notified bodies may impose restrictions to the intended purpose of a device to certain groups of patients or require manufacturers to undertake specific PMCF studies pursuant to Part B of Annex\u00a0XIV.\n\n\n4.\u00a0\u00a0\u00a0Where a notified body finds that the requirements of this Regulation are no longer met by the manufacturer, it shall, taking account of the principle of proportionality, suspend or withdraw the certificate issued or impose any restrictions on it unless compliance with such requirements is ensured by appropriate corrective action taken by the manufacturer within an appropriate deadline set by the notified body. The notified body shall give the reasons for its decision.\n\n\n5.\u00a0\u00a0\u00a0The notified body shall enter in the electronic system referred to in Article\u00a057 any information regarding certificates issued, including amendments and supplements thereto, and regarding suspended, reinstated, withdrawn or refused certificates and restrictions imposed on certificates. Such information shall be accessible to the public.\n\n\n6.\u00a0\u00a0\u00a0In the light of technical progress, the Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 amending the minimum content of the certificates set out in Annex\u00a0XII.\n\n\n\nArticle\u00a057\n\nElectronic system on notified bodies and on certificates of conformity\n\n\n1.\u00a0\u00a0\u00a0The Commission, after consulting the MDCG, shall set up and manage an electronic system to collate and process the following information:\n\n\n\n\n\n\n(a)\n\n\nthe list of subsidiaries referred to in Article\u00a037(3);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe list of experts referred to in Article\u00a040(2);\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe information relating to the notification referred to in Article\u00a042(10) and the amended notifications referred to in Article\u00a046(2);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe list of notified bodies referred to in Article\u00a043(2);\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe summary of the report referred to in Article\u00a044(12);\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe notifications for conformity assessments and certificates referred to in Articles\u00a054(3) and 55(1);\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nwithdrawal or refusals of applications for the certificates as referred to in Article\u00a053(2) and Section\u00a04.3 of Annex\u00a0VII;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe information regarding certificates referred to in Article\u00a056(5);\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nthe summary of safety and clinical performance referred to in Article\u00a032.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The information collated and processed by the electronic system shall be accessible to the competent authorities of the Member\u00a0States, to the Commission, where appropriate to the notified bodies and where provided elsewhere in this regulation or in Regulation\u00a0(EU)\u00a02017/746 to the public.\n\n\n\nArticle\u00a058\n\nVoluntary change of notified body\n\n\n1.\u00a0\u00a0\u00a0In cases where a manufacturer terminates its contract with a notified body and enters into a contract with another notified body in respect of the conformity assessment of the same device, the detailed arrangements for the change of notified body shall be clearly defined in an agreement between the manufacturer, the incoming notified body and, where practicable the outgoing notified body. That agreement shall cover at least the following aspects:\n\n\n\n\n\n\n(a)\n\n\nthe date on which the certificates issued by the outgoing notified body become invalid;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe date until which the identification number of the outgoing notified body may be indicated in the information supplied by the manufacturer, including any promotional material;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe transfer of documents, including confidentiality aspects and property rights;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe date after which the conformity assessment tasks of the outgoing notified body is assigned to the incoming notified body;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe last serial number or lot number for which the outgoing notified body is responsible.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The outgoing notified body shall withdraw the certificates it has issued for the device concerned on the date on which they become invalid.\n\n\n\nArticle\u00a059\n\nDerogation from the conformity assessment procedures\n\n\n1.\u00a0\u00a0\u00a0By way of derogation from Article\u00a052, any competent authority may authorise, on a duly justified request, the placing on the market or putting into service within the territory of the Member\u00a0State concerned, of a specific device for which the procedures referred to in that Article\u00a0have not been carried out but use of which is in the interest of public health or patient safety or health.\n\n\n2.\u00a0\u00a0\u00a0The Member\u00a0State shall inform the Commission and the other Member\u00a0States of any decision to authorise the placing on the market or putting into service of a device in accordance with paragraph\u00a01 where such authorisation is granted for use other than for a single patient.\n\n\n3.\u00a0\u00a0\u00a0Following a notification pursuant to paragraph\u00a02 of this Article, the Commission, in exceptional cases relating to public health or patient safety or health, may, by means of implementing acts, extend for a limited period of time the validity of an authorisation granted by a Member\u00a0State in accordance with paragraph\u00a01 of this Article\u00a0to the territory of the Union and set the conditions under which the device may be placed on the market or put into service. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\nOn duly justified imperative grounds of urgency relating to the health and safety of humans, the Commission shall adopt immediately applicable implementing acts in accordance with the procedure referred to in Article\u00a0114(4).\n\n\n\nArticle\u00a060\n\nCertificate of free sale\n\n\n1.\u00a0\u00a0\u00a0For the purpose of export and upon request by a manufacturer or an authorised representative, the Member\u00a0State in which the manufacturer or the authorised representative has its registered place of business shall issue a certificate of free sale declaring that the manufacturer or the authorised representative, as applicable, has its registered place of business on its territory and that the device in question bearing the CE\u00a0marking in accordance with this Regulation may be marketed in the Union. The certificate of free sale shall set out the Basic UDI-DI of the device as provided to the UDI\u00a0database under Article\u00a029. Where a notified body has issued a certificate pursuant to Article\u00a056, the certificate of free sale shall set out the unique number identifying the certificate issued by the notified body, as referred to in Section\u00a03 of Chapter\u00a0II of Annex\u00a0XII.\n\n\n2.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, establish a model for certificates of free sale, taking into account international practice as regards the use of certificates of free sale. Those implementing acts shall be adopted in accordance with the advisory procedure referred to in Article\u00a0114(2).\n\n\n\n\n\nCHAPTER VI\n\n\nCLINICAL EVALUATION AND CLINICAL INVESTIGATIONS\n\n\n\nArticle\u00a061\n\nClinical evaluation\n\n\n1.\u00a0\u00a0\u00a0Confirmation of conformity with relevant general safety and performance requirements set out in Annex\u00a0I under the normal conditions of the intended use of the device, and the evaluation of the undesirable side-effects and of the acceptability of the benefit-risk- ratio referred to in Sections 1 and 8 of Annex\u00a0I, shall be based on clinical data providing sufficient clinical evidence, including where applicable relevant data as referred to in Annex\u00a0III.\nThe manufacturer shall specify and justify the level of clinical evidence necessary to demonstrate conformity with the relevant general safety and performance requirements. That level of clinical evidence shall be appropriate in view of the characteristics of the device and its intended purpose.\nTo that end, manufacturers shall plan, conduct and document a clinical evaluation in accordance with this Article\u00a0and Part A of Annex\u00a0XIV.\n\n\n2.\u00a0\u00a0\u00a0For all class III devices and for the class IIb devices referred to in point\u00a0(b) of Article\u00a054(1), the manufacturer may, prior to its clinical evaluation and/or investigation, consult an expert panel as referred to in Article\u00a0106, with the aim of reviewing the manufacturer's intended clinical development strategy and proposals for clinical investigation. The manufacturer shall give due consideration to the views expressed by the expert panel. Such consideration shall be documented in the clinical evaluation report referred to in paragraph\u00a012 of this Article.\nThe manufacturer may not invoke any rights to the views expressed by the expert panel with regard to any future conformity assessment procedure.\n\n\n3.\u00a0\u00a0\u00a0A clinical evaluation shall follow a defined and methodologically sound procedure based on the following:\n\n\n\n\n\n\n(a)\n\n\na critical evaluation of the relevant scientific literature currently available relating to the safety, performance, design characteristics and intended purpose of the device, where the following conditions are satisfied:\n\n\n\n\n\n\n\u2014\n\n\nit is demonstrated that the device subject to clinical evaluation for the intended purpose is equivalent to the device to which the data relate, in accordance with Section\u00a03 of Annex\u00a0XIV, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe data adequately demonstrate compliance with the relevant general safety and performance requirements;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\na critical evaluation of the results of all available clinical investigations, taking duly into consideration whether the investigations were performed under Articles\u00a062 to\u00a080, any acts adopted pursuant to Article\u00a081, and Annex\u00a0XV; and\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\na consideration of currently available alternative treatment options for that purpose, if any.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0In the case of implantable devices and class III devices, clinical investigations shall be performed, except if:\n\n\n\n\n\n\n\u2014\n\n\nthe device has been designed by modifications of a device already marketed by the same manufacturer,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe modified device has been demonstrated by the manufacturer to be equivalent to the marketed device, in accordance with Section\u00a03 of Annex\u00a0XIV and this demonstration has been endorsed by the notified body, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe clinical evaluation of the marketed device is sufficient to demonstrate conformity of the modified device with the relevant safety and performance requirements.\n\n\n\n\nIn this case, the notified body shall check that the PMCF plan is appropriate and includes post market studies to demonstrate the safety and performance of the device.\nIn addition, clinical investigations need not be performed in the cases referred to in paragraph\u00a06.\n\n\n5.\u00a0\u00a0\u00a0A manufacturer of a device demonstrated to be equivalent to an already marketed device not manufactured by him, may also rely on paragraph\u00a04 in order not to perform a clinical investigation provided that the following conditions are fulfilled in addition to what is required in that paragraph:\n\n\n\n\n\n\n\u2014\n\n\nthe two manufacturers have a contract in place that explicitly allows the manufacturer of the second device full access to the technical documentation on an ongoing basis, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe original clinical evaluation has been performed in compliance with the requirements of this Regulation,\n\n\n\n\nand the manufacturer of the second device provides clear evidence thereof to the notified body.\n\n\n6.\u00a0\u00a0\u00a0The requirement to perform clinical investigations pursuant to paragraph\u00a04 shall not apply to implantable devices and class III devices:\n\n\n\n\n\n\n(a)\n\n\nwhich have been lawfully placed on the market or put into service in accordance with Directive\u00a090/385/EEC or Directive\u00a093/42/EEC and for which the clinical evaluation:\n\n\n\n\n\n\n\u2014\n\n\nis based on sufficient clinical data, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nis in compliance with the relevant product-specific CS for the clinical evaluation of that kind of device, where such a CS is available; or\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthat are sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips or connectors for which the clinical evaluation is based on sufficient clinical data and is in compliance with the relevant product-specific CS, where such a CS is available.\n\n\n\n\n\n\n7.\u00a0\u00a0\u00a0Cases in which paragraph\u00a04 is not applied by virtue of paragraph\u00a06 shall be justified in the clinical evaluation report by the manufacturer and in the clinical evaluation assessment report by the notified body.\n\n\n8.\u00a0\u00a0\u00a0Where justified in view of well-established technologies, similar to those used in the exempted devices listed in point\u00a0(b) of paragraph\u00a06 of this Article, being used in other devices, or where justified in order to protect the health and safety of patients, users or other persons or other aspects of public health, the Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 to amend the list of exempted devices referred to in the second subparagraph\u00a0of Article\u00a052(4) and in point\u00a0(b) of paragraph\u00a06 of this Article, by adding other types of implantable or class III devices to that list or removing devices therefrom.\n\n\n9.\u00a0\u00a0\u00a0In the case of the products without an intended medical purpose listed in Annex\u00a0XVI, the requirement to demonstrate a clinical benefit in accordance with this Chapter and Annexes\u00a0XIV and XV shall be understood as a requirement to demonstrate the performance of the device. Clinical evaluations of those products shall be based on relevant data concerning safety, including data from post-market surveillance, PMCF, and, where applicable, specific clinical investigation. Clinical investigations shall be performed for those products unless reliance on existing clinical data from an analogous medical device is duly justified.\n\n\n10.\u00a0\u00a0\u00a0Without prejudice to paragraph\u00a04, where the demonstration of conformity with general safety and performance requirements based on clinical data is not deemed appropriate, adequate justification for any such exception shall be given based on the results of the manufacturer's risk management and on consideration of the specifics of the interaction between the device and the human body, the clinical performance intended and the claims of the manufacturer. In such a case, the manufacturer shall duly substantiate in the technical documentation referred to in Annex\u00a0II why it considers a demonstration of conformity with general safety and performance requirements that is based on the results of non-clinical testing methods alone, including performance evaluation, bench testing and pre-clinical evaluation, to be adequate.\n\n\n11.\u00a0\u00a0\u00a0The clinical evaluation and its documentation shall be updated throughout the life cycle of the device concerned with clinical data obtained from the implementation of the manufacturer's PMCF plan in accordance with Part B of Annex\u00a0XIV and the post-market surveillance plan referred to in Article\u00a084.\nFor class III devices and implantable devices, the PMCF evaluation report and, if indicated, the summary of safety and clinical performance referred to in Article\u00a032 shall be updated at least annually with such data.\n\n\n12.\u00a0\u00a0\u00a0The clinical evaluation, its results and the clinical evidence derived from it shall be documented in a clinical evaluation report as referred to in Section\u00a04 of Annex\u00a0XIV, which, except for custom-made devices, shall be part of the technical documentation referred to in Annex\u00a0II relating to the device concerned.\n\n\n13.\u00a0\u00a0\u00a0Where necessary to ensure the uniform application of Annex\u00a0XIV, the Commission may, having due regard to technical and scientific progress, adopt implementing acts to the extent necessary to resolve issues of divergent interpretation and of practical application. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a062\n\nGeneral requirements regarding clinical investigations conducted to demonstrate conformity of devices\n\n\n1.\u00a0\u00a0\u00a0Clinical investigations shall be designed, authorised, conducted, recorded and reported in accordance with the provisions of this Article\u00a0and of Articles\u00a063 to 80, the acts adopted pursuant to Article\u00a081, and Annex\u00a0XV, where carried out as part of the clinical evaluation for conformity assessment purposes, for one or more of the following purposes:\n\n\n\n\n\n\n(a)\n\n\nto establish and verify that, under normal conditions of use, a device is designed, manufactured and packaged in such a way that it is suitable for one or more of the specific purposes listed in point\u00a0(1) of Article\u00a02, and achieves the performance intended as specified by its manufacturer;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nto establish and verify the clinical benefits of a device as specified by its manufacturer;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nto establish and verify the clinical safety of the device and to determine any undesirable side-effects, under normal conditions of use of the device, and assess whether they constitute acceptable risks when weighed against the benefits to be achieved by the device.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0Where the sponsor of a clinical investigation is not established in the Union, that sponsor shall ensure that a natural or legal person is established in the Union as its legal representative. Such legal representative shall be responsible for ensuring compliance with the sponsor's obligations pursuant to this Regulation, and shall be the addressee for all communications with the sponsor provided for in this Regulation. Any communication with that legal representative shall be deemed to be a communication with the sponsor.\nMember\u00a0States may choose not to apply the first subparagraph\u00a0to clinical investigations to be conducted solely on their territory, or on their territory and the territory of a third country, provided that they ensure that the sponsor establishes at least a contact person on their territory in respect of that clinical investigation who shall be the addressee for all communications with the sponsor provided for in this Regulation.\n\n\n3.\u00a0\u00a0\u00a0Clinical investigations shall be designed and conducted in such a way that the rights, safety, dignity and well-being of the subjects participating in a clinical investigation are protected and prevail over all other interests and the clinical data generated are scientifically valid, reliable and robust.\nClinical investigations shall be subject to scientific and ethical review. The ethical review shall be performed by an ethics committee in accordance with national law. Member\u00a0States shall ensure that the procedures for review by ethics committees are compatible with the procedures set out in this Regulation for the assessment of the application for authorisation of a clinical investigation. At least one lay person shall participate in the ethical review.\n\n\n4.\u00a0\u00a0\u00a0A clinical investigation as referred to in paragraph\u00a01 may be conducted only where all of the following conditions are met:\n\n\n\n\n\n\n(a)\n\n\nthe clinical investigation is the subject of an authorisation by the Member\u00a0State(s) in which the clinical investigation is to be conducted, in accordance with this Regulation, unless otherwise stated;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nan ethics committee, set up in accordance with national law, has not issued a negative opinion in relation to the clinical investigation, which is valid for that entire Member\u00a0State under its national law;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe sponsor, or its legal representative or a contact person pursuant to paragraph\u00a02, is established in the Union;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nvulnerable populations and subjects are appropriately protected in accordance with Articles\u00a064 to 68;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe anticipated benefits to the subjects or to public health justify the foreseeable risks and inconveniences and compliance with this condition is constantly monitored;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe subject or, where the subject is not able to give informed consent, his or her legally designated representative has given informed consent in accordance with Article\u00a063;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthe subject or, where the subject is not able to give informed consent, his or her legally designated representative, has been provided with the contact details of an entity where further information can be received in case of need;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe rights of the subject to physical and mental integrity, to privacy and to the protection of the data concerning him or her in accordance with Directive\u00a095/46/EC are safeguarded;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nthe clinical investigation has been designed to involve as little pain, discomfort, fear and any other foreseeable risk as possible for the subjects, and both the risk threshold and the degree of distress are specifically defined in the clinical investigation plan and constantly monitored;\n\n\n\n\n\n\n\n\n\n\n(j)\n\n\nthe medical care provided to the subjects is the responsibility of an appropriately qualified medical doctor or, where appropriate, a qualified dental practitioner or any other person entitled by national law to provide the relevant patient care under clinical investigation conditions;\n\n\n\n\n\n\n\n\n\n\n(k)\n\n\nno undue influence, including that of a financial nature, is exerted on the subject, or, where applicable, on his or her legally designated representatives, to participate in the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(l)\n\n\nthe investigational device(s) in question conform(s) to the applicable general safety and performance requirements set out in Annex\u00a0I apart from the aspects covered by the clinical investigation and that, with regard to those aspects, every precaution has been taken to protect the health and safety of the subjects. This includes, where appropriate, technical and biological safety testing and pre-clinical evaluation, as well as provisions in the field of occupational safety and accident prevention, taking into consideration the state of the art;\n\n\n\n\n\n\n\n\n\n\n(m)\n\n\nthe requirements of Annex\u00a0XV are fulfilled.\n\n\n\n\n\n\n5.\u00a0\u00a0\u00a0Any subject, or, where the subject is not able to give informed consent, his or her legally designated representative, may, without any resulting detriment and without having to provide any justification, withdraw from the clinical investigation at any time by revoking his or her informed consent. Without prejudice to Directive\u00a095/46/EC, the withdrawal of the informed consent shall not affect the activities already carried out and the use of data obtained based on informed consent before its withdrawal.\n\n\n6.\u00a0\u00a0\u00a0The investigator shall be a person exercising a profession which is recognised in the Member\u00a0State concerned as qualifying for the role of investigator on account of having the necessary scientific knowledge and experience in patient care. Other personnel involved in conducting a clinical investigation shall be suitably qualified, by education, training or experience in the relevant medical field and in clinical research methodology, to perform their tasks.\n\n\n7.\u00a0\u00a0\u00a0The facilities where the clinical investigation is to be conducted shall be suitable for the clinical investigation and shall be similar to the facilities where the device is intended to be used.\n\n\n\nArticle\u00a063\n\nInformed consent\n\n\n1.\u00a0\u00a0\u00a0Informed consent shall be written, dated and signed by the person performing the interview referred to in point\u00a0(c) of paragraph\u00a02, and by the subject or, where the subject is not able to give informed consent, his or her legally designated representative after having been duly informed in accordance with paragraph\u00a02. Where the subject is unable to write, consent may be given and recorded through appropriate alternative means in the presence of at least one impartial witness. In that case, the witness shall sign and date the informed consent document. The subject or, where the subject is not able to give informed consent, his or her legally designated representative shall be provided with a copy of the document or the record, as appropriate, by which informed consent has been given. The informed consent shall be documented. Adequate time shall be given for the subject or his or her legally designated representative to consider his or her decision to participate in the clinical investigation.\n\n\n2.\u00a0\u00a0\u00a0Information given to the subject or, where the subject is not able to give informed consent, his or her legally designated representative for the purposes of obtaining his or her informed consent shall:\n\n\n\n\n\n\n(a)\n\n\nenable the subject or his or her legally designated representative to understand:\n\n\n\n\n\n\n(i)\n\n\nthe nature, objectives, benefits, implications, risks and inconveniences of the clinical investigations;\n\n\n\n\n\n\n\n\n\n\n(ii)\n\n\nthe subject's rights and guarantees regarding his or her protection, in particular his or her right to refuse to participate in and the right to withdraw from the clinical investigation at any time without any resulting detriment and without having to provide any justification;\n\n\n\n\n\n\n\n\n\n\n(iii)\n\n\nthe conditions under which the clinical investigations is to be conducted, including the expected duration of the subject's participation in the clinical investigation; and\n\n\n\n\n\n\n\n\n\n\n(iv)\n\n\nthe possible treatment alternatives, including the follow-up measures if the participation of the subject in the clinical investigation is discontinued;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nbe kept comprehensive, concise, clear, relevant, and understandable to the subject or his or her legally designated representative;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nbe provided in a prior interview with a member of the investigating team who is appropriately qualified under national law;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\ninclude information about the applicable damage compensation system referred to in Article\u00a069; and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\ninclude the Union-wide unique single identification number of the clinical investigation referred to in Article\u00a070(1) and information about the availability of the clinical investigation results in accordance with paragraph\u00a06 of this Article.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0The information referred to in paragraph\u00a02 shall be prepared in writing and be available to the subject or, where the subject is not able to give informed consent, his or her legally designated representative.\n\n\n4.\u00a0\u00a0\u00a0In the interview referred to in point\u00a0(c) of paragraph\u00a02, special attention shall be paid to the information needs of specific patient populations and of individual subjects, as well as to the methods used to give the information.\n\n\n5.\u00a0\u00a0\u00a0In the interview referred to in point\u00a0(c) of paragraph\u00a02, it shall be verified that the subject has understood the information.\n\n\n6.\u00a0\u00a0\u00a0The subject shall be informed that a clinical investigation report and a summary presented in terms understandable to the intended user will be made available pursuant to Article\u00a077(5) in the electronic system on clinical investigations referred to in Article\u00a073 irrespective of the outcome of the clinical investigation, and shall be informed, to the extent possible, when they have become available.\n\n\n7.\u00a0\u00a0\u00a0This Regulation is without prejudice to national law requiring that, in addition to the informed consent given by the legally designated representative, a minor who is capable of forming an opinion and assessing the information given to him or her, shall also assent in order to participate in a clinical investigation.\n\n\n\nArticle\u00a064\n\nClinical investigations on incapacitated subjects\n\n\n1.\u00a0\u00a0\u00a0In the case of incapacitated subjects who have not given, or have not refused to give, informed consent before the onset of their incapacity, a clinical investigation may be conducted only where, in addition to the conditions set out in Article\u00a062(4), all of the following conditions are met:\n\n\n\n\n\n\n(a)\n\n\nthe informed consent of their legally designated representative has been obtained;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe incapacitated subjects have received the information referred to in Article\u00a063(2) in a way that is adequate in view of their capacity to understand it;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe explicit wish of an incapacitated subject who is capable of forming an opinion and assessing the information referred to in Article\u00a063(2) to refuse participation in, or to withdraw from, the clinical investigation at any time, is respected by the investigator;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nno incentives or financial inducements are given to subjects or their legally designated representatives, except for compensation for expenses and loss of earnings directly related to the participation in the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe clinical investigation is essential with respect to incapacitated subjects and data of comparable validity cannot be obtained in clinical investigations on persons able to give informed consent, or by other research methods;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe clinical investigation relates directly to a medical condition from which the subject suffers;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthere are scientific grounds for expecting that participation in the clinical investigation will produce a direct benefit to the incapacitated subject outweighing the risks and burdens involved.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The subject shall as far as possible take part in the informed consent procedure.\n\n\n\nArticle\u00a065\n\nClinical investigations on minors\n\nA clinical investigation on minors may be conducted only where, in addition to the conditions set out in Article\u00a062(4), all of the following conditions are met:\n\n\n\n\n\n\n(a)\n\n\nthe informed consent of their legally designated representative has been obtained;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe minors have received the information referred to in Article\u00a063(2) in a way adapted to their age and mental maturity and from investigators or members of the investigating team who are trained or experienced in working with children;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe explicit wish of a minor who is capable of forming an opinion and assessing the information referred to in Article\u00a063(2) to refuse participation in, or to withdraw from, the clinical investigation at any time, is respected by the investigator;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nno incentives or financial inducements are given to the subject or his or her legally designated representative except for compensation for expenses and loss of earnings directly related to the participation in the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe clinical investigation is intended to investigate treatments for a medical condition that only occurs in minors or the clinical investigation is essential with respect to minors to validate data obtained in clinical investigations on persons able to give informed consent or by other research methods;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe clinical investigation either relates directly to a medical condition from which the minor concerned suffers or is of such a nature that it can only be carried out on minors;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthere are scientific grounds for expecting that participation in the clinical investigation will produce a direct benefit to the minor subject outweighing the risks and burdens involved;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe minor shall take part in the informed consent procedure in a way adapted to his or her age and mental maturity;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nif during a clinical investigation the minor reaches the age of legal competence to give informed consent as defined in national law, his or her express informed consent shall be obtained before that subject can continue to participate in the clinical investigation.\n\n\n\n\n\n\nArticle\u00a066\n\nClinical investigations on pregnant or breastfeeding women\n\nA clinical investigation on pregnant or breastfeeding women may be conducted only where, in addition to the conditions set out in Article\u00a062(4), all of the following conditions are met:\n\n\n\n\n\n\n(a)\n\n\nthe clinical investigation has the potential to produce a direct benefit for the pregnant or breastfeeding woman concerned, or her embryo, foetus or child after birth, outweighing the risks and burdens involved;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nwhere research is undertaken on breastfeeding women, particular care is taken to avoid any adverse impact on the health of the child;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nno incentives or financial inducements are given to the subject except for compensation for expenses and loss of earnings directly related to the participation in the clinical investigation.\n\n\n\n\n\n\nArticle\u00a067\n\nAdditional national measures\n\nMember\u00a0States may maintain additional measures regarding persons performing mandatory military service, persons deprived of liberty, persons who, due to a judicial decision, cannot take part in clinical investigations, or persons in residential care institutions.\n\n\nArticle\u00a068\n\nClinical investigations in emergency situations\n\n\n1.\u00a0\u00a0\u00a0By way of derogation from point\u00a0(f) of Article\u00a062(4), from points (a) and (b) of Article\u00a064(1) and from points (a) and (b) of Article\u00a065, informed consent to participate in a clinical investigation may be obtained, and information on the clinical investigation may be given, after the decision to include the subject in the clinical investigation, provided that that decision is taken at the time of the first intervention on the subject, in accordance with the clinical investigation plan for that clinical investigation and that all of the following conditions are fulfilled:\n\n\n\n\n\n\n(a)\n\n\ndue to the urgency of the situation, caused by a sudden life-threatening or other sudden serious medical condition, the subject is unable to provide prior informed consent and to receive prior information on the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthere are scientific grounds to expect that participation of the subject in the clinical investigation will have the potential to produce a direct clinically relevant benefit for the subject resulting in a measurable health-related improvement alleviating the suffering and/or improving the health of the subject, or in the diagnosis of its condition;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nit is not possible within the therapeutic window to supply all prior information to and obtain prior informed consent from his or her legally designated representative;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe investigator certifies that he or she is not aware of any objections to participate in the clinical investigation previously expressed by the subject;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe clinical investigation relates directly to the subject's medical condition because of which it is not possible within the therapeutic window to obtain prior informed consent from the subject or from his or her legally designated representative and to supply prior information, and the clinical investigation is of such a nature that it may be conducted exclusively in emergency situations;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe clinical investigation poses a minimal risk to, and imposes a minimal burden on, the subject in comparison with the standard treatment of the subject's condition.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0Following an intervention pursuant to paragraph\u00a01 of this Article, informed consent in accordance with Article\u00a063 shall be sought to continue the participation of the subject in the clinical investigation, and information on the clinical investigation shall be given, in accordance with the following requirements:\n\n\n\n\n\n\n(a)\n\n\nregarding incapacitated subjects and minors, the informed consent shall be sought by the investigator from his or her legally designated representative without undue delay and the information referred to in Article\u00a063(2) shall be given as soon as possible to the subject and to his or her legally designated representative;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nregarding other subjects, the informed consent shall be sought by the investigator without undue delay from the subject or his or her legally designated representative, whichever can be done sooner, and the information referred to in Article\u00a063(2) shall be given as soon as possible to the subject or his or her legally designated representative, as applicable.\n\n\n\n\nFor the purposes of point\u00a0(b) where informed consent has been obtained from the legally designated representative, informed consent to continue the participation in the clinical investigation shall be obtained from the subject as soon as he or she is capable of giving informed consent.\n\n\n3.\u00a0\u00a0\u00a0If the subject or, where applicable, his or her legally designated representative does not give consent, he or she shall be informed of the right to object to the use of data obtained from the clinical investigation.\n\n\n\nArticle\u00a069\n\nDamage compensation\n\n\n1.\u00a0\u00a0\u00a0Member\u00a0States shall ensure that systems for compensation for any damage suffered by a subject resulting from participation in a clinical investigation conducted on their territory are in place in the form of insurance, a guarantee, or a similar arrangement that is equivalent as regards its purpose and which is appropriate to the nature and the extent of the risk.\n\n\n2.\u00a0\u00a0\u00a0The sponsor and the investigator shall make use of the system referred to in paragraph\u00a01 in the form appropriate for the Member\u00a0State in which the clinical investigation is conducted.\n\n\n\nArticle\u00a070\n\nApplication for clinical investigations\n\n\n1.\u00a0\u00a0\u00a0The sponsor of a clinical investigation shall submit an application to the Member\u00a0State(s) in which the clinical investigation is to be conducted (referred to for the purposes of this Article\u00a0as \u2018Member\u00a0State concerned\u2019) accompanied by the documentation referred to in Chapter II of Annex\u00a0XV.\nThe application shall be submitted by means of the electronic system referred to in Article\u00a073, which shall generate a Union-wide unique single identification number for the clinical investigation, which shall be used for all relevant communication in relation to that clinical investigation. Within 10 days of it receiving the application, the Member\u00a0State concerned shall notify the sponsor as to whether the clinical investigation falls within the scope of this Regulation and as to whether the application dossier is complete in accordance with Chapter II of Annex\u00a0XV.\n\n\n2.\u00a0\u00a0\u00a0Within one week of any change occurring in relation to the documentation referred to in Chapter II of Annex\u00a0XV, the sponsor shall update the relevant data in the electronic system referred to in Article\u00a073 and make that change to the documentation clearly identifiable. The Member\u00a0State concerned shall be notified of the update by means of that electronic system.\n\n\n3.\u00a0\u00a0\u00a0Where the Member\u00a0State concerned finds that the clinical investigation applied for does not fall within the scope of this Regulation or that the application dossier is not complete, it shall inform the sponsor thereof and shall set a time limit of maximum 10 days for the sponsor to comment or to complete the application by means of the electronic system referred to in Article\u00a073. The Member\u00a0State concerned may extend this period by a maximum of 20 days where appropriate.\nWhere the sponsor has not provided comments nor completed the application within the time limit referred to in the first subparagraph, the application shall be deemed to have lapsed. Where the sponsor considers the application does fall under the scope of this Regulation and/or is complete but the Member\u00a0State concerned does not, the application shall be considered to have been rejected. The Member\u00a0State concerned shall provide for an appeal procedure in respect of such refusal.\nThe Member\u00a0State concerned shall notify the sponsor within five days of receipt of the comments or of the requested additional information, whether the clinical investigation is considered as falling within the scope of this Regulation and the application is complete.\n\n\n4.\u00a0\u00a0\u00a0The Member\u00a0State concerned may also extend the period referred to in paragraph\u00a01 and\u00a03 each by a further five\u00a0days.\n\n\n5.\u00a0\u00a0\u00a0For the purposes of this Chapter, the date on which the sponsor is notified in accordance with paragraph\u00a01 or 3 shall be the validation date of the application. Where the sponsor is not notified, the validation date shall be the last day of the periods referred to in paragraphs\u00a01, 3 and 4 respectively.\n\n\n6.\u00a0\u00a0\u00a0During the period when the application is being assessed, the Member\u00a0State may request additional information from the sponsor. The expiry of the period laid down in point\u00a0(b) of paragraph\u00a07 shall be suspended from the date of the first request until such time as the additional information has been received.\n\n\n7.\u00a0\u00a0\u00a0The sponsor may start the clinical investigation in the following circumstances:\n\n\n\n\n\n\n(a)\n\n\nin the case of investigational class I devices or in the case of non-invasive class\u00a0IIa and class\u00a0IIb devices, unless otherwise stated by national law, immediately after the validation date of the application pursuant to paragraph\u00a05, and provided that a negative opinion which is valid for the entire Member\u00a0State, under national law, has not been issued by an ethics committee in the Member\u00a0State concerned in respect of the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nin the case of investigational devices, other than those referred to in point\u00a0(a), as soon as the Member\u00a0State concerned has notified the sponsor of its authorisation, and provided that a negative opinion which is valid for the entire Member\u00a0State, under national law, has not been issued by an ethics committee in the Member\u00a0State concerned in respect of the clinical investigation. The Member\u00a0State shall notify the sponsor of the authorisation within 45\u00a0days of the validation date referred to in paragraph\u00a05. The Member\u00a0State may extend this period by a further 20\u00a0days for the purpose of consulting with experts.\n\n\n\n\n\n\n8.\u00a0\u00a0\u00a0The Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 amending, in the light of technical progress and global regulatory developments, the requirements laid down in Chapter\u00a0II of Annex\u00a0XV.\n\n\n9.\u00a0\u00a0\u00a0In order to ensure the uniform application of the requirements laid down in Chapter\u00a0II of Annex\u00a0XV, the Commission may adopt implementing acts to the extent necessary to resolve issues of divergent interpretation and of practical application. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a071\n\nAssessment by Member\u00a0States\n\n\n1.\u00a0\u00a0\u00a0Member\u00a0States shall ensure that the persons validating and assessing the application, or deciding on it, do not have conflicts of interest, are independent of the sponsor, the investigators involved and of natural or legal persons financing the clinical investigation, as well as free of any other undue influence.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States shall ensure that the assessment is done jointly by an appropriate number of persons who collectively have the necessary qualifications and experience.\n\n\n3.\u00a0\u00a0\u00a0Member\u00a0States shall assess whether the clinical investigation is designed in such a way that potential remaining risks to subjects or third persons, after risk minimization, are justified, when weighed against the clinical benefits to be expected. They shall, while taking into account applicable CS or harmonised standards, examine in particular:\n\n\n\n\n\n\n(a)\n\n\nthe demonstration of compliance of the investigational device(s) with the applicable general safety and performance requirements, apart from the aspects covered by the clinical investigation, and whether, with regard to those aspects, every precaution has been taken to protect the health and safety of the subjects. This includes, where appropriate, assurance of technical and biological safety testing and pre-clinical evaluation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nwhether the risk-minimisation solutions employed by the sponsor are described in harmonised standards and, in those cases where the sponsor does not use harmonised standards, whether the risk-minimisation solutions provide a level of protection that is equivalent to that provided by harmonised standards;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nwhether the measures planned for the safe installation, putting into service and maintenance of the investigational device are adequate;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe reliability and robustness of the data generated in the clinical investigation, taking account of statistical approaches, design of the investigation and methodological aspects, including sample size, comparator and endpoints;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nwhether the requirements of Annex\u00a0XV are met;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nin the case of devices for sterile use, evidence of the validation of the manufacturer's sterilisation procedures or information on the reconditioning and sterilisation procedures which have to be conducted by the investigation site;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthe demonstration of the safety, quality and usefulness of any components of animal or human origin or of substances, which may be considered medicinal products in accordance with Directive\u00a02001/83/EC.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0Member\u00a0States shall refuse the authorisation of the clinical investigation if:\n\n\n\n\n\n\n(a)\n\n\nthe application dossier submitted pursuant to Article\u00a070(1) remains incomplete;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe device or the submitted documents, especially the investigation plan and the investigator's brochure, do not correspond to the state of scientific knowledge, and the clinical investigation, in particular, is not suitable for providing evidence for the safety, performance characteristics or benefit of the device on subjects or patients,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe requirements of Article\u00a062 are not met, or\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nany assessment under paragraph\u00a03 is negative.\n\n\n\n\nMember\u00a0States shall provide for an appeal procedure in respect of a refusal pursuant to the first subparagraph.\n\n\n\nArticle\u00a072\n\nConduct of a clinical investigation\n\n\n1.\u00a0\u00a0\u00a0The sponsor and the investigator shall ensure that the clinical investigation is conducted in accordance with the approved clinical investigation plan.\n\n\n2.\u00a0\u00a0\u00a0In order to verify that the rights, safety and well-being of subjects are protected, that the reported data are reliable and robust, and that the conduct of the clinical investigation is in compliance with the requirements of this Regulation, the sponsor shall ensure adequate monitoring of the conduct of a clinical investigation. The extent and nature of the monitoring shall be determined by the sponsor on the basis of an assessment that takes into consideration all characteristics of the clinical investigation including the following:\n\n\n\n\n\n\n(a)\n\n\nthe objective and methodology of the clinical investigation; and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe degree of deviation of the intervention from normal clinical practice.\n\n\n\n\n\n\n3.\u00a0\u00a0\u00a0All clinical investigation information shall be recorded, processed, handled, and stored by the sponsor or investigator, as applicable, in such a way that it can be accurately reported, interpreted and verified while the confidentiality of records and the personal data of the subjects remain protected in accordance with the applicable law on personal data protection.\n\n\n4.\u00a0\u00a0\u00a0Appropriate technical and organisational measures shall be implemented to protect information and personal data processed against unauthorised or unlawful access, disclosure, dissemination, alteration, or destruction or accidental loss, in particular where the processing involves transmission over a network.\n\n\n5.\u00a0\u00a0\u00a0Member\u00a0States shall inspect, at an appropriate level, investigation site(s) to check that clinical investigations are conducted in accordance with the requirements of this Regulation and with the approved investigation plan.\n\n\n6.\u00a0\u00a0\u00a0The sponsor shall establish a procedure for emergency situations which enables the immediate identification and, where necessary, an immediate recall of the devices used in the investigation.\n\n\n\nArticle\u00a073\n\nElectronic system on clinical investigations\n\n\n1.\u00a0\u00a0\u00a0The Commission shall, in collaboration with the Member\u00a0States, set up, manage and maintain an electronic system:\n\n\n\n\n\n\n(a)\n\n\nto create the single identification numbers for clinical investigations referred to in Article\u00a070(1);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nto be used as an entry point for the submission of all applications or notifications for clinical investigations referred to in Articles\u00a070, 74, 75 and 78 and for all other submission of data, or processing of data in this context;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nfor the exchange of information relating to clinical investigations in accordance with this Regulation between the Member\u00a0States and between them and the Commission including the exchange of information referred to in Articles\u00a070 and\u00a076;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nfor information to be provided by the sponsor in accordance with Article\u00a077, including the clinical investigation report and its summary as required in paragraph\u00a05 of that Article;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nfor reporting on serious adverse events and device deficiencies and related updates referred to in Article\u00a080.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0When setting up the electronic system referred in paragraph\u00a01 of this Article, the Commission shall ensure that it is interoperable with the EU database for clinical trials on medicinal products for human use set up in accordance with Article\u00a081 of Regulation\u00a0(EU)\u00a0No\u00a0536/2014 of the European Parliament and of the Council\u00a0(37) as concerns combined clinical investigations of devices with a clinical trial under that Regulation.\n\n\n3.\u00a0\u00a0\u00a0The information referred to in point\u00a0(c) of paragraph\u00a01 shall only be accessible to the Member\u00a0States and the Commission. The information referred to in the other points of that paragraph\u00a0shall be accessible to the public, unless, for all or parts of that information, confidentiality of the information is justified on any of the following grounds:\n\n\n\n\n\n\n(a)\n\n\nprotection of personal data in accordance with Regulation\u00a0(EC)\u00a0No\u00a045/2001;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nprotection of commercially confidential information, especially in the investigators brochure, in particular through taking into account the status of the conformity assessment for the device, unless there is an overriding public interest in disclosure;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\neffective supervision of the conduct of the clinical investigation by the Member\u00a0State(s) concerned.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0No\u00a0personal data of subjects shall be publicly available.\n\n\n5.\u00a0\u00a0\u00a0The user interface of the electronic system referred to in paragraph\u00a01 shall be available in all official languages of the Union.\n\n\n\nArticle\u00a074\n\nClinical investigations regarding devices bearing the CE marking\n\n\n1.\u00a0\u00a0\u00a0Where a clinical investigation is to be conducted to further assess, within the scope of its intended purpose, a device which already bears the CE marking in accordance with Article\u00a020(1), (\u2018PMCF investigation\u2019), and where the investigation would involve submitting subjects to procedures additional to those performed under the normal conditions of use of the device and those additional procedures are invasive or burdensome, the sponsor shall notify the Member\u00a0States concerned at least 30 days prior to its commencement by means of the electronic system referred to in Article\u00a073. The sponsor shall include the documentation referred to in Chapter II of Annex\u00a0XV as part of the notification. Points (b) to (k) and (m) of Article\u00a062(4), Article\u00a075, Article\u00a076, Article\u00a077, Article\u00a080(5) and the relevant provisions of Annex\u00a0XV shall apply to PMCF\u00a0investigations.\n\n\n2.\u00a0\u00a0\u00a0Where a clinical investigation is to be conducted to assess, outside the scope of its intended purpose, a device which already bears the CE marking in accordance with Article\u00a020(1), Articles\u00a062 to 81 shall apply.\n\n\n\nArticle\u00a075\n\nSubstantial modifications to clinical investigations\n\n\n1.\u00a0\u00a0\u00a0If a sponsor intends to introduce modifications to a clinical investigation that are likely to have a substantial impact on the safety, health or rights of the subjects or on the robustness or reliability of the clinical data generated by the investigation, it shall notify, within one week, by means of the electronic system referred to in Article\u00a073 the Member\u00a0State(s) in which the clinical investigation is being or is to be conducted of the reasons for and the nature of those modifications. The sponsor shall include an updated version of the relevant documentation referred to in Chapter\u00a0II of Annex\u00a0XV as part of the notification. Changes to the relevant documentation shall be clearly identifiable.\n\n\n2.\u00a0\u00a0\u00a0The Member\u00a0State shall assess any substantial modification to the clinical investigation in accordance with the procedure laid down in Article\u00a071.\n\n\n3.\u00a0\u00a0\u00a0The sponsor may implement the modifications referred to in paragraph\u00a01 at the earliest 38\u00a0days after the notification referred to in that paragraph, unless:\n\n\n\n\n\n\n(a)\n\n\nthe Member\u00a0State in which the clinical investigation is being or is to be conducted has notified the sponsor of its refusal based on the grounds referred to in Article\u00a071(4) or on considerations of public health, subject and user safety or health, of public policy, or\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nan ethics committee in that Member\u00a0State has issued a negative opinion in relation to the substantial modification to the clinical investigation, which, in accordance with national law, is valid for that entire Member\u00a0State.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0The Member\u00a0State(s) concerned may extend the period referred to in paragraph\u00a03 by a further seven days, for the purpose of consulting with experts.\n\n\n\nArticle\u00a076\n\nCorrective measures to be taken by Member\u00a0States and information exchange between Member\u00a0States\n\n\n1.\u00a0\u00a0\u00a0Where a Member\u00a0State in which a clinical investigation is being or is to be conducted has grounds for considering that the requirements set out in this Regulation are not met, it may take at least any of the following measures on its territory:\n\n\n\n\n\n\n(a)\n\n\nrevoke the authorisation for the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nsuspend or terminate the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nrequire the sponsor to modify any aspect of the clinical investigation.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0Before the Member\u00a0State concerned takes any of the measures referred to in paragraph\u00a01 it shall, except where immediate action is required, ask the sponsor or the investigator or both for their opinion. That opinion shall be delivered within seven days.\n\n\n3.\u00a0\u00a0\u00a0Where a Member\u00a0State has taken a measure referred to in paragraph\u00a01 of this Article\u00a0or has refused a clinical investigation, or has been notified by the sponsor of the early termination of a clinical investigation on safety grounds, that Member\u00a0State shall communicate the corresponding decision and the grounds therefor to all Member\u00a0States and the Commission by means of the electronic system referred to in Article\u00a073.\n\n\n4.\u00a0\u00a0\u00a0Where an application is withdrawn by the sponsor prior to a decision by a Member\u00a0State, that information shall be made available through the electronic system referred to in Article\u00a073 to all Member\u00a0States and the Commission.\n\n\n\nArticle\u00a077\n\nInformation from the sponsor at the end of a clinical investigation or in the event of a temporary halt or early termination\n\n\n1.\u00a0\u00a0\u00a0If the sponsor has temporarily halted a clinical investigation or has terminated a clinical investigation early, it shall inform within 15 days the Member\u00a0State in which that clinical investigation has been temporarily halted or terminated early, through the electronic system referred to in Article\u00a073, of the temporary halt or early termination, providing a justification. In the event that the sponsor has temporarily halted or terminated early the clinical investigation on safety grounds, it shall inform all Member\u00a0States in which that clinical investigation is being conducted thereof within 24 hours.\n\n\n2.\u00a0\u00a0\u00a0The end of a clinical investigation shall be deemed to coincide with the last visit of the last subject unless another point in time for such end is set out in the clinical investigation plan.\n\n\n3.\u00a0\u00a0\u00a0The sponsor shall notify each Member\u00a0State in which a clinical investigation was being conducted of the end of that clinical investigation in that Member\u00a0State. That notification shall be made within 15 days of the end of the clinical investigation in relation to that Member\u00a0State.\n\n\n4.\u00a0\u00a0\u00a0If an investigation is conducted in more than one Member\u00a0State, the sponsor shall notify all Member\u00a0States in which that clinical investigation was conducted of the end of the clinical investigation in all Member\u00a0States. That notification shall be made within 15 days of that end of the clinical investigation.\n\n\n5.\u00a0\u00a0\u00a0Irrespective of the outcome of the clinical investigation, within one year of the end of the clinical investigation or within three months of the early termination or temporary halt, the sponsor shall submit to the Member\u00a0States in which a clinical investigation was conducted a clinical investigation report as referred to in Section\u00a02.8 of Chapter I and Section\u00a07 of Chapter III of Annex\u00a0XV.\nThe clinical investigation report shall be accompanied by a summary presented in terms that are easily understandable to the intended user. Both the report and summary shall be submitted by the sponsor by means of the electronic system referred to in Article\u00a073.\nWhere, for scientific reasons, it is not possible to submit the clinical investigation report within one year of the end of the investigation, it shall be submitted as soon as it is available. In such case, the clinical investigation plan referred to in Section\u00a03 of Chapter\u00a0II of Annex\u00a0XV shall specify when the results of the clinical investigation are going to be available, together with a justification.\n\n\n6.\u00a0\u00a0\u00a0The Commission shall issue guidelines regarding the content and structure of the summary of the clinical investigation report.\nIn addition, the Commission may issue guidelines for the formatting and sharing of raw data, for cases where the sponsor decides to share raw data on a voluntary basis. Those guidelines may take as a basis and adapt, where possible, existing guidelines for sharing of raw data in the field of clinical investigations.\n\n\n7.\u00a0\u00a0\u00a0The summary and the clinical investigation report referred to in paragraph\u00a05 of this Article\u00a0shall become publicly accessible through the electronic system referred to in Article\u00a073, at the latest when the device is registered in accordance with Article\u00a029 and before it is placed on the market. In cases of early termination or temporary halt, the summary and the report shall become publicly accessible immediately after submission.\nIf the device is not registered in accordance with Article\u00a029 within one year of the summary and the report having been entered into the electronic system pursuant to paragraph\u00a05 of this Article, they shall become publicly accessible at that point in time.\n\n\n\nArticle\u00a078\n\nCoordinated assessment procedure for clinical investigations\n\n\n1.\u00a0\u00a0\u00a0By means of the electronic system referred to in Article\u00a073, the sponsor of a clinical investigation to be conducted in more than one Member\u00a0State may submit, for the purpose of Article\u00a070, a single application that, upon receipt, is transmitted electronically to all Member\u00a0States in which the clinical investigation is to be conducted.\n\n\n2.\u00a0\u00a0\u00a0The sponsor shall propose in the single application referred to in paragraph\u00a01 that one of the Member\u00a0States in which the clinical investigation is to be conducted acts as coordinating Member\u00a0State. The Member\u00a0States in which the clinical investigation is to be conducted shall, within six days of submission of the application, agree on one of them taking the role of the coordinating Member\u00a0State. If they do not agree on a coordinating Member\u00a0State, the coordinating Member\u00a0State proposed by the sponsor shall assume that role.\n\n\n3.\u00a0\u00a0\u00a0Under the direction of the coordinating Member\u00a0State referred to in paragraph\u00a02, the Member\u00a0States concerned shall coordinate their assessment of the application, in particular of the documentation referred to in Chapter II of Annex\u00a0XV.\nHowever, the completeness of the documentation referred to in Sections 1.13, 3.1.3, 4.2, 4.3 and 4.4 of Chapter II of Annex\u00a0XV shall be assessed separately by each Member\u00a0State concerned in accordance with Article\u00a070(1) to (5).\n\n\n4.\u00a0\u00a0\u00a0With regard to documentation other than that referred to in the second subparagraph\u00a0of paragraph\u00a03, the coordinating Member\u00a0State shall:\n\n\n\n\n\n\n(a)\n\n\nwithin six days of receipt of the single application, notify the sponsor that it is the coordinating Member\u00a0State (\u2018notification date\u2019);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nfor the purpose of the validation of the application, take into account any considerations submitted within seven days of the notification date by any Member\u00a0State concerned;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nwithin 10 days of the notification date, assess whether the clinical investigation falls within the scope of this Regulation and whether the application is complete, and shall notify the sponsor accordingly. Article\u00a070(1) and (3) to (5) shall apply to the coordinating Member\u00a0State in relation to that assessment;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nestablish the results of its assessment in a draft assessment report to be transmitted within 26\u00a0days of the validation date to the Member\u00a0States concerned. By day\u00a038 after the validation date, the other Member\u00a0States concerned shall transmit their comments and proposals on the draft assessment report and the underlying application to the coordinating Member\u00a0State which shall take due account of those comments and proposals in its finalisation of the final assessment report, to be transmitted within 45\u00a0days of the validation date to the sponsor and the other Member\u00a0States concerned.\n\n\n\n\nThe final assessment report shall be taken into account by all Member\u00a0States concerned when deciding on the sponsor's application in accordance with Article\u00a070(7).\n\n\n5.\u00a0\u00a0\u00a0As regards the assessment of the documentation referred to in the second subparagraph\u00a0of paragraph\u00a03, each Member\u00a0State concerned may request, on a single occasion, additional information from the sponsor. The sponsor shall submit the requested additional information within the period set by the Member\u00a0State concerned, which shall not exceed 12\u00a0days from the receipt of the request. The expiry of the last deadline pursuant to point\u00a0(d) of paragraph\u00a04 shall be suspended from the date of the request until such time as the additional information has been received.\n\n\n6.\u00a0\u00a0\u00a0For class\u00a0IIb and class\u00a0III devices, the coordinating Member\u00a0State may also extend the periods referred to in paragraph\u00a04 by a further 50 days, for the purpose of consulting with experts.\n\n\n7.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts, further specify the procedures and timescales for coordinated assessments to be taken into account by Member\u00a0States concerned when deciding on the sponsor's application. Such implementing acts may also set out the procedures and timescales for coordinated assessment in the case of substantial modifications pursuant to paragraph\u00a012 of this Article, in the case of reporting of adverse events pursuant to Article\u00a080(4) and in the case of clinical investigations of combination products between medical devices and medicinal products, where the latter are under a concurrent coordinated assessment of a clinical trial under Regulation\u00a0(EU)\u00a0No\u00a0536/2014. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n8.\u00a0\u00a0\u00a0Where the conclusion of the coordinating Member\u00a0State concerning the area of coordinated assessment is that the conduct of the clinical investigation is acceptable or acceptable subject to compliance with specific conditions, that conclusion shall be deemed to be the conclusion of all Member\u00a0States concerned.\nNotwithstanding the first subparagraph, a Member\u00a0State concerned may only disagree with the conclusion of the coordinating Member\u00a0State concerning the area of coordinated assessment on the following grounds:\n\n\n\n\n\n\n(a)\n\n\nwhen it considers that participation in the clinical investigation would lead to a subject receiving treatment inferior to that received in normal clinical practice in that Member\u00a0State concerned;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ninfringement of national law; or\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nconsiderations as regards subject safety and data reliability and robustness submitted under point\u00a0(b) of paragraph\u00a04.\n\n\n\n\nWhere one of the Member\u00a0States concerned disagrees with the conclusion on the basis of the second subparagraph\u00a0of this paragraph, it shall communicate its disagreement, together with a detailed justification, through the electronic system referred to in Article\u00a073, to the Commission, to all other Member\u00a0States concerned and to the sponsor.\n\n\n9.\u00a0\u00a0\u00a0Where the conclusion of the coordinating Member\u00a0State concerning the area of coordinated assessment is that the clinical investigation is not acceptable, that conclusion shall be deemed to be the conclusion of all Member\u00a0States concerned.\n\n\n10.\u00a0\u00a0\u00a0A Member\u00a0State concerned shall refuse to authorise a clinical investigation if it disagrees with the conclusion of the coordinating Member\u00a0State as regards any of the grounds referred to in the second subparagraph\u00a0of paragraph\u00a08, or if it finds, on duly justified grounds, that the aspects addressed in Sections 1.13, 3.1.3, 4.2, 4.3 and 4.4 of Chapter\u00a0II of Annex\u00a0XV are not complied with, or where an ethics committee has issued a negative opinion in relation to that clinical investigation, which is valid, in accordance with national law, for that entire Member\u00a0State. That Member\u00a0State shall provide for an appeal procedure in respect of such refusal.\n\n\n11.\u00a0\u00a0\u00a0Each Member\u00a0State concerned shall notify the sponsor through the electronic system referred to in Article\u00a073 as to whether the clinical investigation is authorised, whether it is authorised subject to conditions, or whether authorisation has been refused. Notification shall be done by way of one single decision within five days of the transmission, pursuant to point\u00a0(d) of paragraph\u00a04, by the coordinating Member\u00a0State of the final assessment report. Where an authorisation of a clinical investigation is subject to conditions, those conditions may only be such that, by their nature, they cannot be fulfilled at the time of that authorisation.\n\n\n12.\u00a0\u00a0\u00a0Any substantial modifications as referred to in Article\u00a075 shall be notified to the Member\u00a0States concerned by means of the electronic system referred to in Article\u00a073. Any assessment as to whether there are grounds for disagreement as referred to in the second subparagraph\u00a0of paragraph\u00a08 of this Article\u00a0shall be carried out under the direction of the coordinating Member\u00a0State, except for substantial modifications concerning Sections 1.13, 3.1.3, 4.2, 4.3 and 4.4 of Chapter II of Annex\u00a0XV, which shall be assessed separately by each Member\u00a0State concerned.\n\n\n13.\u00a0\u00a0\u00a0The Commission shall provide administrative support to the coordinating Member\u00a0State in the accomplishment of its tasks under this Chapter.\n\n\n14.\u00a0\u00a0\u00a0The procedure set out in this Article\u00a0shall, until 27 May 2027, be applied only by those of the Member\u00a0States in which the clinical investigation is to be conducted which have agreed to apply it. After 27 May 2027, all Member\u00a0States shall be required to apply that procedure.\n\n\n\nArticle\u00a079\n\nReview of coordinated assessment procedure\n\nBy 27 May 2026, the Commission shall submit to the European Parliament and to the Council a report on experience gained from the application of Article\u00a078 and, if necessary, propose a review of Article\u00a078(14) and point\u00a0(h) of Article\u00a0123(3).\n\n\nArticle\u00a080\n\nRecording and reporting of adverse events that occur during clinical investigations\n\n\n1.\u00a0\u00a0\u00a0The sponsor shall fully record all of the following:\n\n\n\n\n\n\n(a)\n\n\nany adverse event of a type identified in the clinical investigation plan as being critical to the evaluation of the results of that clinical investigation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nany serious adverse event;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nany device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention had not occurred, or circumstances had been less fortunate;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nany new findings in relation to any event referred to in points (a) to (c).\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The sponsor shall report, without delay to all Member\u00a0States in which the clinical investigation is being conducted, all of the following by means of the electronic system referred to in Article\u00a073:\n\n\n\n\n\n\n(a)\n\n\nany serious adverse event that has a causal relationship with the investigational device, the comparator or the investigation procedure or where such causal relationship is reasonably possible;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nany device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention had not occurred, or circumstances had been less fortunate;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nany new findings in relation to any event referred to in points (a) and (b).\n\n\n\n\nThe period for reporting shall take account of the severity of the event. Where necessary to ensure timely reporting, the sponsor may submit an initial report that is incomplete followed up by a complete report.\nUpon request by any Member\u00a0State in which the clinical investigation is being conducted, the sponsor shall provide all information referred to in paragraph\u00a01.\n\n\n3.\u00a0\u00a0\u00a0The sponsor shall also report to the Member\u00a0States in which the clinical investigation is being conducted any event referred to in paragraph\u00a02 of this Article\u00a0that occurred in third countries in which a clinical investigation is performed under the same clinical investigation plan as the one applying to a clinical investigation covered by this Regulation by means of the electronic system referred to in Article\u00a073.\n\n\n4.\u00a0\u00a0\u00a0In the case of a clinical investigation for which the sponsor has used the single application referred to in Article\u00a078, the sponsor shall report any event as referred to in paragraph\u00a02 of this Article\u00a0by means of the electronic system referred to in Article\u00a073. Upon receipt, this report shall be transmitted electronically to all Member\u00a0States in which the clinical investigation is being conducted.\nUnder the direction of the coordinating Member\u00a0State referred to in Article\u00a078(2), the Member\u00a0States shall coordinate their assessment of serious adverse events and device deficiencies to determine whether to modify, suspend or terminate the clinical investigation or whether to revoke the authorisation for that clinical investigation.\nThis paragraph\u00a0shall not affect the rights of the other Member\u00a0States to perform their own evaluation and to adopt measures in accordance with this Regulation in order to ensure the protection of public health and patient safety. The coordinating Member\u00a0State and the Commission shall be kept informed of the outcome of any such evaluation and the adoption of any such measures.\n\n\n5.\u00a0\u00a0\u00a0In the case of PMCF investigations referred to in Article\u00a074(1), the provisions on vigilance laid down in Articles\u00a087 to 90 and in the acts adopted pursuant to Article\u00a091 shall apply instead of this Article.\n\n\n6.\u00a0\u00a0\u00a0Notwithstanding paragraph\u00a05, this Article\u00a0shall apply where a causal relationship between the serious adverse event and the preceding investigational procedure has been established.\n\n\n\nArticle\u00a081\n\nImplementing acts\n\nThe Commission may, by means of implementing acts, establish the detailed arrangements and procedural aspects necessary for the implementation of this Chapter as regards the following:\n\n\n\n\n\n\n(a)\n\n\nharmonised electronic forms for the application for clinical investigations and their assessment as referred to in Articles\u00a070 and 78, taking into account specific categories or groups of devices;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe functioning of the electronic system referred to in Article\u00a073;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nharmonised electronic forms for the notification of PMCF investigations as referred to in Article\u00a074(1), and of substantial modifications as referred to in Article\u00a075;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe exchange of information between Member\u00a0States as referred to in Article\u00a076;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nharmonised electronic forms for the reporting of serious adverse events and device deficiencies as referred to in Article\u00a080;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe timelines for the reporting of serious adverse events and device deficiencies, taking into account the severity of the event to be reported as referred to in Article\u00a080;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nuniform application of the requirements regarding the clinical evidence or data needed to demonstrate compliance with the general safety and performance requirements set out in Annex\u00a0I.\n\n\n\n\nThe implementing acts referred to in the first paragraph\u00a0shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\nArticle\u00a082\n\nRequirements regarding other clinical investigations\n\n\n1.\u00a0\u00a0\u00a0Clinical investigations, not performed pursuant to any of the purposes listed in Article\u00a062(1), shall comply with the provisions of Article\u00a062 (2) and (3), points (b), (c), (d), (f), (h), and (l) of Article\u00a062(4) and Article\u00a062(6).\n\n\n2.\u00a0\u00a0\u00a0In order to protect the rights, safety, dignity and well-being of subjects and the scientific and ethical integrity of clinical investigations not performed for any of the purposes listed in Article\u00a062(1), each Member\u00a0State shall define any additional requirements for such investigations, as appropriate for each Member\u00a0State concerned.\n\n\n\n\nCHAPTER VII\n\n\nPOST-MARKET SURVEILLANCE, VIGILANCE AND MARKET SURVEILLANCE\n\n\n\n\nSECTION 1\n\n\n\n\nPost-market surveillance\n\n\n\n\nArticle\u00a083\n\nPost-market surveillance system of the manufacturer\n\n\n1.\u00a0\u00a0\u00a0For each device, manufacturers shall plan, establish, document, implement, maintain and update a post-market surveillance system in a manner that is proportionate to the risk class and appropriate for the type of device. That system shall be an integral part of the manufacturer's quality management system referred to in Article\u00a010(9).\n\n\n2.\u00a0\u00a0\u00a0The post-market surveillance system shall be suited to actively and systematically gathering, recording and analysing relevant data on the quality, performance and safety of a device throughout its entire lifetime, and to drawing the necessary conclusions and to determining, implementing and monitoring any preventive and corrective actions.\n\n\n3.\u00a0\u00a0\u00a0Data gathered by the manufacturer's post-market surveillance system shall in particular be used:\n\n\n\n\n\n\n(a)\n\n\nto update the benefit-risk determination and to improve the risk management as referred to in Chapter I of Annex\u00a0I;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nto update the design and manufacturing information, the instructions for use and the labelling;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nto update the clinical evaluation;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nto update the summary of safety and clinical performance referred to in Article\u00a032;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nfor the identification of needs for preventive, corrective or field safety corrective action;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nfor the identification of options to improve the usability, performance and safety of the device;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nwhen relevant, to contribute to the post-market surveillance of other devices; and\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nto detect and report trends in accordance with Article\u00a088.\n\n\n\n\nThe technical documentation shall be updated accordingly.\n\n\n4.\u00a0\u00a0\u00a0If, in the course of the post-market surveillance, a need for preventive or corrective action or both is identified, the manufacturer shall implement the appropriate measures and inform the competent authorities concerned and, where applicable, the notified body. Where a serious incident is identified or a field safety corrective action is implemented, it shall be reported in accordance with Article\u00a087.\n\n\n\nArticle\u00a084\n\nPost-market surveillance plan\n\nThe post-market surveillance system referred to in Article\u00a083 shall be based on a post-market surveillance plan, the requirements for which are set out in Section\u00a01.1 of Annex\u00a0III. For devices other than custom-made devices, the post-market surveillance plan shall be part of the technical documentation specified in Annex\u00a0II.\n\n\nArticle\u00a085\n\nPost-market surveillance report\n\nManufacturers of class I devices shall prepare a post-market surveillance report summarising the results and conclusions of the analyses of the post-market surveillance data gathered as a result of the post-market surveillance plan referred to in Article\u00a084 together with a rationale and description of any preventive and corrective actions taken. The report shall be updated when necessary and made available to the competent authority upon request.\n\n\nArticle\u00a086\n\nPeriodic safety update report\n\n\n1.\u00a0\u00a0\u00a0Manufacturers of class IIa, class IIb and class III devices shall prepare a periodic safety update report (\u2018PSUR\u2019) for each device and where relevant for each category or group of devices summarising the results and conclusions of the analyses of the post-market surveillance data gathered as a result of the post-market surveillance plan referred to in Article\u00a084 together with a rationale and description of any preventive and corrective actions taken. Throughout the lifetime of the device concerned, that PSUR shall set out:\n\n\n\n\n\n\n(a)\n\n\nthe conclusions of the benefit-risk determination;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe main findings of the PMCF; and\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe volume of sales of the device and an estimate evaluation of the size and other characteristics of the population using the device and, where practicable, the usage frequency of the device.\n\n\n\n\nManufacturers of class IIb and class III devices shall update the PSUR at least annually. That PSUR shall, except in the case of custom-made devices, be part of the technical documentation as specified in Annexes\u00a0II and\u00a0III.\nManufacturers of class IIa devices shall update the PSUR when necessary and at least every two years. That PSUR shall, except in the case of custom-made devices, be part of the technical documentation as specified in Annexes\u00a0II and\u00a0III.\nFor custom-made devices, the PSUR shall be part of the documentation referred to in Section\u00a02 of Annex\u00a0XIII.\n\n\n2.\u00a0\u00a0\u00a0For class III devices or implantable devices, manufacturers shall submit PSURs by means of the electronic system referred to in Article\u00a092 to the notified body involved in the conformity assessment in accordance with Article\u00a052. The notified body shall review the report and add its evaluation to that electronic system with details of any action taken. Such PSURs and the evaluation by the notified body shall be made available to competent authorities through that electronic system.\n\n\n3.\u00a0\u00a0\u00a0For devices other than those referred to in paragraph\u00a02, manufacturers shall make PSURs available to the notified body involved in the conformity assessment and, upon request, to competent authorities.\n\n\n\n\n\nSECTION 2\n\n\n\n\nVigilance\n\n\n\n\nArticle\u00a087\n\nReporting of serious incidents and field safety corrective actions\n\n\n1.\u00a0\u00a0\u00a0Manufacturers of devices made available on the Union market, other than investigational devices, shall report, to the relevant competent authorities, in accordance with Articles\u00a092(5) and (7), the following:\n\n\n\n\n\n\n(a)\n\n\nany serious incident involving devices made available on the Union market, except expected side-effects which are clearly documented in the product information and quantified in the technical documentation and are subject to trend reporting pursuant to Article\u00a088;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nany field safety corrective action in respect of devices made available on the Union market, including any field safety corrective action undertaken in a third country in relation to a device which is also legally made available on the Union market, if the reason for the field safety corrective action is not limited to the device made available in the third country.\n\n\n\n\nThe reports referred to in the first subparagraph\u00a0shall be submitted through the electronic system referred to in Article\u00a092.\n\n\n2.\u00a0\u00a0\u00a0As a general rule, the period for the reporting referred to in paragraph\u00a01 shall take account of the severity of the serious incident.\n\n\n3.\u00a0\u00a0\u00a0Manufacturers shall report any serious incident as referred to in point\u00a0(a) of paragraph\u00a01 immediately after they have established the causal relationship between that incident and their device or that such causal relationship is reasonably possible and not later than 15\u00a0days after they become aware of the incident.\n\n\n4.\u00a0\u00a0\u00a0Notwithstanding paragraph\u00a03, in the event of a serious public health threat the report referred to in paragraph\u00a01 shall be provided immediately, and not later than 2 days after the manufacturer becomes aware of that threat.\n\n\n5.\u00a0\u00a0\u00a0Notwithstanding paragraph\u00a03, in the event of death or an unanticipated serious deterioration in a person's state of health the report shall be provided immediately after the manufacturer has established or as soon as it suspects a causal relationship between the device and the serious incident but not later than 10 days after the date on which the manufacturer becomes aware of the serious incident.\n\n\n6.\u00a0\u00a0\u00a0Where necessary to ensure timely reporting, the manufacturer may submit an initial report that is incomplete followed up by a complete report.\n\n\n7.\u00a0\u00a0\u00a0If, after becoming aware of a potentially reportable incident, the manufacturer is uncertain about whether the incident is reportable, it shall nevertheless submit a report within the timeframe required in accordance with paragraphs\u00a02 to 5.\n\n\n8.\u00a0\u00a0\u00a0Except in cases of urgency in which the manufacturer needs to undertake field safety corrective action immediately, the manufacturer shall, without undue delay, report the field safety corrective action referred to in point\u00a0(b) of paragraph\u00a01 in advance of the field safety corrective action being undertaken.\n\n\n9.\u00a0\u00a0\u00a0For similar serious incidents that occur with the same device or device type and for which the root cause has been identified or a field safety corrective action implemented or where the incidents are common and well documented, the manufacturer may provide periodic summary reports instead of individual serious incident reports, on condition that the coordinating competent authority referred to in Article\u00a089(9), in consultation with the competent authorities referred to in point\u00a0(a) of Article\u00a092(8), has agreed with the manufacturer on the format, content and frequency of the periodic summary reporting. Where a single competent authority is referred to in points (a) and (b) of Article\u00a092(8), the manufacturer may provide periodic summary reports following agreement with that competent authority.\n\n\n10.\u00a0\u00a0\u00a0The Member\u00a0States shall take appropriate measures such as organising targeted information campaigns, to encourage and enable healthcare professionals, users and patients to report to the competent authorities suspected serious incidents referred to in point\u00a0(a) of paragraph\u00a01.\nThe competent authorities shall record centrally at national level reports they receive from healthcare professionals, users and patients.\n\n\n11.\u00a0\u00a0\u00a0Where a competent authority of a Member\u00a0State obtains such reports on suspected serious incidents referred to in point\u00a0(a) of paragraph\u00a01 from healthcare professionals, users or patients, it shall take the necessary steps to ensure that the manufacturer of the device concerned is informed of the suspected serious incident without delay.\nWhere the manufacturer of the device concerned considers that the incident is a serious incident, it shall provide a report in accordance with paragraphs 1 to 5 of this Article\u00a0on that serious incident to the competent authority of the Member\u00a0State in which that serious incident occurred and shall take the appropriate follow-up action in accordance with Article\u00a089.\nWhere the manufacturer of the device concerned considers that the incident is not a serious incident or is an expected undesirable side-effect, which will be covered by trend reporting in accordance with Article\u00a088, it shall provide an explanatory statement. If the competent authority does not agree with the conclusion of the explanatory statement, it may require the manufacturer to provide a report in accordance with paragraphs 1 to 5 of this Article\u00a0and require it to ensure that appropriate follow-up action is taken in accordance with Article\u00a089.\n\n\n\nArticle\u00a088\n\nTrend reporting\n\n\n1.\u00a0\u00a0\u00a0Manufacturers shall report, by means of the electronic system referred to in Article\u00a092, any statistically significant increase in the frequency or severity of incidents that are not serious incidents or that are expected undesirable side-effects that could have a significant impact on the benefit-risk analysis referred to in Sections 1 and 5 of Annex\u00a0I and which have led or may lead to risks to the health or safety of patients, users or other persons that are unacceptable when weighed against the intended benefits. The significant increase shall be established in comparison to the foreseeable frequency or severity of such incidents in respect of the device, or category or group of devices, in question during a specific period as specified in the technical documentation and product information.\nThe manufacturer shall specify how to manage the incidents referred to in the first subparagraph\u00a0and the methodology used for determining any statistically significant increase in the frequency or severity of such incidents, as well as the observation period, in the post-market surveillance plan referred to in Article\u00a084.\n\n\n2.\u00a0\u00a0\u00a0The competent authorities may conduct their own assessments on the trend reports referred to in paragraph\u00a01 and require the manufacturer to adopt appropriate measures in accordance with this Regulation in order to ensure the protection of public health and patient safety. Each competent authority shall inform the Commission, the other competent authorities and the notified body that issued the certificate, of the results of such assessment and of the adoption of such measures.\n\n\n\nArticle\u00a089\n\nAnalysis of serious incidents and field safety corrective actions\n\n\n1.\u00a0\u00a0\u00a0Following the reporting of a serious incident pursuant to Article\u00a087(1), the manufacturer shall, without delay, perform the necessary investigations in relation to the serious incident and the devices concerned. This shall include a risk assessment of the incident and field safety corrective action taking into account criteria as referred to in paragraph\u00a03 of this Article\u00a0as appropriate.\nThe manufacturer shall co-operate with the competent authorities and where relevant with the notified body concerned during the investigations referred to in the first subparagraph\u00a0and shall not perform any investigation which involves altering the device or a sample of the batch concerned in a way which may affect any subsequent evaluation of the causes of the incident, prior to informing the competent authorities of such action.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States shall take the necessary steps to ensure that any information regarding a serious incident that has occurred within their territory, or a field safety corrective action that has been or is to be undertaken within their territory, and that is brought to their knowledge in accordance with Article\u00a087 is evaluated centrally at national level by their competent authority, if possible together with the manufacturer, and, where relevant, the notified body concerned.\n\n\n3.\u00a0\u00a0\u00a0In the context of the evaluation referred to in paragraph\u00a02, the competent authority shall evaluate the risks arising from the reported serious incident and evaluate any related field safety corrective actions, taking into account the protection of public health and criteria such as causality, detectability and probability of recurrence of the problem, frequency of use of the device, probability of occurrence of direct or indirect harm, the severity of that harm, the clinical benefit of the device, intended and potential users, and population affected. The competent authority shall also evaluate the adequacy of the field safety corrective action envisaged or undertaken by the manufacturer and the need for, and kind of, any other corrective action, in particular taking into account the principle of inherent safety contained in Annex\u00a0I.\nUpon request by the national competent authority, manufacturers shall provide all documents necessary for the risk assessment.\n\n\n4.\u00a0\u00a0\u00a0The competent authority shall monitor the manufacturer's investigation of a serious incident. Where necessary, a competent authority may intervene in a manufacturer's investigation or initiate an independent investigation.\n\n\n5.\u00a0\u00a0\u00a0The manufacturer shall provide a final report to the competent authority setting out its findings from the investigation by means of the electronic system referred to in Article\u00a092. The report shall set out conclusions and where relevant indicate corrective actions to be taken.\n\n\n6.\u00a0\u00a0\u00a0In the case of devices referred to in the first subparagraph\u00a0of Article\u00a01(8) and where the serious incident or field safety corrective action may be related to a substance which, if used separately, would be considered to be a medicinal product, the evaluating competent authority or the coordinating competent authority referred to in paragraph\u00a09 of this Article\u00a0shall, inform the national competent authority or the EMA, depending on which issued the scientific opinion on that substance under Article\u00a052(9), of that serious incident or field safety corrective action.\nIn the case of devices covered by this Regulation in accordance with point\u00a0(g) of Article\u00a01(6) and where the serious incident or field safety corrective action may be related to the derivatives of tissues or cells of human origin utilised for\u00a0the manufacture of the device, and in the case of devices falling under this Regulation pursuant to Article\u00a01(10), the\u00a0competent authority or the coordinating competent authority referred to in paragraph\u00a09 of this Article\u00a0shall inform the competent authority for human tissues and cells that was consulted by the notified body in accordance with Article\u00a052(10).\n\n\n7.\u00a0\u00a0\u00a0After carrying out the evaluation in accordance with paragraph\u00a03 of this Article, the evaluating competent authority shall, through the electronic system referred to in Article\u00a092, inform, without delay, the other competent authorities of the corrective action taken or envisaged by the manufacturer or required of it to minimise the risk of recurrence of the serious incident, including information on the underlying events and the outcome of its assessment.\n\n\n8.\u00a0\u00a0\u00a0The manufacturer shall ensure that information about the field safety corrective action taken is brought without delay to the attention of users of the device in question by means of a field safety notice. The field safety notice shall be edited in an official Union language or languages determined by the Member\u00a0State in which the field safety corrective action is taken. Except in cases of urgency, the content of the draft field safety notice shall be submitted to the evaluating competent authority or, in the cases referred to in paragraph\u00a09, to the coordinating competent authority to allow it to make comments. Unless duly justified by the situation of the individual Member\u00a0State, the content of the field safety notice shall be consistent in all Member\u00a0States.\nThe field safety notice shall allow the correct identification of the device or devices involved, in particular by including the relevant UDIs, and the correct identification, in particular, by including the SRN, if already issued, of the manufacturer that has undertaken the field safety corrective action. The field safety notice shall explain, in a clear manner, without understating the level of risk, the reasons for the field safety corrective action with reference to the device malfunction and associated risks for patients, users or other persons, and shall clearly indicate all the actions to be taken by users.\nThe manufacturer shall enter the field safety notice in the electronic system referred to in Article\u00a092 through which that notice shall be accessible to the public.\n\n\n9.\u00a0\u00a0\u00a0The competent authorities shall actively participate in a procedure in order to coordinate their assessments referred to in paragraph\u00a03 in the following cases:\n\n\n\n\n\n\n(a)\n\n\nwhere there is concern regarding a particular serious incident or cluster of serious incidents relating to the same device or type of device of the same manufacturer in more than one Member\u00a0State;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nwhere the appropriateness of a field safety corrective action that is proposed by a manufacturer in more than one Member\u00a0State is in question.\n\n\n\n\nThat coordinated procedure shall cover the following:\n\n\n\n\n\n\n\u2014\n\n\ndesignation of a coordinating competent authority on a case by case basis, when required;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndefining the coordinated assessment process, including the tasks and responsibilities of the coordinating competent authority and the involvement of other competent authorities.\n\n\n\n\nUnless otherwise agreed between the competent authorities, the coordinating competent authority shall be the competent authority of the Member\u00a0State in which the manufacturer has its registered place of business.\nThe coordinating competent authority shall, through the electronic system referred to in Article\u00a092, inform the manufacturer, the other competent authorities and the Commission that it has assumed the role of coordinating authority.\n\n\n10.\u00a0\u00a0\u00a0The designation of a coordinating competent authority shall not affect the rights of the other competent authorities to perform their own assessment and to adopt measures in accordance with this Regulation in order to ensure the protection of public health and patient safety. The coordinating competent authority and the Commission shall be kept informed of the outcome of any such assessment and the adoption of any such measures.\n\n\n11.\u00a0\u00a0\u00a0The Commission shall provide administrative support to the coordinating competent authority in the accomplishment of its tasks under this Chapter.\n\n\n\nArticle\u00a090\n\nAnalysis of vigilance data\n\nThe Commission shall, in collaboration with the Member\u00a0States, put in place systems and processes to actively monitor the data available in the electronic system referred to in Article\u00a092, in order to identify trends, patterns or signals in the data that may reveal new risks or safety concerns.\nWhere a previously unknown risk is identified or the frequency of an anticipated risk significantly and adversely changes the benefit-risk determination, the competent authority or, where appropriate, the coordinating competent authority shall inform the manufacturer, or where applicable the authorised representative, which shall then take the necessary corrective actions.\n\n\nArticle\u00a091\n\nImplementing acts\n\nThe Commission may, by means of implementing acts, and after consultation of the MDCG, adopt the detailed arrangements and procedural aspects necessary for the implementation of Articles\u00a085 to\u00a090 and 92 as regards the following:\n\n\n\n\n\n\n(a)\n\n\nthe typology of serious incidents and field safety corrective actions in relation to specific devices, or categories or groups of devices;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe reporting of serious incidents and field safety corrective actions and field safety notices, and the provision of periodic summary reports, post-market surveillance reports, PSURs and trend reports by manufacturers as referred to in Articles\u00a085, 86, 87, 88 and 89 respectively;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nstandard structured forms for electronic and non-electronic reporting, including a minimum data set for reporting of suspected serious incidents by healthcare professionals, users and patients;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\ntimelines for the reporting of field safety corrective actions, and for the provision by manufacturers of periodic summary reports and trend reports, taking into account the severity of the incident to be reported as referred to in Article\u00a087;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nharmonised forms for the exchange of information between competent authorities as referred to in Article\u00a089;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nprocedures for the designation of a coordinating competent authority; the coordinated evaluation process, including tasks and responsibilities of the coordinating competent authority and involvement of other competent authorities in this process.\n\n\n\n\nThe implementing acts referred to in the first paragraph\u00a0shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\nArticle\u00a092\n\nElectronic system on vigilance and on post-market surveillance\n\n\n1.\u00a0\u00a0\u00a0The Commission shall, in collaboration with the Member\u00a0States, set up and manage an electronic system to collate and process the following information:\n\n\n\n\n\n\n(a)\n\n\nthe reports by manufacturers on serious incidents and field safety corrective actions referred to in Article\u00a087(1) and Article\u00a089(5);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe periodic summary reports by manufacturers referred to in Article\u00a087(9);\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe reports by manufacturers on trends referred to in Article\u00a088;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe PSURs referred to in Article\u00a086;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe field safety notices by manufacturers referred to in Article\u00a089(8);\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe information to be exchanged between the competent authorities of the Member\u00a0States and between them and the Commission in accordance with Article\u00a089(7) and\u00a0(9).\n\n\n\n\nThat electronic system shall include relevant links to the UDI database.\n\n\n2.\u00a0\u00a0\u00a0The information referred to in paragraph\u00a01 of this Article\u00a0shall be made available through the electronic system to the competent authorities of the Member\u00a0States and to the Commission. The notified bodies shall also have access to that information to the extent that it relates to devices for which they issued a certificate in accordance with Article\u00a053.\n\n\n3.\u00a0\u00a0\u00a0The Commission shall ensure that healthcare professionals and the public have appropriate levels of access to the electronic system referred to in paragraph\u00a01.\n\n\n4.\u00a0\u00a0\u00a0On the basis of arrangements between the Commission and competent authorities of third countries or international organisations, the Commission may grant those competent authorities or international organisations access to the electronic system referred to in paragraph\u00a01 at the appropriate level. Those arrangements shall be based on reciprocity and make provision for confidentiality and data protection equivalent to those applicable in the Union.\n\n\n5.\u00a0\u00a0\u00a0The reports on serious incidents referred to in point\u00a0(a) of Article\u00a087(1) shall be automatically transmitted, upon receipt, via the electronic system referred to in paragraph\u00a01 of this Article, to the competent authority of the Member\u00a0State in which the incident occurred.\n\n\n6.\u00a0\u00a0\u00a0The trend reports referred to in Article\u00a088(1) shall be automatically transmitted upon receipt via the electronic system referred to in paragraph\u00a01 of this Article\u00a0to the competent authorities of the Member\u00a0State in which the incidents occurred.\n\n\n7.\u00a0\u00a0\u00a0The reports on field safety corrective actions referred to in point\u00a0(b) of Article\u00a087(1) shall be automatically transmitted upon receipt via the electronic system referred to in paragraph\u00a01 of this Article\u00a0to the competent authorities of the following Member\u00a0States:\n\n\n\n\n\n\n(a)\n\n\nthe Member\u00a0States in which the field safety corrective action is being or is to be undertaken;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe Member\u00a0State in which the manufacturer has its registered place of business.\n\n\n\n\n\n\n8.\u00a0\u00a0\u00a0The periodic summary reports referred to in Article\u00a087(9) shall be automatically transmitted upon receipt via the electronic system referred to in paragraph\u00a01 of this Article\u00a0to the competent authority of:\n\n\n\n\n\n\n(a)\n\n\nthe Member\u00a0State or Member\u00a0States participating in the coordination procedure in accordance with Article\u00a089(9) and which have agreed on the periodic summary report;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe Member\u00a0State in which the manufacturer has its registered place of business.\n\n\n\n\n\n\n9.\u00a0\u00a0\u00a0The information referred to in paragraphs 5 to 8 of this Article\u00a0shall be automatically transmitted, upon receipt, through the electronic system referred to in paragraph\u00a01 of this Article, to the notified body that issued the certificate for the device in question in accordance with Article\u00a056.\n\n\n\n\n\nSECTION 3\n\n\n\n\nMarket surveillance\n\n\n\n\nArticle\u00a093\n\nMarket surveillance activities\n\n\n1.\u00a0\u00a0\u00a0The competent authorities shall perform appropriate checks on the conformity characteristics and performance of devices including, where appropriate, a review of documentation and physical or laboratory checks on the basis of adequate samples. The competent authorities shall, in particular, take account of established principles regarding risk assessment and risk management, vigilance data and complaints.\n\n\n2.\u00a0\u00a0\u00a0The competent authorities shall draw up annual surveillance activity plans and allocate a sufficient number of material and competent human resources in order to carry out those activities taking into account the European market surveillance programme developed by the MDCG pursuant to Article\u00a0105 and local circumstances.\n\n\n3.\u00a0\u00a0\u00a0In order to fulfil the obligations laid down in paragraph\u00a01, the competent authorities:\n\n\n\n\n\n\n(a)\n\n\nmay require economic operators to, inter\u00a0alia, make available the documentation and information necessary for the purpose of carrying out the authorities' activities and, where justified, to provide the necessary samples of devices or access to devices free of charge; and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nshall carry out both announced and, if necessary, unannounced inspections of the premises of economic operators, as well as suppliers and/or subcontractors, and, where necessary, at the facilities of professional users.\n\n\n\n\n\n\n4.\u00a0\u00a0\u00a0The competent authorities shall prepare an annual summary of the results of their surveillance activities and make it accessible to other competent authorities by means of the electronic system referred to in Article\u00a0100.\n\n\n5.\u00a0\u00a0\u00a0The competent authorities may confiscate, destroy or otherwise render inoperable devices that present an unacceptable risk or falsified devices where they deem it necessary to do so in the interests of the protection of public health.\n\n\n6.\u00a0\u00a0\u00a0Following each inspection carried out for the purposes referred to in paragraph\u00a01, the competent authority shall draw up a report on the findings of the inspection that concern compliance with the legal and technical requirements applicable under this Regulation. The report shall set out any corrective actions needed.\n\n\n7.\u00a0\u00a0\u00a0The competent authority which carried out the inspection shall communicate the content of the report referred to in paragraph\u00a06 of this Article\u00a0to the economic operator that has been the subject of the inspection. Before adopting the final report, the competent authority shall give that economic operator the opportunity to submit comments. That final inspection report shall be entered in the electronic system provided for in Article\u00a0100.\n\n\n8.\u00a0\u00a0\u00a0The Member\u00a0States shall review and assess the functioning of their market surveillance activities. Such reviews and assessments shall be carried out at least every four years and the results thereof shall be communicated to the other Member\u00a0States and the Commission. Each Member\u00a0State shall make a summary of the results accessible to the public by means of the electronic system referred to in Article\u00a0100.\n\n\n9.\u00a0\u00a0\u00a0The competent authorities of the Member\u00a0States shall coordinate their market surveillance activities, cooperate with each other and share with each other and with the Commission the results thereof, to provide for a harmonised and high level of market surveillance in all Member\u00a0States.\nWhere appropriate, the competent authorities of the Member\u00a0States shall agree on work-sharing, joint market surveillance activities and specialisation.\n\n\n10.\u00a0\u00a0\u00a0Where more than one authority in a Member\u00a0State is responsible for market surveillance and external border controls, those authorities shall cooperate with each other, by sharing information relevant to their role and functions.\n\n\n11.\u00a0\u00a0\u00a0Where appropriate, the competent authorities of the Member\u00a0States shall cooperate with the competent authorities of third countries with a view to exchanging information and technical support and promoting activities relating to market surveillance.\n\n\n\nArticle\u00a094\n\nEvaluation of devices suspected of presenting an unacceptable risk or other non-compliance\n\nWhere the competent authorities of a Member\u00a0State, based on data obtained by vigilance or market surveillance activities or on other information, have reason to believe that a device:\n\n\n\n\n\n\n(a)\n\n\nmay present an unacceptable risk to the health or safety of patients, users or other persons, or to other aspects of the protection of public health; or\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\notherwise does not comply with the requirements laid down in this Regulation,\n\n\n\n\nthey shall carry out an evaluation of the device concerned covering all requirements laid down in this Regulation relating to the risk presented by the device, or to any other non-compliance of the device.\nThe relevant economic operators shall cooperate with the competent authorities.\n\n\nArticle\u00a095\n\nProcedure for dealing with devices presenting an unacceptable risk to health and safety\n\n\n1.\u00a0\u00a0\u00a0Where, having performed an evaluation pursuant to Article\u00a094, the competent authorities find that the device presents an unacceptable risk to the health or safety of patients, users or other persons, or to other aspects of the protection of public health, they shall without delay require the manufacturer of the devices concerned, its authorised representative and all other relevant economic operators to take all appropriate and duly justified corrective action to bring the device into compliance with the requirements of this Regulation relating to the risk presented by the device and, in a manner that is proportionate to the nature of the risk, to restrict the making available of the device on the market, to subject the making available of the device to specific requirements, to withdraw the device from the market, or to recall it, within a reasonable period that is clearly defined and communicated to the relevant economic operator.\n\n\n2.\u00a0\u00a0\u00a0The competent authorities shall, without delay, notify the Commission, the other Member\u00a0States and, where a certificate has been issued in accordance with Article\u00a056 for the device concerned, the notified body that issued that certificate, of the results of the evaluation and of the actions which they have required the economic operators to take, by means of the electronic system referred to in Article\u00a0100.\n\n\n3.\u00a0\u00a0\u00a0The economic operators as referred to in paragraph\u00a01 shall, without delay, ensure that all appropriate corrective action is taken throughout the Union in respect of all the devices concerned that they have made available on the market.\n\n\n4.\u00a0\u00a0\u00a0Where the economic operator as referred to in paragraph\u00a01 does not take adequate corrective action within the period referred to in paragraph\u00a01, the competent authorities shall take all appropriate measures to prohibit or restrict the making available of the device on their national market, to withdraw the device from that market or to recall it.\nThe competent authorities shall notify the Commission, the other Member\u00a0States and the notified body referred to in paragraph\u00a02 of this Article, without delay, of those measures, by means of the electronic system referred to in Article\u00a0100.\n\n\n5.\u00a0\u00a0\u00a0The notification referred to in paragraph\u00a04 shall include all available details, in particular the data necessary for the identification and tracing of the non-compliant device, the origin of the device, the nature of and the reasons for the non-compliance alleged and the risk involved, the nature and duration of the national measures taken and the arguments put forward by the relevant economic operator.\n\n\n6.\u00a0\u00a0\u00a0Member\u00a0States other than the Member\u00a0State initiating the procedure shall, without delay, inform the Commission and the other Member\u00a0States, by means of the electronic system referred to in Article\u00a0100, of any additional relevant information at their disposal relating to the non-compliance of the device concerned and of any measures adopted by them in relation to the device concerned.\nIn the event of disagreement with the notified national measure, they shall, without delay, inform the Commission and the other Member\u00a0States of their objections, by means of the electronic system referred to in Article\u00a0100.\n\n\n7.\u00a0\u00a0\u00a0Where, within two months of receipt of the notification referred to in paragraph\u00a04, no objection has been raised by either a Member\u00a0State or the Commission in respect of any measures taken by a Member\u00a0State, those measures shall be deemed to be justified.\nIn that case, all Member\u00a0States shall ensure that corresponding appropriate restrictive or prohibitive measures, including withdrawing, recalling or limiting the availability of the device on their national market, are taken without delay in respect of the device concerned.\n\n\n\nArticle\u00a096\n\nProcedure for evaluating national measures at Union level\n\n\n1.\u00a0\u00a0\u00a0Where, within two months of receipt of the notification referred to in Article\u00a095(4), objections are raised by a Member\u00a0State against a measure taken by another Member\u00a0State, or where the Commission considers the measure to be contrary to Union law, the Commission shall, after consulting the competent authorities concerned and, where necessary, the economic operators concerned, evaluate that national measure. On the basis of the results of that evaluation, the Commission may decide, by means of implementing acts, whether or not the national measure is justified. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n2.\u00a0\u00a0\u00a0Where the Commission considers the national measure to be justified as referred to in paragraph\u00a01 of this Article, the second subparagraph\u00a0of Article\u00a095(7) shall apply. If the Commission considers the national measure to be unjustified, the Member\u00a0State concerned shall withdraw the measure.\nWhere the Commission does not adopt a decision pursuant to paragraph\u00a01 of this Article\u00a0within eight months of receipt of the notification referred to in Article\u00a095(4), the national measure shall be considered to be justified.\n\n\n3.\u00a0\u00a0\u00a0Where a Member\u00a0State or the Commission considers that the risk to health and safety emanating from a device cannot be mitigated satisfactorily by means of measures taken by the Member\u00a0State or Member\u00a0States concerned, the Commission, at the request of a Member\u00a0State or on its own initiative, may take, by means of implementing acts, the necessary and duly justified measures to ensure the protection of health and safety, including measures restricting or prohibiting the placing on the market and putting into service of the device concerned. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a097\n\nOther non-compliance\n\n\n1.\u00a0\u00a0\u00a0Where, having performed an evaluation pursuant to Article\u00a094, the competent authorities of a Member\u00a0State find that a device does not comply with the requirements laid down in this Regulation but does not present an unacceptable risk to the health or safety of patients, users or other persons, or to other aspects of the protection of public health, they shall require the relevant economic operator to bring the non-compliance concerned to an end within a reasonable period that is clearly defined and communicated to the economic operator and that is proportionate to the non-compliance.\n\n\n2.\u00a0\u00a0\u00a0Where the economic operator does not bring the non-compliance to an end within the period referred to in paragraph\u00a01 of this Article, the Member\u00a0State concerned shall, without delay, take all appropriate measures to restrict or prohibit the product being made available on the market or to ensure that it is recalled or withdrawn from the market. That Member\u00a0State shall inform the Commission and the other Member\u00a0States, without delay, of those measures, by means of the electronic system referred to in Article\u00a0100.\n\n\n3.\u00a0\u00a0\u00a0In order to ensure the uniform application of this Article, the Commission may, by means of implementing acts, specify appropriate measures to be taken by competent authorities to address given types of non-compliance. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a098\n\nPreventive health protection measures\n\n\n1.\u00a0\u00a0\u00a0Where a Member\u00a0State, after having performed an evaluation which indicates a potential risk related to a device or a specific category or group of devices, considers that, in order to protect the health and safety of patients, users or other persons or other aspects of public health, the making available on the market or putting into service of a device or a specific category or group of devices should be prohibited, restricted or made subject to particular requirements or that such device or category or group of devices should be withdrawn from the market or recalled, it may take any necessary and justified measures.\n\n\n2.\u00a0\u00a0\u00a0The Member\u00a0State referred to in paragraph\u00a01 shall immediately notify the Commission and all other Member\u00a0States, giving the reasons for its decision, by means of the electronic system referred to in Article\u00a0100.\n\n\n3.\u00a0\u00a0\u00a0The Commission, in consultation with the MDCG and, where necessary, the economic operators concerned, shall assess the national measures taken. The Commission may decide, by means of implementing acts, whether the national measures are justified or not. In the absence of a Commission decision within six months of their notification, the national measures shall be considered to be justified. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n4.\u00a0\u00a0\u00a0Where the assessment referred to in paragraph\u00a03 of this Article\u00a0demonstrates that the making available on the market or putting into service of a device, specific category or group of devices should be prohibited, restricted or made subject to particular requirements or that such device or category or group of devices should be withdrawn from the market or recalled in all Member\u00a0States in order to protect the health and safety of patients, users or other persons or other aspects of public health, the Commission may adopt implementing acts to take the necessary and duly justified measures. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n\nArticle\u00a099\n\nGood administrative practice\n\n\n1.\u00a0\u00a0\u00a0Any measure adopted by the competent authorities of the Member\u00a0States pursuant to Articles\u00a095 to 98 shall state the exact grounds on which it is based. Where such a measure is addressed to a specific economic operator, the competent authority shall notify without delay the economic operator concerned of that measure, and shall at the same time inform that economic operator of the remedies available under the law or the administrative practice of the Member\u00a0State concerned and of the time limits to which such remedies are subject. Where the measure is of general applicability, it shall be appropriately published.\n\n\n2.\u00a0\u00a0\u00a0Except in cases where immediate action is necessary for reasons of unacceptable risk to human health or safety, the economic operator concerned shall be given the opportunity to make submissions to the competent authority within an appropriate period of time that is clearly defined before any measure is adopted.\nWhere action has been taken without the economic operator having had the opportunity to make submissions as referred to in the first subparagraph, it shall be given the opportunity to make submissions as soon as possible and the action taken shall be reviewed promptly thereafter.\n\n\n3.\u00a0\u00a0\u00a0Any measure adopted shall be immediately withdrawn or amended upon the economic operator's demonstrating that it has taken effective corrective action and that the device is in compliance with the requirements of this Regulation.\n\n\n4.\u00a0\u00a0\u00a0Where a measure adopted pursuant to Articles\u00a095 to 98 concerns a device for which a notified body has been involved in the conformity assessment, the competent authorities shall by means of the electronic system referred to in Article\u00a0100 inform the relevant notified body and the authority responsible for the notified body of the measure taken.\n\n\n\nArticle\u00a0100\n\nElectronic system on market surveillance\n\n\n1.\u00a0\u00a0\u00a0The Commission, in collaboration with the Member\u00a0States, shall set up and manage an electronic system to collate and process the following information:\n\n\n\n\n\n\n(a)\n\n\nsummaries of the results of the surveillance activities referred to in Article\u00a093(4);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe final inspection report referred to in Article\u00a093(7);\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\ninformation in relation to devices presenting an unacceptable risk to health and safety as referred to in Article\u00a095(2), (4) and (6);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\ninformation in relation to non-compliance of products as referred to in Article\u00a097(2);\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\ninformation in relation to the preventive health protection measures referred to in Article\u00a098(2);\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nsummaries of the results of the reviews and assessments of the market surveillance activities of the Member\u00a0States referred to in 93(8).\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0The information referred to in paragraph\u00a01 of this Article\u00a0shall be immediately transmitted through the electronic system to all competent authorities concerned and, where applicable, to the notified body that issued a certificate in accordance with Article\u00a056 for the device concerned and be accessible to the Member\u00a0States and to the Commission.\n\n\n3.\u00a0\u00a0\u00a0Information exchanged between Member\u00a0States shall not be made public where to do so might impair market surveillance activities and co-operation between Member\u00a0States.\n\n\n\n\n\nCHAPTER VIII\n\n\nCOOPERATION BETWEEN MEMBER\u00a0STATES, MEDICAL DEVICE COORDINATION GROUP, EXPERT LABORATORIES, EXPERT PANELS AND DEVICE REGISTERS\n\n\n\nArticle\u00a0101\n\nCompetent authorities\n\nThe Member\u00a0States shall designate the competent authority or authorities responsible for the implementation of this Regulation. They shall entrust their authorities with the powers, resources, equipment and knowledge necessary for the proper performance of their tasks pursuant to this Regulation. The Member\u00a0States shall communicate the names and contact details of the competent authorities to the Commission which shall publish a list of competent authorities.\n\n\nArticle\u00a0102\n\nCooperation\n\n\n1.\u00a0\u00a0\u00a0The competent authorities of the Member\u00a0States shall cooperate with each other and with the Commission. The Commission shall provide for the organisation of exchanges of information necessary to enable this Regulation to be applied uniformly.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States shall, with the support of the Commission, participate, where appropriate, in initiatives developed at international level with the aim of ensuring cooperation between regulatory authorities in the field of medical devices.\n\n\n\nArticle\u00a0103\n\nMedical Device Coordination Group\n\n\n1.\u00a0\u00a0\u00a0A Medical Device Coordination Group (\u2018MDCG\u2019) is hereby established.\n\n\n2.\u00a0\u00a0\u00a0Each Member\u00a0State shall appoint to the MDCG, for a three-year term which may be renewed, one member and one alternate each with expertise in the field of medical devices, and one member and one alternate with expertise in the field of in vitro diagnostic medical devices. A Member\u00a0State may choose to appoint only one member and one alternate, each with expertise in both fields.\nThe members of the MDCG shall be chosen for their competence and experience in the field of medical devices and in vitro diagnostic medical devices. They shall represent the competent authorities of the Member\u00a0States. The names and affiliation of members shall be made public by the Commission.\nThe alternates shall represent and vote for the members in their absence.\n\n\n3.\u00a0\u00a0\u00a0The MDCG shall meet at regular intervals and, where the situation requires, upon request by the Commission or a Member\u00a0State. The meetings shall be attended either by the members appointed for their role and expertise in the field of medical devices, or by the members appointed for their expertise in the field of in vitro diagnostic medical devices, or by the members appointed for their expertise in both fields, or their alternates, as appropriate.\n\n\n4.\u00a0\u00a0\u00a0The MDCG shall use its best endeavours to reach consensus. If such consensus cannot be reached, the MDCG shall decide by a majority of its members. Members with diverging positions may request that their positions and the grounds on which they are based be recorded in the MDCG's position.\n\n\n5.\u00a0\u00a0\u00a0The MDCG shall be chaired by a representative of the Commission. The chair shall not take part in votes of the MDCG.\n\n\n6.\u00a0\u00a0\u00a0The MDCG may invite, on a case-by-case basis, experts and other third parties to attend meetings or provide written contributions.\n\n\n7.\u00a0\u00a0\u00a0The MDCG may establish standing or temporary sub-groups. Where appropriate, organisations representing the interests of the medical device industry, healthcare professionals, laboratories, patients and consumers at Union level shall be invited to such sub-groups in the capacity of observers.\n\n\n8.\u00a0\u00a0\u00a0The MDCG shall establish its rules of procedure which shall, in particular, lay down procedures for the following:\n\n\n\n\n\n\n\u2014\n\n\nthe adoption of opinions or recommendations or other positions, including in cases of urgency;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe delegation of tasks to reporting and co-reporting members;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe implementation of Article\u00a0107 regarding conflict of interests;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe functioning of sub-groups.\n\n\n\n\n\n\n9.\u00a0\u00a0\u00a0The MDCG shall have the tasks laid down in Article\u00a0105 of this Regulation and Article\u00a099 of Regulation (EU)\u00a02017/746.\n\n\n\nArticle\u00a0104\n\nSupport by the Commission\n\nThe Commission shall support the functioning of the cooperation between national competent authorities. It shall, in particular, provide for the organisation of exchanges of experience between the competent authorities and provide technical, scientific and logistic support to the MDCG and its sub-groups. It shall organise the meetings of the MDCG and its sub-groups, participate in those meetings and ensure the appropriate follow-up.\n\n\nArticle\u00a0105\n\nTasks of the MDCG\n\nUnder this Regulation, the MDCG shall have the following tasks:\n\n\n\n\n\n\n(a)\n\n\nto contribute to the assessment of applicant conformity assessment bodies and notified bodies pursuant to the provisions set out in Chapter IV;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nto advise the Commission, at its request, in matters concerning the coordination group of notified bodies as established pursuant to Article\u00a049;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nto contribute to the development of guidance aimed at ensuring effective and harmonised implementation of this Regulation, in particular regarding the designation and monitoring of notified bodies, application of the general safety and performance requirements and conduct of clinical evaluations and investigations by manufacturers, assessment by notified bodies and vigilance activities;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nto contribute to the continuous monitoring of technical progress and assessment of whether the general safety and performance requirements laid down in this Regulation and Regulation\u00a0(EU)\u00a02017/746 are adequate to ensure safety and performance of devices, and thereby contribute to identifying whether there is a need to amend Annex\u00a0I to this Regulation;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nto contribute to the development of device standards, of CS and of scientific guidelines, including product specific guidelines, on clinical investigation of certain devices in particular implantable devices and class III devices;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nto assist the competent authorities of the Member\u00a0States in their coordination activities in particular in the fields of classification and the determination of the regulatory status of devices, clinical investigations, vigilance and market surveillance including the development and maintenance of a framework for a European market surveillance programme with the objective of achieving efficiency and harmonisation of market surveillance in the Union, in accordance with Article\u00a093;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nto provide advice, either on its own initiative or at request of the Commission, in the assessment of any issue related to the implementation of this Regulation;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nto contribute to harmonised administrative practice with regard to devices in the Member\u00a0States.\n\n\n\n\n\n\nArticle\u00a0106\n\nProvision of scientific, technical and clinical opinions and advice\n\n\n1.\u00a0\u00a0\u00a0The Commission shall, by means of implementing acts and in consultation with the MDCG, make provision for expert panels to be designated for the assessment of the clinical evaluation in relevant medical fields as referred to in paragraph\u00a09 of this Article\u00a0and to provide views in accordance with Article\u00a048(6) of Regulation\u00a0(EU)\u00a02017/746 on the performance evaluation of certain in vitro diagnostic medical devices and, where necessary, for categories or groups of devices, or for specific hazards relating to categories or groups of devices, observing the principles of highest scientific competence, impartiality, independence and transparency. The same principles shall apply where the Commission decides to appoint expert laboratories in accordance with paragraph\u00a07 of this Article.\n\n\n2.\u00a0\u00a0\u00a0Expert panels and expert laboratories may be designated in areas where the Commission, in consultation with the MDCG, has identified a need for the provision of consistent scientific, technical and/or clinical advice or laboratory expertise in relation to the implementation of this Regulation. Expert panels and expert laboratories may be appointed on a standing or temporary basis.\n\n\n3.\u00a0\u00a0\u00a0Expert panels shall consist of advisors appointed by the Commission on the basis of up-to-date clinical, scientific or technical expertise in the field and with a geographical distribution that reflects the diversity of scientific and clinical approaches in the Union. The Commission shall determine the number of members of each panel in accordance with the requisite needs.\nThe members of expert panels shall perform their tasks with impartiality and objectivity. They shall neither seek nor take instructions from notified bodies or manufacturers. Each member shall draw up a declaration of interests, which shall be made publicly available.\nThe Commission shall establish systems and procedures to actively manage and prevent potential conflicts of interest.\n\n\n4.\u00a0\u00a0\u00a0Expert panels shall take into account relevant information provided by stakeholders including patients' organisations and healthcare professionals when preparing their scientific opinions.\n\n\n5.\u00a0\u00a0\u00a0The Commission, following consultation with the MDCG, may appoint advisors to expert panels following publication in the Official Journal of the European Union and on the Commission website following a call for expressions of interest. Depending on the type of task and the need for specific expertise, advisors may be appointed to the expert panels for a maximum period of three years and their appointment may be renewed.\n\n\n6.\u00a0\u00a0\u00a0The Commission, following consultation with the MDCG, may include advisors on a central list of available experts who, whilst not being formally appointed to a panel, are available to provide advice and to support the work of the expert panel as needed. That list shall be published on the Commission website.\n\n\n7.\u00a0\u00a0\u00a0The Commission may, by means of implementing acts and following consultation with the MDCG, designate expert laboratories, on the basis of their expertise in:\n\n\n\n\n\n\n\u2014\n\n\nphysico-chemical characterisation, or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmicrobiological, biocompatibility, mechanical, electrical, electronic or non-clinical biological and toxicological testing\n\n\n\n\nof specific devices, categories or groups of devices.\nThe Commission shall only designate expert laboratories for which a Member\u00a0State or the Joint Research Centre has submitted an application for designation.\n\n\n8.\u00a0\u00a0\u00a0Expert laboratories shall satisfy the following criteria:\n\n\n\n\n\n\n(a)\n\n\nhave adequate and appropriately qualified staff with adequate knowledge and experience in the field of the devices for which they are designated;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\npossess the necessary equipment to carry out the tasks assigned to them;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nhave the necessary knowledge of international standards and best practices;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nhave an appropriate administrative organisation and structure;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nensure that their staff observe the confidentiality of information and data obtained in carrying out their tasks.\n\n\n\n\n\n\n9.\u00a0\u00a0\u00a0Expert panels appointed for clinical evaluation in relevant medical fields shall fulfil the tasks provided for in Article\u00a054(1) and Article\u00a061(2) and Section\u00a05.1 of Annex\u00a0IX or Section\u00a06 of Annex\u00a0X, as applicable.\n\n\n10.\u00a0\u00a0\u00a0Expert panels and expert laboratories may have the following tasks, depending on the requisite needs:\n\n\n\n\n\n\n(a)\n\n\nto provide scientific, technical and clinical assistance to the Commission and the MDCG in relation to the implementation of this Regulation;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nto contribute to the development and maintenance of appropriate guidance and CS for:\n\n\n\n\n\n\n\u2014\n\n\nclinical investigations,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclinical evaluation and PMCF,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nperformance studies,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nperformance evaluation and post-market performance follow-up,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nphysico-chemical characterisation, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmicrobiological, biocompatibility, mechanical, electrical, electronic or non-clinical toxicological testing\n\n\n\n\nfor specific devices, or a category or group of devices, or for specific hazards related to a category or group of devices;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nto develop and review clinical evaluation guidance and performance evaluation guidance for performance of conformity assessment in line with the state of the art with regard to clinical evaluation, performance evaluation, physico-chemical characterisation, and microbiological, biocompatibility, mechanical, electrical, electronic or non-clinical toxicological testing;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nto contribute to the development of standards at international level, ensuring that such standards reflect the state of the art;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nto provide opinions in response to consultations by manufacturers in accordance with Article\u00a061(2), notified bodies and Member\u00a0States in accordance with paragraphs\u00a011 to 13 of this Article.\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nto contribute to identification of concerns and emerging issues on the safety and performance of medical devices;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nto provide views in accordance with Article\u00a048(4) of Regulation\u00a0(EU)\u00a02017/746 on the performance evaluation of certain in vitro diagnostic medical devices.\n\n\n\n\n\n\n11.\u00a0\u00a0\u00a0The Commission, shall facilitate the access of Member\u00a0States and notified bodies and manufacturers to advice provided by expert panels and expert laboratories concerning, inter\u00a0alia, the criteria for an appropriate data set for assessment of the conformity of a device, in particular with regard to the clinical data required for clinical evaluation, with regard to physico-chemical characterisation, and with regard to microbiological, biocompatibility, mechanical, electrical, electronic and non-clinical toxicological testing.\n\n\n12.\u00a0\u00a0\u00a0When adopting its scientific opinion in accordance with paragraph\u00a09, the members of the expert panels shall use their best endeavours to reach consensus. If consensus cannot be reached, the expert panels shall decide by a majority of their members, and the scientific opinion shall mention the divergent positions and the grounds on which they are based.\nThe Commission shall publish the scientific opinion and advice delivered in accordance with paragraphs 9 and 11 of this Article, ensuring consideration of aspects of confidentiality as set out in Article\u00a0109. The clinical evaluation guidance referred to in point\u00a0(c) of paragraph\u00a010 shall be published following consultation with the MDCG.\n\n\n13.\u00a0\u00a0\u00a0The Commission may require manufacturers and notified bodies to pay fees for the advice provided by expert panels and expert laboratories. The structure and the level of fees as well as the scale and structure of recoverable costs shall be adopted by the Commission by means of implementing acts, taking into account the objectives of the adequate implementation of this Regulation, protection of health and safety, support of innovation and cost-effectiveness and the necessity to achieve active participation in the expert panels. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\n14.\u00a0\u00a0\u00a0The fees payable to the Commission in accordance with the procedure under paragraph\u00a013 of this Article\u00a0shall be set in a transparent manner and on the basis of the costs for the services provided. The fees payable shall be reduced in the case of a clinical evaluation consultation procedure initiated in accordance with point\u00a0(c) of Section\u00a05.1 of Annex\u00a0IX involving a manufacturer who is a micro, small or medium-sized enterprise within the meaning of Recommendation\u00a02003/361/EC.\n\n\n15.\u00a0\u00a0\u00a0The Commission is empowered to adopt delegated acts in accordance with Article\u00a0115 to amend the tasks of expert panels and expert laboratories referred to in paragraph\u00a010 of this Article.\n\n\n\nArticle\u00a0107\n\nConflict of interests\n\n\n1.\u00a0\u00a0\u00a0Members of the MDCG, its sub-groups, and members of expert panels and expert laboratories shall not have financial or other interests in the medical device industry which could affect their impartiality. They shall undertake to act in the public interest and in an independent manner. They shall declare any direct or indirect interests they may have in the medical device industry and update that declaration whenever a relevant change occurs. The declaration of interests shall be made publicly available on the Commission website. This Article\u00a0shall not apply to the representatives of stakeholder organisations participating in the sub-groups of the MDCG.\n\n\n2.\u00a0\u00a0\u00a0Experts and other third parties invited by the MDCG on a case-by-case basis shall declare any interests they may have in the issue in question.\n\n\n\nArticle\u00a0108\n\nDevice registers and databanks\n\nThe Commission and the Member\u00a0States shall take all appropriate measures to encourage the establishment of registers and databanks for specific types of devices setting common principles to collect comparable information. Such registers and databanks shall contribute to the independent evaluation of the long-term safety and performance of devices, or the traceability of implantable devices, or all of such characteristics.\n\n\n\nCHAPTER IX\n\n\nCONFIDENTIALITY, DATA PROTECTION, FUNDING AND PENALTIES\n\n\n\nArticle\u00a0109\n\nConfidentiality\n\n\n1.\u00a0\u00a0\u00a0Unless otherwise provided for in this Regulation and without prejudice to existing national provisions and practices in the Member\u00a0States on confidentiality, all parties involved in the application of this Regulation shall respect the confidentiality of information and data obtained in carrying out their tasks in order to protect the following:\n\n\n\n\n\n\n(a)\n\n\npersonal data, in accordance with Article\u00a0110;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ncommercially confidential information and trade secrets of a natural or legal person, including intellectual property rights; unless disclosure is in the public interest;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe effective implementation of this Regulation, in particular for the purpose of inspections, investigations or audits.\n\n\n\n\n\n\n2.\u00a0\u00a0\u00a0Without prejudice to paragraph\u00a01, information exchanged on a confidential basis between competent authorities and between competent authorities and the Commission shall not be disclosed without the prior agreement of the originating authority.\n\n\n3.\u00a0\u00a0\u00a0Paragraphs 1 and 2 shall not affect the rights and obligations of the Commission, Member\u00a0States and notified bodies with regard to exchange of information and the dissemination of warnings, nor the obligations of the persons concerned to provide information under criminal law.\n\n\n4.\u00a0\u00a0\u00a0The Commission and Member\u00a0States may exchange confidential information with regulatory authorities of third countries with which they have concluded bilateral or multilateral confidentiality arrangements.\n\n\n\nArticle\u00a0110\n\nData protection\n\n\n1.\u00a0\u00a0\u00a0Member\u00a0States shall apply Directive\u00a095/46/EC to the processing of personal data carried out in the Member\u00a0States pursuant to this Regulation.\n\n\n2.\u00a0\u00a0\u00a0Regulation\u00a0(EC)\u00a0No\u00a045/2001 shall apply to the processing of personal data carried out by the Commission pursuant to this Regulation.\n\n\n\nArticle\u00a0111\n\nLevying of fees\n\n\n1.\u00a0\u00a0\u00a0This Regulation shall be without prejudice to the possibility for Member\u00a0States to levy fees for the activities set out in this Regulation, provided that the level of the fees is set in a transparent manner and on the basis of cost-recovery principles.\n\n\n2.\u00a0\u00a0\u00a0Member\u00a0States shall inform the Commission and the other Member\u00a0States at least three months before the structure and level of fees is to be adopted. The structure and level of fees shall be made publicly available on request.\n\n\n\nArticle\u00a0112\n\nFunding of activities related to designation and monitoring of notified bodies\n\nThe costs associated with joint assessment activities shall be covered by the Commission. The Commission shall, by means of implementing acts, lay down the scale and structure of recoverable costs and other necessary implementing rules. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article\u00a0114(3).\n\n\nArticle\u00a0113\n\nPenalties\n\nThe Member\u00a0States shall lay down the rules on penalties applicable for infringement of the provisions of this Regulation and shall take all measures necessary to ensure that they are implemented. The penalties provided for shall be effective, proportionate, and dissuasive. The Member\u00a0States shall notify the Commission of those rules and of those measures by 25 February 2020 and shall notify it, without delay, of any subsequent amendment affecting them.\n\n\n\nCHAPTER X\n\n\nFINAL PROVISIONS\n\n\n\nArticle\u00a0114\n\nCommittee procedure\n\n\n1.\u00a0\u00a0\u00a0The Commission shall be assisted by a Committee on Medical Devices. That Committee shall be a committee within the meaning of Regulation\u00a0(EU)\u00a0No\u00a0182/2011.\n\n\n2.\u00a0\u00a0\u00a0Where reference is made to this paragraph, Article\u00a04 of Regulation\u00a0(EU)\u00a0No\u00a0182/2011 shall apply.\n\n\n3.\u00a0\u00a0\u00a0Where reference is made to this paragraph, Article\u00a05 of Regulation\u00a0(EU)\u00a0No\u00a0182/2011 shall apply.\nWhere the committee delivers no opinion, the Commission shall not adopt the draft implementing act and the third subparagraph\u00a0of Article\u00a05(4) of Regulation\u00a0(EU)\u00a0No\u00a0182/2011 shall apply.\n\n\n4.\u00a0\u00a0\u00a0Where reference is made to this paragraph, Article\u00a08 of Regulation\u00a0(EU)\u00a0No\u00a0182/2011, in conjunction with Article\u00a04 or 5 thereof, as appropriate, shall apply.\n\n\n\nArticle\u00a0115\n\nExercise of the delegation\n\n\n1.\u00a0\u00a0\u00a0The power to adopt delegated acts is conferred on the Commission subject to the conditions laid down in this Article.\n\n\n2.\u00a0\u00a0\u00a0The power to adopt delegated acts referred to in Articles\u00a01(5), 3, 10(4), 18(3), 19(4), 27(10), 44(11), 52(5), 56(6), 61(8), 70(8) and 106(15) shall be conferred on the Commission for a period of five years from 25 May 2017. The Commission shall draw up a report in respect of the delegation of power not later than nine months before the end of the five-year period. The delegation of power shall be tacitly extended for periods of an identical duration, unless the European Parliament or the Council opposes such extension not later than three months before the end of each period.\n\n\n3.\u00a0\u00a0\u00a0The delegation of power referred to in Articles\u00a01(5), 3, 10(4), 18(3), 19(4), 27(10), 44(11), 52(5), 56(6), 61(8), 70(8) and 106(15) may be revoked at any time by the European Parliament or by the Council. A decision to revoke shall put an end to the delegation of the power specified in that decision. It shall take effect the day following the publication of the decision in the Official Journal of the European Union or at a later date specified therein. It shall not affect the validity of any delegated acts already in force.\n\n\n4.\u00a0\u00a0\u00a0Before adopting a delegated act, the Commission shall consult experts designated by each Member\u00a0State in accordance with the principles laid down in the Interinstitutional Agreement of 13 April 2016 on Better Law-Making.\n\n\n5.\u00a0\u00a0\u00a0As soon as it adopts a delegated act, the Commission shall notify it simultaneously to the European Parliament and to the Council.\n\n\n6.\u00a0\u00a0\u00a0A delegated act adopted pursuant to Articles\u00a01(5), 3, 10(4), 18(3), 19(4), 27(10), 44(11), 52(5), 56(6), 61(8), 70(8) and 106(15) shall enter into force only if no objection has been expressed either by the European Parliament or by the Council within a period of three months of notification of that act to the European Parliament and the Council or if, before the expiry of that period, the European Parliament and the Council have both informed the Commission that they will not object. That period shall be extended by three months at the initiative of the European Parliament or of the Council.\n\n\n\nArticle\u00a0116\n\nSeparate delegated acts for different delegated powers\n\nThe Commission shall adopt a separate delegated act in respect of each power delegated to it pursuant to this Regulation.\n\n\nArticle\u00a0117\n\nAmendment to Directive\u00a02001/83/EC\n\nIn Annex\u00a0I to Directive\u00a02001/83/EC, point 12 of Section\u00a03.2. is replaced by the following:\n\n\n\n\n\n\n\n\u2018(12)\n\n\nWhere, in accordance with the second subparagraph\u00a0of Article\u00a01(8) or the second subparagraph\u00a0of Article\u00a01(9) of Regulation\u00a0(EU)\u00a02017/745 of the European Parliament and of the Council\u00a0(*1), a product is governed by this Directive, the marketing authorisation dossier shall include, where available, the results of the assessment of the conformity of the device part with the relevant general safety and performance requirements set out in Annex\u00a0I to that Regulation contained in the manufacturer's EU declaration of conformity or the relevant certificate issued by a notified body allowing the manufacturer to affix a CE\u00a0marking to the medical device.\nIf the dossier does not include the results of the conformity assessment referred to in the first subparagraph\u00a0and where for the conformity assessment of the device, if used separately, the involvement of a notified body is required in accordance with Regulation\u00a0(EU)\u00a02017/745, the authority shall require the applicant to provide an opinion on the conformity of the device part with the relevant general safety and performance requirements set out in Annex\u00a0I to that Regulation issued by a notified body designated in accordance with that Regulation for the type of device in question.\n\n\n\n\n\n\n\nArticle\u00a0118\n\nAmendment to Regulation\u00a0(EC)\u00a0No\u00a0178/2002\n\nIn the third paragraph\u00a0of Article\u00a02 of Regulation\u00a0(EC)\u00a0No\u00a0178/2002, the following point is added:\n\n\n\n\n\n\n\n\u2018(i)\n\n\nmedical devices within the meaning of Regulation\u00a0(EU)\u00a02017/745 of the European Parliament and of the Council\u00a0(*2).\n\n\n\n\n\n\n\nArticle\u00a0119\n\nAmendment to Regulation\u00a0(EC)\u00a0No\u00a01223/2009\n\nIn Article\u00a02 of Regulation\u00a0(EC)\u00a0No\u00a01223/2009, the following paragraph\u00a0is added:\n\n\n\u20184.\u00a0\u00a0\u00a0The Commission may, at the request of a Member\u00a0State or on its own initiative, adopt the necessary measures to determine whether or not a specific product or group of products falls within the definition \u2018cosmetic product\u2019. Those measures shall be adopted in accordance with the regulatory procedure referred to in Article\u00a032(2).\u2019.\n\n\n\n\nArticle\u00a0120\n\nTransitional provisions\n\n\n1.\u00a0\u00a0\u00a0From 26 May 2020, any publication of a notification in respect of a notified body in accordance with Directives\u00a090/385/EEC and 93/42/EEC shall become void.\n\n\n2.\u00a0\u00a0\u00a0Certificates issued by notified bodies in accordance with Directives\u00a090/385/EEC and 93/42/EEC prior to 25 May 2017 shall remain valid until the end of the period indicated on the certificate, except for certificates issued in accordance with Annex\u00a04 to Directive\u00a090/385/EEC or Annex\u00a0IV to Directive\u00a093/42/EEC which shall become void at the latest on 27 May 2022.\nCertificates issued by notified bodies in accordance with Directives\u00a090/385/EEC and 93/42/EEC from 25 May 2017 shall remain valid until the end of the period indicated on the certificate, which shall not exceed five years from its issuance. They shall however become void at the latest on 27 May 2024.\n\n\n3.\u00a0\u00a0\u00a0By way of derogation from Article\u00a05 of this Regulation, a device with a certificate that was issued in accordance with Directive\u00a090/385/EEC or Directive\u00a093/42/EEC and which is valid by virtue of paragraph\u00a02 of this Article\u00a0may only be placed on the market or put into service provided that from the date of application of this Regulation it continues to comply with either of those Directives, and provided there are no significant changes in the design and intended purpose. However, the requirements of this Regulation relating to post-market surveillance, market surveillance, vigilance, registration of economic operators and of devices shall apply in place of the corresponding requirements in those\u00a0Directives.\nWithout prejudice to Chapter\u00a0IV and paragraph\u00a01 of this Article, the notified body that issued the certificate referred to in the first subparagraph\u00a0shall continue to be responsible for the appropriate surveillance in respect of all of the applicable requirements relating to the devices it has certified.\n\n\n4.\u00a0\u00a0\u00a0Devices lawfully placed on the market pursuant to Directives\u00a090/385/EEC and 93/42/EEC prior to 26 May 2020, and devices placed on the market from 26 May 2020 by virtue of a certificate as referred to in paragraph\u00a02 of this Article, may continue to be made available on the market or put into service until 27 May 2025.\n\n\n5.\u00a0\u00a0\u00a0By way of derogation from Directives\u00a090/385/EEC and 93/42/EEC, devices which comply with this Regulation may be placed on the market prior to 26 May 2020.\n\n\n6.\u00a0\u00a0\u00a0By way of derogation from Directives\u00a090/385/EEC and 93/42/EEC, conformity assessment bodies which comply with this Regulation may be designated and notified prior 26 May 2020. Notified bodies which are designated and notified in accordance with this Regulation may carry out the conformity assessment procedures laid down in this Regulation and issue certificates in accordance with this Regulation prior to 26 May 2020.\n\n\n7.\u00a0\u00a0\u00a0As regards devices subject to the consultation procedure laid down in Article\u00a054, paragraph\u00a05 of this Article\u00a0shall apply provided that the necessary appointments to the MDCG and expert panels have been made.\n\n\n8.\u00a0\u00a0\u00a0By way of derogation from Article\u00a010a and point\u00a0(a) of Article\u00a010b(1) of Directive\u00a090/385/EEC and Article\u00a014(1) and (2) and points (a) and (b) of Article\u00a014a(1) of Directive\u00a093/42/EEC, manufacturers, authorised representatives, importers and notified bodies which, during the period starting on the later of the dates referred to point\u00a0(d) of Article\u00a0123(3) and ending 18 months later, comply with Article\u00a029(4) and Article\u00a056(5) of this Regulation shall be considered to comply with the laws and regulations adopted by Member\u00a0States in accordance with, respectively, Article\u00a010a of Directive\u00a090/385/EEC or Article\u00a014(1) and (2) of Directive\u00a093/42/EEC and with, respectively, point\u00a0(a) of Article\u00a010b(1) of Directive\u00a090/385/EEC or points (a) and (b) of Article\u00a014a(1) of Directive\u00a093/42/EEC as specified in Decision 2010/227/EU.\n\n\n9.\u00a0\u00a0\u00a0Authorisations granted by the competent authorities of the Member\u00a0States in accordance with Article\u00a09(9) of Directive\u00a090/385/EEC or Article\u00a011(13) of Directive\u00a093/42/EEC shall keep the validity indicated in the authorisation.\n\n\n10.\u00a0\u00a0\u00a0Devices falling within the scope of this Regulation in accordance with points (f) and (g) of Article\u00a01(6) which have been legally placed on the market or put into service in accordance with the rules in force in the Member\u00a0States prior to 26 May 2020 may continue to be placed on the market and put into service in the Member\u00a0States concerned.\n\n\n11.\u00a0\u00a0\u00a0Clinical investigations which have started to be conducted in accordance with Article\u00a010 of Directive\u00a090/385/EEC or Article\u00a015 of Directive\u00a093/42/EEC prior to 26 May 2020 may continue to be conducted. As of 26 May 2020, however, the reporting of serious adverse events and device deficiencies shall be carried out in accordance with this Regulation.\n\n\n12.\u00a0\u00a0\u00a0Until the Commission has designated, pursuant to Article\u00a027(2), issuing entities, GS1, HIBCC and ICCBBA shall be considered to be designated issuing entities.\n\n\n\nArticle\u00a0121\n\nEvaluation\n\nBy 27 May 2027, the Commission shall assess the application of this Regulation and produce an evaluation report on the progress towards achievement of the objectives contained herein including an assessment of the resources required to implement this Regulation. Special attention shall be given to the traceability of medical devices through the storage, pursuant to Article\u00a027, of the UDI by economic operators, health institutions and health professionals.\n\n\nArticle\u00a0122\n\nRepeal\n\nWithout prejudice to Articles\u00a0120(3) and (4) of this Regulation, and without prejudice to the obligations of the Member\u00a0States and manufacturers as regards vigilance and to the obligations of manufacturers as regards the making available of documentation, under Directives\u00a090/385/EEC and 93/42/EEC, those Directives are repealed with effect from 26 May 2020, with the exception of:\n\n\n\n\n\n\n\u2014\n\n\nArticles\u00a08 and 10, points (b) and (c) of Article\u00a010b(1), Article\u00a010b(2) and Article\u00a010b(3) of Directive\u00a090/385/EEC, and the obligations relating to vigilance and clinical investigations provided for in the corresponding Annexes, which are repealed with effect from the later of the dates referred to in point\u00a0(d) of Article\u00a0123(3) of this Regulation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a010a and point\u00a0(a) of Article\u00a010b(1) of Directive\u00a090/385/EEC, and the obligations relating to registration of devices and economic operators, and to certificate notifications, provided for in the corresponding Annexes, which are repealed with effect from 18\u00a0months after the later of the dates referred to in point\u00a0(d) of Article\u00a0123(3) of this Regulation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a010, points (c) and (d) of Article\u00a014a(1), Article\u00a014a(2), Article\u00a014a(3) and Article\u00a015 of Directive\u00a093/42/EEC, and the obligations relating to vigilance and clinical investigations provided for in the corresponding Annexes, which are repealed with effect from the later of the dates referred to in point\u00a0(d) of Article\u00a0123(3) of this Regulation; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a014(1) and (2) and points (a) and (b) of Article\u00a014a(1) of Directive\u00a093/42/EEC, and the obligations relating to registration of devices and economic operators, and to certificate notifications, provided for in the corresponding Annexes, which are repealed with effect from 18 months after the later of the dates referred to in point\u00a0(d) of Article\u00a0123(3) of this Regulation.\n\n\n\n\nAs regards the devices referred to in Article\u00a0120 (3) and (4) of this Regulation, the Directives referred to in the first\u00a0paragraph\u00a0shall continue to apply until 27 May 2025 to the extent necessary for the application of those paragraphs.\nNotwithstanding the first paragraph, Regulations (EU)\u00a0No\u00a0207/2012 and (EU)\u00a0No\u00a0722/2012 shall remain in force and continue to apply unless and until repealed by implementing acts adopted by the Commission pursuant to this Regulation.\nReferences to the repealed Directives shall be understood as references to this Regulation and shall be read in accordance with the correlation table laid down in Annex\u00a0XVII to this Regulation.\n\n\nArticle\u00a0123\n\nEntry into force and date of application\n\n\n1.\u00a0\u00a0\u00a0This Regulation shall enter into force on the twentieth day following that of its publication in the Official Journal of the European Union.\n\n\n2.\u00a0\u00a0\u00a0It shall apply from 26 May 2020.\n\n\n3.\u00a0\u00a0\u00a0By way of derogation from paragraph\u00a02:\n\n\n\n\n\n\n(a)\n\n\nArticles\u00a035 to 50 shall apply from 26 November 2017. However, from that date until 26 May 2020, the obligations on notified bodies pursuant to Articles\u00a035 to 50 shall apply only to those bodies which submit an application for designation in accordance with Article\u00a038;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nArticles\u00a0101 and 103 shall apply from 26 November 2017;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nArticle\u00a0102 shall apply from 26 May 2018;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nwithout prejudice to the obligations on the Commission pursuant to Article\u00a034, where, due to circumstances that could not reasonably have been foreseen when drafting the plan referred to in Article\u00a034(1), Eudamed is not fully functional on 26\u00a0May 2020, the obligations and requirements that relate to Eudamed shall apply from the date corresponding to six\u00a0months after the date of publication of the notice referred to in Article\u00a034(3). The provisions referred to in the preceding sentence are:\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a029,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a031,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a032,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a033(4),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe second sentence of Article\u00a040(2),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a042(10),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a043(2),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe second subparagraph\u00a0of Article\u00a044(12),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npoints (d) and (e) of Article\u00a046(7),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a053(2),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a054(3),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a055(1),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticles\u00a070 to 77,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nparagraphs 1 to 13 of Article\u00a078,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticles\u00a079 to 82,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a086(2),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticles\u00a087 and 88,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a089(5) and (7), and the third subparagraph\u00a0of Article\u00a089(8),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a090,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a093(4), (7) and (8),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a095(2) and (4),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe last sentence of Article\u00a097(2),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nArticle\u00a099(4),\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe second sentence of the first subparagraph\u00a0of Article\u00a0120(3).\n\n\n\n\nUntil Eudamed is fully functional, the corresponding provisions of Directives\u00a090/385/EEC and 93/42/EEC shall continue to apply for the purpose of meeting the obligations laid down in the provisions listed in the first paragraph\u00a0of this point regarding exchange of information including, and in particular, information regarding vigilance reporting, clinical investigations, registration of devices and economic operators, and certificate notifications.\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nArticle\u00a029(4) and Article\u00a056(5) shall apply from 18 months after the later of the dates referred to in point\u00a0(d);\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nfor implantable devices and for class III devices Article\u00a027(4) shall apply from 26\u00a0May 2021. For class\u00a0IIa and class\u00a0IIb devices Article\u00a027(4) shall apply from 26\u00a0May 2023. For class I devices Article\u00a027(4) shall apply from 26\u00a0May 2025;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nfor reusable devices that shall bear the UDI carrier on the device itself, Article\u00a027(4) shall apply from two years after the date referred to in point\u00a0(f) of this paragraph\u00a0for the respective class of devices in that point;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nThe procedure set out in Article\u00a078 shall apply from 26 May 2027, without prejudice to Article\u00a078(14);\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nArticle\u00a0120(12) shall apply from 26 May 2019.\n\n\n\n\n\n\n\n\n\n\nThis Regulation shall be binding in its entirety and directly applicable in all Member\u00a0States.\nDone at Strasbourg, 5 April 2017.\n\n\nFor the European Parliament\n\n\nThe President\n\nA. TAJANI\n            \n\n\n\nFor the Council\n\n\nThe President\n\nI. BORG\n            \n\n\n\n\n\n(1)\u00a0\u00a0Opinion of 14 February 2013 (OJ\u00a0C\u00a0133, 9.5.2013, p.\u00a052).\n\n(2)\u00a0\u00a0Position of the European Parliament of 2 April 2014 (not yet published in the Official Journal) and position of the Council at first reading of 7 March 2017 (not yet published in the Official Journal).\n\n(3)\u00a0\u00a0Council Directive\u00a090/385/EEC of 20 June 1990 on the approximation of the laws of the Member\u00a0States relating to active implantable medical devices (OJ\u00a0L\u00a0189, 20.7.1990, p.\u00a017).\n\n(4)\u00a0\u00a0Council Directive\u00a093/42/EEC of 14 June 1993 concerning medical devices (OJ\u00a0L\u00a0169, 12.7.1993, p.\u00a01).\n\n(5)\u00a0\u00a0Regulation (EC)\u00a0No\u00a0178/2002 of the European Parliament and of the Council of 28\u00a0January\u00a02002 laying down the general principles and requirements of food law, establishing the European Food Safety Authority and laying down procedures in matters of food safety (OJ\u00a0L\u00a031, 1.2.2002, p.\u00a01).\n\n(6)\u00a0\u00a0Regulation (EC)\u00a0No\u00a01223/2009 of the European Parliament and of the Council of 30\u00a0November 2009 on cosmetic products (OJ\u00a0L\u00a0342, 22.12.2009, p.\u00a059).\n\n(7)\u00a0\u00a0Directive\u00a02001/83/EC of the European Parliament and of the Council of 6\u00a0November\u00a02001 on the Community code relating to medicinal products for human use (OJ\u00a0L\u00a0311, 28.11.2001, p.\u00a067).\n\n(8)\u00a0\u00a0Regulation (EC)\u00a0No\u00a01394/2007 of the European Parliament and of the Council of 13\u00a0November\u00a02007 on advanced therapy medicinal products and amending Directive\u00a02001/83/EC and Regulation (EC)\u00a0No\u00a0726/2004 (OJ\u00a0L\u00a0324, 10.12.2007, p.\u00a0121).\n\n(9)\u00a0\u00a0Directive\u00a02004/23/EC of the European Parliament and of the Council of 31\u00a0March\u00a02004 on setting standards of quality and safety for the donation, procurement, testing, processing, preservation, storage and distribution of human tissues and cells (OJ\u00a0L\u00a0102, 7.4.2004, p.\u00a048).\n\n(10)\u00a0\u00a0Directive\u00a02002/98/EC of the European Parliament and of the Council of 27\u00a0January\u00a02003 setting standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components (OJ\u00a0L\u00a033, 8.2.2003, p.\u00a030).\n\n(11)\u00a0\u00a0Commission Recommendation 2011/696/EU of 18 October 2011 on the definition of nanomaterial (OJ\u00a0L\u00a0275, 20.10.2011, p.\u00a038).\n\n(12)\u00a0\u00a0Directive\u00a02014/30/EU of the European Parliament and of the Council of 26\u00a0February\u00a02014 on the harmonisation of the laws of the Member\u00a0States relating to electromagnetic compatibility (OJ\u00a0L\u00a096, 29.3.2014. p.\u00a079).\n\n(13)\u00a0\u00a0Council Directive\u00a02013/59/Euratom of 5\u00a0December\u00a02013 laying down basic safety standards for protection against the dangers arising from exposure to ionising radiation, and repealing Directives\u00a089/618/Euratom, 90/641/Euratom, 96/29/Euratom, 97/43/Euratom and 2003/122/Euratom (OJ\u00a0L\u00a013, 17.1.2014, p.\u00a01).\n\n(14)\u00a0\u00a0Directive\u00a0(EU)\u00a02015/1535 of the European Parliament and of the Council of 9\u00a0September\u00a02015 laying down a procedure for the provision of information in the field of technical regulations and of rules on Information Society services (OJ\u00a0L\u00a0241, 17.9.2015, p.\u00a01).\n\n(15)\u00a0\u00a0Regulation (EU)\u00a0No\u00a01025/2012 of the European Parliament and of the Council of 25\u00a0October 2012 on European standardisation, amending Council Directives 89/686/EEC and 93/15/EEC and Directives 94/9/EC, 94/25/EC, 95/16/EC, 97/23/EC, 98/34/EC, 2004/22/EC, 2007/23/EC, 2009/23/EC and 2009/105/EC of the European Parliament and of the Council and repealing Council Decision 87/95/EEC and Decision No\u00a01673/2006/EC of the European Parliament and of the Council (OJ\u00a0L\u00a0316, 14.11.2012, p.\u00a012).\n\n(16)\u00a0\u00a0Directive\u00a098/79/EC of the European Parliament and of the Council of 27\u00a0October\u00a01998 on in\u00a0vitro diagnostic medical devices (OJ\u00a0L\u00a0331, 7.12.1998, p.\u00a01).\n\n(17)\u00a0\u00a0Regulation (EC)\u00a0No\u00a0765/2008 of the European Parliament and of the Council of 9\u00a0July\u00a02008 setting out the requirements for accreditation and market surveillance relating to the marketing of products and repealing Regulation (EEC) No\u00a0339/93 (OJ\u00a0L\u00a0218, 13.8.2008, p.\u00a030).\n\n(18)\u00a0\u00a0Decision No\u00a0768/2008/EC of the European Parliament and of the Council of 9\u00a0July\u00a02008 on a common framework for the marketing of products, and repealing Council Decision\u00a093/465/EEC (OJ\u00a0L\u00a0218, 13.8.2008, p.\u00a082).\n\n(19)\u00a0\u00a0Council Directive\u00a085/374/EEC of 25\u00a0July\u00a01985 on the approximation of the laws, regulations and administrative provisions of the Member\u00a0States concerning liability for defective products (OJ\u00a0L\u00a0210, 7.8.1985, p.\u00a029).\n\n(20)\u00a0\u00a0Judgment of 28\u00a0July\u00a02011 in Orifarm and Paranova, joined cases C-400/09 and C-207/10, ECLI:EU:C:2011:519.\n\n(21)\u00a0\u00a0Commission Decision\u00a02010/227/EU of 19 April 2010 on the European Databank for Medical Devices (OJ\u00a0L\u00a0102, 23.4.2010, p.\u00a045).\n\n(22)\u00a0\u00a0Directive\u00a095/46/EC of the European Parliament and of the Council of 24\u00a0October\u00a01995 on the protection of individuals with regard to the processing of personal data and on the free movement of such data (OJ\u00a0L\u00a0281, 23.11.1995, p.\u00a031).\n\n(23)\u00a0\u00a0Regulation (EC)\u00a0No\u00a045/2001 of the European Parliament and of the Council of 18\u00a0December\u00a02000 on the protection of individuals with regard to the processing of personal data by the Community institutions and bodies and on the free movement of such data (OJ\u00a0L\u00a08, 12.1.2001, p.\u00a01).\n\n(24)\u00a0\u00a0Directive\u00a02010/63/EU of the European Parliament and of the Council of 22\u00a0September\u00a02010 on the protection of animals used for scientific purposes (OJ\u00a0L\u00a0276, 20.10.2010, p.\u00a033).\n\n(25)\u00a0\u00a0Regulation (EU)\u00a02017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision\u00a02010/227/EU (see page 176 of this Official Journal).\n\n(26)\u00a0\u00a0\n            OJ\u00a0L\u00a0123, 12.5.2016, p.\u00a01.\n\n(27)\u00a0\u00a0Regulation (EU)\u00a0No\u00a0182/2011 of the European Parliament and of the Council of 16\u00a0February 2011 laying down the rules and general principles concerning mechanisms for control by Member\u00a0States of the Commission's exercise of implementing powers (OJ\u00a0L\u00a055, 28.2.2011, p.\u00a013).\n\n(28)\u00a0\u00a0Commission Regulation (EU)\u00a0No\u00a0207/2012 of 9\u00a0March\u00a02012 on electronic instructions for use of medical devices (OJ\u00a0L\u00a072, 10.3.2012, p.\u00a028).\n\n(29)\u00a0\u00a0Commission Regulation (EU)\u00a0No\u00a0722/2012 of 8 August 2012 concerning particular requirements as regards the requirements laid down in Council Directives 90/385/EEC and 93/42/EEC with respect to active implantable medical devices and medical devices manufactured utilising tissues of animal origin (OJ\u00a0L\u00a0212, 9.8.2012, p.\u00a03).\n\n(30)\u00a0\u00a0Commission Directive\u00a02003/12/EC of 3 February 2003 on the reclassification of breast implants in the framework of Directive\u00a093/42/EEC concerning medical devices (OJ\u00a0L\u00a028, 4.2.2003, p.\u00a043).\n\n(31)\u00a0\u00a0Commission Directive\u00a02005/50/EC of 11 August 2005 on the reclassification of hip, knee and shoulder joint replacements in the framework of Council Directive\u00a093/42/EEC concerning medical devices (OJ\u00a0L\u00a0210, 12.8.2005, p.\u00a041).\n\n(32)\u00a0\u00a0Commission Implementing Regulation (EU)\u00a0No\u00a0920/2013 of 24 September 2013 on the designation and the supervision of notified bodies under Council Directive\u00a090/385/EEC on active implantable medical devices and Council Directive\u00a093/42/EEC on medical devices (OJ\u00a0L\u00a0253, 25.9.2013, p.\u00a08).\n\n(33)\u00a0\u00a0\n            OJ\u00a0C 358, 7.12.2013, p.\u00a010.\n\n(34)\u00a0\u00a0Regulation\u00a0(EC)\u00a0No\u00a0726/2004 of the European Parliament and of the Council of 31\u00a0March\u00a02004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (OJ\u00a0L\u00a0136, 30.4.2004, p.\u00a01).\n\n(35)\u00a0\u00a0Directive\u00a02006/42/EC of the European Parliament and of the Council of 17\u00a0May\u00a02006 on machinery, and amending Directive\u00a095/16/EC (OJ\u00a0L\u00a0157, 9.6.2006, p.\u00a024).\n\n(36)\u00a0\u00a0Commission Recommendation 2003/361/\u0395C of 6\u00a0May\u00a02003 concerning the definition of micro, small and medium-sized enterprises (OJ\u00a0L\u00a0124, 20.5.2003, p.\u00a036).\n\n(37)\u00a0\u00a0Regulation (EU)\u00a0No\u00a0536/2014 of the European Parliament and of the Council of 16\u00a0April\u00a02014 on clinical trials on medicinal products for human use, and repealing Directive\u00a02001/20/EC (OJ\u00a0L\u00a0158, 27.5.2014, p.\u00a01).\n\n\n\n\nANNEXES\n\nI\u00a0\u00a0\u00a0\n\nGeneral safety and performance requirements\n\n\n\nII\u00a0\u00a0\u00a0\n\nTechnical documentation\n\n\n\nIII\u00a0\u00a0\u00a0\n\nTechnical documentation on post-market surveillance\n\n\n\nIV\u00a0\u00a0\u00a0\n\nEU declaration of conformity\n\n\n\nV\u00a0\u00a0\u00a0\n\nCE marking of conformity\n\n\n\nVI\u00a0\u00a0\u00a0\n\nInformation to be submitted upon the registration of devices and economic operators in accordance with Articles\u00a029(4) and 31; core data elements to be provided to the UDI\u00a0database together with the UDI-DI in accordance with Articles\u00a028 and 29;and the UDI\u00a0system\n\n\n\nVII\u00a0\u00a0\u00a0\n\nRequirements to be met by notified bodies\n\n\n\nVIII\u00a0\u00a0\u00a0\n\nClassification rules\n\n\n\nIX\u00a0\u00a0\u00a0\n\nConformity assessment based on a quality management system and assessment of the technical documentation\n\n\n\nX\u00a0\u00a0\u00a0\n\nConformity assessment based on type examination\n\n\n\nXI\u00a0\u00a0\u00a0\n\nConformity assessment based on product conformity verification\n\n\n\nXII\u00a0\u00a0\u00a0\n\nCertificates issued by a notified body\n\n\n\nXIII\u00a0\u00a0\u00a0\n\nProcedure for custom-made devices\n\n\n\nXIV\u00a0\u00a0\u00a0\n\nClinical evaluation and post-market clinical follow-up\n\n\n\nXV\u00a0\u00a0\u00a0\n\nClinical investigations\n\n\n\nXVI\u00a0\u00a0\u00a0\n\nList of groups of products without an intended medical purpose referred to in Article\u00a01(2)\n\n\n\nXVII\u00a0\u00a0\u00a0\n\nCorrelation table\n\n\n\n\n\n\n\nANNEX I\n\nGENERAL SAFETY AND PERFORMANCE REQUIREMENTS\n\nCHAPTER I\n\n\nGENERAL REQUIREMENTS\n\n\n1.\u00a0\u00a0\u00a0Devices shall achieve the performance intended by their manufacturer and shall be designed and manufactured in such a way that, during normal conditions of use, they are suitable for their intended purpose. They shall be safe and effective and shall not compromise the clinical condition or the safety of patients, or the safety and health of users or, where applicable, other persons, provided that any risks which may be associated with their use constitute acceptable risks when weighed against the benefits to the patient and are compatible with a high level of protection of health and safety, taking into account the generally acknowledged state of the art.\n2.\u00a0\u00a0\u00a0The requirement in this Annex\u00a0to reduce risks as far as possible means the reduction of risks as far as possible without adversely affecting the benefit-risk ratio.\n3.\u00a0\u00a0\u00a0Manufacturers shall establish, implement, document and maintain a risk management system.\nRisk management shall be understood as a continuous iterative process throughout the entire lifecycle of a device, requiring regular systematic updating. In carrying out risk management manufacturers shall:\n\n\n\n\n\n\n(a)\n\n\nestablish and document a risk management plan for each device;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nidentify and analyse the known and foreseeable hazards associated with each device;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nestimate and evaluate the risks associated with, and occurring during, the intended use and during reasonably foreseeable misuse;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\neliminate or control the risks referred to in point\u00a0(c) in accordance with the requirements of Section\u00a04;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nevaluate the impact of information from the production phase and, in particular, from the post-market surveillance system, on hazards and the frequency of occurrence thereof, on estimates of their associated risks, as well as on the overall risk, benefit-risk ratio and risk acceptability; and\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nbased on the evaluation of the impact of the information referred to in point\u00a0(e), if necessary amend control measures in line with the requirements of Section\u00a04.\n\n\n\n\n4.\u00a0\u00a0\u00a0Risk control measures adopted by manufacturers for the design and manufacture of the devices shall conform to safety principles, taking account of the generally acknowledged state of the art. To reduce risks, Manufacturers shall manage risks so that the residual risk associated with each hazard as well as the overall residual risk is judged acceptable. In selecting the most appropriate solutions, manufacturers shall, in the following order of priority:\n\n\n\n\n\n\n(a)\n\n\neliminate or reduce risks as far as possible through safe design and manufacture;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nwhere appropriate, take adequate protection measures, including alarms if necessary, in relation to risks that cannot be eliminated; and\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nprovide information for safety (warnings/precautions/contra-indications) and, where appropriate, training to users.\n\n\n\n\nManufacturers shall inform users of any residual risks.\n5.\u00a0\u00a0\u00a0In eliminating or reducing risks related to use error, the manufacturer shall:\n\n\n\n\n\n\n(a)\n\n\nreduce as far as possible the risks related to the ergonomic features of the device and the environment in which the device is intended to be used (design for patient safety), and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ngive consideration to the technical knowledge, experience, education, training and use environment, where applicable, and the medical and physical conditions of intended users (design for lay, professional, disabled or other users).\n\n\n\n\n6.\u00a0\u00a0\u00a0The characteristics and performance of a device shall not be adversely affected to such a degree that the health or safety of the patient or the user and, where applicable, of other persons are compromised during the lifetime of the device, as indicated by the manufacturer, when the device is subjected to the stresses which can occur during normal conditions of use and has been properly maintained in accordance with the manufacturer's instructions.\n7.\u00a0\u00a0\u00a0Devices shall be designed, manufactured and packaged in such a way that their characteristics and performance during their intended use are not adversely affected during transport and storage, for example, through fluctuations of temperature and humidity, taking account of the instructions and information provided by the manufacturer.\n8.\u00a0\u00a0\u00a0All known and foreseeable risks, and any undesirable side-effects, shall be minimised and be acceptable when weighed against the evaluated benefits to the patient and/or user arising from the achieved performance of the device during normal conditions of use.\n9.\u00a0\u00a0\u00a0For the devices referred to in Annex\u00a0XVI, the general safety requirements set out in Sections 1 and 8 shall be understood to mean that the device, when used under the conditions and for the purposes intended, does not present a risk at all or presents a risk that is no more than the maximum acceptable risk related to the product's use which is consistent with a high level of protection for the safety and health of persons.\nCHAPTER II\n\n\nREQUIREMENTS REGARDING DESIGN AND MANUFACTURE\n\n\n10.\u00a0\u00a0\u00a0Chemical, physical and biological properties\n10.1.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to ensure that the characteristics and performance requirements referred to in Chapter I are fulfilled. Particular attention shall be paid to:\n\n\n\n\n\n\n(a)\n\n\nthe choice of materials and substances used, particularly as regards toxicity and, where relevant, flammability;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe compatibility between the materials and substances used and biological tissues, cells and body fluids, taking account of the intended purpose of the device and, where relevant, absorption, distribution, metabolism and excretion;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe compatibility between the different parts of a device which consists of more than one implantable part;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe impact of processes on material properties;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nwhere appropriate, the results of biophysical or modelling research the validity of which has been demonstrated beforehand;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe mechanical properties of the materials used, reflecting, where appropriate, matters such as strength, ductility, fracture resistance, wear resistance and fatigue resistance;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nsurface properties; and\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe confirmation that the device meets any defined chemical and/or physical specifications.\n\n\n\n\n10.2.\u00a0\u00a0\u00a0Devices shall be designed, manufactured and packaged in such a way as to minimise the risk posed by contaminants and residues to patients, taking account of the intended purpose of the device, and to the persons involved in the transport, storage and use of the devices. Particular attention shall be paid to tissues exposed to those contaminants and residues and to the duration and frequency of exposure.\n10.3.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way that they can be used safely with the materials and substances, including gases, with which they enter into contact during their intended use; if the devices are intended to administer medicinal products they shall be designed and manufactured in such a way as to be compatible with the medicinal products concerned in accordance with the provisions and restrictions governing those medicinal products and that the performance of both the medicinal products and of the devices is maintained in accordance with their respective indications and intended use.\n10.4.\u00a0\u00a0\u00a0Substances\n10.4.1.\u00a0\u00a0\u00a0Design and manufacture of devices\nDevices shall be designed and manufactured in such a way as to reduce as far as possible the risks posed by substances or particles, including wear debris, degradation products and processing residues, that may be released from the device.\nDevices, or those parts thereof or those materials used therein that:\n\n\n\n\n\n\n\u2014\n\n\nare invasive and come into direct contact with the human body,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\n(re)administer medicines, body liquids or other substances, including gases, to/from the body, or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntransport or store such medicines, body fluids or substances, including gases, to be (re)administered to the body,\n\n\n\n\nshall only contain the following substances in a concentration that is above 0,1 % weight by weight (w/w) where justified pursuant to Section\u00a010.4.2:\n\n\n\n\n\n\n(a)\n\n\nsubstances which are carcinogenic, mutagenic or toxic to reproduction (\u2018CMR\u2019), of category\u00a01A or 1B, in accordance with Part 3 of Annex\u00a0VI to Regulation (EC)\u00a0No\u00a01272/2008 of the European Parliament and of the Council\u00a0(1), or\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nsubstances having endocrine-disrupting properties for which there is scientific evidence of probable serious effects to human health and which are identified either in accordance with the procedure set out in Article\u00a059 of Regulation\u00a0(EC)\u00a0No\u00a01907/2006 of the European Parliament and of the Council\u00a0(2) or, once a delegated act has been adopted by the Commission pursuant to the first subparagraph\u00a0of Article\u00a05(3) of Regulation\u00a0(EU)\u00a0No\u00a0528/2012 of the European Parliament and the Council\u00a0(3), in accordance with the criteria that are relevant to human health amongst the criteria established therein.\n\n\n\n\n10.4.2.\u00a0\u00a0\u00a0Justification regarding the presence of CMR and/or endocrine-disrupting substances\nThe justification for the presence of such substances shall be based upon:\n\n\n\n\n\n\n(a)\n\n\nan analysis and estimation of potential patient or user exposure to the substance;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nan analysis of possible alternative substances, materials or designs, including, where available, information about independent research, peer-reviewed studies, scientific opinions from relevant scientific committees and an analysis of the availability of such alternatives;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nargumentation as to why possible substance and/ or material substitutes, if available, or design changes, if feasible, are inappropriate in relation to maintaining the functionality, performance and the benefit-risk ratios of the product; including taking into account if the intended use of such devices includes treatment of children or treatment of pregnant or breastfeeding women or treatment of other patient groups considered particularly vulnerable to such substances and/or materials; and\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nwhere applicable and available, the latest relevant scientific committee guidelines in accordance with Sections 10.4.3. and 10.4.4.\n\n\n\n\n10.4.3.\u00a0\u00a0\u00a0Guidelines on phthalates\nFor the purposes of Section\u00a010.4., the Commission shall, as soon as possible and by 26 May 2018, provide the relevant scientific committee with a mandate to prepare guidelines that shall be ready before 26 May 2020. The mandate for the committee shall encompass at least a benefit-risk assessment of the presence of phthalates which belong to either of the groups of substances referred to in points (a) and (b) of Section\u00a010.4.1. The benefit-risk assessment shall take into account the intended purpose and context of the use of the device, as well as any available alternative substances and alternative materials, designs or medical treatments. When deemed appropriate on the basis of the latest scientific evidence, but at least every five years, the guidelines shall be updated.\n10.4.4.\u00a0\u00a0\u00a0Guidelines on other CMR and endocrine-disrupting substances\nSubsequently, the Commission shall mandate the relevant scientific committee to prepare guidelines as referred to in Section\u00a010.4.3. also for other substances referred to in points\u00a0(a) and (b) of Section\u00a010.4.1., where appropriate.\n10.4.5.\u00a0\u00a0\u00a0Labelling\nWhere devices, parts thereof or materials used therein as referred to in Section\u00a010.4.1. contain substances referred to in points (a) or (b) of Section\u00a010.4.1. in a concentration above 0,1 % weight by weight (w/w), the presence of those substances shall be labelled on the device itself and/or on the packaging for each unit or, where appropriate, on the sales packaging, with the list of such substances. If the intended use of such devices includes treatment of children or treatment of pregnant or breastfeeding women or treatment of other patient groups considered particularly vulnerable to such substances and/or materials, information on residual risks for those patient groups and, if applicable, on appropriate precautionary measures shall be given in the instructions for use.\n10.5.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks posed by the unintentional ingress of substances into the device taking into account the device and the nature of the environment in which it is intended to be used.\n10.6.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks linked to the size and the properties of particles which are or can be released into the patient's or user's body, unless they come into contact with intact skin only. Special attention shall be given to nanomaterials.\n11.\u00a0\u00a0\u00a0Infection and microbial contamination\n11.1.\u00a0\u00a0\u00a0Devices and their manufacturing processes shall be designed in such a way as to eliminate or to reduce as far as possible the risk of infection to patients, users and, where applicable, other persons. The design shall:\n\n\n\n\n\n\n(a)\n\n\nreduce as far as possible and appropriate the risks from unintended cuts and pricks, such as needle stick injuries,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nallow easy and safe handling,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nreduce as far as possible any microbial leakage from the device and/or microbial exposure during use, and\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nprevent microbial contamination of the device or its content such as specimens or fluids.\n\n\n\n\n11.2.\u00a0\u00a0\u00a0Where necessary devices shall be designed to facilitate their safe cleaning, disinfection, and/or re-sterilisation.\n11.3.\u00a0\u00a0\u00a0Devices labelled as having a specific microbial state shall be designed, manufactured and packaged to ensure that they remain in that state when placed on the market and remain so under the transport and storage conditions specified by the manufacturer.\n11.4.\u00a0\u00a0\u00a0Devices delivered in a sterile state shall be designed, manufactured and packaged in accordance with appropriate procedures, to ensure that they are sterile when placed on the market and that, unless the packaging which is intended to maintain their sterile condition is damaged, they remain sterile, under the transport and storage conditions specified by the manufacturer, until that packaging is opened at the point of use. It shall be ensured that the integrity of that packaging is clearly evident to the final user.\n11.5.\u00a0\u00a0\u00a0Devices labelled as sterile shall be processed, manufactured, packaged and, sterilised by means of appropriate, validated methods.\n11.6.\u00a0\u00a0\u00a0Devices intended to be sterilised shall be manufactured and packaged in appropriate and controlled conditions and facilities.\n11.7.\u00a0\u00a0\u00a0Packaging systems for non-sterile devices shall maintain the integrity and cleanliness of the product and, where the devices are to be sterilised prior to use, minimise the risk of microbial contamination; the packaging system shall be suitable taking account of the method of sterilisation indicated by the manufacturer.\n11.8.\u00a0\u00a0\u00a0The labelling of the device shall distinguish between identical or similar devices placed on the market in both a sterile and a non-sterile condition additional to the symbol used to indicate that devices are sterile.\n12.\u00a0\u00a0\u00a0Devices incorporating a substance considered to be a medicinal product and devices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body.\n12.1.\u00a0\u00a0\u00a0In the case of devices referred to in the first subparagraph\u00a0of Article\u00a01(8), the quality, safety and usefulness of the substance which, if used separately, would be considered to be a medicinal product within the meaning of point\u00a0(2) of Article\u00a01 of Directive\u00a02001/83/EC, shall be verified by analogy with the methods specified in Annex\u00a0I to Directive\u00a02001/83/EC, as required by the applicable conformity assessment procedure under this Regulation.\n12.2.\u00a0\u00a0\u00a0Devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body, and that are absorbed by or locally dispersed in the human body shall comply, where applicable and in a manner limited to the aspects not covered by this Regulation, with the relevant requirements laid down in Annex\u00a0I to Directive\u00a02001/83/EC for the evaluation of absorption, distribution, metabolism, excretion, local tolerance, toxicity, interaction with other devices, medicinal products or other substances and potential for adverse reactions, as required by the applicable conformity assessment procedure under this Regulation.\n13.\u00a0\u00a0\u00a0Devices incorporating materials of biological origin\n13.1.\u00a0\u00a0\u00a0For devices manufactured utilising derivatives of tissues or cells of human origin which are non-viable or are rendered non-viable covered by this Regulation in accordance with point\u00a0(g) of Article\u00a01(6), the following shall apply:\n\n\n\n\n\n\n(a)\n\n\ndonation, procurement and testing of the tissues and cells shall be done in accordance with Directive\u00a02004/23/EC;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nprocessing, preservation and any other handling of those tissues and cells or their derivatives shall be carried out so as to provide safety for patients, users and, where applicable, other persons. In particular, safety with regard to viruses and other transmissible agents shall be addressed by appropriate methods of sourcing and by implementation of validated methods of elimination or inactivation in the course of the manufacturing process;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe traceability system for those devices shall be complementary and compatible with the traceability and data protection requirements laid down in Directive\u00a02004/23/EC and in Directive\u00a02002/98/EC.\n\n\n\n\n13.2.\u00a0\u00a0\u00a0For devices manufactured utilising tissues or cells of animal origin, or their derivatives, which are non-viable or rendered non-viable the following shall apply:\n\n\n\n\n\n\n(a)\n\n\nwhere feasible taking into account the animal species, tissues and cells of animal origin, or their derivatives, shall originate from animals that have been subjected to veterinary controls that are adapted to the intended use of the tissues. Information on the geographical origin of the animals shall be retained by manufacturers;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nsourcing, processing, preservation, testing and handling of tissues, cells and substances of animal origin, or their derivatives, shall be carried out so as to provide safety for patients, users and, where applicable, other persons. In particular safety with regard to viruses and other transmissible agents shall be addressed by implementation of validated methods of elimination or viral inactivation in the course of the manufacturing process, except when the use of such methods would lead to unacceptable degradation compromising the clinical benefit of the device;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nin the case of devices manufactured utilising tissues or cells of animal origin, or their derivatives, as referred to in Regulation\u00a0(EU)\u00a0No\u00a0722/2012 the particular requirements laid down in that Regulation shall apply.\n\n\n\n\n13.3.\u00a0\u00a0\u00a0For devices manufactured utilising non-viable biological substances other than those referred to in Sections\u00a013.1 and 13.2, the processing, preservation, testing and handling of those substances shall be carried out so as to provide safety for patients, users and, where applicable, other persons, including in the waste disposal chain. In particular, safety with regard to viruses and other transmissible agents shall be addressed by appropriate methods of sourcing and by implementation of validated methods of elimination or inactivation in the course of the manufacturing process.\n14.\u00a0\u00a0\u00a0Construction of devices and interaction with their environment\n14.1.\u00a0\u00a0\u00a0If the device is intended for use in combination with other devices or equipment the whole combination, including the connection system shall be safe and shall not impair the specified performance of the devices. Any restrictions on use applying to such combinations shall be indicated on the label and/or in the instructions for use. Connections which the user has to handle, such as fluid, gas transfer, electrical or mechanical coupling, shall be designed and constructed in such a way as to minimise all possible risks, such as misconnection.\n14.2.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to remove or reduce as far as possible:\n\n\n\n\n\n\n(a)\n\n\nthe risk of injury, in connection with their physical features, including the volume/pressure ratio, dimensional and where appropriate ergonomic features;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nrisks connected with reasonably foreseeable external influences or environmental conditions, such as magnetic fields, external electrical and electromagnetic effects, electrostatic discharge, radiation associated with diagnostic or therapeutic procedures, pressure, humidity, temperature, variations in pressure and acceleration or radio signal interferences;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe risks associated with the use of the device when it comes into contact with materials, liquids, and substances, including gases, to which it is exposed during normal conditions of use;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe risks associated with the possible negative interaction between software and the IT environment within which it operates and interacts;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe risks of accidental ingress of substances into the device;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe risks of reciprocal interference with other devices normally used in the investigations or for the treatment given; and\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nrisks arising where maintenance or calibration are not possible (as with implants), from ageing of materials used or loss of accuracy of any measuring or control mechanism.\n\n\n\n\n14.3.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to minimise the risks of fire or explosion during normal use and in single fault condition. Particular attention shall be paid to devices the intended use of which includes exposure to or use in association with flammable or explosive substances or substances which could cause combustion.\n14.4.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way that adjustment, calibration, and maintenance can be done safely and effectively.\n14.5.\u00a0\u00a0\u00a0Devices that are intended to be operated together with other devices or products shall be designed and manufactured in such a way that the interoperability and compatibility are reliable and safe.\n14.6\u00a0\u00a0\u00a0Any measurement, monitoring or display scale shall be designed and manufactured in line with ergonomic principles, taking account of the intended purpose, users and the environmental conditions in which the devices are intended to be used.\n14.7.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to facilitate their safe disposal and the safe disposal of related waste substances by the user, patient or other person. To that end, manufacturers shall identify and test procedures and measures as a result of which their devices can be safely disposed after use. Such procedures shall be described in the instructions for use.\n15.\u00a0\u00a0\u00a0Devices with a diagnostic or measuring function\n15.1.\u00a0\u00a0\u00a0Diagnostic devices and devices with a measuring function, shall be designed and manufactured in such a way as to provide sufficient accuracy, precision and stability for their intended purpose, based on appropriate scientific and technical methods. The limits of accuracy shall be indicated by the manufacturer.\n15.2.\u00a0\u00a0\u00a0The measurements made by devices with a measuring function shall be expressed in legal units conforming to the provisions of Council Directive\u00a080/181/EEC\u00a0(4).\n16.\u00a0\u00a0\u00a0Protection against radiation\n16.1.\u00a0\u00a0\u00a0General\n\n\n\n\n\n\n(a)\n\n\nDevices shall be designed, manufactured and packaged in such a way that exposure of patients, users and other persons to radiation is reduced as far as possible, and in a manner that is compatible with the intended purpose, whilst not restricting the application of appropriate specified levels for therapeutic and diagnostic purposes.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nThe operating instructions for devices emitting hazardous or potentially hazardous radiation shall contain detailed information as to the nature of the emitted radiation, the means of protecting the patient and the user, and on ways of avoiding misuse and of reducing the risks inherent to installation as far as possible and appropriate. Information regarding the acceptance and performance testing, the acceptance criteria, and the maintenance procedure shall also be specified.\n\n\n\n\n16.2.\u00a0\u00a0\u00a0Intended radiation\n\n\n\n\n\n\n(a)\n\n\nWhere devices are designed to emit hazardous, or potentially hazardous, levels of ionizing and/or non-ionizing radiation necessary for a specific medical purpose the benefit of which is considered to outweigh the risks inherent to the emission, it shall be possible for the user to control the emissions. Such devices shall be designed and manufactured to ensure reproducibility of relevant variable parameters within an acceptable tolerance.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nWhere devices are intended to emit hazardous, or potentially hazardous, ionizing and/or non-ionizing radiation, they shall be fitted, where possible, with visual displays and/or audible warnings of such emissions.\n\n\n\n\n16.3.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way that exposure of patients, users and other persons to the emission of unintended, stray or scattered radiation is reduced as far as possible. Where possible and appropriate, methods shall be selected which reduce the exposure to radiation of patients, users and other persons who may be affected.\n16.4.\u00a0\u00a0\u00a0Ionising radiation\n\n\n\n\n\n\n(a)\n\n\nDevices intended to emit ionizing radiation shall be designed and manufactured taking into account the requirements of the Directive\u00a02013/59/Euratom laying down basic safety standards for protection against the dangers arising from exposure to ionising radiation.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nDevices intended to emit ionising radiation shall be designed and manufactured in such a way as to ensure that, where possible, taking into account the intended use, the quantity, geometry and quality of the radiation emitted can be varied and controlled, and, if possible, monitored during treatment.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nDevices emitting ionising radiation intended for diagnostic radiology shall be designed and manufactured in such a way as to achieve an image and/or output quality that are appropriate to the intended medical purpose whilst minimising radiation exposure of the patient and user.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nDevices that emit ionising radiation and are intended for therapeutic radiology shall be designed and manufactured in such a way as to enable reliable monitoring and control of the delivered dose, the beam type, energy and, where appropriate, the quality of radiation.\n\n\n\n\n17.\u00a0\u00a0\u00a0Electronic programmable systems \u2014 devices that incorporate electronic programmable systems and software that are devices in themselves\n17.1.\u00a0\u00a0\u00a0Devices that incorporate electronic programmable systems, including software, or software that are devices in themselves, shall be designed to ensure repeatability, reliability and performance in line with their intended use. In the event of a single fault condition, appropriate means shall be adopted to eliminate or reduce as far as possible consequent risks or impairment of performance.\n17.2.\u00a0\u00a0\u00a0For devices that incorporate software or for software that are devices in themselves, the software shall be developed and manufactured in accordance with the state of the art taking into account the principles of development life cycle, risk management, including information security, verification and validation.\n17.3.\u00a0\u00a0\u00a0Software referred to in this Section\u00a0that is intended to be used in combination with mobile computing platforms shall be designed and manufactured taking into account the specific features of the mobile platform (e.g. size and contrast ratio of the screen) and the external factors related to their use (varying environment as regards level of light or noise).\n17.4.\u00a0\u00a0\u00a0Manufacturers shall set out minimum requirements concerning hardware, IT networks characteristics and IT security measures, including protection against unauthorised access, necessary to run the software as intended.\n18.\u00a0\u00a0\u00a0Active devices and devices connected to them\n18.1.\u00a0\u00a0\u00a0For non-implantable active devices, in the event of a single fault condition, appropriate means shall be adopted to eliminate or reduce as far as possible consequent risks.\n18.2.\u00a0\u00a0\u00a0Devices where the safety of the patient depends on an internal power supply shall be equipped with a means of determining the state of the power supply and an appropriate warning or indication for when the capacity of the power supply becomes critical. If necessary, such warning or indication shall be given prior to the power supply becoming critical.\n18.3.\u00a0\u00a0\u00a0Devices where the safety of the patient depends on an external power supply shall include an alarm system to signal any power failure.\n18.4.\u00a0\u00a0\u00a0Devices intended to monitor one or more clinical parameters of a patient shall be equipped with appropriate alarm systems to alert the user of situations which could lead to death or severe deterioration of the patient's state of health.\n18.5.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks of creating electromagnetic interference which could impair the operation of the device in question or other devices or equipment in the intended environment.\n18.6.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to provide a level of intrinsic immunity to electromagnetic interference such that is adequate to enable them to operate as\u00a0intended.\n18.7.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to avoid, as far as possible, the risk of accidental electric shocks to the patient, user or any other person, both during normal use of the device and in the event of a single fault condition in the device, provided the device is installed and maintained as indicated by the manufacturer.\n18.8.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to protect, as far as possible, against unauthorised access that could hamper the device from functioning as intended.\n19.\u00a0\u00a0\u00a0Particular requirements for active implantable devices\n19.1.\u00a0\u00a0\u00a0Active implantable devices shall be designed and manufactured in such a way as to remove or minimize as far as possible:\n\n\n\n\n\n\n(a)\n\n\nrisks connected with the use of energy sources with particular reference, where electricity is used, to insulation, leakage currents and overheating of the devices,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nrisks connected with medical treatment, in particular those resulting from the use of defibrillators or high-frequency surgical equipment, and\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nrisks which may arise where maintenance and calibration are impossible, including:\n\n\n\n\n\n\n\u2014\n\n\nexcessive increase of leakage currents,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nageing of the materials used,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nexcess heat generated by the device,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndecreased accuracy of any measuring or control mechanism.\n\n\n\n\n\n\n\n\n19.2.\u00a0\u00a0\u00a0Active implantable devices shall be designed and manufactured in such a way as to ensure\n\n\n\n\n\n\n\u2014\n\n\nif applicable, the compatibility of the devices with the substances they are intended to administer, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe reliability of the source of energy.\n\n\n\n\n19.3.\u00a0\u00a0\u00a0Active implantable devices and, if appropriate, their component parts shall be identifiable to allow any necessary measure to be taken following the discovery of a potential risk in connection with the devices or their component parts.\n19.4.\u00a0\u00a0\u00a0Active implantable devices shall bear a code by which they and their manufacturer can be unequivocally identified (particularly with regard to the type of device and its year of manufacture); it shall be possible to read this code, if necessary, without the need for a surgical operation.\n20.\u00a0\u00a0\u00a0Protection against mechanical and thermal risks\n20.1.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to protect patients and users against mechanical risks connected with, for example, resistance to movement, instability and moving parts.\n20.2.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to reduce to the lowest possible level the risks arising from vibration generated by the devices, taking account of technical progress and of the means available for limiting vibrations, particularly at source, unless the vibrations are part of the specified performance.\n20.3.\u00a0\u00a0\u00a0Devices shall be designed and manufactured in such a way as to reduce to the lowest possible level the risks arising from the noise emitted, taking account of technical progress and of the means available to reduce noise, particularly at source, unless the noise emitted is part of the specified performance.\n20.4.\u00a0\u00a0\u00a0Terminals and connectors to the electricity, gas or hydraulic and pneumatic energy supplies which the user or other person has to handle, shall be designed and constructed in such a way as to minimise all possible risks.\n20.5.\u00a0\u00a0\u00a0Errors likely to be made when fitting or refitting certain parts which could be a source of risk shall be made impossible by the design and construction of such parts or, failing this, by information given on the parts themselves and/or their housings.\nThe same information shall be given on moving parts and/or their housings where the direction of movement needs to be known in order to avoid a risk.\n20.6.\u00a0\u00a0\u00a0Accessible parts of devices (excluding the parts or areas intended to supply heat or reach given temperatures) and their surroundings shall not attain potentially dangerous temperatures under normal conditions of use.\n21.\u00a0\u00a0\u00a0Protection against the risks posed to the patient or user by devices supplying energy or substances\n21.1.\u00a0\u00a0\u00a0Devices for supplying the patient with energy or substances shall be designed and constructed in such a way that the amount to be delivered can be set and maintained accurately enough to ensure the safety of the patient and of the user.\n21.2.\u00a0\u00a0\u00a0Devices shall be fitted with the means of preventing and/or indicating any inadequacies in the amount of energy delivered or substances delivered which could pose a danger. Devices shall incorporate suitable means to prevent, as far as possible, the accidental release of dangerous levels of energy or substances from an energy and/or substance source.\n21.3.\u00a0\u00a0\u00a0The function of the controls and indicators shall be clearly specified on the devices. Where a device bears instructions required for its operation or indicates operating or adjustment parameters by means of a visual system, such information shall be understandable to the user and, as appropriate, the patient.\n22.\u00a0\u00a0\u00a0Protection against the risks posed by medical devices intended by the manufacturer for use by lay persons\n22.1.\u00a0\u00a0\u00a0Devices for use by lay persons shall be designed and manufactured in such a way that they perform appropriately for their intended purpose taking into account the skills and the means available to lay persons and the influence resulting from variation that can be reasonably anticipated in the lay person's technique and environment. The information and instructions provided by the manufacturer shall be easy for the lay person to understand and apply.\n22.2.\u00a0\u00a0\u00a0Devices for use by lay persons shall be designed and manufactured in such a way as to:\n\n\n\n\n\n\n\u2014\n\n\nensure that the device can be used safely and accurately by the intended user at all stages of the procedure, if necessary after appropriate training and/or information,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreduce, as far as possible and appropriate, the risk from unintended cuts and pricks such as needle stick injuries, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreduce as far as possible the risk of error by the intended user in the handling of the device and, if applicable, in the interpretation of the results.\n\n\n\n\n22.3.\u00a0\u00a0\u00a0Devices for use by lay persons shall, where appropriate, include a procedure by which the lay person:\n\n\n\n\n\n\n\u2014\n\n\ncan verify that, at the time of use, the device will perform as intended by the manufacturer, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif applicable, is warned if the device has failed to provide a valid result.\n\n\n\n\nCHAPTER III\n\n\nREQUIREMENTS REGARDING THE INFORMATION SUPPLIED WITH THE DEVICE\n\n\n23.\u00a0\u00a0\u00a0Label and instructions for use\n23.1.\u00a0\u00a0\u00a0General requirements regarding the information supplied by the manufacturer\nEach device shall be accompanied by the information needed to identify the device and its manufacturer, and by any safety and performance information relevant to the user, or any other person, as appropriate. Such information may appear on the device itself, on the packaging or in the instructions for use, and shall, if the manufacturer has a website, be made available and kept up to date on the website, taking into account the following:\n\n\n\n\n\n\n(a)\n\n\nThe medium, format, content, legibility, and location of the label and instructions for use shall be appropriate to the particular device, its intended purpose and the technical knowledge, experience, education or training of the intended user(s). In particular, instructions for use shall be written in terms readily understood by the intended user and, where appropriate, supplemented with drawings and diagrams.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nThe information required on the label shall be provided on the device itself. If this is not practicable or appropriate, some or all of the information may appear on the packaging for each unit, and/or on the packaging of multiple devices.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nLabels shall be provided in a human-readable format and may be supplemented by machine-readable information, such as radio-frequency identification (\u2018RFID\u2019) or bar codes.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nInstructions for use shall be provided together with devices. By way of exception, instructions for use shall not be required for class I and class IIa devices if such devices can be used safely without any such instructions and unless otherwise provided for elsewhere in this Section.\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nWhere multiple devices are supplied to a single user and/or location, a single copy of the instructions for use may be provided if so agreed by the purchaser who in any case may request further copies to be provided free of charge.\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nInstructions for use may be provided to the user in non-paper format (e.g.\u00a0electronic) to the extent, and only under the conditions, set out in Regulation\u00a0(EU)\u00a0No\u00a0207/2012 or in any subsequent implementing rules adopted pursuant to this Regulation.\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nResidual risks which are required to be communicated to the user and/or other person shall be included as limitations, contra-indications, precautions or warnings in the information supplied by the manufacturer.\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nWhere appropriate, the information supplied by the manufacturer shall take the form of internationally recognised symbols. Any symbol or identification colour used shall conform to the harmonised standards or CS. In areas for which no harmonised standards or CS exist, the symbols and colours shall be described in the documentation supplied with the device.\n\n\n\n\n23.2.\u00a0\u00a0\u00a0Information on the label\nThe label shall bear all of the following particulars:\n\n\n\n\n\n\n(a)\n\n\nthe name or trade name of the device;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe details strictly necessary for a user to identify the device, the contents of the packaging and, where it is not obvious for the user, the intended purpose of the device;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe name, registered trade name or registered trade mark of the manufacturer and the address of its registered place of business;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nif the manufacturer has its registered place of business outside the Union, the name of the authorised representative and address of the registered place of business of the authorised representative;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nwhere applicable, an indication that the device contains or incorporates:\n\n\n\n\n\n\n\u2014\n\n\na medicinal substance, including a human blood or plasma derivative, or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntissues or cells, or their derivatives, of human origin, or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntissues or cells of animal origin, or their derivatives, as referred to in Regulation\u00a0(EU)\u00a0No\u00a0722/2012;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nwhere applicable, information labelled in accordance with Section\u00a010.4.5.;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nthe lot number or the serial number of the device preceded by the words LOT NUMBER or SERIAL NUMBER or an equivalent symbol, as appropriate;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe UDI carrier referred to in Article\u00a027(4) and Part C of Annex\u00a0VII;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nan unambiguous indication of t the time limit for using or implanting the device safely, expressed at least in terms of year and month, where this is relevant;\n\n\n\n\n\n\n\n\n\n\n(j)\n\n\nwhere there is no indication of the date until when it may be used safely, the date of manufacture. This date of manufacture may be included as part of the lot number or serial number, provided the date is clearly identifiable;\n\n\n\n\n\n\n\n\n\n\n(k)\n\n\nan indication of any special storage and/or handling condition that applies;\n\n\n\n\n\n\n\n\n\n\n(l)\n\n\nif the device is supplied sterile, an indication of its sterile state and the sterilisation method;\n\n\n\n\n\n\n\n\n\n\n(m)\n\n\nwarnings or precautions to be taken that need to be brought to the immediate attention of the user of the device, and to any other person. This information may be kept to a minimum in which case more detailed information shall appear in the instructions for use, taking into account the intended users;\n\n\n\n\n\n\n\n\n\n\n(n)\n\n\nif the device is intended for single use, an indication of that fact. A manufacturer's indication of single use shall be consistent across the Union;\n\n\n\n\n\n\n\n\n\n\n(o)\n\n\nif the device is a single-use device that has been reprocessed, an indication of that fact, the number of reprocessing cycles already performed, and any limitation as regards the number of reprocessing cycles;\n\n\n\n\n\n\n\n\n\n\n(p)\n\n\nif the device is custom-made, the words \u2018custom-made device\u2019;\n\n\n\n\n\n\n\n\n\n\n(q)\n\n\nan indication that the device is a medical device. If the device is intended for clinical investigation only, the words \u2018exclusively for clinical investigation\u2019;\n\n\n\n\n\n\n\n\n\n\n(r)\n\n\nin the case of devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed by or locally dispersed in the human body, the overall qualitative composition of the device and quantitative information on the main constituent or constituents responsible for achieving the principal intended action;\n\n\n\n\n\n\n\n\n\n\n(s)\n\n\nfor active implantable devices, the serial number, and for other implantable devices, the serial number or the lot number.\n\n\n\n\n23.3.\u00a0\u00a0\u00a0Information on the packaging which maintains the sterile condition of a device (\u2018sterile packaging\u2019)\nThe following particulars shall appear on the sterile packaging:\n\n\n\n\n\n\n(a)\n\n\nan indication permitting the sterile packaging to be recognised as such,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\na declaration that the device is in a sterile condition,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe method of sterilisation,\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe name and address of the manufacturer,\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\na description of the device,\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nif the device is intended for clinical investigations, the words \u2018exclusively for clinical investigations\u2019,\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nif the device is custom-made, the words \u2018custom-made device\u2019,\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nthe month and year of manufacture,\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\nan unambiguous indication of the time limit for using or implanting the device safely expressed at least in terms of year and month, and\n\n\n\n\n\n\n\n\n\n\n(j)\n\n\nan instruction to check the instructions for use for what to do if the sterile packaging is damaged or unintentionally opened before use.\n\n\n\n\n23.4.\u00a0\u00a0\u00a0Information in the instructions for use\nThe instructions for use shall contain all of the following particulars:\n\n\n\n\n\n\n(a)\n\n\nthe particulars referred to in points (a), (c), (e), (f), (k), (l), (n) and (r) of Section\u00a023.2;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe device's intended purpose with a clear specification of indications, contra-indications, the patient target group or groups, and of the intended users, as appropriate;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nwhere applicable, a specification of the clinical benefits to be expected.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nwhere applicable, links to the summary of safety and clinical performance referred to in Article\u00a032;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe performance characteristics of the device;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nwhere applicable, information allowing the healthcare professional to verify if the device is suitable and select the corresponding software and accessories;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nany residual risks, contra-indications and any undesirable side-effects, including information to be conveyed to the patient in this regard;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nspecifications the user requires to use the device appropriately, e.g. if the device has a measuring function, the degree of accuracy claimed for it;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\ndetails of any preparatory treatment or handling of the device before it is ready for use or during its use, such as sterilisation, final assembly, calibration, etc., including the levels of disinfection required to ensure patient safety and all available methods for achieving those levels of disinfection;\n\n\n\n\n\n\n\n\n\n\n(j)\n\n\nany requirements for special facilities, or special training, or particular qualifications of the device user and/or other persons;\n\n\n\n\n\n\n\n\n\n\n(k)\n\n\nthe information needed to verify whether the device is properly installed and is ready to perform safely and as intended by the manufacturer, together with, where relevant:\n\n\n\n\n\n\n\u2014\n\n\ndetails of the nature, and frequency, of preventive and regular maintenance, and of any preparatory cleaning or disinfection,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nidentification of any consumable components and how to replace them,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation on any necessary calibration to ensure that the device operates properly and safely during its intended lifetime, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmethods for eliminating the risks encountered by persons involved in installing, calibrating or servicing devices;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(l)\n\n\nif the device is supplied sterile, instructions in the event of the sterile packaging being damaged or unintentionally opened before use;\n\n\n\n\n\n\n\n\n\n\n(m)\n\n\nif the device is supplied non-sterile with the intention that it is sterilised before use, the appropriate instructions for sterilisation;\n\n\n\n\n\n\n\n\n\n\n(n)\n\n\nif the device is reusable, information on the appropriate processes for allowing reuse, including cleaning, disinfection, packaging and, where appropriate, the validated method of re-sterilisation appropriate to the Member\u00a0State or Member\u00a0States in which the device has been placed on the market. Information shall be provided to identify when the device should no longer be reused, e.g. signs of material degradation or the maximum number of allowable reuses;\n\n\n\n\n\n\n\n\n\n\n(o)\n\n\nan indication, if appropriate, that a device can be reused only if it is reconditioned under the responsibility of the manufacturer to comply with the general safety and performance requirements;\n\n\n\n\n\n\n\n\n\n\n(p)\n\n\nif the device bears an indication that it is for single use, information on known characteristics and technical factors known to the manufacturer that could pose a risk if the device were to be re-used. This information shall be based on a specific section of the manufacturer's risk management documentation, where such characteristics and technical factors shall be addressed in detail. If in accordance with point\u00a0(d) of Section\u00a023.1. no instructions for use are required, this information shall be made available to the user upon request;\n\n\n\n\n\n\n\n\n\n\n(q)\n\n\nfor devices intended for use together with other devices and/or general purpose equipment:\n\n\n\n\n\n\n\u2014\n\n\ninformation to identify such devices or equipment, in order to obtain a safe combination, and/or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation on any known restrictions to combinations of devices and equipment;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(r)\n\n\nif the device emits radiation for medical purposes:\n\n\n\n\n\n\n\u2014\n\n\ndetailed information as to the nature, type and where appropriate, the intensity and distribution of the emitted radiation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe means of protecting the patient, user, or other person from unintended radiation during use of the device;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(s)\n\n\ninformation that allows the user and/or patient to be informed of any warnings, precautions, contra-indications, measures to be taken and limitations of use regarding the device. That information shall, where relevant, allow the user to brief the patient about any warnings, precautions, contra-indications, measures to be taken and limitations of use regarding the device. The information shall cover, where appropriate:\n\n\n\n\n\n\n\u2014\n\n\nwarnings, precautions and/or measures to be taken in the event of malfunction of the device or changes in its performance that may affect safety,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwarnings, precautions and/or measures to be taken as regards the exposure to reasonably foreseeable external influences or environmental conditions, such as magnetic fields, external electrical and electromagnetic effects, electrostatic discharge, radiation associated with diagnostic or therapeutic procedures, pressure, humidity, or temperature,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwarnings, precautions and/or measures to be taken as regards the risks of interference posed by the reasonably foreseeable presence of the device during specific diagnostic investigations, evaluations, or therapeutic treatment or other procedures such as electromagnetic interference emitted by the device affecting other equipment,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif the device is intended to administer medicinal products, tissues or cells of human or animal origin, or their derivatives, or biological substances, any limitations or incompatibility in the choice of substances to be delivered,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwarnings, precautions and/or limitations related to the medicinal substance or biological material that is incorporated into the device as an integral part of the device; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nprecautions related to materials incorporated into the device that contain or consist of CMR substances or endocrine-disrupting substances, or that could result in sensitisation or an allergic reaction by the patient or user;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(t)\n\n\nin the case of devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body and that are absorbed by or locally dispersed in the human body, warnings and precautions, where appropriate, related to the general profile of interaction of the device and its products of metabolism with other devices, medicinal products and other substances as well as contra-indications, undesirable side-effects and risks relating to overdose;\n\n\n\n\n\n\n\n\n\n\n(u)\n\n\nin the case of implantable devices, the overall qualitative and quantitative information on the materials and substances to which patients can be exposed;\n\n\n\n\n\n\n\n\n\n\n(v)\n\n\nwarnings or precautions to be taken in order to facilitate the safe disposal of the device, its accessories and the consumables used with it, if any. This information shall cover, where appropriate:\n\n\n\n\n\n\n\u2014\n\n\ninfection or microbial hazards such as explants, needles or surgical equipment contaminated with potentially infectious substances of human origin, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nphysical hazards such as from sharps.\n\n\n\n\nIf in accordance with the point\u00a0(d) of Section\u00a023.1 no instructions for use are required, this information shall be made available to the user upon request;\n\n\n\n\n\n\n\n\n\n\n(w)\n\n\nfor devices intended for use by lay persons, the circumstances in which the user should consult a healthcare professional;\n\n\n\n\n\n\n\n\n\n\n(x)\n\n\nfor the devices covered by this Regulation pursuant to Article\u00a01(2), information regarding the absence of a clinical benefit and the risks related to use of the device;\n\n\n\n\n\n\n\n\n\n\n(y)\n\n\ndate of issue of the instructions for use or, if they have been revised, date of issue and identifier of the latest revision of the instructions for use;\n\n\n\n\n\n\n\n\n\n\n(z)\n\n\na notice to the user and/or patient that any serious incident that has occurred in relation to the device should be reported to the manufacturer and the competent authority of the Member\u00a0State in which the user and/or patient is established;\n\n\n\n\n\n\n\n\n\n\n(aa)\n\n\ninformation to be supplied to the patient with an implanted device in accordance with Article\u00a018;\n\n\n\n\n\n\n\n\n\n\n(ab)\n\n\nfor devices that incorporate electronic programmable systems, including software, or software that are devices in themselves, minimum requirements concerning hardware, IT networks characteristics and IT security measures, including protection against unauthorised access, necessary to run the software as intended.\n\n\n\n\n\n\n(1)\u00a0\u00a0Regulation (EC)\u00a0No\u00a01272/2008 of the European Parliament and of the Council of 16\u00a0December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation\u00a0(EC)\u00a0No\u00a01907/2006 ( OJ\u00a0L\u00a0353, 31.12.2008, p.\u00a01).\n\n(2)\u00a0\u00a0Regulation (EC)\u00a0No\u00a01907/2006 of the European Parliament and of the Council of 18\u00a0December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) (OJ\u00a0L\u00a0396, 30.12.2006, p.\u00a01).\n\n(3)\u00a0\u00a0Regulation (EU)\u00a0No\u00a0528/2012 of the European Parliament and the Council of 22\u00a0May\u00a02012 concerning the making available on the market of and use of biocidal products (OJ\u00a0L\u00a0167, 27.6.2012, p.\u00a01).\n\n(4)\u00a0\u00a0Council Directive\u00a080/181/EEC of 20 December 1979 on the approximation of the laws of the Member\u00a0States relating to units of measurement and on the repeal of Directive\u00a071/354/EEC (OJ\u00a0L\u00a039, 15.2.1980, p.\u00a040).\n\n\n\n\n\nANNEX II\n\nTECHNICAL DOCUMENTATION\n\nThe technical documentation and, if applicable, the summary thereof to be drawn up by the manufacturer shall be presented in a clear, organised, readily searchable and unambiguous manner and shall include in particular the elements listed in this Annex.\n1.\u00a0\u00a0\u00a0DEVICE DESCRIPTION AND SPECIFICATION, INCLUDING VARIANTS AND ACCESSORIES\n1.1.\u00a0\u00a0\u00a0Device description and specification\n\n\n\n\n\n\n(a)\n\n\nproduct or trade name and a general description of the device including its intended purpose and intended users;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe Basic UDI-DI as referred to in Part C of Annex\u00a0VI assigned by the manufacturer to the device in question, as soon as identification of this device becomes based on a UDI system, or otherwise a clear identification by means of product code, catalogue number or other unambiguous reference allowing traceability;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe intended patient population and medical conditions to be diagnosed, treated and/or monitored and other considerations such as patient selection criteria, indications, contra-indications, warnings;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nprinciples of operation of the device and its mode of action, scientifically demonstrated if necessary;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe rationale for the qualification of the product as a device;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nthe risk class of the device and the justification for the classification rule(s) applied in accordance with Annex\u00a0VIII;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nan explanation of any novel features;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\na description of the accessories for a device, other devices and other products that are not devices, which are intended to be used in combination with it;\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\na description or complete list of the various configurations/variants of the device that are intended to be made available on the market;\n\n\n\n\n\n\n\n\n\n\n(j)\n\n\na general description of the key functional elements, e.g. its parts/components (including software if appropriate), its formulation, its composition, its functionality and, where relevant, its qualitative and quantitative composition. Where appropriate, this shall include labelled pictorial representations (e.g. diagrams, photographs, and drawings), clearly indicating key parts/components, including sufficient explanation to understand the drawings and diagrams;\n\n\n\n\n\n\n\n\n\n\n(k)\n\n\na description of the raw materials incorporated into key functional elements and those making either direct contact with the human body or indirect contact with the body, e.g., during extracorporeal circulation of body fluids;\n\n\n\n\n\n\n\n\n\n\n(l)\n\n\ntechnical specifications, such as features, dimensions and performance attributes, of the device and any variants/configurations and accessories that would typically appear in the product specification made available to the user, for example in brochures, catalogues and similar publications.\n\n\n\n\n1.2.\u00a0\u00a0\u00a0Reference to previous and similar generations of the device\n\n\n\n\n\n\n(a)\n\n\nan overview of the previous generation or generations of the device produced by the manufacturer, where such devices exist;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nan overview of identified similar devices available on the Union or international markets, where such devices exist.\n\n\n\n\n2.\u00a0\u00a0\u00a0INFORMATION TO BE SUPPLIED BY THE MANUFACTURER\nA complete set of:\n\n\n\n\n\n\n\u2014\n\n\nthe label or labels on the device and on its packaging, such as single unit packaging, sales packaging, transport packaging in case of specific management conditions, in the languages accepted in the Member\u00a0States where the device is envisaged to be sold; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe instructions for use in the languages accepted in the Member\u00a0States where the device is envisaged to be sold.\n\n\n\n\n3.\u00a0\u00a0\u00a0DESIGN AND MANUFACTURING INFORMATION\n\n\n\n\n\n\n(a)\n\n\ninformation to allow the design stages applied to the device to be understood;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ncomplete information and specifications, including the manufacturing processes and their validation, their adjuvants, the continuous monitoring and the final product testing. Data shall be fully included in the technical documentation;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nidentification of all sites, including suppliers and sub-contractors, where design and manufacturing activities are performed.\n\n\n\n\n4.\u00a0\u00a0\u00a0GENERAL SAFETY AND PERFORMANCE REQUIREMENTS\nThe documentation shall contain information for the demonstration of conformity with the general safety and performance requirements set out in Annex\u00a0I that are applicable to the device taking into account its intended purpose, and shall include a justification, validation and verification of the solutions adopted to meet those requirements. The demonstration of conformity shall include:\n\n\n\n\n\n\n(a)\n\n\nthe general safety and performance requirements that apply to the device and an explanation as to why others do not apply;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe method or methods used to demonstrate conformity with each applicable general safety and performance requirement;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe harmonised standards, CS or other solutions applied; and\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe precise identity of the controlled documents offering evidence of conformity with each harmonised standard, CS or other method applied to demonstrate conformity with the general safety and performance requirements. The information referred to under this point shall incorporate a cross-reference to the location of such evidence within the full technical documentation and, if applicable, the summary technical documentation.\n\n\n\n\n5.\u00a0\u00a0\u00a0BENEFIT-RISK ANALYSIS AND RISK MANAGEMENT\nThe documentation shall contain information on:\n\n\n\n\n\n\n(a)\n\n\nthe benefit-risk analysis referred to in Sections 1 and 8 of Annex\u00a0I, and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe solutions adopted and the results of the risk management referred to in Section\u00a03 of Annex\u00a0I.\n\n\n\n\n6.\u00a0\u00a0\u00a0PRODUCT VERIFICATION AND VALIDATION\nThe documentation shall contain the results and critical analyses of all verifications and validation tests and/or studies undertaken to demonstrate conformity of the device with the requirements of this Regulation and in particular the applicable general safety and performance requirements.\n6.1.\u00a0\u00a0\u00a0Pre-clinical and clinical data\n\n\n\n\n\n\n(a)\n\n\nresults of tests, such as engineering, laboratory, simulated use and animal tests, and evaluation of published literature applicable to the device, taking into account its intended purpose, or to similar devices, regarding the pre-clinical safety of the device and its conformity with the specifications;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ndetailed information regarding test design, complete test or study protocols, methods of data analysis, in addition to data summaries and test conclusions regarding in particular:\n\n\n\n\n\n\n\u2014\n\n\nthe biocompatibility of the device including the identification of all materials in direct or indirect contact with the patient or user;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nphysical, chemical and microbiological characterisation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nelectrical safety and electromagnetic compatibility;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsoftware verification and validation (describing the software design and development process and evidence of the validation of the software, as used in the finished device. This information shall typically include the summary results of all verification, validation and testing performed both in-house and in a simulated or actual user environment prior to final release. It shall also address all of the different hardware configurations and, where applicable, operating systems identified in the information supplied by the manufacturer);\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nstability, including shelf life; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nperformance and safety.\n\n\n\n\nWhere applicable, conformity with the provisions of Directive\u00a02004/10/EC of the European Parliament and of the Council\u00a0(1) shall be demonstrated.\nWhere no new testing has been undertaken, the documentation shall incorporate a rationale for that decision. An example of such a rationale would be that biocompatibility testing on identical materials was conducted when those materials were incorporated in a previous version of the device that has been legally placed on the market or put into service;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe clinical evaluation report and its updates and the clinical evaluation plan referred to in Article\u00a061(12) and Part A of Annex\u00a0XIV;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe PMCF plan and PMCF evaluation report referred to in Part B of Annex\u00a0XIV or a justification why a PMCF is not applicable.\n\n\n\n\n6.2.\u00a0\u00a0\u00a0Additional information required in specific cases\n\n\n\n\n\n\n(a)\n\n\nWhere a device incorporates, as an integral part, a substance which, if used separately, may be considered to be a medicinal product within the meaning of point 2 of Article\u00a01 of Directive\u00a02001/83/EC, including a medicinal product derived from human blood or human plasma, as referred to in the first subparagraph\u00a0of Article\u00a01(8), a statement indicating this fact. In this case, the documentation shall identify the source of that substance and contain the data of the tests conducted to assess its safety, quality and usefulness, taking account of the intended purpose of the device.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nWhere a device is manufactured utilising tissues or cells of human or animal origin, or their derivatives, and is covered by this Regulation in accordance with points\u00a0(f) and (g) of Article\u00a01(6, and where a device incorporates, as an integral part, tissues or cells of human origin or their derivatives that have an action ancillary to that of the device and is covered by this Regulation in accordance with the first subparagraph\u00a0of Article\u00a01(10), a statement indicating this fact. In such a case, the documentation shall identify all materials of human or animal origin used and provide detailed information concerning the conformity with Sections 13.1. or 13.2., respectively, of Annex\u00a0I.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nIn the case of devices that are composed of substances or combinations of substances that are intended to be introduced into the human body and that are absorbed by or locally dispersed in the human body, detailed information, including test design, complete test or study protocols, methods of data analysis, and data summaries and test conclusions, regarding studies in relation to:\n\n\n\n\n\n\n\u2014\n\n\nabsorption, distribution, metabolism and excretion;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npossible interactions of those substances, or of their products of metabolism in the human body, with other devices, medicinal products or other substances, considering the target population, and its associated medical conditions;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nlocal tolerance; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntoxicity, including single-dose toxicity, repeat-dose toxicity, genotoxicity, carcinogenicity and reproductive and developmental toxicity, as applicable depending on the level and nature of exposure to the device.\n\n\n\n\nIn the absence of such studies, a justification shall be provided.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nIn the case of devices containing CMR or endocrine-disrupting substances referred to in Section\u00a010.4.1 of Annex\u00a0I, the justification referred to in Section\u00a010.4.2 of that Annex.\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nIn the case of devices placed on the market in a sterile or defined microbiological condition, a description of the environmental conditions for the relevant manufacturing steps. In the case of devices placed on the market in a sterile condition, a description of the methods used, including the validation reports, with respect to packaging, sterilisation and maintenance of sterility. The validation report shall address bioburden testing, pyrogen testing and, if applicable, testing for sterilant residues.\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nIn the case of devices placed on the market with a measuring function, a description of the methods used in order to ensure the accuracy as given in the specifications.\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nIf the device is to be connected to other device(s) in order to operate as intended, a description of this combination/configuration including proof that it conforms to the general safety and performance requirements when connected to any such device(s) having regard to the characteristics specified by the manufacturer.\n\n\n\n\n\n\n(1)\u00a0\u00a0Directive\u00a02004/10/EC of the European Parliament and of the Council of 11\u00a0February\u00a02004 on the harmonisation of laws, regulations and administrative provisions relating to the application of the principles of good laboratory practice and the verification of their applications for tests on chemical substances (OJ\u00a0L\u00a050, 20.2.2004, p.\u00a044).\n\n\n\n\n\nANNEX III\n\nTECHNICAL DOCUMENTATION ON POST-MARKET SURVEILLANCE\n\nThe technical documentation on post-market surveillance to be drawn up by the manufacturer in accordance with Articles\u00a083 to 86 shall be presented in a clear, organised, readily searchable and unambiguous manner and shall include in particular the elements described in this Annex.\n1.1.\u00a0\u00a0\u00a0The post-market surveillance plan drawn up in accordance with Article\u00a084.\nThe manufacturer shall prove in a post-market surveillance plan that it complies with the obligation referred to in Article\u00a083.\n\n\n\n\n\n\n(a)\n\n\nThe post-market surveillance plan shall address the collection and utilization of available information, in particular:\n\n\n\n\n\n\n\u2014\n\n\ninformation concerning serious incidents, including information from PSURs, and field safety corrective actions;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nrecords referring to non-serious incidents and data on any undesirable side-effects;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation from trend reporting;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nrelevant specialist or technical literature, databases and/or registers;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation, including feedbacks and complaints, provided by users, distributors and importers; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npublicly available information about similar medical devices.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nThe post-market surveillance plan shall cover at least:\n\n\n\n\n\n\n\u2014\n\n\na proactive and systematic process to collect any information referred to in point\u00a0(a). The process shall allow a correct characterisation of the performance of the devices and shall also allow a comparison to be made between the device and similar products available on the market;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\neffective and appropriate methods and processes to assess the collected data;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsuitable indicators and threshold values that shall be used in the continuous reassessment of the benefit-risk analysis and of the risk management as referred to in Section\u00a03 of Annex\u00a0I;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\neffective and appropriate methods and tools to investigate complaints and analyse market-related experience collected in the field;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmethods and protocols to manage the events subject to the trend report as provided for in Article\u00a088, including the methods and protocols to be used to establish any statistically significant increase in the frequency or severity of incidents as well as the observation period;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmethods and protocols to communicate effectively with competent authorities, notified bodies, economic operators and users;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreference to procedures to fulfil the manufacturers obligations laid down in Articles\u00a083, 84 and 86;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsystematic procedures to identify and initiate appropriate measures including corrective actions;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\neffective tools to trace and identify devices for which corrective actions might be necessary; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na PMCF plan as referred to in Part B of Annex\u00a0XIV, or a justification as to why a PMCF is not applicable.\n\n\n\n\n\n\n\n\n1.2.\u00a0\u00a0\u00a0The PSUR referred to in Article\u00a086 and the post-market surveillance report referred to in Article\u00a085.\n\n\n\n\n\nANNEX IV\n\nEU DECLARATION OF CONFORMITY\n\nThe EU declaration of conformity shall contain all of the following information:\n\n\n\n\n\n\n1.\n\n\nName, registered trade name or registered trade mark and, if already issued, SRN as referred to in Article\u00a031 of the manufacturer, and, if applicable, its authorised representative, and the address of their registered place of business where they can be contacted and their location be established;\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nA statement that the EU declaration of conformity is issued under the sole responsibility of the manufacturer;\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nThe Basic UDI-DI as referred to in Part C of Annex\u00a0VI;\n\n\n\n\n\n\n\n\n\n\n4.\n\n\nProduct and trade name, product code, catalogue number or other unambiguous reference allowing identification and traceability of the device covered by the EU declaration of conformity, such as a photograph, where appropriate, as well as its intended purpose. Except for the product or trade name, the information allowing identification and traceability may be provided by the Basic UDI-DI referred to in point 3;\n\n\n\n\n\n\n\n\n\n\n5.\n\n\nRisk class of the device in accordance with the rules set out in Annex\u00a0VIII;\n\n\n\n\n\n\n\n\n\n\n6.\n\n\nA statement that the device that is covered by the present declaration is in conformity with this Regulation and, if applicable, with any other relevant Union legislation that provides for the issuing of an EU declaration of conformity;\n\n\n\n\n\n\n\n\n\n\n7.\n\n\nReferences to any CS used and in relation to which conformity is declared;\n\n\n\n\n\n\n\n\n\n\n8.\n\n\nWhere applicable, the name and identification number of the notified body, a description of the conformity assessment procedure performed and identification of the certificate or certificates issued;\n\n\n\n\n\n\n\n\n\n\n9.\n\n\nWhere applicable, additional information;\n\n\n\n\n\n\n\n\n\n\n10.\n\n\nPlace and date of issue of the declaration, name and function of the person who signed it as well as an indication for, and on behalf of whom, that person signed, signature.\n\n\n\n\n\n\n\n\n\nANNEX V\n\nCE MARKING OF CONFORMITY\n\n\n\n\n\n\n\n\n\n1.\n\n\nThe CE marking shall consist of the initials \u2018CE\u2019 taking the following form:\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nIf the CE marking is reduced or enlarged, the proportions given in the above graduated drawing shall be respected.\n\n\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nThe various components of the CE marking shall have substantially the same vertical dimension, which may not be less than 5 mm. This minimum dimension may be waived for small-scale devices.\n\n\n\n\n\n\n\n\n\nANNEX VI\n\nINFORMATION TO BE SUBMITTED UPON THE REGISTRATION OF DEVICES AND ECONOMIC OPERATORS IN ACCORDANCE WITH ARTICLES 29(4) AND 31, CORE DATA ELEMENTS TO BE PROVIDED TO THE UDI DATABASE TOGETHER WITH THE UDI-DI IN ACCORDANCE WITH ARTICLES 28 AND 29, AND THE UDI SYSTEM\n\nPART A\n\nINFORMATION TO BE SUBMITTED UPON THE REGISTRATION OF DEVICES AND ECONOMIC OPERATORS IN ACCORDANCE WITH ARTICLES 29(4) AND 31\n\nManufacturers or, when applicable, authorised representatives, and, when applicable, importers shall submit the information referred to in Section\u00a01 and shall ensure that the information on their devices referred to in Section\u00a02 is complete, correct and updated by the relevant party.\n1.\u00a0\u00a0\u00a0Information relating to the economic operator\n\n\n\n\n\n\n1.1.\n\n\ntype of economic operator(manufacturer, authorised representative, or importer),\n\n\n\n\n\n\n\n\n\n\n1.2.\n\n\nname, address and contact details of the economic operator,\n\n\n\n\n\n\n\n\n\n\n1.3.\n\n\nwhere submission of information is carried out by another person on behalf of any of the economic operators mentioned under Section 1.1, the name, address and contact details of that person,\n\n\n\n\n\n\n\n\n\n\n1.4.\n\n\nname address and contact details of the person or persons responsible for regulatory compliance referred to in Article\u00a015.\n\n\n\n\n2.\u00a0\u00a0\u00a0Information relating to the device\n\n\n\n\n\n\n2.1.\n\n\nBasic UDI-DI,\n\n\n\n\n\n\n\n\n\n\n2.2.\n\n\ntype, number and expiry date of the certificate issued by the notified body and the name or identification number of that notified body and the link to the information that appears on the certificate and was entered by the notified body in the electronic system on notified bodies and certificates,\n\n\n\n\n\n\n\n\n\n\n2.3.\n\n\nMember\u00a0State in which the device is to or has been placed on the market in the Union,\n\n\n\n\n\n\n\n\n\n\n2.4.\n\n\nin the case of class IIa, class IIb or class III devices: Member\u00a0States where the device is or is to be made available,\n\n\n\n\n\n\n\n\n\n\n2.5.\n\n\nrisk class of the device,\n\n\n\n\n\n\n\n\n\n\n2.6.\n\n\nreprocessed single-use device (y/n),\n\n\n\n\n\n\n\n\n\n\n2.7.\n\n\npresence of a substance which, if used separately, may be considered to be a medicinal product and name of that substance,\n\n\n\n\n\n\n\n\n\n\n2.8.\n\n\npresence of a substance which, if used separately, may be considered to be a medicinal product derived from human blood or human plasma and name of this substance,\n\n\n\n\n\n\n\n\n\n\n2.9.\n\n\npresence of tissues or cells of human origin, or their derivatives (y/n),\n\n\n\n\n\n\n\n\n\n\n2.10.\n\n\npresence of tissues or cells of animal origin, or their derivatives, as referred to in Regulation\u00a0(EU)\u00a0No\u00a0722/2012 (y/n),\n\n\n\n\n\n\n\n\n\n\n2.11.\n\n\nwhere applicable, the single identification number of the clinical investigation or investigations conducted in relation to the device or a link to the clinical investigation registration in the electronic system on clinical investigations,\n\n\n\n\n\n\n\n\n\n\n2.12.\n\n\nin the case of devices listed in Annex\u00a0XVI, specification as to whether the intended purpose of the device is other than a medical purpose,\n\n\n\n\n\n\n\n\n\n\n2.13.\n\n\nin the case of devices designed and manufactured by another legal or natural person as referred in Article\u00a010(15), the name, address and contact details of that legal or natural person,\n\n\n\n\n\n\n\n\n\n\n2.14.\n\n\nin the case of class III or implantable devices, the summary of safety and clinical performance,\n\n\n\n\n\n\n\n\n\n\n2.15.\n\n\nstatus of the device (on the market, no longer placed on the market, recalled, field safety corrective action initiated).\n\n\n\n\nPART B\n\nCORE DATA ELEMENTS TO BE PROVIDED TO THE UDI DATABASE TOGETHER WITH THE UDI-DI IN ACCORDANCE WITH ARTICLES 28 AND 29\n\nThe manufacturer shall provide to the UDI database the UDI-DI and all of the following information relating to the manufacturer and the device:\n\n\n\n\n\n\n1.\n\n\nquantity per package configuration,\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nthe Basic UDI-DI as referred to in Article\u00a029 and any additional UDI-DIs,\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nthe manner in which production of the device is controlled (expiry date or manufacturing date, lot number, serial number),\n\n\n\n\n\n\n\n\n\n\n4.\n\n\nif applicable, the unit of use UDI-DI (where a UDI is not labelled on the device at the level of its unit of use, a \u2018unit of use\u2019 DI shall be assigned so as to associate the use of a device with a patient),\n\n\n\n\n\n\n\n\n\n\n5.\n\n\nname and address of the manufacturer (as indicated on the label),\n\n\n\n\n\n\n\n\n\n\n6.\n\n\nthe SRN issued in accordance with Article\u00a031(2),\n\n\n\n\n\n\n\n\n\n\n7.\n\n\nif applicable, name and address of the authorised representative (as indicated on the label),\n\n\n\n\n\n\n\n\n\n\n8.\n\n\nthe medical device nomenclature code as provided for in Article\u00a026,\n\n\n\n\n\n\n\n\n\n\n9.\n\n\nrisk class of the device,\n\n\n\n\n\n\n\n\n\n\n10.\n\n\nif applicable, name or trade name,\n\n\n\n\n\n\n\n\n\n\n11.\n\n\nif applicable, device model, reference, or catalogue number,\n\n\n\n\n\n\n\n\n\n\n12.\n\n\nif applicable, clinical size (including volume, length, gauge, diameter),\n\n\n\n\n\n\n\n\n\n\n13.\n\n\nadditional product description (optional),\n\n\n\n\n\n\n\n\n\n\n14.\n\n\nif applicable, storage and/or handling conditions (as indicated on the label or in the instructions for use),\n\n\n\n\n\n\n\n\n\n\n15.\n\n\nif applicable, additional trade names of the device,\n\n\n\n\n\n\n\n\n\n\n16.\n\n\nlabelled as a single-use device (y/n),\n\n\n\n\n\n\n\n\n\n\n17.\n\n\nif applicable, the maximum number of reuses,\n\n\n\n\n\n\n\n\n\n\n18.\n\n\ndevice labelled sterile (y/n),\n\n\n\n\n\n\n\n\n\n\n19.\n\n\nneed for sterilisation before use (y/n),\n\n\n\n\n\n\n\n\n\n\n20.\n\n\ncontaining latex (y/n),\n\n\n\n\n\n\n\n\n\n\n21.\n\n\nwhere applicable, information labelled in accordance with Section\u00a010.4.5 of Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n22.\n\n\nURL for additional information, such as electronic instructions for use (optional),\n\n\n\n\n\n\n\n\n\n\n23.\n\n\nif applicable, critical warnings or contra-indications,\n\n\n\n\n\n\n\n\n\n\n24.\n\n\nstatus of the device (on the market, no longer placed on the market, recalled, field safety corrective action initiated).\n\n\n\n\nPART C\n\nTHE UDI SYSTEM\n\n1.\u00a0\u00a0\u00a0Definitions\nAutomatic identification and data capture (\u2018AIDC\u2019)\nAIDC is a technology used to automatically capture data. AIDC technologies include bar codes, smart cards, biometrics and RFID.\nBasic UDI-DI\nThe Basic UDI-DI is the primary identifier of a device model. It is the DI assigned at the level of the device unit of use. It is the main key for records in the UDI database and is referenced in relevant certificates and EU declarations of conformity.\nUnit of Use DI\nThe Unit of Use DI serves to associate the use of a device with a patient in instances in which a UDI is not labelled on the individual device at the level of its unit of use, for example in the event of several units of the same device being packaged together.\nConfigurable device\nA configurable device is a device that consists of several components which can be assembled by the manufacturer in multiple configurations. Those individual components may be devices in themselves.\nConfigurable devices include computed tomography (CT) systems, ultrasound systems, anaesthesia systems, physiological Monitoring systems, radiology information systems\u00a0(RIS).\nConfiguration\nConfiguration is a combination of items of equipment, as specified by the manufacturer, that operate together as a device to achieve an intended purpose. The combination of items may be modified, adjusted or customized to meet specific needs.\nConfigurations include inter alia:\n\n\n\n\n\n\n\u2014\n\n\ngantries, tubes, tables, consoles and other items of equipment that can be configured/combined to deliver an intended function in computed tomography.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nventilators, breathing circuits, vaporizers combined to deliver an intended function in anaesthesia.\n\n\n\n\nUDI-DI\nThe UDI-DI is a unique numeric or alphanumeric code specific to a model of device and that is also used as the \u2018access key\u2019 to information stored in a UDI database.\nHuman Readable Interpretation (\u2018HRI\u2019)\nHRI is a legible interpretation of the data characters encoded in the UDI carrier.\nPackaging levels\nPackaging levels means the various levels of device packaging that contain a defined quantity of devices, such as a carton or case.\nUDI-PI\nThe UDI-PI is a numeric or alphanumeric code that identifies the unit of device production.\nThe different types of UDI-PIs include serial number, lot number, software identification and manufacturing or expiry date or both types of date.\nRadio Frequency Identification RFID\nRFID is a technology that uses communication through the use of radio waves to exchange data between a reader and an electronic tag attached to an object, for the purpose of identification.\nShipping containers\nA shipping container is a container in relation to which traceability is controlled by a process specific to logistics systems.\nUnique Device Identifier (\u2018UDI\u2019)\nThe UDI is a series of numeric or alphanumeric characters that is created through a globally accepted device identification and coding standard. It allows the unambiguous identification of a specific device on the market. The UDI is comprised of the UDI-DI and the UDI-PI.\nThe word \u2018Unique\u2019 does not imply serialisation of individual production units.\nUDI carrier\nThe UDI carrier is the means of conveying the UDI by using AIDC and, if applicable, its\u00a0HRI.\nUDI carriers include, inter alia, ID/linear bar code, 2D/Matrix bar code, RFID.\n2.\u00a0\u00a0\u00a0General requirements\n2.1.\u00a0\u00a0\u00a0The affixing of the UDI is an additional requirement \u2014 it does not replace any other marking or labelling requirements laid down in Annex\u00a0I to this Regulation.\n2.2.\u00a0\u00a0\u00a0The manufacturer shall assign and maintain unique UDIs for its devices.\n2.3.\u00a0\u00a0\u00a0Only the manufacturer may place the UDI on the device or its packaging.\n2.4.\u00a0\u00a0\u00a0Only coding standards provided by issuing entities designated by the Commission pursuant to Article\u00a027(2) may be used.\n3.\u00a0\u00a0\u00a0The UDI\n3.1.\u00a0\u00a0\u00a0A UDI shall be assigned to the device itself or its packaging. Higher levels of packaging shall have their own UDI.\n3.2.\u00a0\u00a0\u00a0Shipping containers shall be exempted from the requirement in Section\u00a03.1. By way of example, a UDI shall not be required on a logistics unit; where a healthcare provider orders multiple devices using the UDI or model number of individual devices and the manufacturer places those devices in a container for shipping or to protect the individually packaged devices, the container (logistics unit) shall not be subject to UDI requirements.\n3.3.\u00a0\u00a0\u00a0The UDI shall contain two parts: a UDI-DI and a UDI-PI.\n3.4.\u00a0\u00a0\u00a0The UDI-DI shall be unique at each level of device packaging.\n3.5.\u00a0\u00a0\u00a0If a lot number, serial number, software identification or expiry date appears on the label, it shall be part of the UDI-PI. If there is also a manufacturing date on the label, it does not need to be included in the UDI-PI. If there is only a manufacturing date on the label, this shall be used as the UDI-PI.\n3.6.\u00a0\u00a0\u00a0Each component that is considered to be a device and is commercially available on its own shall be assigned a separate UDI unless the components are part of a configurable device that is marked with its own UDI.\n3.7.\u00a0\u00a0\u00a0Systems and procedure packs as referred to in Article\u00a022 shall be assigned and bear their own UDI.\n3.8.\u00a0\u00a0\u00a0The manufacturer shall assign the UDI to a device following the relevant coding standard.\n3.9.\u00a0\u00a0\u00a0A new UDI-DI shall be required whenever there is a change that could lead to misidentification of the device and/or ambiguity in its traceability; in particular, any change of one of the following UDI database data elements shall require a new UDI-DI:\n\n\n\n\n\n\n(a)\n\n\nname or trade name,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ndevice version or model,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nlabelled as single use,\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\npackaged sterile,\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nneed for sterilization before use,\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nquantity of devices provided in a package,\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\ncritical warnings or contra-indications: e.g. containing latex or DEHP.\n\n\n\n\n3.10.\u00a0\u00a0\u00a0Manufacturers that repackage and/or relabel devices, with their own label shall retain a record of the original device manufacturer's UDI.\n4.\u00a0\u00a0\u00a0UDI carrier\n4.1.\u00a0\u00a0\u00a0The UDI carrier (AIDC and HRI representation of the UDI) shall be placed on the label or on the device itself and on all higher levels of device packaging. Higher levels do not include shipping containers.\n4.2.\u00a0\u00a0\u00a0In the event of there being significant space constraints on the unit of use packaging, the UDI carrier may be placed on the next higher packaging level.\n4.3.\u00a0\u00a0\u00a0For single-use devices of classes I and IIa packaged and labelled individually, the UDI\u00a0carrier shall not be required to appear on the packaging but it shall appear on a higher level of packaging, e.g. a carton containing several individually packaged devices. However, when the healthcare provider is not expected to have access, in cases such as in home healthcare settings, to the higher level of device packaging, the UDI shall be placed on the packaging of the individual device.\n4.4.\u00a0\u00a0\u00a0For devices exclusively intended for retail point of sale the UDI-PIs in AIDC shall not be required to appear on the point of sale packaging.\n4.5.\u00a0\u00a0\u00a0When AIDC carriers other than the UDI carrier are part of the product labelling, the UDI\u00a0carrier shall be readily identifiable.\n4.6.\u00a0\u00a0\u00a0If linear bar codes are used, the UDI-DI and UDI-PI may be concatenated or non-concatenated in two or more bar codes. All parts and elements of the linear bar code shall be distinguishable and identifiable.\n4.7.\u00a0\u00a0\u00a0If there are significant constraints limiting the use of both AIDC and HRI on the label, only the AIDC format shall be required to appear on the label. For devices intended to be used outside healthcare facilities, such as devices for home care, the HRI shall however appear on the label even if this results in there being no space for the AIDC.\n4.8.\u00a0\u00a0\u00a0The HRI format shall follow the rules of the UDI code-issuing entity.\n4.9.\u00a0\u00a0\u00a0If the manufacturer is using RFID technology, a linear or 2D bar code in line with the standard provided by the issuing entities shall also be provided on the label.\n4.10.\u00a0\u00a0\u00a0Devices that are reusable shall bear a UDI carrier on the device itself. The UDI carrier for reusable devices that require cleaning, disinfection, sterilisation or refurbishing between patient uses shall be permanent and readable after each process performed to make the device ready for the subsequent use throughout the intended lifetime of the device. The requirement of this Section\u00a0shall not apply to devices in the following circumstances:\n\n\n\n\n\n\n(a)\n\n\nany type of direct marking would interfere with the safety or performance of the device;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe device cannot be directly marked because it is not technologically feasible.\n\n\n\n\n4.11.\u00a0\u00a0\u00a0The UDI carrier shall be readable during normal use and throughout the intended lifetime of the device.\n4.12.\u00a0\u00a0\u00a0If the UDI carrier is readily readable or, in the case of AIDC, scannable, through the device's packaging, the placing of the UDI carrier on the packaging shall not be required.\n4.13.\u00a0\u00a0\u00a0In the case of single finished devices made up of multiple parts that must be assembled before their first use, it shall be sufficient to place the UDI carrier on only one part of each device.\n4.14.\u00a0\u00a0\u00a0The UDI carrier shall be placed in a manner such that the AIDC can be accessed during normal operation or storage.\n4.15.\u00a0\u00a0\u00a0Bar code carriers that include both a UDI-DI and a UDI-PI may also include essential data for the device to operate or other data.\n5.\u00a0\u00a0\u00a0General principles of the UDI database\n5.1.\u00a0\u00a0\u00a0The UDI database shall support the use of all core UDI database data elements referred to in Part B of this Annex.\n5.2.\u00a0\u00a0\u00a0Manufacturers shall be responsible for the initial submission and updates of the identifying information and other device data elements in the UDI database.\n5.3.\u00a0\u00a0\u00a0Appropriate methods/procedures for validation of the data provided shall be implemented.\n5.4.\u00a0\u00a0\u00a0Manufacturers shall periodically verify the correctness of all of the data relevant to devices they have placed on the market, except for devices that are no longer available on the market.\n5.5.\u00a0\u00a0\u00a0The presence of the device UDI-DI in the UDI database shall not be assumed to mean that the device is in conformity with this Regulation.\n5.6.\u00a0\u00a0\u00a0The database shall allow for the linking of all the packaging levels of the device.\n5.7.\u00a0\u00a0\u00a0The data for new UDI-DIs shall be available at the time the device is placed on the market.\n5.8.\u00a0\u00a0\u00a0Manufacturers shall update the relevant UDI database record within 30 days of a change being made to an element, which does not require a new UDI-DI.\n5.9.\u00a0\u00a0\u00a0Internationally-accepted standards for data submission and updates shall, wherever possible, be used by the UDI database.\n5.10.\u00a0\u00a0\u00a0The user interface of the UDI database shall be available in all official languages of the Union. The use of free-text fields shall, however, be minimized in order to reduce translations.\n5.11.\u00a0\u00a0\u00a0Data relating to devices that are no longer available on the market shall be retained in the UDI database.\n6.\u00a0\u00a0\u00a0Rules for specific device types\n6.1.\u00a0\u00a0\u00a0Implantable devices:\n\n\n\n\n\n\n6.1.1.\n\n\nImplantable devices shall, at their lowest level of packaging (\u2018unit packs\u2019), be identified, or marked using AIDC, with a UDI (UDI-DI + UDI-PI);\n\n\n\n\n\n\n\n\n\n\n6.1.2.\n\n\nThe UDI-PI shall have at least the following characteristics:\n\n\n\n\n\n\n(a)\n\n\nthe serial number for active implantable devices,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe serial number or lot number for other implantable devices.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n6.1.3.\n\n\nThe UDI of the implantable device shall be identifiable prior to implantation.\n\n\n\n\n6.2.\u00a0\u00a0\u00a0Reusable devices requiring cleaning, disinfection, sterilisation or refurbishing between uses\n6.2.1.\u00a0\u00a0\u00a0The UDI of such devices shall be placed on the device and be readable after each procedure to make the device ready for the next use.\n6.2.2.\u00a0\u00a0\u00a0The UDI-PI characteristics such as the lot or serial number shall be defined by the manufacturer.\n6.3.\u00a0\u00a0\u00a0Systems and procedure packs as referred to in Article\u00a022\n6.3.1.\u00a0\u00a0\u00a0The natural or legal person referred to in Article\u00a022 shall be responsible for identifying the system or procedure pack with a UDI including both UDI-DI and UDI-PI.\n6.3.2.\u00a0\u00a0\u00a0Device contents of system or procedure packs shall bear a UDI carrier on their packaging or on the device itself.\nExemptions:\n\n\n\n\n\n\n(a)\n\n\nindividual single-use disposable devices, the uses of which are generally known to the persons by whom they are intended to be used, which are contained within a system or procedure pack, and which are not intended for individual use outside the context of the system or procedure pack, shall not be required to bear their own UDI\u00a0carrier;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\ndevices that are exempted from bearing a UDI carrier on the relevant level of packaging shall not be required to bear a UDI carrier when included within a system or procedure pack.\n\n\n\n\n6.3.3.\u00a0\u00a0\u00a0Placement of the UDI carrier on systems or procedure packs\n\n\n\n\n\n\n(a)\n\n\nThe system or procedure pack UDI carrier shall as a general rule be affixed to the outside of the packaging.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nThe UDI carrier shall be readable, or, in the case of AIDC, scannable, whether placed on the outside of the packaging of the system or procedure pack or inside transparent packaging.\n\n\n\n\n6.4.\u00a0\u00a0\u00a0Configurable devices:\n6.4.1.\u00a0\u00a0\u00a0A UDI shall be assigned to the configurable device in its entirety and shall be called the configurable device UDI.\n6.4.2.\u00a0\u00a0\u00a0The configurable device UDI-DI shall be assigned to groups of configurations, not per configuration within the group.\u00a0A group of configurations is defined as the collection of possible configurations for a given device as described in the technical documentation.\n6.4.3.\u00a0\u00a0\u00a0A configurable device UDI-PI shall be assigned to each individual configurable device.\n6.4.4.\u00a0\u00a0\u00a0The carrier of the configurable device UDI shall be placed on the assembly that is most unlikely to be exchanged during the lifetime of the system and shall be identified as the configurable device UDI.\n6.4.5.\u00a0\u00a0\u00a0Each component that is considered a device and is commercially available on its own shall be assigned a separate UDI.\n6.5.\u00a0\u00a0\u00a0Device Software\n6.5.1.\u00a0\u00a0\u00a0UDI assignment Criteria\nThe UDI shall be assigned at the system level of the software. Only software which is commercially available on its own and software which constitutes a device in itself shall be subject to that requirement.\nThe software identification shall be considered to be the manufacturing control mechanism and shall be displayed in the UDI-PI.\n6.5.2.\u00a0\u00a0\u00a0A new UDI-DI shall be required whenever there is a modification that changes:\n\n\n\n\n\n\n(a)\n\n\nthe original performance;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe safety or the intended use of the software;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\ninterpretation of data.\n\n\n\n\nSuch modifications include new or modified algorithms, database structures, operating platform, architecture or new user interfaces or new channels for interoperability.\n6.5.3.\u00a0\u00a0\u00a0Minor software revisions shall require a new UDI-PI and not a new UDI-DI.\nMinor software revisions are generally associated with bug fixes, usability enhancements that are not for safety purposes, security patches or operating efficiency.\nMinor software revisions shall be identified by a manufacturer-specific form of identification.\n6.5.4.\u00a0\u00a0\u00a0UDI placement criteria for software\n\n\n\n\n\n\n(a)\n\n\nwhere the software is delivered on a physical medium, e.g. CD or DVD, each packaging level shall bear the human readable and AIDC representation of the complete UDI. The UDI that is applied to the physical medium containing the software and its packaging shall be identical to the UDI assigned to the system level software;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe UDI shall be provided on a readily accessible screen for the user in an easily-readable plain-text format, such as an \u2018about\u2019 file, or included on the start-up screen;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nsoftware lacking a user interface such as middleware for image conversion, shall be capable of transmitting the UDI through an application programming interface (API);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nonly the human readable portion of the UDI shall be required in electronic displays of the software. The marking of UDI using AIDC shall not be required in the electronic displays, such as \u2018about\u2019 menu, splash screen etc.;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe human readable format of the UDI for the software shall include the Application Identifiers (AI) for the standard used by the issuing entities, so as to assist the user in identifying the UDI and determining which standard is being used to create the UDI.\n\n\n\n\n\n\n\n\n\nANNEX VII\n\nREQUIREMENTS TO BE MET BY NOTIFIED BODIES\n\n1.\u00a0\u00a0\u00a0ORGANISATIONAL AND GENERAL REQUIREMENTS\n1.1.\u00a0\u00a0\u00a0Legal status and organisational structure\n1.1.1.\u00a0\u00a0\u00a0Each notified body shall be established under the national law of a Member\u00a0State, or under the law of a third country with which the Union has concluded an agreement in this respect. Its legal personality and status shall be fully documented. Such documentation shall include information about ownership and the legal or natural persons exercising control over the notified body.\n1.1.2.\u00a0\u00a0\u00a0If the notified body is a legal entity that is part of a larger organisation, the activities of that organisation as well as its organisational structure and governance, and the relationship with the notified body shall be clearly documented. In such cases, the requirements of Section\u00a01.2 are applicable to both the notified body and the organisation to which it belongs.\n1.1.3.\u00a0\u00a0\u00a0If a notified body wholly or partly owns legal entities established in a Member\u00a0State or in a third country or is owned by another legal entity, the activities and responsibilities of those entities, as well as their legal and operational relationships with the notified body, shall be clearly defined and documented. Personnel of those entities performing conformity assessment activities under this Regulation shall be subject to the applicable requirements of this Regulation.\n1.1.4.\u00a0\u00a0\u00a0The organisational structure, allocation of responsibilities, reporting lines and operation of the notified body shall be such that they ensure that there is confidence in the performance by the notified body and in the results of the conformity assessment activities it conducts.\n1.1.5.\u00a0\u00a0\u00a0The notified body shall clearly document its organisational structure and the functions, responsibilities and authority of its top-level management and of other personnel who may have an influence upon the performance by the notified body and upon the results of its conformity assessment activities.\n1.1.6.\u00a0\u00a0\u00a0The notified body shall identify the persons in top-level management that have overall authority and responsibility for each of the following:\n\n\n\n\n\n\n\u2014\n\n\nthe provision of adequate resources for conformity assessment activities;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe development of procedures and policies for the operation of the notified body;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe supervision of implementation of the procedures, policies and quality management systems of the notified body;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe supervision of the notified body's finances;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe activities and decisions taken by the notified body, including contractual agreements;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe delegation of authority to personnel and/or committees, where necessary, for the performance of defined activities;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe interaction with the authority responsible for notified bodies and the obligations regarding communications with other competent authorities, the Commission and other notified bodies.\n\n\n\n\n1.2.\u00a0\u00a0\u00a0Independence and impartiality\n1.2.1.\u00a0\u00a0\u00a0The notified body shall be a third-party body that is independent of the manufacturer of the device in relation to which it performs conformity assessment activities. The notified body shall also be independent of any other economic operator having an interest in the device as well as of any competitors of the manufacturer. This does not preclude the notified body from carrying out conformity assessment activities for competing manufacturers.\n1.2.2.\u00a0\u00a0\u00a0The notified body shall be organised and operated so as to safeguard the independence, objectivity and impartiality of its activities. The notified body shall document and implement a structure and procedures for safeguarding impartiality and for promoting and applying the principles of impartiality throughout its organisation, personnel and assessment activities. Such procedures shall provide for the identification, investigation and resolution of any case in which a conflict of interest may arise, including involvement in consultancy services in the field of devices prior to taking up employment with the notified body. The investigation, outcome and its resolution shall be documented.\n1.2.3.\u00a0\u00a0\u00a0The notified body, its top-level management and the personnel responsible for carrying out the conformity assessment tasks shall not:\n\n\n\n\n\n\n(a)\n\n\nbe the designer, manufacturer, supplier, installer, purchaser, owner or maintainer of devices which they assess, nor the authorised representative of any of those parties. Such restriction shall not preclude the purchase and use of assessed devices that are necessary for the operations of the notified body and the conduct of the conformity assessment, or the use of such devices for personal purposes;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nbe involved in the design, manufacture or construction, marketing, installation and use, or maintenance of the devices for which they are designated, nor represent the parties engaged in those activities;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nengage in any activity that may conflict with their independence of judgement or integrity in relation to conformity assessment activities for which they are designated;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\noffer or provide any service which may jeopardise the confidence in their independence, impartiality or objectivity. In particular, they shall not offer or provide consultancy services to the manufacturer, its authorised representative, a supplier or a commercial competitor as regards the design, construction, marketing or maintenance of devices or processes under assessment, and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nbe linked to any organisation which itself provides consultancy services as referred to in point\u00a0(d). Such restriction does not preclude general training activities that are not client specific and that relate to regulation of devices or to related standards.\n\n\n\n\n1.2.4.\u00a0\u00a0\u00a0Involvement in consultancy services in the field of devices prior to taking up employment with a notified body shall be fully documented at the time of employment and potential conflicts of interest shall be monitored and resolved in accordance with this Annex. Personnel who were formerly employed by a specific client, or provided consultancy services in the field of devices to that specific client prior to taking up employment with a notified body, shall not be assigned for conformity assessment activities for that specific client or companies belonging to the same group for a period of three years.\n1.2.5.\u00a0\u00a0\u00a0The impartiality of notified bodies, of their top-level management and of the assessment personnel shall be guaranteed. The level of the remuneration of the top-level management and assessment personnel of a notified body and subcontractors, involved in assessment activities shall not depend on the results of the assessments. Notified bodies shall make publicly available the declarations of interest of their top-level management.\n1.2.6.\u00a0\u00a0\u00a0If a notified body is owned by a public entity or institution, independence and absence of any conflict of interest shall be ensured and documented between, on the one hand, the authority responsible for notified bodies and/or the competent authority and, on the other hand, the notified body.\n1.2.7.\u00a0\u00a0\u00a0The notified body shall ensure and document that the activities of its subsidiaries or subcontractors, or of any associated body, including the activities of its owners do not affect its independence, impartiality or the objectivity of its conformity assessment activities.\n1.2.8.\u00a0\u00a0\u00a0The notified body shall operate in accordance with a set of consistent, fair and reasonable terms and conditions, taking into account the interests of small and medium-sized enterprises as defined in Recommendation\u00a02003/361/EC in relation to fees.\n1.2.9.\u00a0\u00a0\u00a0The requirements laid down in this Section\u00a0in no way preclude exchanges of technical information and regulatory guidance between a notified body and a manufacturer applying for conformity assessment.\n1.3.\u00a0\u00a0\u00a0Confidentiality\n1.3.1.\u00a0\u00a0\u00a0The notified body shall have documented procedures in place ensuring that its personnel, committees, subsidiaries, subcontractors, and any associated body or personnel of external bodies respect the confidentiality of the information which comes into its possession during the performance of conformity assessment activities, except when disclosure is required by law.\n1.3.2.\u00a0\u00a0\u00a0The personnel of a notified body shall observe professional secrecy in carrying out their tasks under this Regulation or any provision of national law giving effect to it, except in relation to the authorities responsible for notified bodies, competent authorities for medical devices in the Member\u00a0States or the Commission. Proprietary rights shall be protected. The notified body shall have documented procedures in place in respect of the requirements of this Section.\n1.4.\u00a0\u00a0\u00a0Liability\n1.4.1.\u00a0\u00a0\u00a0The notified body shall take out appropriate liability insurance for its conformity assessment activities, unless liability is assumed by the Member\u00a0State in question in accordance with national law or that Member\u00a0State is directly responsible for the conformity assessment.\n1.4.2.\u00a0\u00a0\u00a0The scope and overall financial value of the liability insurance shall correspond to the level and geographic scope of activities of the notified body and be commensurate with the risk profile of the devices certified by the notified body. The liability insurance shall cover cases where the notified body may be obliged to withdraw, restrict or suspend certificates.\n1.5.\u00a0\u00a0\u00a0Financial requirements\nThe notified body shall have at its disposal the financial resources required to conduct its conformity assessment activities within its scope of designation and related business operations. It shall document and provide evidence of its financial capacity and its long-term economic viability, taking into account, where relevant, any specific circumstances during an initial start-up phase.\n1.6.\u00a0\u00a0\u00a0Participation in coordination activities\n1.6.1.\u00a0\u00a0\u00a0The notified body shall participate in, or ensure that its assessment personnel is informed of, any relevant standardisation activities and in the activities of the notified body coordination group referred to in Article\u00a049 and that its assessment and decision-making personnel are informed of all relevant legislation, guidance and best practice documents adopted in the framework of this Regulation.\n1.6.2.\u00a0\u00a0\u00a0The notified body shall take into consideration guidance and best practice documents.\n2.\u00a0\u00a0\u00a0QUALITY MANAGEMENT REQUIREMENTS\n2.1.\u00a0\u00a0\u00a0The notified body shall establish, document, implement, maintain and operate a quality management system that is appropriate to the nature, area and scale of its conformity assessment activities and is capable of supporting and demonstrating the consistent fulfilment of the requirements of this Regulation.\n2.2.\u00a0\u00a0\u00a0The quality management system of the notified body shall address at least the following:\n\n\n\n\n\n\n\u2014\n\n\nmanagement system structure and documentation, including policies and objectives for its activities;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npolicies for assignment of activities and responsibilities to personnel;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nassessment and decision-making processes in accordance with the tasks, responsibilities and role of the notified body's personnel and top-level management;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe planning, conduct, evaluation and, if necessary, adaptation of its conformity assessment procedures;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncontrol of documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncontrol of records;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmanagement reviews;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninternal audits;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncorrective and preventive actions;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncomplaints and appeals; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncontinuous training.\n\n\n\n\nWhere documents are used in various languages, the notified body shall ensure and control that they have the same content.\n2.3.\u00a0\u00a0\u00a0The top-level management of the notified body shall ensure that the quality management system is fully understood, implemented and maintained throughout the notified body organisation including subsidiaries and subcontractors involved in conformity assessment activities pursuant to this Regulation.\n2.4.\u00a0\u00a0\u00a0The notified body shall require all personnel to formally commit themselves by a signature or equivalent to comply with the procedures defined by the notified body. That commitment shall cover aspects relating to confidentiality and to independence from commercial and other interests, and any existing or prior association with clients. The personnel shall be required to complete written statements indicating their compliance with confidentiality, independence and impartiality principles.\n3.\u00a0\u00a0\u00a0RESOURCE REQUIREMENTS\n3.1.\u00a0\u00a0\u00a0General\n3.1.1.\u00a0\u00a0\u00a0Notified bodies shall be capable of carrying out all the tasks falling to them under this Regulation with the highest degree of professional integrity and the requisite competence in the specific field, whether those tasks are carried out by notified bodies themselves or on their behalf and under their responsibility.\nIn particular, notified bodies shall have the necessary personnel and possess or have access to all equipment, facilities and competence needed to perform properly the technical, scientific and administrative tasks entailed in the conformity assessment activities in relation to which they have been designated.\nSuch requirement presupposes at all times and for each conformity assessment procedure and each type of devices in relation to which they have been designated, that the notified body has permanent availability of sufficient administrative, technical and scientific personnel who possess experience and knowledge relating to the relevant devices and the corresponding technologies. Such personnel shall be in sufficient numbers to ensure that the notified body in question can perform the conformity assessment tasks, including the assessment of the medical functionality, clinical evaluations and the performance and safety of devices, for which it has been designated, having regard to the requirements of this Regulation, in particular, those set out in Annex\u00a0I.\nA notified body's cumulative competences shall be such as to enable it to assess the types of devices for which it is designated. The notified body shall have sufficient internal competence to critically evaluate assessments conducted by external expertise. Tasks which a notified body is precluded from subcontracting are set out in Section\u00a04.1.\nPersonnel involved in the management of the operation of a notified body's conformity assessment activities for devices shall have appropriate knowledge to set up and operate a system for the selection of assessment and verification staff, for verification of their competence, for authorisation and allocation of their tasks, for organisation of their initial and ongoing training and for the assignment of their duties and the monitoring of those staff, in order to ensure that personnel who carry out and perform assessment and verification operations are competent to fulfil the tasks required of them.\nThe notified body shall identify at least one individual within its top-level management as having overall responsibility for all conformity assessment activities in relation to devices.\n3.1.2.\u00a0\u00a0\u00a0The notified body shall ensure that personnel involved in conformity assessment activities maintain their qualification and expertise by implementing a system for exchange of experience and a continuous training and education programme.\n3.1.3.\u00a0\u00a0\u00a0The notified body shall clearly document the extent and limits of duties and responsibilities and the level of authorisation of the personnel, including any subcontractors and external experts, involved in conformity assessment activities and inform those personnel accordingly.\n3.2.\u00a0\u00a0\u00a0Qualification criteria in relation to personnel\n3.2.1.\u00a0\u00a0\u00a0The Notified Body shall establish and document qualification criteria and procedures for selection and authorisation of persons involved in conformity assessment activities, including as regards knowledge, experience and other competence required, and the required initial and ongoing training. The qualification criteria shall address the various functions within the conformity assessment process, such as auditing, product evaluation or testing, technical documentation review and decision-making, as well as the devices, technologies and areas, such as biocompatibility, sterilisation, tissues and cells of human and animal origin and clinical evaluation, covered by the scope of designation.\n3.2.2.\u00a0\u00a0\u00a0The qualification criteria referred to in Section\u00a03.2.1 shall refer to the scope of a notified body's designation in accordance with the scope description used by the Member\u00a0State for the notification referred to in Article\u00a042(3), providing a sufficient level of detail for the required qualification within the subdivisions of the scope description.\nSpecific qualification criteria shall be defined at least for the assessment of:\n\n\n\n\n\n\n\u2014\n\n\nthe pre-clinical evaluation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclinical evaluation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntissues and cells of human and animal origin,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nfunctional safety,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsoftware,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npackaging,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndevices that incorporate as an integral part a medicinal product,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndevices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe different types of sterilisation processes.\n\n\n\n\n3.2.3.\u00a0\u00a0\u00a0The personnel responsible for establishing qualification criteria and for authorising other personnel to perform specific conformity assessment activities shall be employed by the notified body itself and shall not be external experts or subcontracted. They shall have proven knowledge and experience in all of the following:\n\n\n\n\n\n\n\u2014\n\n\nUnion devices legislation and relevant guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe conformity assessment procedures provided for in this Regulation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na broad base of knowledge of device technologies and the design and manufacture of devices;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe notified body's quality management system, related procedures and the required qualification criteria;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntraining relevant to personnel involved in conformity assessment activities in relation to devices;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nadequate experience in conformity assessments under this Regulation or previously applicable law within a notified body.\n\n\n\n\n3.2.4.\u00a0\u00a0\u00a0The notified body shall have permanent availability of personnel with relevant clinical expertise and where possible such personnel shall be employed by the notified body itself. Such personnel shall be integrated throughout the notified body's assessment and decision-making process in order to:\n\n\n\n\n\n\n\u2014\n\n\nidentify when specialist input is required for the assessment of the clinical evaluation conducted by the manufacturer and identify appropriately qualified experts;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriately train external clinical experts in the relevant requirements of this Regulation, CS, guidance and harmonised standards and ensure that the external clinical experts are fully aware of the context and implications of their assessment and the advice they provide;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbe able to review and scientifically challenge the clinical data contained within the clinical evaluation, and any associated clinical investigations, and appropriately guide external clinical experts in the assessment of the clinical evaluation presented by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbe able to scientifically evaluate and, if necessary, challenge the clinical evaluation presented, and the results of the external clinical experts' assessment of the manufacturer's clinical evaluation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbe able to ascertain the comparability and consistency of the assessments of clinical evaluations conducted by clinical experts;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbe able to make an assessment of the manufacturer's clinical evaluation and a clinical judgement of the opinion provided by any external expert and make a recommendation to the notified body's decision maker; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbe able to draw up records and reports demonstrating that the relevant conformity assessment activities have been appropriately carried out.\n\n\n\n\n3.2.5.\u00a0\u00a0\u00a0The personnel responsible for carrying out product-related reviews (product reviewers), such as technical documentation reviews or type examination, including aspects such as clinical evaluation, biological safety, sterilisation and software validation, shall have all of the following proven qualifications:\n\n\n\n\n\n\n\u2014\n\n\nsuccessful completion of a university or a technical college degree or equivalent qualification in relevant studies, e.g. medicine, pharmacy, engineering or other relevant sciences;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nfour years' professional experience in the field of healthcare products or related activities, such as in manufacturing, auditing or research, of which two years shall be in the design, manufacture, testing or use of the device or technology to be assessed or related to the scientific aspects to be assessed;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nknowledge of device legislation, including the general safety and performance requirements set out in Annex\u00a0I;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge and experience of relevant harmonised standards, CS and guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge and experience of risk management and related device standards and guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge and experience of clinical evaluation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge of the devices which they are assessing;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge and experience of the conformity assessment procedures laid down in Annexes\u00a0IX to\u00a0XI, in particular of the aspects of those procedures for which they are responsible, and adequate authorisation for carrying out those assessments;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe ability to draw up records and reports demonstrating that the relevant conformity assessment activities have been appropriately carried out.\n\n\n\n\n3.2.6.\u00a0\u00a0\u00a0The personnel responsible for carrying out audits of the manufacturer's quality management system (site auditors) shall have all of the following proven qualifications:\n\n\n\n\n\n\n\u2014\n\n\nsuccessful completion of a university or a technical college degree or equivalent qualification in relevant studies, such as medicine, pharmacy, engineering or other relevant sciences;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nfour years' professional experience in the field of healthcare products or related activities, such as in manufacturing, auditing or research, of which two years shall be in the area of quality management;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge of devices legislation as well as related harmonised standards, CS and guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge and experience of risk management and related device standards and guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge of quality management systems and related standards and guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nappropriate knowledge and experience of the conformity assessment procedures laid down in Annexes\u00a0IX to\u00a0XI, in particular of the aspects of those procedures for which they are responsible, and adequate authorisation for carrying out those audits;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntraining in auditing techniques enabling them to challenge quality management systems;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe ability to draw up records and reports demonstrating that the relevant conformity assessment activities have been appropriately carried out.\n\n\n\n\n3.2.7.\u00a0\u00a0\u00a0The personnel with overall responsibility for final reviews and decision-making on certification shall be employed by the notified body itself and shall not be external experts or be subcontracted. Those personnel shall, as a group, have proven knowledge and comprehensive experience of all of the following:\n\n\n\n\n\n\n\u2014\n\n\ndevices legislation and relevant guidance documents;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe device conformity assessments relevant to this Regulation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe types of qualifications, experience and expertise relevant to device conformity assessment;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na broad base of knowledge of device technologies, including sufficient experience of conformity assessment of devices being reviewed for certification, the device industry and the design and manufacture of devices;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe notified body's quality management system, related procedures and the required qualifications for personnel involved;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe ability to draw up records and reports demonstrating that the conformity assessment activities have been appropriately carried out.\n\n\n\n\n3.3.\u00a0\u00a0\u00a0Documentation of qualification, training and authorisation of personnel\n3.3.1.\u00a0\u00a0\u00a0The notified body shall have a procedure in place to fully document the qualification of each member of personnel involved in conformity assessment activities and the satisfaction of the qualification criteria referred to in Section\u00a03.2. Where in exceptional circumstances the fulfilment of the qualification criteria set out in Section\u00a03.2. cannot be fully demonstrated, the notified body shall justify to the authority responsible for notified bodies the authorisation of those members of personnel to carry out specific conformity assessment activities.\n3.3.2.\u00a0\u00a0\u00a0For all of its personnel referred to in Sections 3.2.3 to 3.2.7, the notified body shall establish and maintain up to date:\n\n\n\n\n\n\n\u2014\n\n\na matrix detailing the authorisations and responsibilities of the personnel in respect of conformity assessment activities; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nrecords attesting to the required knowledge and experience for the conformity assessment activity for which they are authorised. The records shall contain a rationale for defining the scope of the responsibilities for each of the assessment personnel and records of the conformity assessment activities carried out by each of them.\n\n\n\n\n3.4.\u00a0\u00a0\u00a0Subcontractors and external experts\n3.4.1.\u00a0\u00a0\u00a0Notified bodies may, without prejudice to Section\u00a03.2, subcontract certain clearly defined component parts of a conformity assessment activity.\nThe subcontracting of the auditing of quality management systems or of product related reviews as a whole shall not be permitted; nevertheless parts of those activities may be conducted by subcontractors and external auditors and experts working on behalf of the notified body. The notified body in question shall retain full responsibility for being able to produce appropriate evidence of the competence of subcontractors and experts to fulfil their specific tasks, for making a decision based on a subcontractor's assessment and for the work conducted by subcontractors and experts on its behalf.\nThe following activities may not be subcontracted by notified bodies:\n\n\n\n\n\n\n\u2014\n\n\nreview of the qualifications and monitoring of the performance of external experts;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nauditing and certification activities where the subcontracting in question is to auditing or certification organisations;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nallocation of work to external experts for specific conformity assessment activities; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nfinal review and decision making functions.\n\n\n\n\n3.4.2.\u00a0\u00a0\u00a0Where a notified body subcontracts certain conformity assessment activities either to an organisation or an individual, it shall have a policy describing the conditions under which subcontracting may take place, and shall ensure that:\n\n\n\n\n\n\n\u2014\n\n\nthe subcontractor meets the relevant requirements of this Annex;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsubcontractors and external experts do not further subcontract work to organisations or personnel; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe natural or legal person that applied for conformity assessment has been informed of the requirements referred to in the first and second indent.\n\n\n\n\nAny subcontracting or consultation of external personnel shall be properly documented, shall not involve any intermediaries and shall be subject to a written agreement covering, among other things, confidentiality and conflicts of interest. The notified body in question shall take full responsibility for the tasks performed by subcontractors.\n3.4.3.\u00a0\u00a0\u00a0Where subcontractors or external experts are used in the context of a conformity assessment, in particular regarding novel, invasive and implantable devices or technologies, the notified body in question shall have internal competence in each product area for which it is designated that is adequate for the purpose of leading the overall conformity assessment, verifying the appropriateness and validity of expert opinions and making decisions on certification.\n3.5.\u00a0\u00a0\u00a0Monitoring of competences, training and exchange of experience\n3.5.1.\u00a0\u00a0\u00a0The notified body shall establish procedures for the initial evaluation and on-going monitoring of the competence, conformity assessment activities and performance of all internal and external personnel, and subcontractors, involved in conformity assessment activities.\n3.5.2.\u00a0\u00a0\u00a0Notified bodies shall review at regular intervals, the competence of their personnel, identify training needs and draw up a training plan to maintain the required level of qualification and knowledge of individual personnel. That review shall at a minimum, verify that personnel:\n\n\n\n\n\n\n\u2014\n\n\nare aware of Union and national law in force on devices, relevant harmonised standards, CS, guidance documents and the results of the coordination activities referred to in Section\u00a01.6; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntake part in the internal exchange of experience and the continuous training and education programme referred to in Section\u00a03.1.2.\n\n\n\n\n4.\u00a0\u00a0\u00a0PROCESS REQUIREMENTS\n4.1.\u00a0\u00a0\u00a0General\nThe notified body shall have in place documented processes and sufficiently detailed procedures for the conduct of each conformity assessment activity for which it is designated, comprising the individual steps from pre-application activities up to decision making and surveillance and taking into account, when necessary, the respective specificities of the devices.\nThe requirements laid down in Sections 4.3, 4.4, 4.7 and 4.8 shall be fulfilled as part of the internal activities of notified bodies and shall not be subcontracted.\n4.2.\u00a0\u00a0\u00a0Notified body quotations and pre-application activities\nThe notified body shall:\n\n\n\n\n\n\n(a)\n\n\npublish a publicly available description of the application procedure by which manufacturers can obtain certification from it. That description shall include which languages are acceptable for submission of documentation and for any related correspondence;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nhave documented procedures relating to, and documented details about, fees charged for specific conformity assessment activities and any other financial conditions relating to notified bodies' assessment activities for devices;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nhave documented procedures in relation to advertising of their conformity assessment services. Those procedures shall ensure that advertising or promotional activities in no way imply or are capable of leading to an inference that their conformity assessment will offer manufacturers earlier market access or be quicker, easier or less stringent than that of other notified bodies;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nhave documented procedures requiring the review of pre-application information, including the preliminary verification that the product is covered by this Regulation and its classification, prior to issuing any quotation to the manufacturer relating to a specific conformity assessment; and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nensure that all contracts relating to the conformity assessment activities covered by this Regulation are concluded directly between the manufacturer and the notified body and not with any other organisation.\n\n\n\n\n4.3.\u00a0\u00a0\u00a0Application review and contract\nThe notified body shall require a formal application signed by a manufacturer or an authorised representative containing all of the information and the manufacturer's declarations required by the relevant conformity assessment as referred to in Annexes\u00a0IX to\u00a0XI.\nThe contract between a notified body and a manufacturer shall take the form of a written agreement signed by both parties. It shall be kept by the notified body. This contract shall have clear terms and conditions and contain obligations that enable the notified body to act as required under this Regulation, including an obligation on the manufacturer to inform the notified body of vigilance reports, the right of the notified body to suspend, restrict or withdraw certificates issued and the duty of the notified body to fulfil its information obligations.\nThe notified body shall have documented procedures to review applications, addressing:\n\n\n\n\n\n\n(a)\n\n\nthe completeness of those applications with respect to the requirements of the relevant conformity assessment procedure, as referred to in the corresponding Annex, under which approval has been sought,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe verification of the qualification of products covered by those applications as devices and their respective classifications,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nwhether the conformity assessment procedures chosen by the applicant are applicable to the device in question under this Regulation,\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe ability of the notified body to assess the application based on its designation, and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe availability of sufficient and appropriate resources.\n\n\n\n\nThe outcome of each review of an application shall be documented. Refusals or withdrawals of applications shall be notified to the electronic system referred to in Article\u00a057 and shall be accessible to other notified bodies.\n4.4.\u00a0\u00a0\u00a0Allocation of resources\nThe notified body shall have documented procedures to ensure that all conformity assessment activities are conducted by appropriately authorised and qualified personnel who are sufficiently experienced in the evaluation of the devices, systems and processes and related documentation that are subject to conformity assessment.\nFor each application, the notified body shall determine the resources needed and identify one individual responsible for ensuring that the assessment of that application is conducted in accordance with the relevant procedures and for ensuring that the appropriate resources including personnel are utilised for each of the tasks of the assessment. The allocation of tasks required to be carried out as part of the conformity assessment and any changes subsequently made to this allocation shall be documented.\n4.5.\u00a0\u00a0\u00a0Conformity assessment activities\n4.5.1.\u00a0\u00a0\u00a0General\nThe notified body and its personnel shall carry out the conformity assessment activities with the highest degree of professional integrity and the requisite technical and scientific competence in the specific fields.\nThe notified body shall have expertise, facilities and documented procedures that are sufficient to effectively conduct the conformity assessment activities for which the notified body in question is designated, taking account of the relevant requirements set out in Annexes\u00a0IX to XI, and in particular all of the following requirements:\n\n\n\n\n\n\n\u2014\n\n\nappropriately plan the conduct of each individual project,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure that the composition of the assessment teams is such that there is sufficient experience in relation to the technology concerned, and that there is continuous objectivity and independence, and to provide for rotation of the members of the assessment team at appropriate intervals,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nspecify the rationale for fixing time limits for completion of conformity assessment activities,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nassess the manufacturer's technical documentation and the solutions adopted to meet the requirements laid down in Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreview the manufacturer's procedures and documentation relating to the evaluation of pre-clinical aspects,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreview the manufacturer's procedures and documentation relating to clinical evaluation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\naddress the interface between the manufacturer's risk management process and its appraisal and analysis of the pre-clinical and clinical evaluation and to evaluate their relevance for the demonstration of conformity with the relevant requirements in Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncarry out the specific procedures referred to in Sections 5.2 to 5.4 of Annex\u00a0IX,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nin the case of class IIa or class IIb devices, assess the technical documentation of devices selected on a representative basis,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nplan and periodically carry out appropriate surveillance audits and assessments, carry out or request certain tests to verify the proper functioning of the quality management system and to perform unannounced on site audits,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nrelating to the sampling of devices, verify that the manufactured device is in conformity with the technical documentation; such requirements shall define the relevant sampling criteria and testing procedure prior to sampling,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nevaluate and verify a manufacturer's compliance with relevant Annexes.\n\n\n\n\nThe notified body shall, where relevant, take into consideration available CS, guidance and best practice documents and harmonised standards, even if the manufacturer does not claim to be in compliance.\n4.5.2.\u00a0\u00a0\u00a0Quality management system auditing\n\n\n\n\n\n\n(a)\n\n\nAs part of the assessment of the quality management system, a notified body shall prior to an audit and in accordance with its documented procedures:\n\n\n\n\n\n\n\u2014\n\n\nassess the documentation submitted in accordance with the relevant conformity assessment Annex, and draw up an audit programme which clearly identifies the number and sequence of activities required to demonstrate complete coverage of a manufacturer's quality management system and to determine whether it meets the requirements of this Regulation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nidentify links between, and allocation of responsibilities among, the various manufacturing sites, and identify relevant suppliers and/or subcontractors of the manufacturer, and consider the need to specifically audit any of those suppliers or subcontractors or both,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclearly define, for each audit identified in the audit programme, the objectives, criteria and scope of the audit, and draw up an audit plan that adequately addresses and takes account of the specific requirements for the devices, technologies and processes involved,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndraw up and keep up to date, for class IIa and class IIb devices, a sampling plan for the assessment of technical documentation as referred to in Annexes\u00a0II and III covering the range of such devices covered by the manufacturer's application. That plan shall ensure that all devices covered by the certificate are sampled over the period of validity of the certificate, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nselect and assign appropriately qualified and authorised personnel for conducting the individual audits. The respective roles, responsibilities and authorities of the team members shall be clearly defined and documented.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nBased on the audit programme it has drawn up, the notified body shall, in accordance with its documented procedures:\n\n\n\n\n\n\n\u2014\n\n\naudit the manufacturer's quality management system, in order to verify that the quality management system ensures that the devices covered conform to the relevant provisions of this Regulation which apply to devices at every stage, from design through final quality control to ongoing surveillance, and shall determine whether the requirements of this Regulation are met,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbased on relevant technical documentation and in order to determine whether the manufacturer meets the requirements referred to in the relevant conformity assessment Annex, review and audit the manufacturer's processes and subsystems, in particular for:\n\n\n\n\n\n\n\u2014\n\n\ndesign and development,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nproduction and process controls,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nproduct documentation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npurchasing controls including verification of purchased devices,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncorrective and preventive actions, including for post-market surveillance, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nPMCF,\n\n\n\n\nand review and audit requirements and provisions adopted by the manufacturer, including those in relation to fulfilling the general safety and performance requirements set out in Annex\u00a0I.\nThe documentation shall be sampled in such a manner as to reflect the risks associated with the intended use of the device, the complexity of the manufacturing technologies, the range and classes of devices produced and any available post-market surveillance information,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif not already covered by the audit programme, audit the control of processes on the premises of the manufacturer's suppliers, when the conformity of finished devices is significantly influenced by the activity of suppliers and, in particular when the manufacturer cannot demonstrate sufficient control over its suppliers,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nconduct assessments of the technical documentation based on its sampling plan and taking account of Sections 4.5.4. and\u00a04.5.5. for pre-clinical and clinical evaluations, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe notified body shall ensure that audit findings are appropriately and consistently classified in accordance with the requirements of this Regulation and with relevant standards, or with best practice documents developed or adopted by the MDCG.\n\n\n\n\n\n\n\n\n4.5.3.\u00a0\u00a0\u00a0Product verification\nAssessment of the technical documentation\nFor assessment of the technical documentation conducted in accordance with Chapter\u00a0II of Annex\u00a0IX, notified bodies shall have sufficient expertise, facilities and documented procedures for:\n\n\n\n\n\n\n\u2014\n\n\nthe allocation of appropriately qualified and authorised personnel for the examination of individual aspects such as use of the device, biocompatibility, clinical evaluation, risk management, and sterilisation, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe assessment of conformity of the design with this Regulation, and for taking account of Sections 4.5.4. to\u00a04.5.6. That assessment shall include examination of the implementation by manufacturers of incoming, in-process and final checks and the results thereof. If further tests or other evidence is required for the assessment of conformity with the requirements of this Regulation, the notified body in question shall carry out adequate physical or laboratory tests in relation to the device or request the manufacturer to carry out such tests.\n\n\n\n\nType-examinations\nThe notified body shall have documented procedures, sufficient expertise and facilities for the type-examination of devices in accordance with Annex\u00a0X including the capacity to:\n\n\n\n\n\n\n\u2014\n\n\nexamine and assess the technical documentation taking account of Sections 4.5.4. to\u00a04.5.6., and verify that the type has been manufactured in conformity with that documentation;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nestablish a test plan identifying all relevant and critical parameters which need to be tested by the notified body or under its responsibility;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndocument its rationale for the selection of those parameters;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncarry out the appropriate examinations and tests in order to verify that the solutions adopted by the manufacturer meet the general safety and performance requirements set out in Annex\u00a0I. Such examinations and tests shall include all tests necessary to verify that the manufacturer has in fact applied the relevant standards it has opted to use;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nagree with the applicant as to where the necessary tests will be performed if they are not to be carried out directly by the notified body; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nassume full responsibility for test results. Test reports submitted by the manufacturer shall only be taken into account if they have been issued by conformity assessment bodies which are competent and independent of the manufacturer.\n\n\n\n\nVerification by examination and testing of every product\nThe notified body shall:\n\n\n\n\n\n\n(a)\n\n\nhave documented procedures, sufficient expertise and facilities for the verification by examination and testing of every product in accordance with Part B of Annex\u00a0XI;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nestablish a test plan identifying all relevant and critical parameters which need to be tested by the notified body or under its responsibility in order to:\n\n\n\n\n\n\n\u2014\n\n\nverify, for class IIb devices, the conformity of the device with the type described in the EU type-examination certificate and with the requirements of this Regulation which apply to those devices,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nconfirm, for class IIa devices, the conformity with the technical documentation referred to in Annexes\u00a0II and III and with the requirements of this Regulation which apply to those devices;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\ndocument its rationale for the selection of the parameters referred to in point\u00a0(b);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nhave documented procedures to carry out the appropriate assessments and tests in order to verify the conformity of the device with the requirements of this Regulation by examining and testing every product as specified in Section\u00a015 of Annex\u00a0XI;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nhave documented procedures providing for the reaching of an agreement with the applicant concerning when and where necessary tests that are not to be carried out by the notified body itself are to be performed; and\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nassume full responsibility for test results in accordance with documented procedures; test reports submitted by the manufacturer shall only be taken into account if they have been issued by conformity assessment bodies which are competent and independent of the manufacturer.\n\n\n\n\n4.5.4.\u00a0\u00a0\u00a0Pre-clinical evaluation assessment\nThe notified body shall have documented procedures in place for the review of the manufacturer's procedures and documentation relating to the evaluation of pre-clinical aspects. The notified body shall examine, validate and verify that the manufacturer's procedures and documentation adequately address:\n\n\n\n\n\n\n(a)\n\n\nthe planning, conduct, assessment, reporting and, where appropriate, updating of the pre-clinical evaluation, in particular of\n\n\n\n\n\n\n\u2014\n\n\nthe scientific pre-clinical literature search, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe pre-clinical testing, for example laboratory testing, simulated use testing, computer modelling, the use of animal models,\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe nature and duration of body contact and the specific associated biological risks,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe interface with the risk management process, and\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe appraisal and analysis of the available pre-clinical data and its relevance with regard to demonstrating conformity with the relevant requirements in Annex\u00a0I.\n\n\n\n\nThe notified body's assessment of pre-clinical evaluation procedures and documentation shall address the results of literature searches and all validation, verification and testing performed and conclusions drawn, and shall typically include considering the use of alternative materials and substances and take account of the packaging, stability, including shelf life, of the finished device. Where no new testing has been undertaken by a manufacturer or where there are deviations from procedures, the notified body in question shall critically examine the justification presented by the manufacturer.\n4.5.5.\u00a0\u00a0\u00a0Clinical evaluation assessment\nThe notified body shall have documented procedures in place relating to the assessment of a manufacturer's procedures and documentation relating to clinical evaluation both for initial conformity assessment and on an ongoing basis. The notified body shall examine, validate and verify that manufacturers' procedures and documentation adequately address:\n\n\n\n\n\n\n\u2014\n\n\nthe planning, conduct, assessment, reporting and updating of the clinical evaluation as referred to in Annex\u00a0XIV,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npost-market surveillance and PMCF,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe interface with the risk management process,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe appraisal and analysis of the available data and its relevance with regard to demonstrating conformity with the relevant requirements in Annex\u00a0I, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe conclusions drawn with regard to the clinical evidence and drawing up of the clinical evaluation report.\n\n\n\n\nThese procedures referred to in the first paragraph\u00a0shall take into consideration available CS, guidance and best practice documents.\nThe notified body's assessment of clinical evaluations as referred to in Annex\u00a0XIV shall cover:\n\n\n\n\n\n\n\u2014\n\n\nthe intended use specified by the manufacturer and claims for the device defined by it,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe planning of the clinical evaluation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe methodology for the literature search,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nrelevant documentation from the literature search,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe clinical investigation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nvalidity of equivalence claimed in relation to other devices, the demonstration of equivalence, the suitability and conclusions data from equivalent and similar devices,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\npost-market surveillance and PMCF,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe clinical evaluation report, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\njustifications in relation to non-performance of clinical investigations or PMCF.\n\n\n\n\nIn relation to clinical data from clinical investigations included within the clinical evaluation, the notified body in question shall ensure that the conclusions drawn by the manufacturer are valid in the light of the approved clinical investigation plan.\nThe notified body shall ensure that the clinical evaluation adequately addresses the relevant safety and performance requirements provided for in Annex\u00a0I, that it is appropriately aligned with the risk management requirements, that it is conducted in accordance with Annex\u00a0XIV and that it is appropriately reflected in the information provided relating to the device.\n4.5.6.\u00a0\u00a0\u00a0Specific Procedures\nThe notified body shall have documented procedures, sufficient expertise and facilities for the procedures referred to in Sections 5 and 6 of Annex\u00a0IX, Section\u00a06 of Annex\u00a0X and Section\u00a016 of Annex\u00a0XI, for which they are designated.\nIn the case of devices manufactured utilising tissues or cells of animal origin or their derivatives, such as from TSE susceptible species, as referred to in Regulation\u00a0(EU)\u00a0No\u00a0722/2012, the notified body shall have documented procedures in place that fulfil the requirements laid down in that Regulation, including for the preparation of a summary evaluation report for the relevant competent authority.\n4.6.\u00a0\u00a0\u00a0Reporting\nThe notified body shall:\n\n\n\n\n\n\n\u2014\n\n\nensure that all steps of the conformity assessment are documented so that the conclusions of the assessment are clear and demonstrate compliance with the requirements of this Regulation and can represent objective evidence of such compliance to persons that are not themselves involved in the assessment, for example personnel in designating authorities,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure that records that are sufficient to provide a discernible audit trail are available for quality management system audits,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclearly document the conclusions of its assessment of clinical evaluation in a clinical evaluation assessment report, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nfor each specific project, provide a detailed report which shall be based on a standard format containing a minimum set of elements determined by the MDCG.\n\n\n\n\nThe report of the notified body shall:\n\n\n\n\n\n\n\u2014\n\n\nclearly document the outcome of its assessment and draw clear conclusions from the verification of the manufacturer's conformity with the requirements of this Regulation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmake a recommendation for a final review and for a final decision to be taken by the notified body; this recommendation shall be signed off by the member of personnel responsible in the notified body, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nbe provided to the manufacturer in question.\n\n\n\n\n4.7.\u00a0\u00a0\u00a0Final review\nThe notified body shall prior to making a final decision:\n\n\n\n\n\n\n\u2014\n\n\nensure that the personnel assigned for the final review and decision-making on specific projects are appropriately authorised and are different from the personnel who have conducted the assessments,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nverify that the report or reports and supporting documentation needed for decision making, including concerning resolution of non-conformities noted during assessment, are complete and sufficient with respect to the scope of the application, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nverify whether there are any unresolved non-conformities preventing issuance of a certificate.\n\n\n\n\n4.8.\u00a0\u00a0\u00a0Decisions and Certifications\nThe notified body shall have documented procedures for decision-making including as regards the allocation of responsibilities for the issuance, suspension, restriction and withdrawal of certificates. Those procedures shall include the notification requirements laid down in Chapter V of this Regulation. The procedures shall allow the notified body in question to:\n\n\n\n\n\n\n\u2014\n\n\ndecide, based on the assessment documentation and additional information available, whether the requirements of this Regulation are fulfilled,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndecide, based on the results of its assessment of the clinical evaluation and risk management, whether the post-market surveillance plan, including the PMCF plan, is adequate,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndecide on specific milestones for further review by the notified body of the up to date clinical evaluation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndecide whether specific conditions or provisions need to be defined for the certification,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndecide, based on the novelty, risk classification, clinical evaluation and conclusions from the risk analysis of the device, on a period of certification not exceeding five\u00a0years,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclearly document decision making and approval steps including approval by signature of the members of personnel responsible,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclearly document responsibilities and mechanisms for communication of decisions, in particular, where the final signatory of a certificate differs from the decision maker or decision makers or does not fulfil the requirements laid down in Section\u00a03.2.7,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nissue a certificate or certificates in accordance with the minimum requirements laid down in Annex\u00a0XII for a period of validity not exceeding five years and shall indicate whether there are specific conditions or limitations associated with the certification,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nissue a certificate or certificates for the applicant alone and shall not issue certificates covering multiple entities, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure that the manufacturer is notified of the outcome of the assessment and the resultant decision and that they are entered into the electronic system referred to in Article\u00a057.\n\n\n\n\n4.9.\u00a0\u00a0\u00a0Changes and modifications\nThe notified body shall have documented procedures and contractual arrangements with manufacturers in place relating to the manufacturers' information obligations and the assessment of changes to:\n\n\n\n\n\n\n\u2014\n\n\nthe approved quality management system or systems or to the product-range covered,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe approved design of a device,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe intended use of or claims made for the device,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe approved type of a device, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nany substance incorporated in or utilised for the manufacturing of a device and being subject to the specific procedures in accordance with Section\u00a04.5.6.\n\n\n\n\nThe procedures and contractual arrangements referred to in the first paragraph\u00a0shall include measures for checking the significance of the changes referred to in the first paragraph.\nIn accordance with its documented procedures, the notified body in question shall:\n\n\n\n\n\n\n\u2014\n\n\nensure that manufacturers submit for prior approval plans for changes as referred to in the first paragraph\u00a0and relevant information relating to such changes,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nassess the changes proposed and verify whether, after these changes, the quality management system, or the design of a device or type of a device, still meets the requirements of this Regulation, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nnotify the manufacturer of its decision and provide a report or as applicable a supplementary report, which shall contain the justified conclusions of its assessment.\n\n\n\n\n4.10.\u00a0\u00a0\u00a0Surveillance activities and post-certification monitoring\nThe notified body shall have documented procedures:\n\n\n\n\n\n\n\u2014\n\n\ndefining how and when surveillance activities of manufacturers are to be conducted. Those procedures shall include arrangements for unannounced on-site audits of manufacturers and, where applicable, subcontractors and suppliers carrying out product tests and the monitoring of compliance with any conditions binding manufacturers and associated with certification decisions, such as updates to clinical data at defined intervals,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nfor screening relevant sources of scientific and clinical data and post-market information relating to the scope of their designation. Such information shall be taken into account in the planning and conduct of surveillance activities, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nto review vigilance data to which they have access under Article\u00a092(2) in order to estimate its impact, if any, on the validity of existing certificates. The results of the evaluation and any decisions taken shall be thoroughly documented.\n\n\n\n\nThe notified body in question shall, upon receipt of information about vigilance cases from a manufacturer or competent authorities, decide which of the following options to apply:\n\n\n\n\n\n\n\u2014\n\n\nnot to take action on the basis that the vigilance case is clearly not related to the certification granted,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nobserve the manufacturer's and competent authority's activities and the results of the manufacturer's investigation so as to determine whether the certification granted is at risk or whether adequate corrective action has been taken,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nperform extraordinary surveillance measures, such as document reviews, short-notice or unannounced audits and product testing, where it is likely that the certification granted is at risk,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nincrease the frequency of surveillance audits,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nreview specific products or processes on the occasion of the next audit of the manufacturer, or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ntake any other relevant measure.\n\n\n\n\nIn relation to surveillance audits of manufacturers, the notified body shall have documented procedures to:\n\n\n\n\n\n\n\u2014\n\n\nconduct surveillance audits of the manufacturer on at least an annual basis which shall be planned and conducted in line with the relevant requirements in Section\u00a04.5,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure adequate assessment of the manufacturer's documentation on, and application of the provisions on, vigilance, the post-market surveillance, and PMCF,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsample and test devices and technical documentation, during audits, according to pre-defined sampling criteria and testing procedures to ensure that the manufacturer continuously applies the approved quality management system,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure that the manufacturer complies with the documentation and information obligations laid down in the relevant Annexes\u00a0and that its procedures take into account best practices in the implementation of quality management systems,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure that the manufacturer does not use quality management system or device approvals in a misleading manner,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ngather sufficient information to determine if the quality management system continues to comply with the requirements of this Regulation,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nask the manufacturer, if non-conformities are detected, for corrections, corrective actions and, where applicable, preventive actions, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwhere necessary, impose specific restrictions on the relevant certificate, or suspend or withdraw it.\n\n\n\n\nThe notified body shall, if listed as part of the conditions for certification:\n\n\n\n\n\n\n\u2014\n\n\nconduct an in-depth review of the clinical evaluation as most recently updated by the manufacturer based on the manufacturer's post-market surveillance, on its PMCF and on clinical literature relevant to the condition being treated with the device or on clinical literature relevant to similar devices,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclearly document the outcome of the in-depth review and address any specific concerns to the manufacturer or impose any specific conditions on it, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nensure that the clinical evaluation as most recently updated, is appropriately reflected in the instructions for use and, where applicable, the summary of safety and performance.\n\n\n\n\n4.11.\u00a0\u00a0\u00a0Re-certification\nThe notified body shall have documented procedures in place relating to the re-certification reviews and the renewal of certificates. Re-certification of approved quality management systems or EU technical documentation assessment certificates or EU type-examination certificates shall occur at least every five years.\nThe notified body shall have documented procedures relating to renewals of EU technical documentation assessment certificates and EU type-examination certificates and those procedures shall require the manufacturer in question to submit a summary of changes and scientific findings for the device, including:\n\n\n\n\n\n\n(a)\n\n\nall changes to the originally approved device, including changes not yet notified,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nexperience gained from post-market surveillance,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nexperience from risk management,\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nexperience from updating the proof of compliance with the general safety and performance requirements set out in Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nexperience from reviews of the clinical evaluation, including the results of any clinical investigations and PMCF,\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nchanges to the requirements, to components of the device or to the scientific or regulatory environment,\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nchanges to applied or new harmonised standards, CS or equivalent documents, and\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nchanges in medical, scientific and technical knowledge, such as:\n\n\n\n\n\n\n\u2014\n\n\nnew treatments,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nchanges in test methods,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nnew scientific findings on materials and components, including findings on their biocompatibility,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nexperience from studies on comparable devices,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndata from registers and registries,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nexperience from clinical investigations with comparable devices.\n\n\n\n\n\n\n\n\nThe notified body shall have documented procedures to assess the information referred to in the second paragraph\u00a0and shall pay particular attention to clinical data from post-market surveillance and PMCF activities undertaken since the previous certification or re-certification, including appropriate updates to manufacturers' clinical evaluation reports.\nFor the decision on re-certification, the notified body in question shall use the same methods and principles as for the initial certification decision. If necessary, separate forms shall be established for re-certification taking into account the steps taken for certification such as application and application review.\n\n\n\n\n\nANNEX\u00a0VIII\n\nCLASSIFICATION RULES\n\nCHAPTER I\n\nDEFINITIONS SPECIFIC TO CLASSIFICATION RULES\n\n1.\u00a0\u00a0\u00a0DURATION OF USE\n1.1.\u00a0\u00a0\u00a0\n                     \u2018Transient\u2019 means normally intended for continuous use for less than 60 minutes.\n1.2.\u00a0\u00a0\u00a0\n                     \u2018Short term\u2019 means normally intended for continuous use for between 60 minutes and 30\u00a0days.\n1.3.\u00a0\u00a0\u00a0\n                     \u2018Long term\u2019 means normally intended for continuous use for more than 30 days.\n2.\u00a0\u00a0\u00a0INVASIVE AND ACTIVE DEVICES\n2.1.\u00a0\u00a0\u00a0\n                     \u2018Body orifice\u2019 means any natural opening in the body, as well as the external surface of the eyeball, or any permanent artificial opening, such as a stoma.\n2.2.\u00a0\u00a0\u00a0\n                     \u2018Surgically invasive device\u2019 means:\n\n\n\n\n\n\n(a)\n\n\nan invasive device which penetrates inside the body through the surface of the body, including through mucous membranes of body orifices with the aid or in the context of a surgical operation; and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\na device which produces penetration other than through a body orifice.\n\n\n\n\n2.3.\u00a0\u00a0\u00a0\n                     \u2018Reusable surgical instrument\u2019 means an instrument intended for surgical use in cutting, drilling, sawing, scratching, scraping, clamping, retracting, clipping or similar procedures, without a connection to an active device and which is intended by the manufacturer to be reused after appropriate procedures such as cleaning, disinfection and sterilisation have been carried out.\n2.4.\u00a0\u00a0\u00a0\n                     \u2018Active therapeutic device\u2019 means any active device used, whether alone or in combination with other devices, to support, modify, replace or restore biological functions or structures with a view to treatment or alleviation of an illness, injury or disability.\n2.5.\u00a0\u00a0\u00a0\n                     \u2018Active device intended for diagnosis and monitoring\u2019 means any active device used, whether alone or in combination with other devices, to supply information for detecting, diagnosing, monitoring or treating physiological conditions, states of health, illnesses or congenital deformities.\n2.6.\u00a0\u00a0\u00a0\n                     \u2018Central circulatory system\u2019 means the following blood vessels: arteriae pulmonales, aorta ascendens, arcus aortae, aorta descendens to the bifurcatio aortae, arteriae coronariae, arteria carotis communis, arteria carotis externa, arteria carotis interna, arteriae cerebrales, truncus brachiocephalicus, venae cordis, venae pulmonales, vena cava superior and vena cava inferior.\n2.7.\u00a0\u00a0\u00a0\n                     \u2018Central nervous system\u2019 means the brain, meninges and spinal cord.\n2.8.\u00a0\u00a0\u00a0\n                     \u2018Injured skin or mucous membrane\u2019 means an area of skin or a mucous membrane presenting a pathological change or change following disease or a wound.\nCHAPTER II\n\nIMPLEMENTING RULES\n\n3.1.\u00a0\u00a0\u00a0Application of the classification rules shall be governed by the intended purpose of the devices.\n3.2.\u00a0\u00a0\u00a0If the device in question is intended to be used in combination with another device, the classification rules shall apply separately to each of the devices. Accessories for a medical device and for a product listed in Annex\u00a0XVI shall be classified in their own right separately from the device with which they are used.\n3.3.\u00a0\u00a0\u00a0Software, which drives a device or influences the use of a device, shall fall within the same class as the device.\nIf the software is independent of any other device, it shall be classified in its own right.\n3.4.\u00a0\u00a0\u00a0If the device is not intended to be used solely or principally in a specific part of the body, it shall be considered and classified on the basis of the most critical specified use.\n3.5.\u00a0\u00a0\u00a0If several rules, or if, within the same rule, several sub-rules, apply to the same device based on the device's intended purpose, the strictest rule and sub-rule resulting in the higher classification shall apply.\n3.6.\u00a0\u00a0\u00a0In calculating the duration referred to in Section\u00a01, continuous use shall mean:\n\n\n\n\n\n\n(a)\n\n\nthe entire duration of use of the same device without regard to temporary interruption of use during a procedure or temporary removal for purposes such as cleaning or disinfection of the device. Whether the interruption of use or the removal is temporary shall be established in relation to the duration of the use prior to and after the period when the use is interrupted or the device removed; and\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe accumulated use of a device that is intended by the manufacturer to be replaced immediately with another of the same type.\n\n\n\n\n3.7.\u00a0\u00a0\u00a0A device is considered to allow direct diagnosis when it provides the diagnosis of the disease or condition in question by itself or when it provides decisive information for the diagnosis.\nCHAPTER III\n\nCLASSIFICATION RULES\n\n4.\u00a0\u00a0\u00a0NON-INVASIVE DEVICES\n4.1.\u00a0\u00a0\u00a0Rule 1\nAll non-invasive devices are classified as class I, unless one of the rules set out hereinafter applies.\n4.2.\u00a0\u00a0\u00a0Rule 2\nAll non-invasive devices intended for channelling or storing blood, body liquids, cells or tissues, liquids or gases for the purpose of eventual infusion, administration or introduction into the body are classified as class IIa:\n\n\n\n\n\n\n\u2014\n\n\nif they may be connected to a class\u00a0IIa, class\u00a0IIb or class\u00a0III active device; or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif they are intended for use for channelling or storing blood or other body liquids or for storing organs, parts of organs or body cells and tissues, except for blood bags; blood bags are classified as class\u00a0IIb.\n\n\n\n\nIn all other cases, such devices are classified as class\u00a0I.\n4.3.\u00a0\u00a0\u00a0Rule 3\nAll non-invasive devices intended for modifying the biological or chemical composition of human tissues or cells, blood, other body liquids or other liquids intended for implantation or administration into the body are classified as class IIb, unless the treatment for which the device is used consists of filtration, centrifugation or exchanges of gas, heat, in which case they are classified as class\u00a0IIa.\nAll non-invasive devices consisting of a substance or a mixture of substances intended to be used in vitro in direct contact with human cells, tissues or organs taken from the human body or used in vitro with human embryos before their implantation or administration into the body are classified as class\u00a0III.\n4.4.\u00a0\u00a0\u00a0Rule 4\nAll non-invasive devices which come into contact with injured skin or mucous membrane are classified as:\n\n\n\n\n\n\n\u2014\n\n\nclass I if they are intended to be used as a mechanical barrier, for compression or for absorption of exudates;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIb if they are intended to be used principally for injuries to skin which have breached the dermis or mucous membrane and can only heal by secondary intent;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIa if they are principally intended to manage the micro-environment of injured skin or mucous membrane; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIa in all other cases.\n\n\n\n\nThis rule applies also to the invasive devices that come into contact with injured mucous membrane.\n5.\u00a0\u00a0\u00a0INVASIVE DEVICES\n5.1.\u00a0\u00a0\u00a0Rule 5\nAll invasive devices with respect to body orifices, other than surgically invasive devices, which are not intended for connection to an active device or which are intended for connection to a class I active device are classified as:\n\n\n\n\n\n\n\u2014\n\n\nclass I if they are intended for transient use;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass IIa if they are intended for short-term use, except if they are used in the oral cavity as far as the pharynx, in an ear canal up to the ear drum or in the nasal cavity, in which case they are classified as class I; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIb if they are intended for long-term use, except if they are used in the oral cavity as far as the pharynx, in an ear canal up to the ear drum or in the nasal cavity and are not liable to be absorbed by the mucous membrane, in which case they are classified as class\u00a0IIa.\n\n\n\n\nAll invasive devices with respect to body orifices, other than surgically invasive devices, intended for connection to a class\u00a0IIa, class\u00a0IIb or class\u00a0III active device, are classified as class\u00a0IIa.\n5.2.\u00a0\u00a0\u00a0Rule 6\nAll surgically invasive devices intended for transient use are classified as class\u00a0IIa unless they:\n\n\n\n\n\n\n\u2014\n\n\nare intended specifically to control, diagnose, monitor or correct a defect of the heart or of the central circulatory system through direct contact with those parts of the body, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare reusable surgical instruments, in which case they are classified as class\u00a0I;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended specifically for use in direct contact with the heart or central circulatory system or the central nervous system, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to supply energy in the form of ionising radiation in which case they are classified as class\u00a0IIb;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nhave a biological effect or are wholly or mainly absorbed in which case they are classified as class\u00a0IIb; or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to administer medicinal products by means of a delivery system, if such administration of a medicinal product is done in a manner that is potentially hazardous taking account of the mode of application, in which case they are classified as class\u00a0IIb.\n\n\n\n\n5.3.\u00a0\u00a0\u00a0Rule 7\nAll surgically invasive devices intended for short-term use are classified as class IIa unless they:\n\n\n\n\n\n\n\u2014\n\n\nare intended specifically to control, diagnose, monitor or correct a defect of the heart or of the central circulatory system through direct contact with those parts of the body, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended specifically for use in direct contact with the heart or central circulatory system or the central nervous system, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to supply energy in the form of ionizing radiation in which case they are classified as class\u00a0IIb;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nhave a biological effect or are wholly or mainly absorbed in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to undergo chemical change in the body in which case they are classified as class\u00a0IIb, except if the devices are placed in the teeth; or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to administer medicines, in which case they are classified as class\u00a0IIb.\n\n\n\n\n5.4.\u00a0\u00a0\u00a0Rule 8\nAll implantable devices and long-term surgically invasive devices are classified as class\u00a0IIb unless they:\n\n\n\n\n\n\n\u2014\n\n\nare intended to be placed in the teeth, in which case they are classified as class\u00a0IIa;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to be used in direct contact with the heart, the central circulatory system or the central nervous system, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nhave a biological effect or are wholly or mainly absorbed, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to undergo chemical change in the body in which case they are classified as class\u00a0III, except if the devices are placed in the teeth;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare intended to administer medicinal products, in which case they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare active implantable devices or their accessories, in which cases they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare breast implants or surgical meshes, in which cases they are classified as class\u00a0III;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare total or partial joint replacements, in which case they are classified as class\u00a0III, with the exception of ancillary components such as screws, wedges, plates and instruments; or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nare spinal disc replacement implants or are implantable devices that come into contact with the spinal column, in which case they are classified as class\u00a0III with the exception of components such as screws, wedges, plates and instruments.\n\n\n\n\n6.\u00a0\u00a0\u00a0ACTIVE DEVICES\n6.1.\u00a0\u00a0\u00a0Rule 9\nAll active therapeutic devices intended to administer or exchange energy are classified as class IIa unless their characteristics are such that they may administer energy to or exchange energy with the human body in a potentially hazardous way, taking account of the nature, the density and site of application of the energy, in which case they are classified as class\u00a0IIb.\nAll active devices intended to control or monitor the performance of active therapeutic class IIb devices, or intended directly to influence the performance of such devices are classified as class\u00a0IIb.\nAll active devices intended to emit ionizing radiation for therapeutic purposes, including devices which control or monitor such devices, or which directly influence their performance, are classified as class\u00a0IIb.\nAll active devices that are intended for controlling, monitoring or directly influencing the performance of active implantable devices are classified as class\u00a0III.\n6.2.\u00a0\u00a0\u00a0Rule 10\nActive devices intended for diagnosis and monitoring are classified as class\u00a0IIa:\n\n\n\n\n\n\n\u2014\n\n\nif they are intended to supply energy which will be absorbed by the human body, except for devices intended to illuminate the patient's body, in the visible spectrum, in which case they are classified as class I;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif they are intended to image in vivo distribution of radiopharmaceuticals; or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif they are intended to allow direct diagnosis or monitoring of vital physiological processes, unless they are specifically intended for monitoring of vital physiological parameters and the nature of variations of those parameters is such that it could result in immediate danger to the patient, for instance variations in cardiac performance, respiration, activity of the central nervous system, or they are intended for diagnosis in clinical situations where the patient is in immediate danger, in which cases they are classified as class\u00a0IIb.\n\n\n\n\nActive devices intended to emit ionizing radiation and intended for diagnostic or therapeutic radiology, including interventional radiology devices and devices which control or monitor such devices, or which directly influence their performance, are classified as class\u00a0IIb.\n6.3.\u00a0\u00a0\u00a0Rule 11\nSoftware intended to provide information which is used to take decisions with diagnosis or therapeutic purposes is classified as class IIa, except if such decisions have an impact that may cause:\n\n\n\n\n\n\n\u2014\n\n\ndeath or an irreversible deterioration of a person's state of health, in which case it is in class\u00a0III; or\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na serious deterioration of a person's state of health or a surgical intervention, in which case it is classified as class\u00a0IIb.\n\n\n\n\nSoftware intended to monitor physiological processes is classified as class\u00a0IIa, except if it is intended for monitoring of vital physiological parameters, where the nature of variations of those parameters is such that it could result in immediate danger to the patient, in which case it is classified as class\u00a0IIb.\nAll other software is classified as class\u00a0I.\n6.4.\u00a0\u00a0\u00a0Rule 12\nAll active devices intended to administer and/or remove medicinal products, body liquids or other substances to or from the body are classified as class\u00a0IIa, unless this is done in a manner that is potentially hazardous, taking account of the nature of the substances involved, of the part of the body concerned and of the mode of application in which case they are classified as class\u00a0IIb.\n6.5.\u00a0\u00a0\u00a0Rule 13\nAll other active devices are classified as class\u00a0I.\n7.\u00a0\u00a0\u00a0SPECIAL RULES\n7.1.\u00a0\u00a0\u00a0Rule 14\nAll devices incorporating, as an integral part, a substance which, if used separately, can be considered to be a medicinal product, as defined in point\u00a02 of Article\u00a01 of Directive\u00a02001/83/EC, including a medicinal product derived from human blood or human plasma, as defined in point\u00a010 of Article\u00a01 of that Directive, and that has an action ancillary to that of the devices, are classified as class\u00a0III.\n7.2.\u00a0\u00a0\u00a0Rule 15\nAll devices used for contraception or prevention of the transmission of sexually transmitted diseases are classified as class\u00a0IIb, unless they are implantable or long term invasive devices, in which case they are classified as class\u00a0III.\n7.3.\u00a0\u00a0\u00a0Rule 16\nAll devices intended specifically to be used for disinfecting, cleaning, rinsing or, where appropriate, hydrating contact lenses are classified as class\u00a0IIb.\nAll devices intended specifically to be used for disinfecting or sterilising medical devices are classified as class IIa, unless they are disinfecting solutions or washer-disinfectors intended specifically to be used for disinfecting invasive devices, as the end point of processing, in which case they are classified as class\u00a0IIb.\nThis rule does not apply to devices that are intended to clean devices other than contact lenses by means of physical action only.\n7.4.\u00a0\u00a0\u00a0Rule 17\nDevices specifically intended for recording of diagnostic images generated by X-ray radiation are classified as class\u00a0IIa.\n7.5.\u00a0\u00a0\u00a0Rule 18\nAll devices manufactured utilising tissues or cells of human or animal origin, or their derivatives, which are non-viable or rendered non-viable, are classified as class\u00a0III, unless such devices are manufactured utilising tissues or cells of animal origin, or their derivatives, which are non-viable or rendered non-viable and are devices intended to come into contact with intact skin only.\n7.6.\u00a0\u00a0\u00a0Rule 19\nAll devices incorporating or consisting of nanomaterial are classified as:\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0III if they present a high or medium potential for internal exposure;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIb if they present a low potential for internal exposure; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIa if they present a negligible potential for internal exposure.\n\n\n\n\n7.7.\u00a0\u00a0\u00a0Rule 20\nAll invasive devices with respect to body orifices, other than surgically invasive devices, which are intended to administer medicinal products by inhalation are classified as class\u00a0IIa, unless their mode of action has an essential impact on the efficacy and safety of the administered medicinal product or they are intended to treat life-threatening conditions, in which case they are classified as class\u00a0IIb.\n7.8.\u00a0\u00a0\u00a0Rule 21\nDevices that are composed of substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed by or locally dispersed in the human body are classified as:\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0III if they, or their products of metabolism, are systemically absorbed by the human body in order to achieve the intended purpose;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0III if they achieve their intended purpose in the stomach or lower gastrointestinal tract and they, or their products of metabolism, are systemically absorbed by the human body;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIa if they are applied to the skin or if they are applied in the nasal or oral cavity as far as the pharynx, and achieve their intended purpose on those cavities; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nclass\u00a0IIb in all other cases.\n\n\n\n\n7.9.\u00a0\u00a0\u00a0Rule 22\nActive therapeutic devices with an integrated or incorporated diagnostic function which significantly determines the patient management by the device, such as closed loop systems or automated external defibrillators, are classified as class\u00a0III.\n\n\n\n\n\nANNEX IX\n\nCONFORMITY ASSESSMENT BASED ON A QUALITY MANAGEMENT SYSTEM AND ON ASSESSMENT OF TECHNICAL DOCUMENTATION\n\nCHAPTER I\n\nQUALITY MANAGEMENT SYSTEM\n\n1.\u00a0\u00a0\u00a0The manufacturer shall establish, document and implement a quality management system as described in Article\u00a010(9) and maintain its effectiveness throughout the life cycle of the devices concerned. The manufacturer shall ensure the application of the quality management system as specified in Section\u00a02 and shall be subject to audit, as laid down in Sections\u00a02.3 and 2.4, and to surveillance as specified in Section\u00a03.\n2.\u00a0\u00a0\u00a0Quality management system assessment\n2.1.\u00a0\u00a0\u00a0The manufacturer shall lodge an application for assessment of its quality management system with a notified body. The application shall include:\n\n\n\n\n\n\n\u2014\n\n\nthe name of the manufacturer and address of its registered place of business and any additional manufacturing site covered by the quality management system, and, if the manufacturer's application is lodged by its authorised representative, the name of the authorised representative and the address of the authorised representative's registered place of business,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nall relevant information on the device or group of devices covered by the quality management system,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na written declaration that no application has been lodged with any other notified body for the same device-related quality management system, or information about any previous application for the same device-related quality management system,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na draft of an EU declaration of conformity in accordance with Article\u00a019 and Annex\u00a0IV for the device model covered by the conformity assessment procedure,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation on the manufacturer's quality management system,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na documented description of the procedures in place to fulfil the obligations arising from the quality management system and required under this Regulation and the undertaking by the manufacturer in question to apply those procedures,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na description of the procedures in place to ensure that the quality management system remains adequate and effective, and the undertaking by the manufacturer to apply those procedures,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation on the manufacturer's post-market surveillance system and, where applicable, on the PMCF plan, and the procedures put in place to ensure compliance with the obligations resulting from the provisions on vigilance set out in Articles\u00a087 to\u00a092,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na description of the procedures in place to keep up to date the post-market surveillance system, and, where applicable, the PMCF plan, and the procedures ensuring compliance with the obligations resulting from the provisions on vigilance set out in Articles\u00a087 to 92, as well as the undertaking by the manufacturer to apply those procedures,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndocumentation on the clinical evaluation plan, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na description of the procedures in place to keep up to date the clinical evaluation plan, taking into account the state of the art.\n\n\n\n\n2.2.\u00a0\u00a0\u00a0Implementation of the quality management system shall ensure compliance with this Regulation. All the elements, requirements and provisions adopted by the manufacturer for its quality management system shall be documented in a systematic and orderly manner in the form of a quality manual and written policies and procedures such as quality programmes, quality plans and quality records.\nMoreover, the documentation to be submitted for the assessment of the quality management system shall include an adequate description of, in particular:\n\n\n\n\n\n\n(a)\n\n\nthe manufacturer's quality objectives;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe organisation of the business and in particular:\n\n\n\n\n\n\n\u2014\n\n\nthe organisational structures with the assignment of staff responsibilities in relation to critical procedures, the responsibilities of the managerial staff and their organisational authority,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe methods of monitoring whether the operation of the quality management system is efficient and in particular the ability of that system to achieve the desired design and device quality, including control of devices which fail to conform,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwhere the design, manufacture and/or final verification and testing of the devices, or parts of any of those processes, is carried out by another party, the methods of monitoring the efficient operation of the quality management system and in particular the type and extent of control applied to the other party, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwhere the manufacturer does not have a registered place of business in a Member\u00a0State, the draft mandate for the designation of an authorised representative and a letter of intention from the authorised representative to accept the mandate;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nthe procedures and techniques for monitoring, verifying, validating and controlling the design of the devices and the corresponding documentation as well as the data and records arising from those procedures and techniques. Those procedures and techniques shall specifically cover:\n\n\n\n\n\n\n\u2014\n\n\nthe strategy for regulatory compliance, including processes for identification of relevant legal requirements, qualification, classification, handling of equivalence, choice of and compliance with conformity assessment procedures,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nidentification of applicable general safety and performance requirements and solutions to fulfil those requirements, taking applicable CS and, where opted for, harmonised standards or other adequate solutions into account,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nrisk management as referred to in Section\u00a03 of Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe clinical evaluation, pursuant to Article\u00a061 and Annex\u00a0XIV, including post-market clinical follow-up,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsolutions for fulfilling the applicable specific requirements regarding design and construction, including appropriate pre-clinical evaluation, in particular the requirements of Chapter II of Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nsolutions for fulfilling the applicable specific requirements regarding the information to be supplied with the device, in particular the requirements of Chapter III of Annex\u00a0I,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe device identification procedures drawn up and kept up to date from drawings, specifications or other relevant documents at every stage of manufacture, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nmanagement of design or quality management system changes; and\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nthe verification and quality assurance techniques at the manufacturing stage and in particular the processes and procedures which are to be used, particularly as regards sterilisation and the relevant documents; and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe appropriate tests and trials which are to be carried out before, during and after manufacture, the frequency with which they are to take place, and the test equipment to be used; it shall be possible to trace back adequately the calibration of that test equipment.\n\n\n\n\nIn addition, the manufacturer shall grant the notified body access to the technical documentation referred to in Annexes\u00a0II and III.\n2.3.\u00a0\u00a0\u00a0Audit\nThe notified body shall audit the quality management system to determine whether it meets the requirements referred to in Section\u00a02.2. Where the manufacturer uses a harmonised standard or CS related to a quality management system, the notified body shall assess conformity with those standards or CS. The notified body shall assume that a quality management system which satisfies the relevant harmonised standards or CS conforms to the requirements covered by those standards or CS, unless it duly substantiates not doing so.\nThe audit team of the notified body shall include at least one member with past experience of assessments of the technology concerned in accordance with Sections 4.3. to 4.5. of Annex\u00a0VII. In circumstances where such experience is not immediately obvious or applicable, the notified body shall provide a documented rationale for the composition of that team. The assessment procedure shall include an audit on the manufacturer's premises and, if appropriate, on the premises of the manufacturer's suppliers and/or subcontractors to verify the manufacturing and other relevant processes.\nMoreover, in the case of class IIa and class IIb devices, the quality management system assessment shall be accompanied by the assessment of technical documentation for devices selected on a representative basis in accordance with Sections 4.4 to 4.8. In choosing representative samples, the notified body shall take into account the published guidance developed by the MDCG pursuant to Article\u00a0105 and in particular the novelty of the technology, similarities in design, technology, manufacturing and sterilisation methods, the intended purpose and the results of any previous relevant assessments such as with regard to physical, chemical, biological or clinical properties, that have been carried out in accordance with this Regulation. The notified body in question shall document its rationale for the samples taken.\nIf the quality management system conforms to the relevant provisions of this Regulation, the notified body shall issue an EU quality management system certificate. The notified body shall notify the manufacturer of its decision to issue the certificate. The decision shall contain the conclusions of the audit and a reasoned report.\n2.4.\u00a0\u00a0\u00a0The manufacturer in question shall inform the notified body which approved the quality management system of any plan for substantial changes to the quality management system, or the device-range covered. The notified body shall assess the changes proposed, determine the need for additional audits and verify whether after those changes the quality management system still meets the requirements referred to in Section\u00a02.2. It shall notify the manufacturer of its decision which shall contain the conclusions of the assessment, and where applicable, conclusions of additional audits. The approval of any substantial change to the quality management system or the device-range covered shall take the form of a supplement to the EU quality management system certificate.\n3.\u00a0\u00a0\u00a0Surveillance assessment applicable to class IIa, class IIb and class III devices\n3.1.\u00a0\u00a0\u00a0The aim of surveillance is to ensure that the manufacturer duly fulfils the obligations arising from the approved quality management system.\n3.2.\u00a0\u00a0\u00a0The manufacturer shall give authorisation to the notified body to carry out all the necessary audits, including on-site audits, and supply it with all relevant information, in particular:\n\n\n\n\n\n\n\u2014\n\n\nthe documentation on its quality management system,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndocumentation on any findings and conclusions resulting from the application of the post-market surveillance plan, including the PMCF plan, for a representative sample of devices, and of the provisions on vigilance set out in Articles\u00a087 to 92,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe data stipulated in the part of the quality management system relating to design, such as the results of analyses, calculations, tests and the solutions adopted regarding the risk-management as referred to in Section\u00a04 of Annex\u00a0I, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe data stipulated in the part of the quality management system relating to manufacture, such as quality control reports and test data, calibration data, and records on the qualifications of the personnel concerned.\n\n\n\n\n3.3.\u00a0\u00a0\u00a0Notified bodies shall periodically, at least once every 12 months, carry out appropriate audits and assessments to make sure that the manufacturer in question applies the approved quality management system and the post-market surveillance plan. Those audits and assessments shall include audits on the premises of the manufacturer and, if appropriate, of the manufacturer's suppliers and/or subcontractors. At the time of such on-site audits, the notified body shall, where necessary, carry out or ask for tests in order to check that the quality management system is working properly. It shall provide the manufacturer with a surveillance audit report and, if a test has been carried out, with a test report.\n3.4.\u00a0\u00a0\u00a0The notified body shall randomly perform at least once every five years unannounced audits on the site of the manufacturer and, where appropriate, of the manufacturer's suppliers and/or subcontractors, which may be combined with the periodic surveillance assessment referred to in Section\u00a03.3. or be performed in addition to that surveillance assessment. The notified body shall establish a plan for such unannounced on-site audits but shall not disclose it to the manufacturer.\nWithin the context of such unannounced on-site audits, the notified body shall test an adequate sample of the devices produced or an adequate sample from the manufacturing process to verify that the manufactured device is in conformity with the technical documentation, with the exception of the devices referred to in the second subparagraph\u00a0of Article\u00a052(8). Prior to unannounced on-site audits, the notified body shall specify the relevant sampling criteria and testing procedure.\nInstead of, or in addition to, sampling referred to in the second paragraph, the notified body shall take samples of devices from the market to verify that the manufactured device is in conformity with the technical documentation, with the exception of the devices referred to in the second subparagraph\u00a0of Article\u00a052(8). Prior to the sampling, the notified body in question shall specify the relevant sampling criteria and testing procedure.\nThe notified body shall provide the manufacturer in question with an on-site audit report which shall include, if applicable, the result of the sample test.\n3.5.\u00a0\u00a0\u00a0In the case of class IIa and class IIb devices, the surveillance assessment shall also include an assessment of the technical documentation as referred to in Sections 4.4 to 4.8 for the device or devices concerned on the basis of further representative samples chosen in accordance with the rationale documented by the notified body in accordance with the second paragraph\u00a0of Section\u00a02.3.\nIn the case of class III devices, the surveillance assessment shall also include a test of the approved parts and/or materials that are essential for the integrity of the device, including, where appropriate, a check that the quantities of produced or purchased parts and/or materials correspond to the quantities of finished devices.\n3.6.\u00a0\u00a0\u00a0The notified body shall ensure that the composition of the assessment team is such that there is sufficient experience with the evaluation of the devices, systems and processes concerned, continuous objectivity and neutrality; this shall include a rotation of the members of the assessment team at appropriate intervals. As a general rule, a lead auditor shall neither lead nor attend audits for more than three consecutive years in respect of the same manufacturer.\n3.7.\u00a0\u00a0\u00a0If the notified body finds a divergence between the sample taken from the devices produced or from the market and the specifications laid down in the technical documentation or the approved design, it shall suspend or withdraw the relevant certificate or impose restrictions on it.\nCHAPTER II\n\nASSESSMENT OF THE TECHNICAL DOCUMENTATION\n\n4.\u00a0\u00a0\u00a0Assessment of the technical documentation applicable to class III devices and to the class\u00a0IIb devices referred to in the second subparagraph\u00a0of Article\u00a052(4)\n4.1.\u00a0\u00a0\u00a0In addition to the obligations laid down in Section\u00a02, the manufacturer shall lodge with the notified body an application for assessment of the technical documentation relating to the device which it plans to place on the market or put into service and which is covered by the quality management system referred to in Section\u00a02.\n4.2.\u00a0\u00a0\u00a0The application shall describe the design, manufacture and performance of the device in question. It shall include the technical documentation as referred to in Annexes\u00a0II and III.\n4.3.\u00a0\u00a0\u00a0The notified body shall examine the application by using staff, employed by it, with proven knowledge and experience regarding the technology concerned and its clinical application. The notified body may require the application to be completed by having further tests carried out or requesting further evidence to be provided to allow assessment of conformity with the relevant requirements of the Regulation. The notified body shall carry out adequate physical or laboratory tests in relation to the device or request the manufacturer to carry out such tests.\n4.4.\u00a0\u00a0\u00a0The notified body shall review the clinical evidence presented by the manufacturer in the clinical evaluation report and the related clinical evaluation that was conducted. The notified body shall employ device reviewers with sufficient clinical expertise and, if necessary, use external clinical experts with direct and current experience relating to the device in question or the clinical condition in which it is utilised, for the purposes of that review.\n4.5.\u00a0\u00a0\u00a0The notified body shall, in circumstances in which the clinical evidence is based partly or totally on data from devices which are claimed to be equivalent to the device under assessment, assess the suitability of using such data, taking into account factors such as new indications and innovation. The notified body shall clearly document its conclusions on the claimed equivalence, and on the relevance and adequacy of the data for demonstrating conformity. For any characteristic of the device claimed as innovative by the manufacturer or for new indications, the notified body shall assess to what extent specific claims are supported by specific pre-clinical and clinical data and risk analysis.\n4.6.\u00a0\u00a0\u00a0The notified body shall verify that the clinical evidence and the clinical evaluation are adequate and shall verify the conclusions drawn by the manufacturer on the conformity with the relevant general safety and performance requirements. That verification shall include consideration of the adequacy of the benefit-risk determination, the risk management, the instructions for use, the user training and the manufacturer's post-market surveillance plan, and include a review of the need for, and the adequacy of, the PMCF plan proposed, where applicable.\n4.7.\u00a0\u00a0\u00a0Based on its assessment of the clinical evidence, the notified body shall consider the clinical evaluation and the benefit-risk determination, and whether specific milestones need to be defined to allow the notified body to review updates to the clinical evidence that result from post-market surveillance and PMCF data.\n4.8.\u00a0\u00a0\u00a0The notified body shall clearly document the outcome of its assessment in the clinical evaluation assessment report.\n4.9.\u00a0\u00a0\u00a0The notified body shall provide the manufacturer with a report on the technical documentation assessment, including a clinical evaluation assessment report. If the device conforms to the relevant provisions of this Regulation, the notified body shall issue an EU\u00a0technical documentation assessment certificate. The certificate shall contain the conclusions of the technical documentation assessment, the conditions of the certificate's validity, the data needed for identification of the approved design, and, where appropriate, a description of the intended purpose of the device.\n4.10.\u00a0\u00a0\u00a0Changes to the approved device shall require approval from the notified body which issued the EU technical documentation assessment certificate where such changes could affect the safety and performance of the device or the conditions prescribed for use of the device. Where the manufacturer plans to introduce any of the above-mentioned changes it shall inform the notified body which issued the EU technical documentation assessment certificate thereof. The notified body shall assess the planned changes and decide whether the planned changes require a new conformity assessment in accordance with Article\u00a052 or whether they could be addressed by means of a supplement to the EU technical documentation assessment certificate. In the latter case, the notified body shall assess the changes, notify the manufacturer of its decision and, where the changes are approved, provide it with a supplement to the EU technical documentation assessment certificate.\n5.\u00a0\u00a0\u00a0Specific additional procedures\n5.1.\u00a0\u00a0\u00a0Assessment procedure for certain class III and class IIb devices\n\n\n\n\n\n\n(a)\n\n\nFor class III implantable devices, and for class IIb active devices intended to administer and/or remove a medicinal product as referred to in Section\u00a06.4. of Annex\u00a0VIII (Rule\u00a012), the notified body shall, having verified the quality of clinical data supporting the clinical evaluation report of the manufacturer referred to in Article\u00a061(12), prepare a clinical evaluation assessment report which sets out its conclusions concerning the clinical evidence provided by the manufacturer, in particular concerning the benefit-risk determination, the consistency of that evidence with the intended purpose, including the medical indication or indications and the PMCF plan referred to in Article\u00a010(3) and Part B of Annex\u00a0XIV.\nThe notified body shall transmit its clinical evaluation assessment report, along with the manufacturer's clinical evaluation documentation, referred to in points (c) and (d) of Section\u00a06.1 of Annex\u00a0II, to the Commission.\nThe Commission shall immediately transmit those documents to the relevant expert panel referred to in Article\u00a0106.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nThe notified body may be requested to present its conclusions as referred to in point\u00a0(a) to the expert panel concerned.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nThe expert panel shall decide, under the supervision of the Commission, on the basis of all of the following criteria:\n\n\n\n\n\n\n(i)\n\n\nthe novelty of the device or of the related clinical procedure involved, and the possible major clinical or health impact thereof;\n\n\n\n\n\n\n\n\n\n\n(ii)\n\n\na significantly adverse change in the benefit-risk profile of a specific category or group of devices due to scientifically valid health concerns in respect of components or source material or in respect of the impact on health in the case of failure of the device;\n\n\n\n\n\n\n\n\n\n\n(iii)\n\n\na significantly increased rate of serious incidents reported in accordance with Article\u00a087 in respect of a specific category or group of devices,\n\n\n\n\nwhether to provide a scientific opinion on the clinical evaluation assessment report of the notified body based on the clinical evidence provided by the manufacturer, in particular concerning the benefit-risk determination, the consistency of that evidence with the medical indication or indications and the PMCF plan. That scientific opinion shall be provided within a period of 60 days, starting on the day of receipt of the documents from the Commission as referred to in point\u00a0(a). The reasons for the decision to provide a scientific opinion on the basis of the criteria in points (i), (ii) and (iii) shall be included in the scientific opinion. Where the information submitted is not sufficient for the expert panel to reach a conclusion, this shall be stated in the scientific opinion.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nThe expert panel may decide, under the supervision of the Commission, on the basis of the criteria laid down in point\u00a0(c) not to provide a scientific opinion, in which case it shall inform the notified body as soon as possible and in any event within 21\u00a0days of receipt of the documents as referred to in point\u00a0(a) from the Commission. The expert panel shall within that time limit provide the notified body and the Commission with the reasons for its decision, whereupon the notified body may proceed with the certification procedure of that device.\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nThe expert panel shall within 21 days of receipt of the documents from the Commission notify the Commission, through Eudamed whether it intends to provide a scientific opinion, pursuant to point\u00a0(c), or whether it intends not to provide a scientific opinion, pursuant to point\u00a0(d).\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nWhere no opinion has been delivered within a period of 60 days, the notified body may proceed with the certification procedure of the device in question.\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nThe notified body shall give due consideration to the views expressed in the scientific opinion of the expert panel. Where the expert panel finds that the level of clinical evidence is not sufficient or otherwise gives rise to serious concerns about the benefit-risk determination, the consistency of that evidence with the intended purpose, including the medical indication(s), and with the PMCF plan, the notified body shall, if necessary, advise the manufacturer to restrict the intended purpose of the device to certain groups of patients or certain medical indications and/or to impose a limit on the duration of validity of the certificate, to undertake specific PMCF studies, to adapt the instructions for use or the summary of safety and performance, or to impose other restrictions in its conformity assessment report, as appropriate. The notified body shall provide a full justification where it has not followed the advice of the expert panel in its conformity assessment report and the Commission shall without prejudice to Article\u00a0109 make both the scientific opinion of the expert panel and the written justification provided by the notified body publicly available via Eudamed.\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nThe Commission, after consultation with the Member\u00a0States and relevant scientific experts shall provide guidance for expert panels for consistent interpretation of the criteria in point\u00a0(c) before 26 May 2020.\n\n\n\n\n5.2.\u00a0\u00a0\u00a0Procedure in the case of devices incorporating a medicinal substance\n\n\n\n\n\n\n(a)\n\n\nWhere a device incorporates, as an integral part, a substance which, if used separately, may be considered to be a medicinal product within the meaning of point\u00a02 of Article\u00a01 of Directive\u00a02001/83/EC, including a medicinal product derived from human blood or human plasma and that has an action ancillary to that of the device, the quality, safety and usefulness of the substance shall be verified by analogy with the methods specified in Annex\u00a0I to Directive\u00a02001/83/EC.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nBefore issuing an EU technical documentation assessment certificate, the notified body shall, having verified the usefulness of the substance as part of the device and taking account of the intended purpose of the device, seek a scientific opinion from one of the competent authorities designated by the Member\u00a0States in accordance with Directive\u00a02001/83/EC or from the EMA, either of which to be referred to in this Section\u00a0as \u2018the medicinal products authority consulted\u2019 depending on which has been consulted under this point, on the quality and safety of the substance including the benefit or risk of the incorporation of the substance into the device. Where the device incorporates a human blood or plasma derivative or a substance that, if used separately, may be considered to be a medicinal product falling exclusively within the scope of the Annex to Regulation (EC)\u00a0No\u00a0726/2004, the notified body shall seek the opinion of the EMA.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nWhen issuing its opinion, the medicinal products authority consulted shall take into account the manufacturing process and the data relating to the usefulness of incorporation of the substance into the device as determined by the notified body.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nThe medicinal products authority consulted shall provide its opinion to the notified body within 210 days of receipt of all the necessary documentation.\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nThe scientific opinion of the medicinal products authority consulted, and any possible update of that opinion, shall be included in the documentation of the notified body concerning the device. The notified body shall give due consideration to the views expressed in the scientific opinion when making its decision. The notified body shall not deliver the certificate if the scientific opinion is unfavourable and shall convey its final decision to the medicinal products authority consulted.\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nBefore any change is made with respect to an ancillary substance incorporated in a device, in particular related to its manufacturing process, the manufacturer shall inform the notified body of the changes. That notified body shall seek the opinion of the medicinal products authority consulted, in order to confirm that the quality and safety of the ancillary substance remain unchanged. The medicinal products authority consulted shall take into account the data relating to the usefulness of incorporation of the substance into the device as determined by the notified body, in order to ensure that the changes have no negative impact on the risk or benefit previously established concerning the incorporation of the substance into the device. The medicinal products authority consulted shall provide its opinion within 60 days after receipt of all the necessary documentation regarding the changes. The notified body shall not deliver the supplement to the EU technical documentation assessment certificate if the scientific opinion provided by the medicinal products authority consulted is unfavourable. The notified body shall convey its final decision to the medicinal products authority consulted.\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nWhere the medicinal products authority consulted obtains information on the ancillary substance, which could have an impact on the risk or benefit previously established concerning the incorporation of the substance into the device, it shall advise the notified body as to whether this information has an impact on the risk or benefit previously established concerning the incorporation of the substance into the device. The notified body shall take that advice into account in reconsidering its assessment of the conformity assessment procedure.\n\n\n\n\n5.3.\u00a0\u00a0\u00a0Procedure in the case of devices manufactured utilising, or incorporating, tissues or cells of human or animal origin, or their derivatives, that are non-viable or rendered non-viable\n5.3.1.\u00a0\u00a0\u00a0Tissues or cells of human origin or their derivatives\n\n\n\n\n\n\n(a)\n\n\nFor devices manufactured utilising derivatives of tissues or cells of human origin that are covered by this Regulation in accordance with point\u00a0(g) of Article\u00a01(6) and for devices that incorporate, as an integral part, tissues or cells of human origin, or their derivatives, covered by Directive\u00a02004/23/EC, that have an action ancillary to that of the device, the notified body shall, prior to issuing an EU technical documentation assessment certificate, seek a scientific opinion from one of the competent authorities designated by the Member\u00a0States in accordance with Directive\u00a02004/23/EC (\u2018human tissues and cells competent authority\u2019) on the aspects relating to the donation, procurement and testing of tissues or cells of human origin or their derivatives. The notified body shall submit a summary of the preliminary conformity assessment which provides, among other things, information about the non-viability of the human tissues or cells in question, their donation, procurement and testing and the risk or benefit of the incorporation of the tissues or cells of human origin or their derivatives into the device.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nWithin 120 days of receipt of all the necessary documentation, the human tissues and cells competent authority shall provide to the notified body its opinion.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nThe scientific opinion of the human tissues and cells competent authority, and any possible update, shall be included in the documentation of the notified body concerning the device. The notified body shall give due consideration to the views expressed in the scientific opinion of the human tissues and cells competent authority when making its decision. The notified body shall not deliver the certificate if that scientific opinion is unfavourable. It shall convey its final decision to the human tissues and cells competent authority concerned.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nBefore any change is made with respect to non-viable tissues or cells of human origin or their derivatives incorporated in a device, in particular relating to their donation, testing or procurement, the manufacturer shall inform the notified body of the intended changes. The notified body shall consult the authority that was involved in the initial consultation, in order to confirm that the quality and safety of the tissues or cells of human origin or their derivatives incorporated in the device are maintained. The human tissues and cells competent authority concerned shall take into account the data relating to the usefulness of incorporation of the tissues or cells of human origin or their derivatives into the device as determined by the notified body, in order to ensure that the changes have no negative impact on the established benefit-risk ratio of the addition of the tissues or cells of human origin or their derivatives in the device. It shall provide its opinion within 60\u00a0days of receipt of all the necessary documentation regarding the intended changes. The notified body shall not deliver a supplement to the EU technical documentation assessment certificate if the scientific opinion is unfavourable and shall convey its final decision to the human tissues and cells competent authority concerned.\n\n\n\n\n5.3.2.\u00a0\u00a0\u00a0Tissues or cells of animal origin or their derivatives\nIn the case of devices manufactured utilising animal tissue which is rendered non-viable or utilising non-viable products derived from animal tissue, as referred to in Regulation\u00a0(EU)\u00a0No\u00a0722/2012, the notified body shall apply the relevant requirements laid down in that Regulation.\n5.4.\u00a0\u00a0\u00a0Procedure in the case of devices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body\n\n\n\n\n\n\n(a)\n\n\nThe quality and safety of devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed by, or locally dispersed in, the human body, shall be verified where applicable and only in respect of the requirements not covered by this Regulation, in accordance with the relevant requirements laid down in Annex\u00a0I to Directive\u00a02001/83/EC for the evaluation of absorption, distribution, metabolism, excretion, local tolerance, toxicity, interaction with other devices, medicinal products or other substances and potential for adverse reactions.\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nIn addition, for devices, or their products of metabolism, that are systemically absorbed by the human body in order to achieve their intended purpose, the notified body shall seek a scientific opinion from one of the competent authorities designated by the Member\u00a0States in accordance with Directive\u00a02001/83/EC or from the EMA, either of which to be referred to in this Section\u00a0as \u2018the medicinal products authority consulted\u2019 depending on which has been consulted under this point, on the compliance of the device with the relevant requirements laid down in Annex\u00a0I to Directive\u00a02001/83/EC.\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nThe opinion of the medicinal products authority consulted shall be drawn up within 150\u00a0days of receipt of all the necessary documentation.\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nThe scientific opinion of the medicinal products authority consulted, and any possible update, shall be included in the documentation of the notified body concerning the device. The notified body shall give due consideration to the views expressed in the scientific opinion when making its decision and shall convey its final decision to the medicinal products authority consulted.\n\n\n\n\n6.\u00a0\u00a0\u00a0Batch verification in the case of devices incorporating, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma as referred to in Article\u00a01(8)\nUpon completing the manufacture of each batch of devices that incorporate, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma as referred to in the first subparagraph\u00a0of Article\u00a01(8), the manufacturer shall inform the notified body of the release of the batch of devices and send it the official certificate concerning the release of the batch of human blood or plasma derivative used in the device, issued by a Member\u00a0State laboratory or a laboratory designated for that purpose by a Member\u00a0State in accordance with Article\u00a0114(2) of Directive\u00a02001/83/EC.\nCHAPTER III\n\nADMINISTRATIVE PROVISIONS\n\n7.\u00a0\u00a0\u00a0The manufacturer or, where the manufacturer does not have a registered place of business in a Member\u00a0State, its authorised representative shall, for a period ending no sooner than 10 years, and in the case of implantable devices no sooner than 15 years, after the last device has been placed on the market, keep at the disposal of the competent authorities:\n\n\n\n\n\n\n\u2014\n\n\nthe EU declaration of conformity,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation referred to in the fifth indent of Section\u00a02.1 and in particular the data and records arising from the procedures referred to in point\u00a0(c) of the second paragraph\u00a0of Section\u00a02.2,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation on the changes referred to in Section\u00a02.4,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation referred to in Section\u00a04.2, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe decisions and reports from the notified body as referred to in this Annex.\n\n\n\n\n8.\u00a0\u00a0\u00a0Each Member\u00a0State shall require that the documentation referred to in Section\u00a07 is kept at the disposal of competent authorities for the period indicated in that Section\u00a0in case a manufacturer, or its authorised representative, established within its territory goes bankrupt or ceases its business activity prior to the end of that period.\n\n\n\n\n\nANNEX\u00a0X\n\nCONFORMITY ASSESSMENT BASED ON TYPE-EXAMINATION\n\n1.\u00a0\u00a0\u00a0EU type-examination is the procedure whereby a notified body ascertains and certifies that a device, including its technical documentation and relevant life cycle processes and a corresponding representative sample of the device production envisaged, fulfils the relevant provisions of this Regulation.\n2.\u00a0\u00a0\u00a0Application\nThe manufacturer shall lodge an application for assessment with a notified body. The application shall include:\n\n\n\n\n\n\n\u2014\n\n\nthe name of the manufacturer and address of the registered place of business of the manufacturer and, if the application is lodged by the authorised representative, the name of the authorised representative and the address of its registered place of business,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe technical documentation referred to in Annexes\u00a0II and III. The applicant shall make a representative sample of the device production envisaged (\u2018type\u2019) available to the notified body. The notified body may request other samples as necessary, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na written declaration that no application has been lodged with any other notified body for the same type, or information about any previous application for the same type that was refused by another notified body or was withdrawn by the manufacturer or its authorised representative before that other notified body made its final assessment.\n\n\n\n\n3.\u00a0\u00a0\u00a0Assessment\nThe notified body shall:\n\n\n\n\n\n\n(a)\n\n\nexamine the application by using staff with proven knowledge and experience regarding the technology concerned and its clinical application. The notified body may require the application to be completed by having further tests carried out or requesting further evidence to be provided to allow assessment of conformity with the relevant requirements of this Regulation. The notified body shall carry out adequate physical or laboratory tests in relation to the device or request the manufacturer to carry out such tests;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nexamine and assess the technical documentation for conformity with the requirements of this Regulation that are applicable to the device and verify that the type has been manufactured in conformity with that documentation; it shall also record the items designed in conformity with the applicable standards referred to in Article\u00a08 or with applicable CS, and record the items not designed on the basis of the relevant standards referred to in Article\u00a08 or of the relevant CS;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nreview the clinical evidence presented by the manufacturer in the clinical evaluation report in accordance with Section\u00a04 of Annex\u00a0XIV. The notified body shall employ device reviewers with sufficient clinical expertise and, if necessary, use external clinical experts with direct and current experience relating to the device in question or to the clinical condition in which it is utilised, for the purposes of that review;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nin circumstances in which the clinical evidence is based partly or totally on data from devices which are claimed to be similar or equivalent to the device under assessment, assess the suitability of using such data, taking into account factors such as new indications and innovation. The notified body shall clearly document its conclusions on the claimed equivalence, and on the relevance and adequacy of the data for demonstrating conformity;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nclearly document the outcome of its assessment in a pre-clinical and clinical evaluation assessment report as part of the EU type examination report referred to in point\u00a0(i);\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\ncarry out or arrange for the appropriate assessments and the physical or laboratory tests necessary to verify whether the solutions adopted by the manufacturer meet the general safety and performance requirements laid down in this Regulation, in the event that the standards referred to in Article\u00a08 or the CS have not been applied. Where the device has to be connected to another device or devices in order to operate as intended, proof shall be provided that it conforms to the general safety and performance requirements when connected to any such device or devices having the characteristics specified by the manufacturer;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\ncarry out or arrange for the appropriate assessments and the physical or laboratory tests necessary to verify whether, in the event that the manufacturer has chosen to apply the relevant harmonised standards, those standards have actually been applied;\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\nagree with the applicant on the place where the necessary assessments and tests are to be carried out; and\n\n\n\n\n\n\n\n\n\n\n(i)\n\n\ndraw up an EU type-examination report on the results of the assessments and tests carried out under points (a) to (g).\n\n\n\n\n4.\u00a0\u00a0\u00a0Certificate\nIf the type conforms to this Regulation, the notified body shall issue an EU\u00a0type-examination certificate. The certificate shall contain the name and address of the manufacturer, the conclusions of the type examination assessment, the conditions of the certificate's validity and the data needed for identification of the type approved. The certificate shall be drawn up in accordance with Annex\u00a0XII. The relevant parts of the documentation shall be annexed to the certificate and a copy kept by the notified body.\n5.\u00a0\u00a0\u00a0Changes to the type\n5.1.\u00a0\u00a0\u00a0The applicant shall inform the notified body which issued the EU type-examination certificate of any planned change to the approved type or of its intended purpose and conditions of use.\n5.2.\u00a0\u00a0\u00a0Changes to the approved device including limitations of its intended purpose and conditions of use shall require approval from the notified body which issued the EU\u00a0type-examination certificate where such changes may affect conformity with the general safety and performance requirements or with the conditions prescribed for use of the product. The notified body shall examine the planned changes, notify the manufacturer of its decision and provide him with a supplement to the EU type-examination report. The approval of any change to the approved type shall take the form of a supplement to the EU\u00a0type-examination certificate.\n5.3.\u00a0\u00a0\u00a0Changes to the intended purpose and conditions of use of the approved device, with the exception of limitations of the intended purpose and conditions of use, shall necessitate a new application for a conformity assessment.\n6.\u00a0\u00a0\u00a0Specific additional procedures\nSection\u00a05 of Annex\u00a0IX shall apply with the proviso that any reference to an EU technical documentation assessment certificate shall be understood as a reference to an EU\u00a0type-examination certificate.\n7.\u00a0\u00a0\u00a0Administrative provisions\nThe manufacturer or, where the manufacturer does not have a registered place of business in a Member\u00a0State, its authorised representative shall, for a period ending no sooner than 10 years, and in the case of implantable devices no sooner than 15 years, after the last device has been placed on the market, keep at the disposal of the competent authorities:\n\n\n\n\n\n\n\u2014\n\n\nthe documentation referred to in the second indent of Section\u00a02,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation on the changes referred to in Section\u00a05, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ncopies of EU type-examination certificates, scientific opinions and reports and their additions/supplements.\n\n\n\n\nSection\u00a08 of Annex\u00a0IX shall apply.\n\n\n\n\n\nANNEX\u00a0XI\n\nCONFORMITY ASSESSMENT BASED ON PRODUCT CONFORMITY VERIFICATION\n\n1.\u00a0\u00a0\u00a0The objective of the conformity assessment based on product conformity verification is to ensure that devices conform to the type for which an EU type-examination certificate has been issued, and that they meet the provisions of this Regulation which apply to them.\n2.\u00a0\u00a0\u00a0Where an EU type-examination certificate has been issued in accordance with Annex\u00a0X, the manufacturer may either apply the procedure set out in Part A (production quality assurance) or the procedure set out in Part B (product verification) of this Annex.\n3.\u00a0\u00a0\u00a0By way of derogation from Sections 1 and 2 above, the procedures in this Annex\u00a0coupled with the drawing up of technical documentation as set out in Annexes\u00a0II and III may also be applied by manufacturers of class IIa devices.\nPART A\n\nPRODUCTION QUALITY ASSURANCE\n\n4.\u00a0\u00a0\u00a0The manufacturer shall ensure that the quality management system approved for the manufacture of the devices concerned is implemented, shall carry out a final verification, as specified in Section\u00a06, and shall be subject to the surveillance referred to in Section\u00a07.\n5.\u00a0\u00a0\u00a0When the manufacturer fulfils the obligations laid down in Section\u00a04, it shall draw up and keep an EU declaration of conformity in accordance with Article\u00a019 and Annex\u00a0IV for the device covered by the conformity assessment procedure. By issuing an EU declaration of conformity, the manufacturer shall be deemed to ensure and to declare that the device concerned conforms to the type described in the EU type-examination certificate and meets the requirements of this Regulation which apply to the device.\n6.\u00a0\u00a0\u00a0Quality management system\n6.1.\u00a0\u00a0\u00a0The manufacturer shall lodge an application for assessment of its quality management system with a notified body. The application shall include:\n\n\n\n\n\n\n\u2014\n\n\nall elements listed in Section\u00a02.1 of Annex\u00a0IX,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe technical documentation referred to in Annexes\u00a0II and III for the types approved, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na copy of the EU type-examination certificates referred to in Section\u00a04 of Annex\u00a0X; if the EU type-examination certificates have been issued by the same notified body with which the application is lodged, a reference to the technical documentation and its updates and the certificates issued shall also be included in the application.\n\n\n\n\n6.2.\u00a0\u00a0\u00a0Implementation of the quality management system shall be such as to ensure that there is compliance with the type described in the EU type-examination certificate and with the provisions of this Regulation which apply to the devices at each stage. All the elements, requirements and provisions adopted by the manufacturer for its quality management system shall be documented in a systematic and orderly manner in the form of a quality manual and written policies and procedures, such as quality programmes, quality plans and quality records.\nThat documentation shall, in particular, include an adequate description of all elements listed in points (a), (b), (d) and (e) of Section\u00a02.2 of Annex\u00a0IX.\n6.3.\u00a0\u00a0\u00a0The first and second paragraph\u00a0of Section\u00a02.3 of Annex\u00a0IX shall apply.\nIf the quality management system is such that it ensures that the devices conform to the type described in the EU type-examination certificate and that it conforms to the relevant provisions of this Regulation, the notified body shall issue an EU quality assurance certificate. The notified body shall notify the manufacturer of its decision to issue the certificate. That decision shall contain the conclusions of the notified body's audit and a reasoned assessment.\n6.4.\u00a0\u00a0\u00a0Section\u00a02.4 of Annex\u00a0IX shall apply.\n7.\u00a0\u00a0\u00a0Surveillance\nSection\u00a03.1, the first, second and fourth indents of Section\u00a03.2, Sections\u00a03.3, 3.4, 3.6 and 3.7 of Annex\u00a0IX shall apply.\nIn the case of class III devices, surveillance shall also include a check that the quantities of produced or purchased raw material or crucial components approved for the type and correspond to the quantities of finished devices.\n8.\u00a0\u00a0\u00a0Batch verification in the case of devices incorporating, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma referred to in Article\u00a01(8).\nUpon completing the manufacture of each batch of devices that incorporate, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma referred to in the first subparagraph\u00a0of Article\u00a01(8), the manufacturer shall inform the notified body of the release of the batch of devices and send it the official certificate concerning the release of the batch of human blood or plasma derivative used in the device, issued by a Member\u00a0State laboratory or a laboratory designated for that purpose by a Member\u00a0State in accordance with Article\u00a0114(2) of Directive\u00a02001/83/EC.\n9.\u00a0\u00a0\u00a0Administrative provisions\nThe manufacturer or, where the manufacturer does not have a registered place of business in a Member\u00a0State, its authorised representative shall, for a period ending no sooner than 10 years, and in the case of implantable devices no sooner than 15 years, after the last device has been placed on the market, keep at the disposal of the competent authorities:\n\n\n\n\n\n\n\u2014\n\n\nthe EU declaration of conformity,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation referred to in the fifth indent of Section\u00a02.1 of Annex\u00a0IX,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation referred to in the eighth indent of Section\u00a02.1 of Annex\u00a0IX, including the EU type-examination certificate referred to in Annex\u00a0X,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ninformation on the changes referred to in Section\u00a02.4 of Annex\u00a0IX, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe decisions and reports from the notified body as referred to in Sections 2.3, 3.3 and 3.4 of Annex\u00a0IX.\n\n\n\n\nSection\u00a08 of Annex\u00a0IX shall apply.\n10.\u00a0\u00a0\u00a0Application to class IIa devices\n10.1.\u00a0\u00a0\u00a0By way of derogation from Section\u00a05, by virtue of the EU declaration of conformity the manufacturer shall be deemed to ensure and to declare that the class IIa devices in question are manufactured in conformity with the technical documentation referred to in Annexes\u00a0II and III and meet the requirements of this Regulation which apply to them.\n10.2.\u00a0\u00a0\u00a0For class IIa devices the notified body shall assess, as part of the assessment referred to in Section\u00a06.3, whether the technical documentation as referred to in Annexes\u00a0II and III for the devices selected on a representative basis is compliant with this Regulation.\nIn choosing a representative sample or samples of devices, the notified body shall take into account the novelty of the technology, similarities in design, technology, manufacturing and sterilisation methods, the intended use and the results of any previous relevant assessments (e.g. with regard to physical, chemical, biological or clinical properties) that have been carried out in accordance with this Regulation. The notified body shall document its rationale for the sample or samples of devices taken.\n10.3.\u00a0\u00a0\u00a0Where the assessment under Section\u00a010.2. confirms that the class IIa devices in question conform to the technical documentation referred to in Annexes\u00a0II and III and meet the requirements of this Regulation which apply to them, the notified body shall issue a certificate pursuant to this Part of this Annex.\n10.4.\u00a0\u00a0\u00a0Samples additional to those taken for the initial conformity assessment of devices shall be assessed by the notified body as part of the surveillance assessment referred to in Section\u00a07.\n10.5.\u00a0\u00a0\u00a0By way of derogation from Section\u00a06, the manufacturer or its authorised representative shall, for a period ending no sooner than 10 years after the last device has been placed on the market, keep at the disposal of the competent authorities:\n\n\n\n\n\n\n\u2014\n\n\nthe EU declaration of conformity,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe technical documentation referred to in Annexes\u00a0II and III, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe certificate referred to in Section\u00a010.3.\n\n\n\n\nSection\u00a08 of Annex\u00a0IX shall apply.\nPART B\n\nPRODUCT VERIFICATION\n\n11.\u00a0\u00a0\u00a0Product verification shall be understood to be the procedure whereby after examination of every manufactured device, the manufacturer, by issuing an EU declaration of conformity in accordance with Article\u00a019 and Annex\u00a0IV, shall be deemed to ensure and to declare that the devices which have been subject to the procedure set out in Sections 14 and 15 conform to the type described in the EU type-examination certificate and meet the requirements of this Regulation which apply to them.\n12.\u00a0\u00a0\u00a0The manufacturer shall take all the measures necessary to ensure that the manufacturing process produces devices which conform to the type described in the EU type-examination certificate and to the requirements of the Regulation which apply to them. Prior to the start of manufacture, the manufacturer shall prepare documents defining the manufacturing process, in particular as regards sterilisation where necessary, together with all routine, pre-established procedures to be implemented to ensure homogeneous production and, where appropriate, conformity of the devices with the type described in the EU\u00a0type-examination certificate and with the requirements of this Regulation which apply to them.\nIn addition, for devices placed on the market in a sterile condition, and only for those aspects of the manufacturing process designed to secure and maintain sterility, the manufacturer shall apply the provisions of Sections 6 and 7.\n13.\u00a0\u00a0\u00a0The manufacturer shall undertake to institute and keep up to date a post-market surveillance plan, including a PMCF plan, and the procedures ensuring compliance with the obligations of the manufacturer resulting from the provisions on vigilance and post-market surveillance system set out in Chapter VII.\n14.\u00a0\u00a0\u00a0The notified body shall carry out the appropriate examinations and tests in order to verify the conformity of the device with the requirements of the Regulation by examining and testing every product as specified in Section\u00a015.\nThe examinations and tests referred to in the first paragraph\u00a0of this Section\u00a0shall not apply to aspects of the manufacturing process designed to secure sterility.\n15.\u00a0\u00a0\u00a0Verification by examination and testing of every product\n15.1.\u00a0\u00a0\u00a0Every device shall be examined individually and the appropriate physical or laboratory tests as defined in the relevant standard or standards referred to in Article\u00a08, or equivalent tests and assessments, shall be carried out in order to verify, where appropriate, the conformity of the devices with the type described in the EU type-examination certificate and with the requirements of this Regulation which apply to them.\n15.2.\u00a0\u00a0\u00a0The notified body shall affix, or have affixed, its identification number to each approved device and shall draw up an EU product verification certificate relating to the tests and assessments carried out.\n16.\u00a0\u00a0\u00a0Batch verification in the case of devices incorporating, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma referred to in Article\u00a01(8).\nUpon completing the manufacture of each batch of devices that incorporate, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma referred to in the first subparagraph\u00a0of Article\u00a01(8), the manufacturer shall inform the notified body of the release of the batch of devices and send it the official certificate concerning the release of the batch of human blood or plasma derivative used in the device, issued by a Member\u00a0State laboratory or a laboratory designated for that purpose by a Member\u00a0State in accordance with Article\u00a0114(2) of Directive\u00a02001/83/EC.\n17.\u00a0\u00a0\u00a0Administrative provisions\nThe manufacturer or its authorised representative shall, for a period ending no sooner than 10 years, and in the case of implantable devices no sooner than 15 years, after the last device has been placed on the market, keep at the disposal of the competent authorities:\n\n\n\n\n\n\n\u2014\n\n\nthe EU declaration of conformity,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe documentation referred to in Section\u00a012,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe certificate referred to in Section\u00a015.2, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe EU type-examination certificate referred to in Annex\u00a0X.\n\n\n\n\nSection\u00a08 of Annex\u00a0IX shall apply.\n18.\u00a0\u00a0\u00a0Application to class IIa devices\n18.1.\u00a0\u00a0\u00a0By way of derogation from Section\u00a011, by virtue of the EU declaration of conformity the manufacturer shall be deemed to ensure and to declare that the class IIa devices in question are manufactured in conformity with the technical documentation referred to in Annexes\u00a0II and III and meet the requirements of this Regulation which apply to them.\n18.2.\u00a0\u00a0\u00a0The verification conducted by the notified body in accordance with Section\u00a014 is intended to confirm the conformity of the class IIa devices in question with the technical documentation referred to in Annexes\u00a0II and III and with the requirements of this Regulation which apply to them.\n18.3.\u00a0\u00a0\u00a0If the verification referred to in Section\u00a018.2 confirms that the class IIa devices in question conform to the technical documentation referred to in Annexes\u00a0II and III and meet the requirements of this Regulation which apply to them, the notified body shall issue a certificate pursuant to this Part of this Annex.\n18.4.\u00a0\u00a0\u00a0By way of derogation from Section\u00a017, the manufacturer or its authorised representative shall, for a period ending no sooner than 10 years after the last device has been placed on the market, keep at the disposal of the competent authorities:\n\n\n\n\n\n\n\u2014\n\n\nthe EU declaration of conformity,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe technical documentation referred to in Annexes\u00a0II and III, and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe certificate referred to in Section\u00a018.3.\n\n\n\n\nSection\u00a08 of Annex\u00a0IX shall apply.\n\n\n\n\n\nANNEX XII\n\nCERTIFICATES ISSUED BY A NOTIFIED BODY\n\nCHAPTER I\n\nGENERAL REQUIREMENTS\n\n\n\n\n\n\n\n\n\n1.\n\n\nCertificates shall be drawn up in one of the official languages of the Union.\n\n\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nEach certificate shall refer to only one conformity assessment procedure.\n\n\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nCertificates shall only be issued to one manufacturer. The name and address of the manufacturer included in the certificate shall be the same as that registered in the electronic system referred to in Article\u00a030.\n\n\n\n\n\n\n\n\n\n\n\n\n4.\n\n\nThe scope of the certificates shall unambiguously identify the device or devices covered:\n\n\n\n\n\n\n(a)\n\n\nEU technical documentation assessment certificates, EU type-examination certificates and EU product verification certificates shall include a clear identification, including the name, model and type, of the device or devices, the intended purpose, as included by the manufacturer in the instructions for use and in relation to which the device has been assessed in the conformity assessment procedure, risk classification and the Basic UDI-DI as referred to in Article\u00a027(6);\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nEU quality management system certificates and EU quality assurance certificates shall include the identification of the devices or groups of devices, the risk classification, and, for class IIb devices, the intended purpose.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n5.\n\n\nThe notified body shall be able to demonstrate on request, which (individual) devices are covered by the certificate. The notified body shall set up a system that enables the determination of the devices, including their classification, covered by the certificate.\n\n\n\n\n\n\n\n\n\n\n\n\n6.\n\n\nCertificates shall contain, if applicable, a note that, for the placing on the market of the device or devices it covers, another certificate issued in accordance with this Regulation is required.\n\n\n\n\n\n\n\n\n\n\n\n\n7.\n\n\nEU quality management system certificates and EU quality assurance certificates for class\u00a0I devices for which the involvement of a notified body is required pursuant to Article\u00a052(7) shall include a statement that the audit by the notified body of the quality management system was limited to the aspects required under that paragraph.\n\n\n\n\n\n\n\n\n\n\n\n\n8.\n\n\nWhere a certificate is supplemented, modified or re-issued, the new certificate shall contain a reference to the preceding certificate and its date of issue with identification of the changes.\n\n\n\n\nCHAPTER II\n\nMINIMUM CONTENT OF THE CERTIFICATES\n\n\n\n\n\n\n\n1.\n\n\nname, address and identification number of the notified body;\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nname and address of the manufacturer and, if applicable, of the authorised representative;\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nunique number identifying the certificate;\n\n\n\n\n\n\n\n\n\n\n4.\n\n\nif already issued, the SRN of the manufacturer referred to in to Article\u00a031(2);\n\n\n\n\n\n\n\n\n\n\n5.\n\n\ndate of issue;\n\n\n\n\n\n\n\n\n\n\n6.\n\n\ndate of expiry;\n\n\n\n\n\n\n\n\n\n\n7.\n\n\ndata needed for the unambiguous identification of the device or devices where applicable as specified in Section\u00a04 of Part I;\n\n\n\n\n\n\n\n\n\n\n8.\n\n\nif applicable, reference to any previous certificate as specified in Section\u00a08 of Chapter I;\n\n\n\n\n\n\n\n\n\n\n9.\n\n\nreference to this Regulation and the relevant Annex\u00a0in accordance with which the conformity assessment has been carried out;\n\n\n\n\n\n\n\n\n\n\n10.\n\n\nexaminations and tests performed, e.g. reference to relevant CS, harmonised standards, test reports and audit report(s);\n\n\n\n\n\n\n\n\n\n\n11.\n\n\nif applicable, reference to the relevant parts of the technical documentation or other certificates required for the placing on the market of the device or devices covered;\n\n\n\n\n\n\n\n\n\n\n12.\n\n\nif applicable, information about the surveillance by the notified body;\n\n\n\n\n\n\n\n\n\n\n13.\n\n\nconclusions of the notified body's conformity assessment with regard to the relevant Annex;\n\n\n\n\n\n\n\n\n\n\n14.\n\n\nconditions for or limitations to the validity of the certificate;\n\n\n\n\n\n\n\n\n\n\n15.\n\n\nlegally binding signature of the notified body in accordance with the applicable national law.\n\n\n\n\n\n\n\n\n\nANNEX XIII\n\nPROCEDURE FOR CUSTOM-MADE DEVICES\n\n\n\n\n\n\n\n\n\n1.\n\n\nFor custom-made devices, the manufacturer or its authorised representative shall draw up a statement containing all of the following information:\n\n\n\n\n\n\n\u2014\n\n\nthe name and address of the manufacturer, and of all manufacturing sites,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nif applicable, the name and address of the authorised representative,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\ndata allowing identification of the device in question,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na statement that the device is intended for exclusive use by a particular patient or user, identified by name, an acronym or a numerical code,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe name of the person who made out the prescription and who is authorised by national law by virtue of their professional qualifications to do so, and, where applicable, the name of the health institution concerned,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nthe specific characteristics of the product as indicated by the prescription,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na statement that the device in question conforms to the general safety and performance requirements set out in Annex\u00a0I and, where applicable, indicating which general safety and performance requirements have not been fully met, together with the grounds,\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nwhere applicable, an indication that the device contains or incorporates a medicinal substance, including a human blood or plasma derivative, or tissues or cells of human origin, or of animal origin as referred to in Regulation\u00a0(EU)\u00a0No\u00a0722/2012.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nThe manufacturer shall undertake to keep available for the competent national authorities documentation that indicates its manufacturing site or sites and allows an understanding to be formed of the design, manufacture and performance of the device, including the expected performance, so as to allow assessment of conformity with the requirements of this Regulation.\n\n\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nThe manufacturer shall take all the measures necessary to ensure that the manufacturing process produces devices which are manufactured in accordance with the documentation referred to in Section\u00a02.\n\n\n\n\n\n\n\n\n\n\n\n\n4.\n\n\nThe statement referred to in the introductory part of Section\u00a01 shall be kept for a period of at least 10 years after the device has been placed on the market. In the case of implantable devices, the period shall be at least 15 years.\nSection\u00a08 of Annex\u00a0IX shall apply.\n\n\n\n\n\n\n\n\n\n\n\n\n5.\n\n\nThe manufacturer shall review and document experience gained in the post-production phase, including from PMCF as referred to in Part B of Annex\u00a0XIV, and implement appropriate means to apply any necessary corrective action, In that context, it shall report in accordance with Article\u00a087(1) to the competent authorities any serious incidents or field safety corrective actions or both as soon as it learns of them.\n\n\n\n\n\n\n\n\n\nANNEX XIV\n\nCLINICAL EVALUATION AND POST-MARKET CLINICAL FOLLOW-UP\n\nPART A\n\nCLINICAL EVALUATION\n\n1.\u00a0\u00a0\u00a0To plan, continuously conduct and document a clinical evaluation, manufacturers shall:\n\n\n\n\n\n\n(a)\n\n\nestablish and update a clinical evaluation plan, which shall include at least:\n\n\n\n\n\n\n\u2014\n\n\nan identification of the general safety and performance requirements that require support from relevant clinical data;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na specification of the intended purpose of the device;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na clear specification of intended target groups with clear indications and contra-indications;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na detailed description of intended clinical benefits to patients with relevant and specified clinical outcome parameters;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na specification of methods to be used for examination of qualitative and quantitative aspects of clinical safety with clear reference to the determination of residual risks and side-effects;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nan indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nan indication how benefit-risk issues relating to specific components such as use of pharmaceutical, non-viable animal or human tissues, are to be addressed; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na clinical development plan indicating progression from exploratory investigations, such as first-in-man studies, feasibility and pilot studies, to confirmatory investigations, such as pivotal clinical investigations, and a PMCF as referred to in Part B of this Annex\u00a0with an indication of milestones and a description of potential acceptance criteria;\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nidentify available clinical data relevant to the device and its intended purpose and any gaps in clinical evidence through a systematic scientific literature review;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nappraise all relevant clinical data by evaluating their suitability for establishing the safety and performance of the device;\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\ngenerate, through properly designed clinical investigations in accordance with the clinical development plan, any new or additional clinical data necessary to address outstanding issues; and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nanalyse all relevant clinical data in order to reach conclusions about the safety and clinical performance of the device including its clinical benefits.\n\n\n\n\n2.\u00a0\u00a0\u00a0The clinical evaluation shall be thorough and objective, and take into account both favourable and unfavourable data. Its depth and extent shall be proportionate and appropriate to the nature, classification, intended purpose and risks of the device in question, as well as to the manufacturer's claims in respect of the device.\n3.\u00a0\u00a0\u00a0A clinical evaluation may be based on clinical data relating to a device for which equivalence to the device in question can be demonstrated. The following technical, biological and clinical characteristics shall be taken into consideration for the demonstration of equivalence:\n\n\n\n\n\n\n\u2014\n\n\nTechnical: the device is of similar design; is used under similar conditions of use; has similar specifications and properties including physicochemical properties such as intensity of energy, tensile strength, viscosity, surface characteristics, wavelength and software algorithms; uses similar deployment methods, where relevant; has similar principles of operation and critical performance requirements;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nBiological: the device uses the same materials or substances in contact with the same human tissues or body fluids for a similar kind and duration of contact and similar release characteristics of substances, including degradation products and leachables;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nClinical: the device is used for the same clinical condition or purpose, including similar severity and stage of disease, at the same site in the body, in a similar population, including as regards age, anatomy and physiology; has the same kind of user; has similar relevant critical performance in view of the expected clinical effect for a specific intended purpose.\n\n\n\n\nThe characteristics listed in the first paragraph\u00a0shall be similar to the extent that there would be no clinically significant difference in the safety and clinical performance of the device. Considerations of equivalence shall be based on proper scientific justification. It shall be clearly demonstrated that manufacturers have sufficient levels of access to the data relating to devices with which they are claiming equivalence in order to justify their claims of equivalence.\n4.\u00a0\u00a0\u00a0The results of the clinical evaluation and the clinical evidence on which it is based shall be documented in a clinical evaluation report which shall support the assessment of the conformity of the device.\nThe clinical evidence together with non-clinical data generated from non-clinical testing methods and other relevant documentation shall allow the manufacturer to demonstrate conformity with the general safety and performance requirements and shall be part of the technical documentation for the device in question.\nBoth favourable and unfavourable data considered in the clinical evaluation shall be included in the technical documentation.\nPART B\n\nPOST-MARKET CLINICAL FOLLOW-UP\n\n5.\u00a0\u00a0\u00a0PMCF shall be understood to be a continuous process that updates the clinical evaluation referred to in Article\u00a061 and Part A of this Annex\u00a0and shall be addressed in the manufacturer's post-market surveillance plan. When conducting PMCF, the manufacturer shall proactively collect and evaluate clinical data from the use in or on humans of a device which bears the CE marking and is placed on the market or put into service within its intended purpose as referred to in the relevant conformity assessment procedure, with the aim of confirming the safety and performance throughout the expected lifetime of the device, of ensuring the continued acceptability of identified risks and of detecting emerging risks on the basis of factual evidence.\n6.\u00a0\u00a0\u00a0PMCF shall be performed pursuant to a documented method laid down in a PMCF plan.\n6.1.\u00a0\u00a0\u00a0The PMCF plan shall specify the methods and procedures for proactively collecting and evaluating clinical data with the aim of:\n\n\n\n\n\n\n(a)\n\n\nconfirming the safety and performance of the device throughout its expected lifetime,\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nidentifying previously unknown side-effects and monitoring the identified side-effects and contraindications,\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\nidentifying and analysing emergent risks on the basis of factual evidence,\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\nensuring the continued acceptability of the benefit-risk ratio referred to in Sections\u00a01 and 9 of Annex\u00a0I, and\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nidentifying possible systematic misuse or off-label use of the device, with a view to verifying that the intended purpose is correct.\n\n\n\n\n6.2.\u00a0\u00a0\u00a0The PMCF plan shall include at least:\n\n\n\n\n\n\n(a)\n\n\nthe general methods and procedures of the PMCF to be applied, such as gathering of clinical experience gained, feedback from users, screening of scientific literature and of other sources of clinical data;\n\n\n\n\n\n\n\n\n\n\n(b)\n\n\nthe specific methods and procedures of PMCF to be applied, such as evaluation of suitable registers or PMCF studies;\n\n\n\n\n\n\n\n\n\n\n(c)\n\n\na rationale for the appropriateness of the methods and procedures referred to in points (a) and (b);\n\n\n\n\n\n\n\n\n\n\n(d)\n\n\na reference to the relevant parts of the clinical evaluation report referred to in Section\u00a04 and to the risk management referred to in Section\u00a03 of Annex\u00a0I;\n\n\n\n\n\n\n\n\n\n\n(e)\n\n\nthe specific objectives to be addressed by the PMCF;\n\n\n\n\n\n\n\n\n\n\n(f)\n\n\nan evaluation of the clinical data relating to equivalent or similar devices;\n\n\n\n\n\n\n\n\n\n\n(g)\n\n\nreference to any relevant CS, harmonised standards when used by the manufacturer, and relevant guidance on PMCF; and\n\n\n\n\n\n\n\n\n\n\n(h)\n\n\na detailed and adequately justified time schedule for PMCF activities (e.g. analysis of PMCF data and reporting) to be undertaken by the manufacturer.\n\n\n\n\n7.\u00a0\u00a0\u00a0The manufacturer shall analyse the findings of the PMCF and document the results in a PMCF evaluation report that shall be part of the clinical evaluation report and the technical documentation.\n8.\u00a0\u00a0\u00a0The conclusions of the PMCF evaluation report shall be taken into account for the clinical evaluation referred to in Article\u00a061 and Part A of this Annex\u00a0and in the risk management referred to in Section\u00a03 of Annex\u00a0I. If, through the PMCF, the need for preventive and/or corrective measures has been identified, the manufacturer shall implement them.\n\n\n\n\n\nANNEX XV\n\nCLINICAL INVESTIGATIONS\n\nCHAPTER I\n\nGENERAL REQUIREMENTS\n\n1.\u00a0\u00a0\u00a0Ethical principles\nEach step in the clinical investigation, from the initial consideration of the need for and justification of the study to the publication of the results, shall be carried out in accordance with recognised ethical principles.\n2.\u00a0\u00a0\u00a0Methods\n2.1.\u00a0\u00a0\u00a0Clinical investigations shall be performed on the basis of an appropriate plan of investigation reflecting the latest scientific and technical knowledge and defined in such a way as to confirm or refute the manufacturer's claims regarding the safety, performance and aspects relating to benefit-risk of devices as referred to in Article\u00a062(1); the clinical investigations shall include an adequate number of observations to guarantee the scientific validity of the conclusions. The rationale for the design and chosen statistical methodology shall be presented as further described in Section\u00a03.6 of Chapter II of this Annex.\n2.2.\u00a0\u00a0\u00a0The procedures used to perform the clinical investigation shall be appropriate to the device under investigation.\n2.3.\u00a0\u00a0\u00a0The research methodologies used to perform the clinical investigation shall be appropriate to the device under investigation.\n2.4.\u00a0\u00a0\u00a0Clinical investigations shall be performed in accordance with the clinical investigation plan by a sufficient number of intended users and in a clinical environment that is representative of the intended normal conditions of use of the device in the target patient population. Clinical investigations shall be in line with the clinical evaluation plan as referred to in Part\u00a0A of Annex\u00a0XIV.\n2.5.\u00a0\u00a0\u00a0All the appropriate technical and functional features of the device, in particular those involving safety and performance, and their expected clinical outcomes shall be appropriately addressed in the investigational design. A list of the technical and functional features of the device and the related expected clinical outcomes shall be provided.\n2.6.\u00a0\u00a0\u00a0The endpoints of the clinical investigation shall address the intended purpose, clinical benefits, performance and safety of the device. The endpoints shall be determined and assessed using scientifically valid methodologies. The primary endpoint shall be appropriate to the device and clinically relevant.\n2.7.\u00a0\u00a0\u00a0Investigators shall have access to the technical and clinical data regarding the device. Personnel involved in the conduct of an investigation shall be adequately instructed and trained in the proper use of the investigational device, and as regards the clinical investigation plan and good clinical practice. This training shall be verified and where necessary arranged by the sponsor and documented appropriately.\n2.8.\u00a0\u00a0\u00a0The clinical investigation report, signed by the investigator, shall contain a critical evaluation of all the data collected during the clinical investigation, and shall include any negative findings.\nCHAPTER II\n\nDOCUMENTATION REGARDING THE APPLICATION FOR CLINICAL INVESTIGATION\n\nFor investigational devices covered by Article\u00a062, the sponsor shall draw up and submit the application in accordance with Article\u00a070 accompanied by the following documents:\n1.\u00a0\u00a0\u00a0Application form\nThe application form shall be duly filled in, containing information regarding:\n\n\n\n\n\n\n1.1.\n\n\nname, address and contact details of the sponsor and, if applicable, name, address and contact details of its contact person or legal representative in accordance with Article\u00a062(2) established in the Union;\n\n\n\n\n\n\n\n\n\n\n1.2.\n\n\nif different from those in Section\u00a01.1, name, address and contact details of the manufacturer of the device intended for clinical investigation and, if applicable, of its authorised representative;\n\n\n\n\n\n\n\n\n\n\n1.3.\n\n\ntitle of the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n1.4.\n\n\nstatus of the clinical investigation application (i.e. first submission, resubmission, significant amendment);\n\n\n\n\n\n\n\n\n\n\n1.5.\n\n\ndetails and/or reference to the clinical evaluation plan;\n\n\n\n\n\n\n\n\n\n\n1.6.\n\n\nIf the application is a resubmission with regard to a device for which an application has been already submitted, the date or dates and reference number or numbers of the earlier application or in the case of significant amendment, reference to the original application. The sponsor shall identify all of the changes from the previous application together with a rationale for those changes, in particular, whether any changes have been made to address conclusions of previous competent authority or ethics committee reviews;\n\n\n\n\n\n\n\n\n\n\n1.7.\n\n\nif the application is submitted in parallel with an application for a clinical trial in accordance with Regulation\u00a0(EU)\u00a0No\u00a0536/2014, reference to the official registration number of the clinical trial;\n\n\n\n\n\n\n\n\n\n\n1.8.\n\n\nidentification of the Member\u00a0States and third countries in which the clinical investigation is to be conducted as part of a multicentre or multinational study at the time of application;\n\n\n\n\n\n\n\n\n\n\n1.9.\n\n\na brief description of the investigational device, its classification and other information necessary for the identification of the device and device type;\n\n\n\n\n\n\n\n\n\n\n1.10.\n\n\ninformation as to whether the device incorporates a medicinal substance, including a human blood or plasma derivative or whether it is manufactured utilising non-viable tissues or cells of human or animal origin, or their derivatives;\n\n\n\n\n\n\n\n\n\n\n1.11.\n\n\nsummary of the clinical investigation plan including the objective or objectives of the clinical investigation, the number and gender of subjects, criteria for subject selection, whether there are subjects under 18 years of age, design of the investigation such as controlled and/or randomised studies, planned dates of commencement and of completion of the clinical investigation;\n\n\n\n\n\n\n\n\n\n\n1.12.\n\n\nif applicable, information regarding a comparator device, its classification and other information necessary for the identification of the comparator device;\n\n\n\n\n\n\n\n\n\n\n1.13.\n\n\nevidence from the sponsor that the clinical investigator and the investigational site are capable of conducting the clinical investigation in accordance with the clinical investigation plan;\n\n\n\n\n\n\n\n\n\n\n1.14.\n\n\ndetails of the anticipated start date and duration of the investigation;\n\n\n\n\n\n\n\n\n\n\n1.15.\n\n\ndetails to identify the notified body, if already involved at the stage of application for a clinical investigation;\n\n\n\n\n\n\n\n\n\n\n1.16.\n\n\nconfirmation that the sponsor is aware that the competent authority may contact the ethics committee that is assessing or has assessed the application; and\n\n\n\n\n\n\n\n\n\n\n1.17.\n\n\nthe statement referred to in Section\u00a04.1.\n\n\n\n\n2.\u00a0\u00a0\u00a0Investigator's Brochure\nThe investigator's brochure (IB) shall contain the clinical and non-clinical information on the investigational device that is relevant for the investigation and available at the time of application. Any updates to the IB or other relevant information that is newly available shall be brought to the attention of the investigators in a timely manner. The IB shall be clearly identified and contain in particular the following information:\n\n\n\n\n\n\n2.1.\n\n\nIdentification and description of the device, including information on the intended purpose, the risk classification and applicable classification rule pursuant to Annex\u00a0VIII, design and manufacturing of the device and reference to previous and similar generations of the device.\n\n\n\n\n\n\n\n\n\n\n2.2.\n\n\nManufacturer's instructions for installation, maintenance, maintaining hygiene standards and for use, including storage and handling requirements, as well as, to the extent that such information is available, information to be placed on the label, and instructions for use to be provided with the device when placed on the market. In addition, information relating to any relevant training required.\n\n\n\n\n\n\n\n\n\n\n2.3.\n\n\nPre-clinical evaluation based on relevant pre-clinical testing and experimental data, in particular regarding in-design calculations, in vitro tests, ex vivo tests, animal tests, mechanical or electrical tests, reliability tests, sterilisation validation, software verification and validation, performance tests, evaluation of biocompatibility and biological safety, as applicable.\n\n\n\n\n\n\n\n\n\n\n2.4.\n\n\nExisting clinical data, in particular:\n\n\n\n\n\n\n\u2014\n\n\nfrom relevant scientific literature available relating to the safety, performance, clinical benefits to patients, design characteristics and intended purpose of the device and/or of equivalent or similar devices;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nother relevant clinical data available relating to the safety, performance, clinical benefits to patients, design characteristics and intended purpose of equivalent or similar devices of the same manufacturer, including length of time on the market and a review of performance, clinical benefit and safety-related issues and any corrective actions taken.\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n2.5.\n\n\nSummary of the benefit-risk analysis and the risk management, including information regarding known or foreseeable risks, any undesirable effects, contraindications and warnings.\n\n\n\n\n\n\n\n\n\n\n2.6.\n\n\nIn the case of devices that incorporate a medicinal substance, including a human blood or plasma derivative or devices manufactured utilising non-viable tissues or cells of human or animal origin, or their derivatives, detailed information on the medicinal substance or on the tissues, cells or their derivatives, and on the compliance with the relevant general safety and performance requirements and the specific risk management in relation to the substance or tissues, cells or their derivatives, as well as evidence for the added value of incorporation of such constituents in relation to the clinical benefit and/or safety of the device.\n\n\n\n\n\n\n\n\n\n\n2.7.\n\n\nA list detailing the fulfilment of the relevant general safety and performance requirements set out in Annex\u00a0I, including the standards and CS applied, in full or in part, as well as a description of the solutions for fulfilling the relevant general safety and performance requirements, in so far as those standards and CS have not or have only been partly fulfilled or are lacking.\n\n\n\n\n\n\n\n\n\n\n2.8.\n\n\nA detailed description of the clinical procedures and diagnostic tests used in the course of the clinical investigation and in particular information on any deviation from normal clinical practice.\n\n\n\n\n3.\u00a0\u00a0\u00a0Clinical Investigation Plan\nThe clinical investigation plan (CIP) shall set out the rationale, objectives, design methodology, monitoring, conduct, record-keeping and the method of analysis for the clinical investigation. It shall contain in particular the information as laid down in this Annex. If part of this information is submitted in a separate document, it shall be referenced in the CIP.\n3.1.\u00a0\u00a0\u00a0General\n3.1.1.\u00a0\u00a0\u00a0Single identification number of the clinical investigation, as referred to in Article\u00a070(1).\n3.1.2.\u00a0\u00a0\u00a0Identification of the sponsor \u2014 name, address and contact details of the sponsor and, where applicable, the name, address and contact details of the sponsor's contact person or legal representative in accordance with Article\u00a062(2) established in the Union.\n3.1.3.\u00a0\u00a0\u00a0Information on the principal investigator at each investigational site, the coordinating investigator for the investigation, the address details for each investigational site and the emergency contact details for the principal investigator at each site. The roles, responsibilities and qualifications of the various kinds of investigators shall be specified in the CIP.\n3.1.4.\u00a0\u00a0\u00a0A brief description of how the clinical investigation is financed and a brief description of the agreement between the sponsor and the site.\n3.1.5.\u00a0\u00a0\u00a0Overall synopsis of the clinical investigation, in an official Union language determined by the Member\u00a0State concerned.\n3.2.\u00a0\u00a0\u00a0Identification and description of the device, including its intended purpose, its manufacturer, its traceability, the target population, materials coming into contact with the human body, the medical or surgical procedures involved in its use and the necessary training and experience for its use, background literature review, the current state of the art in clinical care in the relevant field of application and the proposed benefits of the new device.\n3.3.\u00a0\u00a0\u00a0Risks and clinical benefits of the device to be examined, with justification of the corresponding expected clinical outcomes in the clinical investigation plan.\n3.4.\u00a0\u00a0\u00a0Description of the relevance of the clinical investigation in the context of the state of the art of clinical practice.\n3.5.\u00a0\u00a0\u00a0Objectives and hypotheses of the clinical investigation.\n3.6.\u00a0\u00a0\u00a0Design of the clinical investigation with evidence of its scientific robustness and validity.\n3.6.1.\u00a0\u00a0\u00a0General information such as type of investigation with rationale for choosing it, for its endpoints and for its variables as set out in the clinical evaluation plan.\n3.6.2.\u00a0\u00a0\u00a0Information on the investigational device, on any comparator and on any other device or medication to be used in the clinical investigation.\n3.6.3.\u00a0\u00a0\u00a0Information on subjects, selection criteria, size of investigation population, representativeness of investigation population in relation to target population and, if applicable, information on vulnerable subjects involved such as children, pregnant women, immuno-compromised or, elderly subjects.\n3.6.4.\u00a0\u00a0\u00a0Details of measures to be taken to minimise bias, such as randomisation, and management of potential confounding factors.\n3.6.5.\u00a0\u00a0\u00a0Description of the clinical procedures and diagnostic methods relating to the clinical investigation and in particular highlighting any deviation from normal clinical practice.\n3.6.6.\u00a0\u00a0\u00a0Monitoring plan.\n3.7.\u00a0\u00a0\u00a0Statistical considerations, with justification, including a power calculation for the sample size, if applicable.\n3.8.\u00a0\u00a0\u00a0Data management.\n3.9.\u00a0\u00a0\u00a0Information about any amendments to the CIP.\n3.10.\u00a0\u00a0\u00a0Policy regarding follow-up and management of any deviations from the CIP at the investigational site and clear prohibition of use of waivers from the CIP.\n3.11.\u00a0\u00a0\u00a0Accountability regarding the device, in particular control of access to the device, follow-up in relation to the device used in the clinical investigation and the return of unused, expired or malfunctioning devices.\n3.12.\u00a0\u00a0\u00a0Statement of compliance with the recognised ethical principles for medical research involving humans, and the principles of good clinical practice in the field of clinical investigations of devices, as well as with the applicable regulatory requirements.\n3.13.\u00a0\u00a0\u00a0Description of the Informed consent process.\n3.14.\u00a0\u00a0\u00a0Safety reporting, including definitions of adverse events and serious adverse events, device deficiencies, procedures and timelines for reporting.\n3.15.\u00a0\u00a0\u00a0Criteria and procedures for follow-up of subjects following the end, temporary halt or early termination of an investigation, for follow-up of subjects who have withdrawn their consent and procedures for subjects lost to follow-up.\u00a0Such procedures shall for implantable devices, cover as a minimum traceability.\n3.16.\u00a0\u00a0\u00a0A description of the arrangements for taking care of the subjects after their participation in the clinical investigation has ended, where such additional care is necessary because of the subjects' participation in the clinical investigation and where it differs from that normally expected for the medical condition in question.\n3.17.\u00a0\u00a0\u00a0Policy as regards the establishment of the clinical investigation report and publication of results in accordance with the legal requirements and the ethical principles referred to in Section\u00a01 of Chapter I.\n3.18.\u00a0\u00a0\u00a0List of the technical and functional features of the device, with specific mention of those covered by the investigation.\n3.19.\u00a0\u00a0\u00a0Bibliography.\n4.\u00a0\u00a0\u00a0Other information\n4.1.\u00a0\u00a0\u00a0A signed statement by the natural or legal person responsible for the manufacture of the investigational device that the device in question conforms to the general safety and performance requirements apart from the aspects covered by the clinical investigation and that, with regard to those aspects, every precaution has been taken to protect the health and safety of the subject.\n4.2.\u00a0\u00a0\u00a0Where applicable according to national law, copy of the opinion or opinions of the ethics committee or committees concerned. Where according to national law the opinion or opinions of the ethics committee or committees is not required at the time of the submission of the application, a copy of the opinion or opinions shall be submitted as soon as available.\n4.3.\u00a0\u00a0\u00a0Proof of insurance cover or indemnification of subjects in case of injury, pursuant to Article\u00a069 and the corresponding national law.\n4.4.\u00a0\u00a0\u00a0Documents to be used to obtain informed consent, including the patient information sheet and the informed consent document.\n4.5.\u00a0\u00a0\u00a0Description of the arrangements to comply with the applicable rules on the protection and confidentiality of personal data, in particular:\n\n\n\n\n\n\n\u2014\n\n\norganisational and technical arrangements that will be implemented to avoid unauthorised access, disclosure, dissemination, alteration or loss of information and personal data processed;\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na description of measures that will be implemented to ensure confidentiality of records and personal data of subjects; and\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\na description of measures that will be implemented in case of a data security breach in order to mitigate the possible adverse effects.\n\n\n\n\n4.6.\u00a0\u00a0\u00a0Full details of the available technical documentation, for example detailed risk analysis/management documentation or specific test reports, shall, upon request, be submitted to the competent authority reviewing an application.\nCHAPTER III\n\nOTHER OBLIGATIONS OF THE SPONSOR\n\n1.\u00a0\u00a0\u00a0The sponsor shall undertake to keep available for the competent national authorities any documentation necessary to provide evidence for the documentation referred to in Chapter\u00a0II of this Annex. If the sponsor is not the natural or legal person responsible for the manufacture of the investigational device, that obligation may be fulfilled by that person on behalf of the sponsor.\n2.\u00a0\u00a0\u00a0The Sponsor shall have an agreement in place to ensure that any serious adverse events or any other event as referred to in Article\u00a080(2) are reported by the investigator or investigators to the sponsor in a timely manner.\n3.\u00a0\u00a0\u00a0The documentation mentioned in this Annex\u00a0shall be kept for a period of at least 10 years after the clinical investigation with the device in question has ended, or, in the event that the device is subsequently placed on the market, at least 10 years after the last device has been placed on the market. In the case of implantable devices, the period shall be at least 15 years.\nEach Member\u00a0State shall require that this documentation is kept at the disposal of the competent authorities for the period referred to in the first subparagraph\u00a0in case the sponsor, or its contact person or legal representative as referred to in Article\u00a062(2) established within its territory, goes bankrupt or ceases its activity prior to the end of this period.\n4.\u00a0\u00a0\u00a0The Sponsor shall appoint a monitor that is independent from the investigational site to ensure that the investigation is conducted in accordance with the CIP, the principles of good clinical practice and this Regulation.\n5.\u00a0\u00a0\u00a0The Sponsor shall complete the follow-up of investigation subjects.\n6.\u00a0\u00a0\u00a0The Sponsor shall provide evidence that the investigation is being conducted in line with good clinical practice, for instance through internal or external inspection.\n7.\u00a0\u00a0\u00a0The Sponsor shall prepare a clinical investigation report which includes at least the following:\n\n\n\n\n\n\n\u2014\n\n\nCover/introductory page or pages indicating the title of the investigation, the investigational device, the single identification number, the CIP number and the details with signatures of the coordinating investigators and the principal investigators from each investigational site.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nDetails of the author and date of the report.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nA summary of the investigation covering the title, purpose of the investigation, description of the investigation, investigational design and methods used, the results of the investigation and conclusion of the investigation. The completion date of the investigation, and in particular details of early termination, temporary halts or suspensions of investigations.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nInvestigational device description, in particular clearly defined intended purpose.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nA summary of the clinical investigation plan covering objectives, design, ethical aspects, monitoring and quality measures, selection criteria, target patient populations, sample size, treatment schedules, follow-up duration, concomitant treatments, statistical plan, including hypothesis, sample size calculation and analysis methods, as well as a justification.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nResults of the clinical investigation covering, with rationale and justification, subject demographics, analysis of results related to chosen endpoints, details of subgroup analysis, as well as compliance with the CIP, and covering follow-up of missing data and of patients withdrawing from the clinical investigation, or lost to follow-up.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nSummary of serious adverse events, adverse device effects, device deficiencies and any relevant corrective actions.\n\n\n\n\n\n\n\n\n\n\n\u2014\n\n\nDiscussion and overall conclusions covering safety and performance results, assessment of risks and clinical benefits, discussion of clinical relevance in accordance with clinical state of the art, any specific precautions for specific patient populations, implications for the investigational device, limitations of the investigation.\n\n\n\n\n\n\n\n\n\nANNEX XVI\n\nLIST OF GROUPS OF PRODUCTS WITHOUT AN INTENDED MEDICAL PURPOSE REFERRED TO IN ARTICLE 1(2)\n\n\n\n\n\n\n\n\n\n1.\n\n\nContact lenses or other items intended to be introduced into or onto the eye.\n\n\n\n\n\n\n\n\n\n\n\n\n2.\n\n\nProducts intended to be totally or partially introduced into the human body through surgically invasive means for the purpose of modifying the anatomy or fixation of body parts with the exception of tattooing products and piercings.\n\n\n\n\n\n\n\n\n\n\n\n\n3.\n\n\nSubstances, combinations of substances, or items intended to be used for facial or other dermal or mucous membrane filling by subcutaneous, submucous or intradermal injection or other introduction, excluding those for tattooing.\n\n\n\n\n\n\n\n\n\n\n\n\n4.\n\n\nEquipment intended to be used to reduce, remove or destroy adipose tissue, such as equipment for liposuction, lipolysis or lipoplasty.\n\n\n\n\n\n\n\n\n\n\n\n\n5.\n\n\nHigh intensity electromagnetic radiation (e.g. infra-red, visible light and ultra-violet) emitting equipment intended for use on the human body, including coherent and non-coherent sources, monochromatic and broad spectrum, such as lasers and intense pulsed light equipment, for skin resurfacing, tattoo or hair removal or other skin treatment.\n\n\n\n\n\n\n\n\n\n\n\n\n6.\n\n\nEquipment intended for brain stimulation that apply electrical currents or magnetic or electromagnetic fields that penetrate the cranium to modify neuronal activity in the brain."}, {"title": "Guidance-on-Article-15-MDR-IVDR-Person-responsible-for-Regulatory-Compliance.pdf.txt", "text": "This document has been endorsed by the Medical Device Coordination Group (MDCG) \nestablished by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of \nrepresentatives of all Member States and it is chaired by a representative of the European \nCommi ssion.  \nThe document is not a European Commission document and it cannot be regarded as \nreflecting the official position of the European Commission. Any views expressed in this \ndocument are not legally binding and only the Court of Justice of the European Union can give \nbinding interpretations of Union law.  \n1 \n MDCG 2019- 7 \nGuidance  on Article 15 of the Medical Device Regulation (MDR) and \nin vitro Diagnostic Device Regulation (IVDR) regarding a \u2018person \nresponsible for regulatory compliance\u2019 (PRRC)  \nManufacturers1 (paragraph 1)  \n\u201cManufacturers shall have available within their organisation at least one person \nresponsible for regulatory compliance who possesses the requisite expertise in the \nfield of medical devices. The requisite expertise shall be demonstrated by either of the \nfollowing qualifications:   \n(a) a diploma, certificate or other evidence of formal qualification, awarded on \ncompletion of a university degree or of a course of study recognised as equivalent by \nthe Member State concerned, in law, medicine, pharmacy, engineering or another \nrelevant scientific discipline, and at least one year of professional experience in \nregulatory affairs or in quality management systems relating to medical devices;  \n(b) four years of professional experience in regulatory affairs or in quality management \nsystems relating to medical devices.  \nWithout prejudice to national provisions regarding professional qualifications, \nmanufacturers of custom -made devices may demonstrate the requisite expertise \nreferred to in the first subparagraph by having at least two years of professional \nexperience within a relevant field of manufacturing. \u201d \nClarification on qualifications  \nIt shall be noted that : \n- For the purpose of fulfilling the requirement laid down in point \u201c a\u201d of Article 15 \n(1), any qualification acquired outside the EU, including any university diplomas \nor certificates, should have been recognised by an EU Member State as \nequivalent to the EU corresponding qualification.  \n                                                           \n1  Enterprises which employ at least  50 persons and whose annual turnover and/or annual balance sheet total \nexceeds EUR 10 million (Commission Recommendation 2003/361/\u0395 C of 6 May 2003) . 2 \n - Professional experience in regulatory a ffairs or in quality management systems \nrelating to medical devices  should be related to the EU requirements in the field .  \nMeaning of \u201cwithin their organisation\u201d  \nThe person responsible for regulatory compliance (PRRC) appointed would need to \nbe an employee of the organisation.  \nOrganisations with more than one legal manufacturer  \nOrganisations with more than one legal manufacturer under the parent company would \nneed to ensure that each legal manufacturer has its own PRRC.2 \nCan the PRRC be located out side the EU?  \nAs to the location of the PRRC, it is important that a close linkage, of a permanent and \ncontinuous nature, is established between the PRRC and the manufacturing activities. \nFor this reason,  for manufacturers located outside the EU, it must be assumed that the \nPRRC should also be located outside the EU. On the other hand, for manufacturers \nlocated in the EU, it must be assumed that the PRRC should also be located in the EU.  \nMicro and small manufacturers3 (paragraph 2)  \n\u201cMicro and small enterpri ses within the meaning of Commission Recommendation \n2003/361/EC shall not be required to have the person responsible for regulatory \ncompliance within their organisation but shall have such person permanently \nand continuously at their disposal .\u201d \nMeaning of \u201cpermanently and continuously at their disposal\u201d  \nThe micro or small enterprise may subcontract the responsibilities of a person \nresponsible for regulatory compliance to a third party, so long as the qualification \ncriteria is met and the manufacturer can de monstrate and document how they can \nmeet their legal obligations. For example, the PRRC may be part of an external \norganisation, with which the manufacturer has established a contract lay ing down \nprovisions so as to ensure the permanent and continuous availability of that party. The \ncontract should mention the relevant person\u2019s qualifications allowing compliance with \npoints a and b of Article 15 (1).  \nCan the PRRC be located outside the EU?  \nFor micro or small enterpr ises located in the EU, it must be assumed that any person \nto be permanent ly and continuously at their  disposal should be also located in the EU . \n                                                           \n2  In the context of Article 15, the obligation for having available within the organisation at least one PRRC refers \nto the individual legal manufacturer.  \n3  Enterprises which employ fewer than  50 persons and whose annual turnover and/or annual balance sheet \ntotal does not exceed EUR 10 million (Commission Recommendation 2003/361/\u0395C of 6 May 2003) . 3 \n Authorised representatives (paragraph 6)  \n\u201cAuthorised representatives shall have permanently and continuously at their \ndisposal  at least one person responsible for regulatory compliance who possesses \nthe requisite expertise regarding the regulatory requirements for medical devices in the \nUnion. The requisite expertise shall be demonstrated by either of the followi ng \nqualifications:  \n(a) a diploma, certificate or other evidence of formal qualification, awarded on \ncompletion of a university degree or of a course of study recognised as equivalent by \nthe Member State concerned, in law, medicine, pharmacy, engineering or another \nrelevant scientific discipline, and at least one year of professional experience in \nregulatory affairs or in quality management systems relating to medical devices;  \n(b) four years of professional experience in regulatory affairs or in quality management \nsystems relating to medical devices. \u201d \nMeaning of \u201cpermanently and continuously at their disposal\u201d  \nThe authorised representative may subcontract the responsibilities of a person \nresponsible for regulatory compliance to a third party, so long as the qualification \ncriteria is met and the authorised representative can demonstrate and document how \nthey can meet their legal obligations. For example, the PRRC may be part of an \nexternal organisation with which the authorised representative has established e a \ncontract laying down provisions so as to ensure the permanent and continuous \navailability of that party.  The contract should mention the relevant person\u2019s \nqualifications allowing compliance with points a and b of Article 15 (1).  \nCan the PRRC be located outside the EU?  \nTaking into account that the Authorised Representative is located in the EU, it must be \nassumed that any person to be permanently and continuously at its disposal should be \nalso located in the EU . \nRoles and responsibilities of the person r esponsible for regulatory compliance \nwithin a manufacturer (paragraph 3)  \nFor the purpose of this position paper, the roles and responsibilities of a PRRC have \nbeen cross -referred to the roles and responsibilities of a manufacturer, as stated in \nArticle 10 of the MDR and IVDR. This paper does not interpret the roles and \nresponsibilities of a PRRC. We recommend that any guidance on post -market \nsurveillance, vigilance, clinical investigations and performance studies, created at a \nEuropean level, should cross -refer to Article 15, paragraph 3 to provide guidance on \nwhat a PRRC of a manufacturer would be expected to do in these areas.  \n  4 \n \u201cThe person responsible for regulatory compliance shall at least be responsible for \nensuring that:  \n(a) the conformity of the dev ices is appropriately checked, in accordance with the \nquality management system under which the devices are manufactured, before a \ndevice is released; \u201d  \nManufacturers \u201cof devices, other than investigational [performance study] devices, \nshall establish, document, implement, maintain, keep up to date and continually \nimprove a quality management system that shall ensure compliance with this \nRegulation in the most effective manner and in a manner that is proportionate to the \nrisk class and the type of device\u201d (Article 10(9) of the MDR and Article 10(8) of the \nIVDR).  \n\u201c(b) the technical documentation and the EU declaration of conformity are drawn up \nand kept up- to-date; \u201d \nManufacturers \u201c[of devices other than custom -made devices] shall draw up and keep \nup to date technical documentation for those devices\u201d (Article 10(4) of the MDR and \nIVDR) and \u201cshall draw up an EU declaration of conformity\u201d (Article 10(6) of the MDR \nand Article 10(5) of the IVDR).  \n\u201c(c) the post -market surveillance obligations are complied with in accordance with \nArticle 10(10) [Article 10(9) of the IVDR]; \u201d \nManufacturers \u201cof devices shall implement and keep up to date the post -market \nsurveillance system\u201d (Article 10(10) of the MDR and Article 10(9) of the IVDR).  \n\u201c(d) the reporting obligations ref erred to in Articles 87 to 91 [Article 82 and 86 of the \nIVDR] are fulfilled; \u201d \nManufacturers \u201cshall have a system for recording and reporting of incidents and field \nsafety corrective actions as described in Articles 87 and 88\u201d (Article 10(13) of the MDR \nand Article 10(12) of the IVDR).  \n\u201c(e) in the case of investigational devices, the statement referred to in Section 4.1 of \nChapter II of Annex XV [Section 4.1 of Annex XIV of the IVDR] is issued. \u201d \nManufacturers shall ensure that \u201ca signed statement by the natural or legal person \nresponsible for the manufacture of the investigational device [for performance study] \nthat the device in question conforms to the general safety and performance \nrequirements apart from the aspects covered by the clinical investigati on [performance \nstudy] and that, with regard to those aspects, every precaution has been taken to \nprotect the health and safety of the subject.\u201d  \n  5 \n Roles and responsibilities of the person responsible for regulatory compliance \nwithin an authorised represent ative (paragraph 3)  \nThe PRRC of an AR should be responsible for ensuring that the tasks of an AR  as \nspecified in the given mandate, in accordance with Article 11(3), are fulfilled. . \nCan one individual be the PRRC for a manufacturer and its authorised representative?  \nThe person responsible for regulatory compliance for an authorised representative and \nfor an 'outside EU' manufacturer cannot be the same person. There is a clear desire \nwithin the Regulations for the authorised representative to be adding an additional level \nof scrutiny and ensure that the supervision and control of the manufacture of devices, \nand the relevant post -market surveillance and vigilance activities  are adequately \neffected. If the two roles were conducted by the same person, the additional level of \nscrutiny would be undermined.  \nFor the same reason, the PRRC of a micro or small enterprise and the PRRC of the \nauthorised representative of that same enterprise shall not belong to the same external \norganisation."}, {"title": "md_mfr_stepbystep.pdf.txt", "text": "Implementation Model for\nMedical Devices  \nRegulation  \nStep by Step Guide\nMEDICAL DEVICES  CHANGE OF LEGISLATION\n1STEP  INTENTION / ACTION\nPre-assessmentBrief management to ensure a clear understanding of the importance and  \nbusiness implications of the MDR\nConsider organisational challenges: management awareness,  \nstaffing capability and availability, budget implications\nGAP analysis and actions  \nresulting from thisAssess impact on products, internal resources, organisation and budget\nCheck new classification rules (MDR Classes I, IIa, IIb and III) and confirm conformity \nassessment routes for existing and future products\nCheck the new definition of MD, particularly with respect to its expanded scope. \nThis also applies to products covered in Annex XVI\nReview the changes needed to existing technical documentation (Technical Files)\nReview and upgrade quality management system (QMS) (point 3 below)\nCheck the adequacy of available clinical evidence and risk  \nmanagement and identify any gaps (Article 61)\nReview product labelling (Annex I Chapter III)\nEnsure post-market surveillance (PMS) arrangements are adequate (Chapter VII \nSection 1)\nPrepare a post-market clinical follow-up plan (PMCF, Annex XIV Part B)\nGet ready for the new vigilance requirements (Chapter VII Section 2)\nEnsure the respect of traceability obligations (Chapter III) \nQuality Management  \nSystem (QMS)Review adequacy of QMS to meet standards and processes for medical devices \nunder the new Regulation\nBuild new regulatory requirements into the QMS\nIdentify/hire the person responsible for regulatory compliance within your  \norganisation (Article 15) and be sure it is adequately qualified and trained1\n2\n3What you need to know!\nInternal market, \nIndustry,  \nEntrepreneurship  \nand SMEs2Legal entitiesClarify how the company is affected: legal entities, obligation of economic  \noperators, organisational structures and resources\nConsider organisational challenges: management awareness, staffing capability \nand availability, budget implications\nEnsure product liability insurance is adequate\nPortfolioDo a cost/benefit analysis for your product portfolio; bear in mind costs for the \npossible upgrade of risk class of MDs and for the new procedures for conformity \nassessment as well as the costs for post-market surveillance and gaps in the \ntechnical documentation, and plan your transition to the MDR accordingly\nReview supply chain provisions, and clarify roles and responsibilities of business \npartners (authorised representatives, importers, distributors)\nMaster  \nimplementation planBuild a roadmap for implementation, including definition of sub-projects,  \nresource requirements and a steering group, and ensure overall responsibility for \nMDR implementation has been established\nGive special consideration to certificate expiry dates, bearing in mind the  \ntransitional period, transitional provisions and availability of your Notified Bodies\nNotified BodiesContact the selected Notified Bodies and determine their capacity and  \navailability to service the implementation plan\nRegulatory trainingEmpower and train staff through MDR implementation and transition workshops\nExecute master  \nimplementation planImplement the various sub-projects (clinical evaluation, technical documentation, \nrelation with other economic operators, Unique Device Identification, labelling,  \nregistration, post-market surveillance, vigilance, and reporting IT systems)\nEnsure a cross-functional project management team is in place to cover all \naspects of implementation\nEnsure overall and individual responsibilities for MDR implementation have been \nestablished\nReview efficiency and  \neffectivenessImplement regular meetings on project status and progress, discrepancy and \ngap analyses, risks, next steps and requirements\nHold regular progress reviews against the MDR implementation plan and include \nthese in the management review process\nNotified Body submissionDiscuss submission dates to avoid delays in the approval process\nOngoing monitoringActively monitor the still-developing European regulatory environment and \nguidelines expected in the coming months (check DG GROW web pages on  \nmedical devices and subscribe to the newsletter)\nEstablish a procedure for dealing with unannounced inspections from Notified Bodies\nRegularly review the MDR implementation plan, identifying and addressing key \nareas of risk4\n5\n6\n7\n8\n9\n10\n11\n12\n\u00a9 European Union, [2018]  Reuse is authorised provided the source is acknowledged.\nThe reuse policy of European Commission documents is regulated by Decision 2011/833/EU (OJ L 330, 14.12.2011, p. 39).\nET-03-18-103-EN-N\nISBN: 978-92-79-89702-3    DOI: 10.2873/66341"}, {"title": "MDCG 2019-8 v2 Implant guidance Card.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document                                               MDCG 2019-8 v2    \n \n \n \n       \n   MDCG 2019-8 v2  \nGuidance document \nImplant Card relating to the application  \n       of Article 18 Regulation (EU) 2017/745  \n       of the European Pa rliament and of the Council  \n       of 5 April 2017 on medical devices           \n \n             March 2020 \n \n \n  \n \nThis document has been endorsed b y the Medical Device Coordinat ion Group (MDCG) established by \nArticle 103 of Regulation (EU) 2017/745. The MDCG is composed o f representatives of all Member \nStates and it is chaired by a representative of the European Co mmission. \nThe document is not a European Commission document and it canno t be regarded as reflecting the \nofficial position of the European Commission. Any views express ed in this document are not legally \nbinding and only the Court of Justice of the European Union can  give binding interpretations of Union \nlaw. \n \n \n  Medical Devices: Guidance document \nImplant Card relating to the app lication of Article 18 Regulati on (EU) 2017/745 of the \nEuropean Parliament and of the Council of 5 April 2017 on medic al devices \n \n  List of Content \n \n1. Scope ............................................................................................................... 4  \n2. Purposes of the Implant Card ..................................................................... 4  \n3. Legal consideration on Implant Card design ........................................... 4  \n4. Information to be provided by the manufacturer on the Implant Card \nand information to be added by the health institution ........................... 5  \n5. Use of symbols .............................................................................................. 6  \n6. Language requirements on specific fields ................................................ 7  \n7. Benefits of an informativ e instruction leaflet ........................................... 7  \n8. Implant Card for implantable systems ...................................................... 7  \nAnnex I examples of principle designs of Implant Cards and leaflets ....... 8  \n \n  1. Scope \nThis document provides guidance for Memb er States, concerned industry and other \nstakeholders on a blueprint of an implant card (IC) required by the MDR (Regulation (EU) \n2017/745). It describes the intended use, cont ent and information to be provided by the \nmanufacturer together on the IC and a definition of fields to be completed by the implanting \nhealthcare institutions or healthcare provider s according to national law in Member States. \nWhereas the intended purpose and most of the da ta elements of the IC are already defined in \nArticle 18 of the MDR, this document contains the description of other data elements which must be completed by the healthcare institution or healthcare provider and which must be considered by the individual Member State wh en implementing Article 18 MDR as required\n1. \n2. Purposes of the Implant Card \nThe aim of introducing an IC has been to achieve three main objectives: \n1. Enable the patient to identify the impl anted devices and to get access to other \ninformation related to the implanted device (e.g. via EUDAMED, and other websites). \n2. Enable patients to identify themselves as persons requiring special care in relevant \nsituations e.g. security checks. \n3. Enabling e.g. emergency clinical staff or fi rst responder to be informed about special \ncare/needs for relevant patients in case of emergency situations. \n3. Legal consideration on Implant Card design \nArticle 18 MDR describes the requirements rega rding the IC which shall be provided by the \nmanufacturer together with the device. Wherea s Article 18 para 1a) describes the information \nwhich shall be provided by the manufacturer on the IC, Article 18 pa r a  2  l a y s  d o w n  t h e  \nobligation of Member States to require health in stitutions to provide the IC to the concerned \npatient. In accordance with Article 18, 1a) the manufact urer should provide th e following information \non the IC (preferably on the card itself or, alternatively, as stickers to be placed by the clinician): \n\u0081 Device name; \n\u0081 Serial number, lot number; \n\u0081 Unique device identification (UDI); \n\u0081 Name, address and the website of manufacturer; \n\u0081 Device type.\n2  \nArticle 18, 2 lays down that Member States shall require health institutions (or healthcare \nproviders) inter alia to make available the IC to the relevant patient. The IC should bear their \n                                                      \n1 This guidance doesn\u2019t include the patient information described in Ar ticle 18 para 1 (b-d) which might \nbe provided by the manufacturer by any means that allow rapid access to that information and that \nshall be stated in the language(s) determined by the concerned Member State.  \n2 In Article 18 1a) of the MDR, the term \u201cdevice model\u201d  is used. However, this term which is not defined \nin the MDR, is part of the UDI-DI related info r m a t i o n  t o  b e  p r o v i d e d  t o  E U D A M E D .  T o  a v o i d  \nduplication and in the context of the intended purpos e of the IC (to be used in situations requiring \nspecial care or in emergency situations), it is cons idered that reference to device model in the MDR for \nthe purpose of the IC shall be read as reference to device type, like \u201cpacemaker\u201d, \u201chip implant\u201d, etc. \nWhen the European Medical device nomenclature is made available, a \u201cstandardised\u201d set of terms of \nthis nomenclature should be recommended for use in relation to the field \u201cdevice type\u201d.  identity . For this purpose, the IC provided togeth er with the device should contain blank \nfields which shall be filled out by the health institution or healthcare provider, respectively. \nSince the establishment of (and the logistics behind) many different national IC designs is very \nexpensive and of no additional benefit, Member States should ensure that, in the context of \nnational implementation of Article 18 of the MD R, only the following information is required \nto be provided by the health institution or healthcare provider on the IC (together with the information provided by the manufacturer). Accordingly, a European or international \nblueprint for an IC which supports the purposes  described in Article 18, 2 should contain the \nfollowing blank fields: \n1. Name of the patient or patient ID; \n2. Name and address of the health institution or healthcare provider who performed the \nimplantation; \n3. Date of implantation. \nIn order to be fit for the purposes described in Article 18, the outer dimensions of the IC should \nbe the same as those of credit cards, ATM cards or ID cards (85.60 mm \u00d7 53.98 mm /3 3 \u20448 \u00d7 \n2 1\u20448  inches) and with a radius of 2.88\u20133.48 mm\n3. \n4. Information to be provided by the  manufacturer on the Implant \nCard and information to be adde d by the health institution \nThe manufacturer shall provide the following necessary information: \n1. Device name; \n2. Device type; \n3. Serial number or, where app licable, lot or batch number; \n4. Unique device identification (UDI); the UDI as AIDC4 format and the UDI-DI as HRI5 \n5. Name and address of the manufacturer of the medical device; \n6. Website of the manufacturer of the medical device. \nThe text provided on the IC and on the instru ction for completing the IC by the healthcare \ninstitution or healthcare provider must be legible and at least 2 millimetres high. \u2018Text\u2019 includes any: number, letter,  symbol, or  letter or number in a symbol.   \nIn addition, the manufacturer shou ld design the IC in a way that the following blank fields to \nbe filled out by the implanting healthcare institution or healthcare provider are available: \n1. Name of the patient or patient ID; \n2. Name and address of the healthcare inst itution which performed the implantation; \n3. Date of implantation. \n  \n                                                      \n3 Dimensions to conform to the standard ISO/IEC 7810 ID-1.  \n4 AIDC - Automatic identification and data capture format (e.g. linear or 2D-Barcodes)  \n5 HRI - Human readable interpretation   5. Use of symbols \nTo avoid national versions of the IC , the use of symbols is advisable.  \nThe following list contains symbols which have either been validated by users and have been \nsubmitted and accepted for inclusion in an upco ming international standard or already exist \nin the ISO database (Online Browsing Platform). The explanation of symbols on the IC should \nbe provided in a leaflet (see section  7) or  on the back of the IC, if space allows. \nArticle 18(1) lays down that the information provided in the IC shall be stated in the \nlanguage(s) determined by the concerned Member State. \nList of symbols recommended for use on the IC6: \n \n \n  \n Patient Name or patient ID\n \n \n \n \n Date of implantation  \n \n \n \n  Name and Address of the implanting healthcare \ninstitution/provide\nr  \n \n \n \n Name and Address of the manufacturer  \n Information website for patients  \n Device Name7 \n \n Serial Number  \n \n \n Lot Number/Batch Code  \n \n                                                      \n6 The symbols for patient name or patient ID, name and ad dress of the implanting healthcare institution/provider, \ndate of implantation, name and address of the manufacturer, serial number, lot number/batch code are already available and published in existing ISO standards. The symbols for device name, patient information website and \nUDI have been validated by users according to the ISO 15223-2 process. Note that the symbols listed here to indicate \nthe following terms: \u2018Device Name\u2019, \u2018Patient Name or Pati ent ID\u2019, \u2018Date of Implantation\u2019, \u2018Name and address of the \nimplanting healthcare institution/provider\u2019 on the implant card, are used in the ISO context to indicate \u2018Medical Device\u2019, \u2018Patient Identification\u2019, \u2018Date\u2019, \u2018Health Care Center or Doctor\u2019.   \n7 Please note that in the ISO context, the \u2018MD\u2019 symbol is used to identify that the product in question is a medical \ndevice. On the implant card, this symbol is used to indicate the device name.  \n \n UDI as AIDC format  \nUDI-DI information in a HRI format should  be introduced by the wording \u201cUDI-DI\u201d. \n6. Language requirements on specific fields \nDespite the nearly complete list of symbols for fields on the IC, there is currently no symbol \navailable for the required field \u201cDevice Type\u201d. \nThe lack of a symbol and the purpose of this field makes it necessary that the information on \nthe device type must be provided in the language accepted/required by the concerned \nMember State. \nThere are several possibilities available to provid e this information in the necessary languages, \ne.g. the information is already printed on the IC in the different languages or stickers are \nprovided with the IC and the healthcare professional selects the right one etc. \n7. Benefits of an informati ve instruction leaflet8 \nAs mentioned above (section 5), there is a need to provide, together with the IC, instructions \non how to complete the IC and to explain the us ed symbols. This information shall be stated \nin the language(s) determined by the concerned Member State. For this reason, the use of a leaflet, containing the relevant information, to be provided together with the IC and the \nimplantable device, is the recommended solution.  \nAs part of the risk management, the manufacturer has to investigate, by means of an \nergonomic analysis or ergonomic usability test procedure, if the provided instructions are \nsufficient to enable the health professional to complete the IC correctly. The instructions must reflect the solution chosen by the manufacturer (e .g. pre-printed IC, blank IC with sticker(s) to \nbe added, mixture of both). Special considerat ions might be needed when providing a system \nIC or an IC for a separate implantable compon ent, when there is not yet a common practice \n(standard) established.  \n8. Implant Card for implantable systems \nIf an implantable device contains implantable components which might be replaced by other \n(or the same) components, for example in case of a later revision, the manufacturers should \nconsider the use of a System IC. In Annex I to this guide an example is provided. \nW a y s  c o u l d  b e  e x p l o r e d  b y  r e l e v a n t  s t a k e h o l d e r s  t o  d e v e l o p  c o m m o n  r u l e s  o n  h o w  t h e  \nnecessary information to be placed on the Sy stem IC is delivered with the replaceable \ncomponent and how health professionals could en sure t hat  the  System  I C is  appropriately  \nupdated, when necessary. \n  \n                                                      \n8 This leaflet should not be confused with any possible vector of information referred to in points \u201cb\u201d, \u201cc\u201d and \u201cd\u201d \nof Article 18(1) of the MDR.  UDI Annex I examples of principle designs of Implant Cards and leaf lets \n \nGENERAL NOTE: All examples contained in this  Annex are to be intended as illustrative \nexamples only.9  \nThe basic shape of the IC shall be designed in  compliance with ISO/IEC 7810 ID-1 (credit card \nform). \nThe following pictures provide exam ples for individual device ICs.  \nExample 1: \n \nFront \u2013 Not to scale (handwritten text on pre-printed content) \n \n \n \n \n \n \n \n \n \nBack \u2013 Not to scale (blank \u2013 serial printed content in \nproduction) \n \n \n \n \n  \n                                                      \n9 Please note that this includes translations (into languages other than English) shown in Examples \nthroughout Annex 1, which are machine translated and not intended to be read as official translations \ninto EU languages. International Implant Card \nhttps://www.genericmed.com/patientimplantinfo John Smith\n27/05/2021\nABC Healthcare Center\n123 Medical Parkway, Cork, Ireland\nDr. H.C. Professional\nPM-5503  Pacer Advanced \nUDI-DI: (01)01865494261654  \nSN79856214  \nGenericmed \n500 Genericmed Place, Minneapolis, MN 55123 USA \nwww.genericmed.com \n \n \n \n    Example 2: \nBack \u2013 Not to scale (blank \u2013 batch/lot printed content in \nproduction) \n \n \n \n \n \n \n \n \n \n \n \n  PM-5503  Pacer Advanced \nUDI-DI: (01)03584124658462  \nGenericmed \n500 Genericmed Place, Minneapolis, MN 55123 USA \nwww.genericmed.com AO.582122\nExample 3 (suggested design of a foldable System IC): \nTo be able to represent medical device syst ems in one IC, the IC shall be available in \ncollapsible form.  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n     ABC Healthcare CenterInternational Implant Card \nwww.genericmed.com/patientimplantinfo John Smith \n27/05/2021 \n123 Medical Parkway\nDr. H.C. Professional\nGenericmed  \n500 Genericmed Place,  \nMinneapolis, MN 55123 USA \nwww.genericmed.com  \nCork, Ireland PM-5503 \nPacer Advanced Pacemaker \nUDI-DI: (01)85412654285216 \nSN65695452 \nGenericmed  \n500 Genericmed Place,  \nMinneapolis, MN 55123 USA \nwww.genericmed.com  PL-55-4 \nPacer Lead Pro Pacemaker Lead \nUDI-DI: (01)89654213882154 \nSN86223214 \n \nExamples of IC Leaflet  \nFront 1 (no stickers \u2013 preferred option) \n \nInstruction for completion (to be provided in the language(s) determined by the concerned member State(s)) \n1. Name of the patient or patient ID. To be f illed by the healthcare institution/provider. \n2. Date of implantation. To be filled by  the healthcare institution/provider. \n3. Name and address of the healthcare institutio n/provider. To be filled by the healthcare \ninstitution/provider. \n \n   \n \n \n  \nPM-5503  \nPacer Advanced  \n(01)8541265428\n5216  \nSN65695452 \nGenericmed  \n500 Genericmed Place,  \nMinneapolis, MN 55123 www.genericmed.com/patientimplantinfo \n \n \nFront 2 (sticker only for device type information) \n \nInstruction for completion (to be provided in the language(s) determined by the concerned member State(s)) \n1. Name of the patient or patient ID. To be f illed by the healthcare institution/provider. \n2. Date of implantation. To be filled by  the healthcare institution/provider. \n3. Name and address of the healthcare instit ution. To be filled by the healthcare \ninstitution/provider. \n5. Add sticker with device type in required language. \n  \n \n \n \n \n \n  \n   \n \n \n  \n \nStickers (to be detached and placed on the righ t place at the IC according to the numbers)  \n \n  \nPM-5503  \nPacer Advanced  \n(01)85412654285216 \nGenericmed  \n500 Genericmed Place,  \nMinneapolis, MN 55123 SN65695452 www.genericmed.com/patientimplantinfo \n5 \n \nFront 3 (stickers)  \n \nInstruction for completion (to be provided in the language(s) determined by the concerned member State(s)) \n1. Name of the patient or patient ID. To be f illed by the healthcare institution/provider. \n2. Date of implantation. To be filled by  the healthcare institution/provider. \n3. Name and address of the healthcare institutio n/provider. To be filled by the healthcare \ninstitution/provider. \n4. Manufacturer\u2019s information website.  \n5. Device type in required language.  \n6. Device name.  \n7. UDI-DI Code (HRI). \n8. UDI code (AIDC format). \n9. Serial number. \n10. Name and address of the \nmanufacturer of the implanted \nmedical device.  \n \nNOTE: Fields 4-10 might be filled \nwith stickers (though this is not the \npreferred solution) \n  \n \n \n  \n \n \nStickers (to be detached and plac ed on the right place at the IC  according to the numbers)  \n5, 6 \n \n9 \n \n    8           \n \n 7 2 081019001 002 4  \n10 \n \n4 \n \nBack  \n Explanation/ transl ation of symbols \n Patient Name or patient ID, \u0418\u043c\u0435 \u043d\u0430 \u043f\u0430\u0446\u0438\u0435\u043d\u0442\u0430 , Jm\u00e9no pacienta, Patientens navn, \nPatientenname, \u038c\u03bd\u03bf\u03bc\u03b1 \u03b1\u03c3\u03b8\u03b5\u03bd\u03bf\u03cd\u03c2 , Nombre del paciente, Patsiendi nimi, Potilaan nimi, \nNom du patient, Ime i prezime bolesnika, Imi \u0119 i nazwisko pacjenta, A beteg neve, \nNome del paziente, Paciento vardas ir pavard \u0117, Pacienta v \u0101rds, uzv\u0101rds, Naam pati\u00ebnt  \nPasientens navn, A beteg neve, Nome do doente, Nume pacient, Meno pacienta, Ime bolnika, Patientens namn \n Name and Address of the implanting healthcare institution/provide r , \u00e9tablissement \nsanitaire, centro de salud, struttura sanitaria, Gesundheitseinrichtung, \ngezondheidszorginstelling, plac\u00f3wka s\u0142u \u017cby zdrowia, \u0437\u0434\u0440\u0430\u0432\u043d\u043e  \u0437\u0430\u0432\u0435\u0434\u0435\u043d\u0438\u0435, vesel\u012bbas \napr\u016bpes iest\u0101de, \u03b5\u03b3\u03ba\u03b1\u03c4\u03ac\u03c3\u03c4\u03b1\u03c3\u03b7 \u03b3\u03b9\u03b1 \u03c4\u03b7\u03bd \u03c5\u03b3\u03b5\u03af\u03b1  \n Date of Implantation , \u0414\u0430\u0442\u0430  \u043d\u0430 \u0438\u043c\u043f\u043b\u0430\u043d\u0442\u0438\u0440\u0430\u043d\u0435, Datum implantace, Implanteringsdato, \nImplantationsdatum, \u0397\u03bc\u03b5\u03c1\u03bf\u03bc\u03b7\u03bd\u03af\u03b1  \u03b5\u03bc\u03c6\u03cd\u03c4\u03b5\u03c5\u03c3\u03b7\u03c2,  \nFecha de implantaci\u00f3n, Implanteerimiskuup\u00e4ev, Implantointip\u00e4iv\u00e4m\u00e4\u00e4r\u00e4, Date d\u2019implantation, Datum implantacije, Be\u00fcltet\u00e9s d\u00e1tuma, Data dell'impianto, Implantavimo data, Implant \u0113\u0161anas datums, \nImplantatiedatum, Data wszczepienia , Data do implante, Data implant \u0103rii, D\u00e1tum \nimplant\u00e1cie, Datum vsaditve \n Device Name, Nazwa urz \u0105dzenia medy \ncznego, N\u00e1zev zdravotnick\u00fdch prost \u0159edk\u016f, Medicinsk enhed, Name des \nMedizinprodukts, Nombre del dispositivo m\u00e9dico, Nom du dispositif m\u00e9dical, Orvosi eszk\u00f6z neve, Namn p\u00e5 medicinsk enhet, Ime medicinske naprave Nome do dispositivo m\u00e9dico \n \u03ba\u03b1\u03c4\u03b1\u03c3\u03ba\u03b5\u03c5\u03b1\u03c3\u03c4\u03ae\u03c2, Producent, Fabrikant, Produttore, Fabricante, Fa bricant, manufacturer, \nHersteller  \n Information website for patients , Webov\u00e1 str\u00e1nka s informacemi pro pacienta, \nInformationswebsite for patienten, Webseite mit Informationen f\u00fcr Patienten, Sitio web \ncon informaci\u00f3n para el paciente, Site d'in formations pour le patient, Inform\u00e1ci\u00f3s \nhonlap betegek sz\u00e1m\u00e1ra, Sito web con le informazioni per i pazienti, Website met informatie voor pati\u00ebnten, Strona internetowa z informacjami dla pacjenta \n \n Translation of serial number in required languages. \n \n Translation of LOT number in required languages. \n Explanation of unique device identi fier (UDI) in required languages. \n \n \nPlace to attach the  \nImplant card"}, {"title": "md_guidance-manufacturers_en.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document    MDCG  2019 -15 rev1   \n \n \n \n \n \n \n \n \n \nMDCG  2019 -15 rev.1  \n        GUIDANCE NOTES FOR MANUFACTURERS  \n        OF CLASS I MEDICAL DEVICES              \n \n             December   2019  \n July 2020 rev.1  \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) established by \nArticle 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member \nStates and it is chaired by a representative of the European Commission.  \nThe document is not a European Commission document and it cannot be regarded as reflecting the \nofficial position of the European Commission. Any views expressed in this doc ument are not legally \nbinding and only the Court of Justice of the European Union can give binding interpretations of Union \nlaw. \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n2 \n  \nMDCG 2019 -15 revision 1 changes  \nMDR postponement dates: from 2020 to 2021  \n \n \n \n \n \nGUIDANCE NOTES FOR MANUFACTURERS  \nOF CLASS I  MEDICAL DEVICES  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n3 \n Contents  \nList of acronyms  ................................ ................................ ................................ ................................ .... 4 \nForeword  ................................ ................................ ................................ ................................ ................  5 \nIntroduction  ................................ ................................ ................................ ................................ ...........  5 \nDefinitions  ................................ ................................ ................................ ................................ ..............  8 \nPlacing on the market of Class I medical devices: The necessary steps  ................................ .........  11 \n0) Integrate MDR  in the Quality Management System (QMS).  ................................ ..................  11 \n1) Confirm product as a medical device  ................................ ................................ ........................  11 \n2) Confirm product as a Class I medical device  ................................ ................................ ............  11 \n3) Procedures before placing on the market  ................................ ................................ ..................  12 \na) Meet the general safety and performance requirements  ................................ .......................  12 \nb) Conduct clinical evaluation  ................................ ................................ ................................ ... 12 \nc) Prepare technical documentation  ................................ ................................ ..........................  14 \nd) Request Notified Body involvement  ................................ ................................ .....................  16 \ne) Prepare Instructions for Use and Labelling  ................................ ................................ ...........  16 \n4) Check compliance with general obligations for manufacturers  ................................ ................  17 \n5) Draw -up the EU Declaration of Conformity  ................................ ................................ .............  18 \n6) Affix the CE marking  ................................ ................................ ................................ ................  18 \n7) Registration of devices and manufacturers in Eudamed  ................................ ...........................  19 \n8) Post Market Surveillance (PMS)  ................................ ................................ ...............................  20 \na) Review experience gained from Post -Market Surveillance  ................................ ..................  20 \nb) Vigilance  ................................ ................................ ................................ ...............................  20 \nc) Non conforming products  ................................ ................................ ................................ ..... 22 \n \n \n \n \n \n \n \n \n \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n4 \n List of acronyms  \nMDD \u2013 Medical Devices Directive  \nMDR \u2013 Medical Devices Regulation  \nFSCA \u2013 Field Safety Corrective Action  \nFSN - Field Safety Notice  \nUDI - Unique Device Identifier  \nSRN - Single Registration Number  \nNB - Notified Body  \nISO - International Organization for Standardization  \nIEC - International Electrotechnical Commission  \nCA \u2013 Competent Authority  \nPPE \u2013 Personal Protective Equipment  \nQMS - Quality Management System  \nIm \u2013 Class I devices with measuring function  \nIs \u2013 Class I sterile devices  \nIr \u2013 Class I reusable surgical instruments  \nDI \u2013 Device Identifier  \nEudamed - European database on medical devices  \nMD - Medical Device   \nCS - Common Specification   \nPMS \u2013 Post Market Surveillance  \nIFU \u2013 Instructions for use   \nPMCF - Post Market Clinical Follow -up   Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n5 \n Foreword  \nThese guidance notes do not aim to be a definitive interpretation of Regulation (EU) 2017/745 of the \nEuropean Parliament and of the Council of 5 April 2017 on medical devices (MDR) and are intended for  \nguidance purposes only.  \n \nIntroduction  \nThe purpose of this document is to provide guidance to manufacturers of Class I medical devices (other \nthan custom made devices) who place on the Union market medical devices (from now on referred to as \ndevices) under their name or trade mark, to help them meet the provi sions of the MDR.  This guidance \nshould also be applicable for situations when an importer, distributor or any other legal person assumes \nthe obligations incumbent on manufacturers, as per Article 16 (1), while not  covering the exception \nindicated by Artic le 16 (2).  \nThe MDR has changed the scope of the medical device legislation and it now extends its application to \nall economic operators in the supply chain (manufacturer, authorised representative, importer and \ndistributor) as well as a broadened range of products such as those specifically intended for the cleaning, \ndisinfection or sterilization of devices (Article 2 (1)) and products without an intended medical purpose \n(such as certain aesthetic products, as indicated in Annex XVI of the MDR). In addition , more emphasis \nis placed on a life -cycle approach to safety, backed up by clinical data and new requirements such as \ntransparency and traceability1. \nBefore placing a device on the market, the manufacturer will affix the CE mark in accordance with \nAnnex V and draw up the EU declaration of conformity, including all the information required by \nAnnex IV. Prior to that, the manufacturer will demonstrate conformity with the MDR and compliance \nwith the applicable general safety and performance requirements laid o ut in Annex I.  \nIn order to accomplish the abovementioned tasks, the manufacturer will carry out the following:   \n\uf02d Put in place a quality management system and a system for risk management according to Article \n10(2) and 10(9).  \n\uf02d Conduct a clinical evaluation i n accordance with Article 61, as established in Article 10(3) and \nAnnex XV.   \n\uf02d Conduct a conformity assessment according to Article 52(7). In specific cases ( sterile devices, \ndevices with measuring function, reusable surgical instruments ) defined in the referred Article, \nthe manufacturer will request the involvement of a Notified Body (NB).    \n\uf02d Draw up and keep up -to-date technical documentation related to devices as set out in Annexes II \nand III, in accordance with Article 10(4).  \n\uf02d Draw up an EU declaration of conformity in accordance with Article 19.  \n\uf02d Submit the required information to the electronic system for registration of economic operators \n(Eudamed) and comply with the registration obligation. The manufacturer will use the Single \nRegis tration Number (SRN) when applying to a NB for conformity assessment, if applicable and \nfor further accessing Eudamed2 in order to fulfil its obligations related to registration of the \ndevices.  \n\uf02d Register the device in Eudamed assigning the Basic UDI -DI to t he device, as defined in Part C of \nAnnex VI, and provide this to the UDI database together with the other core data elements \nreferred in Part B of Annex VI related to that device.  \n\uf02d Assign to the device and, if applicable, to all higher levels of packaging,  a UDI which will allow \nidentification and traceability.  \n                                                      \n1  More information can be found at  https://ec.europa.eu/health/md_sector/overview   \n2  Regarding all references to Eudamed in this document, please be advised that for the purposes of this guidance, obligations s trictly related to \nEudamed will only apply when it is fully functional and any u pdates will be published on the EU Commission webpage.    Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n6 \n \uf02d Ensure that the device is accompanied by the information needed to identify it and its \nmanufacturer, and any safety and performance information relevant to the user, or any other \nperson, as appropria te (Article 10(11)). This information, set out according to Section 23 of \nAnnex I, must be provided in an official Union language(s) determined by the Member State in \nwhich the device is made available to the user or patient. The particulars on the label w ill be \nindelible, easily legible and clearly comprehensible to the intended user or patient.   \n\uf02d Implement a post -market surveillance system in accordance with Article 83 (Article 10(10)) \nproportional to the risk class and appropriate for the type of device,  this includes additional \naspects to be taken into account in case of devices placed on the market in sterile condition, with \na measuring function or that are reusable surgical instruments. This system will be an integral \npart of the manufacturer's quality  management system based on a post -market surveillance plan \n(Article 84) , which will be part of the technical documentation specified in Annex III.  \n\uf02d Implement a system for recording and reporting incidents and field safety corrective actions as \ndescribed in  Articles 87 and 88 (Article 10(13)).  \n\uf02d Put measures in place to provide sufficient financial coverage in respect of their potential liability \nunder Directive 85/374/EEC3, without prejudice to more protective measures under national law. \nThese measures will be proportional to the risk class, type of device and the size of the enterprise \n(Article 10(16)).  \nFurther detail on the aforementioned list of obligations is provided in the chapter \u201cPlacing Class I \nmedical devices on the market \u201d.  \nFor devices placed on the market in a sterile condition, with a measuring function or which are reusable \nsurgical instruments, the manufacturer will apply the procedures set out in Chapters I and III of Annex \nIX, or in Part A of Annex XI which require a NB assessment, limited t o critical aspects such as those \nconcerning sterile condition, metrological requirements and the reuse of the device, as relevant, \naccording with Article 52 (7 a, b and c).  \n                                                      \n3  Council Directive 85/374/EEC of 25 July 1985 on the approximation of the laws, regulations and administrative provisions of t he Member \nStates concerning liability for defective products  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n7 \n  \nFigure 1. Illustration of the conformity procedures for  the assessment of Class I devices with and \nwithout NB involvement.  \nFor big and medium size enterprises, the manufacturer will have available within their organization at \nleast one person responsible for regulatory compliance4, as established by Article 15. Micro and small \nenterprises5 are required to have such person permanently and continuously at their disposal.  \nA manufacturer with a registered place of business outside the Union will designate a sole authorised \nrepresentative, at least per each gener ic device group, according to a written mandate. Such a mandate \nwill establish the tasks to be performed by the authorised representative. To enable the fulfilment of \nthese tasks, the manufacturer ensures that the authorised representative has the necessar y documentation \npermanently available and up -to date. The mandate will require the authorised representative to perform \nat least the tasks described in Article 11(3),  however the manufacturer cannot delegate its obligations \nlaid down in Article 10(1), (2),  (3), (4), (6), (7), (9), (10), (11) and (12). In case of the  change of \nauthorised representative, Article 12 establishes the minimum content of agreement to be addressed \nbetween the manufacturer, where practicable the outgoing authorised representative, a nd the incoming \nauthorised representative.  \nUpon request, the manufacturer will provide all the information and documentation necessary to \ndemonstrate conformity of the device to competent authorities and cooperate with them on any \ncorrective action. If th e manufacturer does not cooperate or does not provide the requested information \nor documentation, the competent authority (CA) can adopt restrictive measures.  \nThe manufacturer should periodically verify whether implementing and delegated acts, common \nspeci fications, technical standards and guidelines might be available on the European Commission \nwebsite6. Such documents might for example cover specific parts of legislation (e.g. classification of \n                                                      \n4  See the  relevant MDCG guidance on Article 15 of MDR and IVDR regarding a \"person responsible for regulatory compliance\" (PRRC)  \n5  See Commission Recommendation 2003/361/EC  \n6  https://ec.europa.eu/health/md_sector/overview     \nClass I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n8 \n medical devices, clinical evaluation) or specific requirement s regarding certain medical device \ntechnologies (e.g. software, 3D printing ) that can also be applicable for Class I devices.  \nDuring the transitional period, manufacturers might be tempted to refer to guidance documents \ndeveloped under the Directive 93/42/ EC. However, the old guidance documents, unless otherwise \nupdated in line with the MDR, may have only some limited indicative value under the MDR. For the \npurpose of the MDR, only the text of the Regulation is valid in law and sets out requirements not \nreflected in the old guidance. Hence, the MDR alone can be relied upon as a  legal basis . \nDefinitions  \nFor the complete list of definitions refer to Article 2 of the MDR. This is an excerpt of some definitions.  \nAccessory for a medical device - means an article  which, whilst not being itself a medical device, is \nintended by its manufacturer to be used together with one or several particular medical device(s) to \nspecifically enable the medical device(s) to be used in accordance with its/their intended  purpose(s)  or \nto specifically and directly assist the medical functionality of the medical device(s) in terms of its/their \nintended purpose(s) (Article 2(2)) . \nAuthorised representative - means any natural or legal person established within the Union who has \nreceived  and accepted a written mandate from a manufacturer, located outside the Union, to act on the \nmanufacturer's behalf in relation to specified tasks with regard to the latter's obligations under the MDR \n(Arti cle 2(32)). The designation of an authorised repre sentative will be in compliance with Article 11 \nand effective at least for all devices o f the same generic device group  (Article 11(2)) . \nAdverse event - means any untoward medical occurrence, unintended disease or injury or any untoward \nclinical signs, inc luding an abnormal laboratory finding, in subjects, users or other persons, in the \ncontext of a clinical investigation, whether or not related to the investigational device  (Article 2(57)) . \nBenefit -risk determination  - means the analysis of all assessments of benefit and risk of possible \nrelevance for the use of the device for the intended purpose, when used in accordance with the intended \npurpose given by the manufacturer (Article 2(24)) . \nClass I medical devices with  measuring function - are considered Class I medical devices which measure \nphysiological parameters or anatomical parameter  or energy, respectively, or volume of medicinal \nproducts, body liquids or other substances administered to or removed from the body and display or \nindicate its value in a unit of measurement (example: urine bags, non -active thermometers,  measuring \nspoons).   \nNote: According to section 15.2 of Annex I, measurements made by devices with a measuring function \nwill be expressed in legal un its7. \nCE marking of conformity or CE marking - means a marking by which a manufacturer indicates that a \ndevice is in conformity with the applicable requirements set out in the MDR and other applicable \nUnion harmonisation legislation providing for its affix ing (Article 2(43)) . \nNote: CE marking will be made in accordance with Annex V.  \nClinical evaluation - means a systematic and planned process to continuously generate, collect, analyse \nand assess the clinical data pertaining to a device in order to verify th e safety and performance, \nincluding clinical benefits, of the device when used as intended by the manufacturer. (Article 2(44)).  \nClinical data - means information concerning safety or performance that is generated from the use of a \ndevice and is sourced fr om the following:  \n\uf0b7 clinical investigation(s) of the device concerned,  \n                                                      \n7  In conformance to the provisions of Council Directive  80/181/EEC   Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n9 \n \uf0b7 clinical investigation(s) or other studies reported in scientific literature, of a device for which \nequivalence to the device in question can be demonstrated,  \n\uf0b7 reports published in peer re viewed scientific literature on other clinical experience of either the \ndevice in question or a device for which equivalence to the device in question can be \ndemonstrated,  \n\uf0b7 clinically relevant information coming from post -market surveillance, in particular the post -\nmarket clinical follow -up. (Article 2(48))  \nConformity Assessment \u2013 The process demonstrating whether the requirements of the MDR relating to a \ndevice have been fulfilled. (Article 2(40)). This process depends on the medical device classification, \naccording to the procedures described in the MDR, in particular Article 52 (7) applicable for class I \ndevices.  \nDistributor  - means any natural or legal person in the supply chain, other than the manufacturer or the \nimporter that makes a device available on  the market, up until the point of putting into service (Article \n2(34)) . \nEconomic operator  - means a manufacturer, an authorised representative, an importer, a distributor or \nthe person referre d to in Article 22(1) and 22(3)  (Article 2(35)) . \nField safety corrective action  - means corrective action taken by a manufacturer for technical or \nmedical reasons to prevent or reduce the risk of a serious incident in relation to a device made available \non the market (Article 2(68)) . \nField safety notice - means a com munication sent by a manufacturer to users or customers in relation to \na field safety corrective action  (Article 2(69)) . \nHarmonised standard - means a European standard as defined in point (1)(c) of Article 2 of Regulation \n(EU) N\u00b0 1025/20128, (as referred on the Article 2(70)) \u2013 means a European standard adopted on the basis \nof a request made by the Commission for the application of Union harmonisation legislation.  \nImporter  - means any natural or legal person established within the Union that places a devic e from a \nthird country on the Union market  (Article 2(33)).  \nIntended purpose/intended use - means the use for which a device is intended according to the data \nsupplied by the manufacturer on the label, in the instructions for use or in promotional or sales  materials \nor statements and as specified by the manufacturer in the clinical evaluation (Article 2(12)).  \nInstructions for use  - means the information provided by the manufacturer to inform the user of a device's \nintended purpose and proper use, and of any  precautions to be taken (Article 2(14)).  \nLabel  - means the written, printed or graphic information appearing either on the device itself, or on the \npackaging of each unit or on the packaging of multiple devices (Article 2(13)).  \nMedical device  - means any instrument, apparatus, appliance, software, implant, reagent, material or \nother article intended by the manufacturer to be used, alone or in combination, for human beings for one \nor more of the following specific medical purposes:  \n\u2012 diagnosis, prevention, m onitoring, prediction, prognosis, treatment or alleviation of disease,  \n\u2012 diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability,  \n\u2012 investigation, replacement or modification of the anatomy or of a physiological or path ological \nprocess or state,  \n\u2012 providing information by means of in vitro examination of specimens derived from the human \nbody, including organ, blood and tissue donations,  \n  \n                                                      \n8  Regulation  (EU) No 1025/2012 of the European Parliament and of the Council , of 25 October 2012 , on European standardization  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n10 \n and which does not achieve its principal intended action by pharmacological, immuno logical or \nmetabolic means, in or on the human body, but which may be assisted in its function by such means. \nThe following products shall also be deemed to be medical devices:  \n\u2012 devices for the control or support of conception;  \n\u2012 products specifically intended for the cleaning, disinfection or sterilisation of devices as referred to \nin Article 1(4) and of those referred to in the first paragraph of this point. (Article 2(1))  \nManufacturer -  means a natural or legal person who manufactures or fully refur bishes a device or has a \ndevice designed, manufactured or fully refurbished, and markets that device under its name or \ntrademark ; (Article 2(30)).  \nNotified Body - means a conformity assessment body designated in accordance with the MDR (Article \n2(42)).  \nPlacing on the market  - means the first making available of a device, other than an investigational device, \non the Union market (Article 2(28)).  \nPost-market surveillance - means all activities carried out by manufacturers in cooperation with other \neconomic op erators to institute and keep up to date a systematic procedure to proactively collect and \nreview experience gained from devices they place on the market, make available on the market or put into \nservice for the purpose of identifying any need to immediate ly apply any necessary corrective or \npreventive actions (Article 2(60)).  \nRisk - means the combination of the probability of occurrence of harm and the severity of that harm \n(Article 2(23)).  \nSerious incident  - means any incident that directly or indirectly led, might have led or might lead to any of \nthe following:  \n(a) the death of a patient, user or other person,  \n(b) the temporary or permanent serious deterioration of a patient's, user's or other person's state \nof health,  \n(c) a serious public health threat; ((Article 2( 65)) \nSerious public health threat -  means an event which could result in imminent risk of death, serious \ndeterioration in a person's state of health, or serious illness, that may require prompt remedial action, and \nthat may cause significant morbidity or mortality in humans, or that is unusual or unexpected for the \ngiven place and time (Article 2(66)) . \nUnique Device Identifier (UDI) - means a series of numeric or alphanumeric characters that is created \nthrough internationally accepted device identification  and coding standards and that allows unambiguous \nidentification of specific devices on the market (Article 2(15)).  \nUser - means any healthcare professional or lay person who uses a device  (Article 2(37)).  \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n11 \n Placing Class I medical devices on the market:  \nThe necessary steps  \nManufacturers that intend to place Class I medical devices on the market must guarantee compliance \nwith all the requirements below. Please note that some of the described requirements are inter -dependent \nand can be performed in a differe nt order than the one presented.  \nFor Class I devices already placed on the market in accordance with the MDD, the manufacturer will \nconduct a gap analysis in order to guarantee that all the necessary requirements outlined below are fully \ncompleted at the d ate of the application of MDR.  \n0) Integrate MDR in the Quality Management System (QMS).  \nThe applicable provisions of the MDR will be integrated into the QMS of the manufacturer. This will \nallow the correct assessment/decision to be made and  the proper documented evidence to be created, \nensuring compliance with the following requirements.  \n1) Confirm product as a medical device  \nConfirm that the product qualifies as a medical device as defined in Article 2(1) in accordance with its \nintended purpose and principal mode of action. If the manufacturer assigns several different intended \npurposes to their product, not all of which fall under the scope of the MDR, such a product qualifies as a \nmedical device only with respect to those intended medical purposes which are covered by Article 2(1). \nThis is applicable, for instance, for the case of examination gloves that are intended by the manufacturer \nto be used to protect the patient (medical purpose - MD) and also to protect the healthcare professional \n(protecti on purpose \u2013 PPE9). In that case the relevant requirements of both legislations will be applicable.  \nIn the case of accessories to medical devices, despite not being medical devices per se, they are covered \nby MDR provisions and fall under the term \u201cdevice\u201d  in the meaning of the MDR. However, accessories \nto devices covered by the MDR by virtue of its Annex XVI are not covered by the MDR.  \nFor borderline  products where such a determination could be difficult, please consult primarily the \ninformation10 available  on the European Commission website. Your CA may be able to provide \nguidance on where to find published information and regulatory requirements.  \n2) Confirm product as a Class I medical device  \nConsult Annex VIII of the MDR to confirm that the product is correc tly classified as Class I. It should be \nnoted that some Class I devices according to MDD will be reclassified under the MDR considering the \nnew classification rules of that annex, this is the case for most software (rule 11) and devices that are \ncomposed o f substances or of combination of substances (rule 21) . \nFor devices that were reclassified from Class I to higher risk classes by application of the MDR, the \npresent guideline cannot be applied.   \nThe application of the classification rules will be governe d by the intended purpose of the device and \n                                                      \n9  Directive 89/686/EEC is repealed with effect from 21 April 2018 by Regulation (EU) 2016/425  \n10  Guidelines available on  https://ec.europa.eu/health/md_sector/new_regulations/guidance_en   Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n12 \n their inherent risks linked to the duration of use, part of the body, whether it is active or not, whether it is \ninvasive or non -invasive.  \nIf more than one rule according to Annex VIII applies to the intended pur poses of the device, the highest \nclassification applies to the device, i.e. it must be classified on the basis of the most critical specified \nuse. \nFor classification issues, please primarily consult the information11 available on the European \nCommission web site. Your CA may be able to provide guidance on where to find published information \nand regulatory requirements.  \n3) Procedures before placing on the market  \na) Meet the general safety and performance requirements  \nThe devices will meet the general safety and per formance requirements  set out in Annex I of the MDR \nwhich apply to them, taking into account the purposes intended by their manufacturers.  \nParticular attention will be given to devices that are also machinery, within the meaning of Article 2(2), \npoint (a) , Machinery Directive 2006/42/EC12, where the relevant requirements of that directive will also \nbe covered given their specificity (according to Article 1(12)).  \nThe manufacturer will establish and implement a risk management system, which will allow for the  \nidentification and analysis of the hazards associated with each device, estimation and evaluation of the \nassociated risks, elimination or control of residual risks and evaluation of the adopted measures based on \nthe information collected from the post -market surveillance system.  \nThe risk management will be understood as a continuous iterative process throughout the entire lifecycle \nof a device, requiring regular systematic updating. To carry out this process the manufacturer can find \nsolutions in common sp ecifications, or in harmonised standards, published in the Official Journal of the \nEuropean Union, or in other referential materials. Where a harmonised standard exists but the \nmanufacturer is following other referential, the application of that referentia l should guarantee at least \nthe same level of safety and performance. Conformity with the relevant harmonized standards will \nprovide presumption of conformity with the requirements of the MDR covered by those standards or \nparts thereof.  Where common speci fications are available the manufacturer is obliged to follow them \nunless they can duly justify that they have adopted a solution at least with the same level of safety and \nperformance.  \nThe risk management, clinical evaluation processes and PMS will be inter-dependent and will be \nperiodically updated.  \nb) Conduct clinical evaluation  \nAll devices, regardless of risk classification, require a clinical evaluation as part of the technical \ndocumentation requirements of the MD R13. \nThe manufacturer will specify and justify the level of clinical evidence necessary to demonstrate \n                                                      \n11  Guidelines available on  https://ec.europa.eu/health/md_sector/new_regulations/guidance_en%20   \n12  Directive 2006/42/EC  of  the  European  Parliament  and  of  the  Council  of  17  May 2006  on  machinery, and amending \nDirective  95/16/EC (OJ  L 157, 9.6.2006,  p. 24) \n13  For further, see Annex II of the MDR  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n13 \n conformity with the relevant general safety and performance requirements described in Annex I. That \nlevel of clinical evidence will be appropriate in view of the characteristics of the device and its intended \npurpose. In order to do that, manufacturers will plan, conduct and document a clinical evaluation in \naccordance with Article 61 and Part A of Annex XIV.  \nGuidance on the process of conducting clinical eval uation is also available on the Commission website.14  \nConformity to Annex I requirements can only be assumed when the following items are aligned with each \nother:  \n\uf0b7 Risk management;  \n\uf0b7 The information materials supplied by the manufacturer, including:  \no labelling ,  \no instructions for use (where required),   \no available promotional materials,  \no any accompanying documents foreseen by the manufacturer;  \n\uf0b7 The clinical evaluation (the device description used for the clinical evaluation, other contents of the \nclinical evaluati on report);  \n\uf0b7 The available clinical data (such as results of clinical investigations, publications, Post Market \nSurveillance studies, clinical registries, etc.).  \nThe MDR reinforces the need to consider the following aspects when carrying out a clinical eval uation:  \n\u2022 Consideration of available alternative treatment options  is required as part of clinical \nevaluation for the MDR15. Whilst the existence of better alternative treatment options does not \ninfluence the compliance of the device with the MDR, the manufacturer needs to be able to \njustify the clinical benefit of using their device if alternatives are available.  \n\u2022 The incorpo ration of clinical data  obtained throughout the life cycle of the device from the \nmanufacturers post -market clinical follow -up plan and post -market surveillance plan to update \nthe clinic al evaluation and documentation16. \n\u2022 The acceptability of the benefit -risk ratio  must be based upon sufficient clinical data and  \nwill be continuously monitored and reassessed from clinical data collected through the post -\nmark et surveillance phase. The post -market surveillance plan should incorporate suitable \nindicators and thr eshold values to be used in this reassessment 17. \nIf available clinical data are not sufficient to demonstrate compliance with the MDR, further clinical \ndata will be obtained or generated by clinical investigations.  \nFor devices which are currently certifie d with respect to the Directive 93/42/EC, and for which the \navailable clinical data are not sufficient to demonstrate compliance with MDR, additional clinical data \nmay be obtained by post -market clinical follow -up studies of the device. Sometimes, even dat a from the \ngeneral post -market follow -up might suffice to close the gap18. \nNote : if a clinical investigation is required, then the Member State requires advance notification of the \nproposal and the provisions of Article 62 and Annex XV will be applicable.  \n                                                      \n14  https://ec.europa.eu/health/md_sector/new_regulations/guidance_en       \n15  MDR, Article 61(3)(c)  \n16  MDR, Article 61(11)  \n17  MDR, Article 61(1) and Annex III 1.1b  \n18  An MDCG guidance is intended to be published  on this matter including \u2018sufficient clinical da ta\u2019 in 2020 and will be availabl e at the EU \nCommission webpage  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n14 \n In duly justified and substantiated cases, some Class I devices manufacturers may exceptionally \ndemonstrate that the conformity with general safety and performance requirements based on clinical data \nis not deemed appropriate. Such a justification by the m anufacturer must be based upon an evaluation of \nevidence in accordance with Article 61(10).  \nThe clinical evaluation, risk management processes and PMS will be inter -dependent and will be \nperiodically updated.  \nc) Prepare technical documentation  \nThe manufactur er will draw up and keep up to date the technical documentation that demonstrates the \nconformity of their devices with the technical requirements of the MDR. This technical documentation \nmust be prepared according to Annex II and III and prior to drawing u p the EU declaration of \nconformity.  \nThe technical documentation  and, if applicable, its summary, will be drawn up and presented by the \nmanufacturer in a clear, organised, readily searchable and unambiguous manner.  \nThe manufacturer must make the technical d ocumentation available to the CA, the authorised \nrepresentative (when applicable) and NB (when applicable).  \nThe technical documentation will be prepared following review of the general safety and performance \nrequirements  and relevant technical provisions o f the MDR and, if applicable, of the Machinery \nDirective19 and will cover all the relevant aspects from Annex II and III, such as:  \n- Rationale for the  qualification as a medical device and  the risk class  attributed.  \n- Description and specification  - A general d escription of the device, including its intended \npurpose and intended users/patient population and, if applicable, accessories and variants of the \nproduct (for example trade names, model numbers, references, sizes). In addition , the Basic \nUDI-DI as per Par t C of Annex VI will be provided.  \n- Technical Specifications of the device - Specifications including details of raw materials, \ndrawings of components and/or master patterns and any quality control  procedures.  \n- Information to be supplied by the manufacturer - Labels on the device and packaging, such  as \nsingle  unit packaging,  sales  packaging,  transport packaging  in case of specific  management  \nconditions and instruction for use (if applicable),  in the languages determined by  the Member  \nStates  where  the device is envisaged to be sold.  \n- Reference to previous generations of the device and to similar devices  - Provide an overview of \nprevious generation(s) of the device and similar devices available on the market as ap plicable  \n- Design and manufacturing information \u2013 Information that allows the understanding of the \ndesign and manufacturing of a device, including the results of qualifications tests and design \ncalculations relevant to the intended use of the product, includ ing connections to other devices \nin order for it to operate as intended. If the manufacturer can provide information showing that \na safe design has been established for a number of years and that product has been performing \nas intended during that time suc h information is likely to be sufficient to cover this  \n                                                      \n19  According to Article 1 (12)  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n15 \n requirement. The identification of all sites, suppliers and sub -contractors, where design and \nmanufacturing activities are performed will also be included.  \n- General safety and performance requirements \u2013 information for the demonstration of \nconformity with the general safety and performance requirements, set out in Annex I. In order \nto do this, the manufacturer will refer to all the methods and solutions used for conformity \ndemonstration with each safety and performance requirement, including harmonised standards \nand/or common specifications (CS). The same applies for the requirements contained in the \nMachinery Directive.  \n- Demonstration of conformity  with the requirements set out in Annex I should typically be \npresented in the form of a checklist. This should list all requirements referred to in Annex I and \nspecify:  \n(1) the applicability of each requirement to the device,  \n(2) the solution adopted by the man ufacturer to comply with each applicable requirement,  \n(3) the reference to any possible CS or harmonized standards applied in full or in part and  \n(4) the reference to where to find evidence of the solution adopted in the technical \ndocumentation.  \nManufacturers wil l list the relevant harmonised standards (concerning for example sterilisation, \nlabelling and information to be supplied with the device, biocompatibility, specific groups of \nproducts) which have been applied in full or in part. If harmonised standards hav e not been \napplied in full, additional data will be required and provided detailing remaining solutions \nadopted to meet the concerned requirements.  \nInformation on standards harmonised under the MDR will be made available in the Official \nJournal of the Euro pean Union.  \nChanges on the harmonised standards used to demonstrate the conformity of device will be \nadequately taken into account in a timely manner.  \nPlease note that no standard harmonized under the Directive 93/42/EC, has ever covered all the \nrequirements of the Annex I to that Directive. Hence,  it is not likely that any one standard \nharmonized under the MDR will cover all the requirements of the Anne x I to the MDR. The \nscope of coverage is indicated in the so -called Annex Z to the European \u201cEN\u201d standard. The \nscope of coverage is never to be found in the ISO or IEC standard text.  \n- Benefit -risk analysis (sections 1 and 8 of Annex I) and Risk management ( section 3 of Annex I).  \n- Pre-clinical and Clinical evaluation data \u2013 Information to be provided on the results from pre -\nclinical and clinical evaluation.  \n- The post -market surveillance system  - The technical documentation on post -market surveillance \nto be dr awn up by the manufacturer in accordance with Articles 83 to 85 will be presented in a \nclear, organized, readily searchable and unambiguous manner. It shall address and cover the \nelements of point 1.1 of Annex III. The plan will cover  the post -market clini cal follow up plan as \nreferred to in part B of Annex XIV or a justification as to why it is not applicable. The PMS \nreport of article 85 shall be part of the technical documentation on post -market surveillance.  \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n16 \n - Records  - Manufacturers will keep the techn ical documentation, the EU declaration of \nconformity and, if applicable, a copy of any relevant certificate, including any amendments and \nsupplements, issued in accordance with Article 56, available for the competent authorities for a \nperiod of at least 10  years after the last device covered by the EU declaration of conformity has \nbeen placed on the market (Article 10(8)).  \nAvailability of documentation  \u2013 In case of request by the CA, the manufacturer will provide the required \ntechnical documentation in an official Union language determined by the Member State concerned \n(Article 10(14)).  \nd)  Request Notified Body involvement  \nIn the case of devices placed on the market in sterile condition, having a measuring function or being \nreusable surgical instruments, the manufacturer will apply the procedures set out in Chapters I and III of \nAnnex IX, or in Part A of Annex XI of MDR. This requires the involvement of a NB. In all other cases \nthe intervention of a NB is not required for Class I devices. If involvement of  the NB is needed it is \nlimited:  \n- In the case of devices placed on the market in sterile condition, to the aspects of manufacture \nconcerned with securing and maintaining sterile  conditions;  \n- In the case of devices with a measuring function, to the aspects of man ufacture concerned with \nthe conformity of the devices with the metrological  requirements;  \n- In the case of reusable surgical instruments20,  to the aspects relating to the reuse of the device, in \nparticular cleaning, disinfection, sterilization, maintenance a nd functional testing and the related \ninstructions for use.  \nManufacturers can choose any NB designated according to the MDR for the relevant codes and \ncorresponding types of devices as established by Regulation (EU) 2017/2185 (code MDS 1005 for \n\u201cDevices in  sterile condition\u201d, code MDS 1006 for \u201cReusable surgical instruments\u201d and code MDS 1010 \nfor \u201cDevices with a measuring function\u201d) . The list of designated NBs is available in the NANDO \ndatabase at the following link: http://ec.europa.eu/growth/tools -databases/nando/  \nPlease note that notification under the Directive 93/42/EC, become s void after the application of the MDR \non the 26 May 202 1.  Hence, it is necessary to consult the NANDO database for the MDR.  \ne) Prepare Instructions for Use and Labelling  \nEach device must be accompanied by any safety and performance information needed to use it safely \nand to identify the device as well as the manufacturer and/or the authorised representative, taking \naccount of the training and knowledge of the potential users. This information comprises the label, \ndevice packaging and the data in the instructions for use. By way of derogation to the general principles, \nno instructions for use are required for Class I de vices if they can be used properly and safely without \nsuch instruction. An exception is most likely posed for Class Ir devices as reprocessing (cleaning and \nsterilization) will require an instruction.  \nThe requirements regarding the information to be suppl ied with the device will be found in Annex I, \nChapter III (23). In the labelling and instructions for use as well as in promotional materials of the \ndevice, the manufacturer may not (Article 7):  \n                                                      \n20  Please also note that involvement of a Notified Body in the case of reusable surgical instruments is a new requirement under the MDR, which \ndid not exist under the MDD. Manufacturers of such products are advised to take this into consideration for their pl ans to meet the provisions \nof the MDR before its application on the 26 May 202 1. Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n17 \n - Ascribe functions and properties to the device which the devi ce does not have;  \n- Create a false impression regarding treatment or diagnosis, functions or properties which the \ndevice does not have;  \n- Fail to inform the user or the patient of a likely risk associated with the use of the device in line \nwith its intended purpose;  \n- Suggest uses for the device other than those stated to form part of the intended purpose for \nwhich the conformity assessment was carried out.  \nNational language requirements must be taken into account in relation to the labelling and instructions \nfor use. Versions of labelling  and IFU ( in each of the relevant national languages) will be included in the \ntechnical documentation.  \nNote : According to Article 16(2), a distributor or importer may provide a translation of the information \nprovided according to Section 23 of Annex I. The manufacturer will be informed about the intended \ntranslation and receive a copy 28 days prior to the date of making the device available in the respective \ncountry. It is advisable to perform a review of the translation, as a w rong or misleading translation can \ncause harm to patients or others, leading to possible liability of the manufacturer.  \nWhere appropriate, the information supplied by the manufacturer will take the form of internationally \nrecognised symbols. Any symbol or identification colour used will conform to harmonised standards or \ncommon specifications (CS). In areas for which no harmonised standards or CS exist, the symbols and \ncolours will be described in the documentation supplied with the device.  \nThe label should  have the indication that the product is a \u201cmedical device\u201d.  \n4) Check compliance with general obligations for manufacturers  \nBefore placing a device on the market, the manufacturer will make sure to comply with the general \nobligations for manufacturers as est ablished in Article 10.  \nSpecial attention will be given to the establishment of an appropriate QMS that will ensure compliance \nwith the MDR in the most effective manner, for example by means of an internal audit. The QMS will \nbe documented, implemented, m aintained, kept up to date and continually improved and will cover at \nleast the following aspects:  \na) a strategy for regulatory compliance;  \nb) identification of applicable general safety and performance requirements and exploration of \noptions to address those requirements;  \nc) responsibility of the management;  \nd) resource management, including selection and control of suppliers and sub -contractors;  \ne) risk management;  \nf) clinical evaluation, including post market clinical follow -up (PMCF);  \ng) product realisation, including planning, design, development, production and service provision;  \nh) verification of the UDI assignments;  \ni) setting -up, implementation and ma intenance of a post -market surveillance system;  \nj) handling communication with competent authorities, notified bodies, other economic operators, \ncustomers and/or other stakeholders;  \nk) processes for reporting of serious incidents and field safety corrective ac tions in the context of \nvigilance;  \nl) management of corrective and preventive actions and verification of their effectiveness;  \nm) processes for monitoring and measurement of output, data analysis and product improvement.  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n18 \n The QMS will be established at least in  parallel, if not prior to chapter 3 a) and 3 b) as described in this \nguidance note.  \nNatural or legal persons may claim compensation for damage caused by a defective device in \naccordance with applicable Union and national law. Therefore, manufacturers sha ll, in a manner that is \nproportionate to the risk class, type of device and size of the enterprise, have measures in place to \nprovide sufficient financial coverage in respect of their potential liability under Directive 85/374/EEC, \nwithout prejudice to mor e protective measures under national law.  \n5)  Draw -up the EU Declaration of Conformity  \nThe EU declaration of conformity, referred to in Article 19, is the procedure whereby the manufacturer, \nwho fulfils the obligations imposed by Article 52(7), declares that the devices concerned fulfil the \nrequirements of the MDR which apply to them. The declaration of conformity will contain as a \nminimum all information referred to in Annex IV and will be available to the CA.  \nThe manufacturer will continuously update the EU declaration of conformity and will translate it into an \nofficial union language or languages required by Member States in which the device is made available.  \nIf, in addition to the MDR, a device is covered by other Union legislation which also requires an EU \ndeclaration of conformity, the manufacturers will elaborate a single EU declaration of conformity where \nall the Union legislation applied to the product are referred to.  \nBy drawing up the EU declaration of conformity the manufacturer assumes the respon sibility for the \nregulatory compliance of the device with all Union legislation applicable to it.  \nBefore affixing a CE mark, for class Ir, Im and Is devices, the manufacturer will have an EC certificate \nissued by NB according to the Annex IX, Chapter I and III, or to Annex XI, Part A.  \n6)  Affix the CE marking  \nAll Class I medical devices placed on the mar ket will bear the CE marking of conformity, which will be \naffixed in a visible, legible and indelible form on the device or on its sterile packaging. Where such \naffixing is not possible or not warranted on account of the nature of the device, the CE markin g shall be \naffixed to the packaging. The CE marking shall also appear  on the instructions for use, as well as on any \nsales packaging.  \nIn the case of Class I medical devices placed on the market in a sterile condition and/or devices with \nmeasuring function  and/or reusable surgical instruments, the CE marking will be accompanied by the \nidentification number of the relevant NB.  \nIt is prohibited to affix marks which are likely to mislead third parties with regard to the meaning of the \nCE marking. Other additio nal marks may be affixed to the device, to the packaging or the instructions \nfor use, but must not impair the visibility or legibility of the CE marking.  \nThe CE marking format will be in compliance with Annex V. Where the device is very small the \nminimum d imensions of the CE mark may be waived.  \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n19 \n 7) Registration of devices and manufacturers in Eudamed  \nBefore placing a device on the market, the manufacturer of a Class I medical device will register the \ndevice in Eudamed.  \nIn order to register the device, the manufacturer will submit to the electronic system referred to in \nArticle 30 the information referred to in Section 1 of Part A of Annex VI, provided that they have not \nalready been registered in accordance with Article 31. In cases where the conformity ass essment \nprocedure requires the involvement of a NB pursuant to Article 52, the information referred to in \nSection 1 of Part A of Annex VI will be provided to that electronic system before applying to the NB.  \nAfter having verified the data about the manufac turer, the CA will validate it in Eudamed and the \nmanufacturer will obtain a SRN from said electronic system.  \nThe manufacturer will use the SRN when applying to a NB for conformity assessment and for accessing \nEudamed in order to fulfil its obligations und er Article 29.  \nNote: Authorised representatives and importers are also required to register to get an SRN in order to \naccess Eudamed and provide data, as appropriate  \nThe registration of a device in Eudamed by the manufacturer includes:  \n\uf0b7 Assignment of a UDI -DI (with a Basic UDI -DI) as defined in Part C of Annex VI to the device \n(in accordance with the rules of the issuing entity referred to in Article 27(2) and introduction of \nthe UDI -DI (with a Basic UDI -DI) to the UDI database together with the other core d ata elements \nreferred to in Part B of Annex VI related to that device.  \n\uf0b7 Entering, or if already provided, verifying in Eudamed the information referred to in Section 2 of \nPart A of Annex VI, with the exception of Section 2.2 thereof, and thereafter keeping the \ninformation updated.  \nIf the manufacturer has its devices designed or manufactured by another legal or natural person, the \ninformation on the identity of that person will be part of the information (Section 2.13 of Part A of \nAnnex VI) to be submitted to  Eudamed before the registration of the device.  \nNote 1  \u2013 The Unique Device Identification system will allow the identification and facilitate the \ntraceability of devices (as referred on Article 27). [Special attention will be given to point 11 of Article \n27]. \nNote 2  \u2013 The Basic UDI -DI as defined in Part C of Annex VI is the primary identifier of a device model. \nIt is the main key for records in the UDI database and is referenced in relevant certificates and EU \ndeclarations of conformity21. \nNote 3 \u2013 For Class I devices placed on the market according to MDD, afte r the date of application of \nMDR manufacturers will have in consideration the guidance documents applicable to legacy devices \ntimelines22 and registration in Eudamed23. \n                                                      \n21  For more information on the Basic UDI -DI, please refer to https://ec.europa.eu/docsroom/documents/28667   \n22  See at EU Commission webpage the relevant guidance on timelines for registration of device data elements in EUDAMED23  See at EU \nCommission webpage the relevant guidance on the registration of legacy devices in EUDAMED  \n23  See at EU Commission webpage the relevant guidance on the registration of legacy devices in EUDAMED  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n20 \n   Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n21 \n All devices including legacy devices of the manufacturer portfolio which are placed on the market or put \ninto service will have to be registered in Eudamed.  However, until Eudamed is fully functional the \nmanufacturer of a Class I medical device, or, where the manufacturer has no place of business in the EU, \nits authorised representative must  inform the CA of the country in which they have their registered place \nof business and provide a description of the device that is sufficient to identify it. The manufacturer or \nits authorised representative will contact their relevant CA for the required  procedures and forms \nrequired for such notifications. A fee might be applicable.  \n8) Post Market Surveillance (PMS)  \nAfter placing the Class I device on the market, the manufacturer will follow the next PMS steps:  \na) Review experience gained from Post -Market Sur veillance  \nThe manufacturer will put in place the required post market surveillance (PMS) system and actively \nkeep this PMS up to date in accordance with Article 83 of MDR. This includes actively and regularly \ncollecting the user experience from devices on the market, reviewing these and ensuring timely \nimplementation of any necessary corrective action, taking account of the nature and risks in relation to \nthe product.  In addition, there should be an evaluation of whether the intended benefits are achieved a nd \nwhether the benefit -risk profile stays positive.  The manufacturer will involve the distributors of the \ndevice and where applicable, the authorised representative and importers of the device in this system, in \norder to obtain the relevant  information from the market.  \nThis system will be part of the QMS, and be supported by the manufacturer\u2019s PMS plan, which must \naddress a range of information (Annex III), such as information from the vigilance context, information \nfrom trending and trend reporting, inf ormation and data on any undesirable side -effects, information \nfrom reports, complaints and incidents, provided by users and economic operators, related to the device. \nMoreover, the manufacturer will gather and assess the relevant information such as techn ical literature, \ndatabases, registers review and public information for the device itself as well as for similar devices \nalready present on the market.  \nA PMS report will be prepared according to Article 85, summarizing the results and conclusions of the \nanalysis of all of the data from the market. This report will be updated when necessary, for example  the \nintended benefits are not achieved or there is a change in the benefit -risk balance. The report can be \nrequested by the CA at any time.  \nData gathered from PMS system must be used to actively update the clinical evaluation, benefit -risk \ndetermination, improve risk management, as well as other technical documentation on a regular basis.  \nb) Vigilance   \nThe manufacturer is responsible for reporting all serious incidents and field safety corrective actions \n(FSCA) to the relevant CAs, according to Article 87 (1) of the MDR. After serious incident notification, \nthe manufacturer is obliged to make investigations, according to Article 89, which will include a risk \nassessment of the incident. If needed, a FSCA will be implemented in order to reduce the risk associated \nwith the use of the device.  \nThe manufacturer will involve the distributors of the device and, where applicable, the authorised \nrepresentative and import ers in the system, in order to obtain the information needed from the market, \nespecially for FSCA and issued field safety notices (FSN) to ensure that required actions are followed \nand completed in a timely manner.  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n22 \n When Eudamed is available, serious incide nts and FSCAs will be submitted via this electronic system \nonly.  \nManufacturers will report any serious incident immediately after they have established the causal \nrelationship between that incident and their device or that such a causal relationship is re asonably \npossible.  \nThe timeframe to report serious incidents must not exceed the following upper limits:  \n\uf0b7 In the event of a serious public health threat, a report will be submitted not later than 2 days \nafter becoming aware of the threat. (Article 87 (4))  \n\uf0b7 In the event of death or an unanticipated deterioration in a person\u2019s state of health a report will \nbe submitted not later than 10 days after becoming aware of the serious incident. (Article 87 \n(5)) \n\uf0b7 In all other cases not later than 15 days after becoming aware of the serious incident (Article 87 \n(3)) \nWhere necessary to ensure timely reporting of serious incidents, the manufacturer may submit an initial \nreport that is incomplete followed up by a complete report. If, after becoming aware of a potentially \nreportable incident, the manufacturer is uncertain about whether the incident is reportable, it shall \nnevertheless submit a report. Serious incidents will be reported only to the competent authority of the \ncountry in which the serious incident occurred via Eu damed.  \nThe manufacturer will provide a final report to that competent authority via Eudamed setting out its \nfindings from the investigation. The report will set out conclusions and - where relevant - indicate \ncorrective actions to be taken.  \nWhen the compet ent authority notifies a manufacturer of a suspected serious incident, communicated to \nthe competent authority by a healthcare professional, patient or user, the manufacturer is obliged to:  \n\uf0b7 submit a report of this serious incident to the notifying competen t authority via Eudamed within \nthe timeframes described above;  \n\uf0b7 submit an explanatory statement, to the competent authority, if the manufacturer believes the \nsuspected serious incident does not fulfil the reporting criteria.  \nIn case the competent authority disagrees with the explanatory statement provided by the manufacturer a \nreport of the serious incident may be required to be provided to the competent authority that does not \nagree via Eudamed by the manufacturer.  \nIf a FSCA is undertaken, manufacturers wil l without unnecessary delay report the field safety corrective \naction via Eudamed in advance of the carrying out of the FSCA unless urgency demands the \nmanufacturer to undertake the actions immediately.  \nManufacturers will ensure that the information relate d to the FSCA is brought without delay to the \nattention of users of the device in question by means of a FSN. Except in cases of urgency, the content \nof the draft FSN will be submitted to the evaluating competent authority or to the coordinating \ncompetent authority to allow it to make comments. Unless duly justified by the situation of the \nindividual Member State, the content of the field safety notice will be consistent in all Member States. \nManufacturers will also report the FSN(s) to Eudamed.  \n  Class I Guidance MDCG MSWG  - MDCG  2019 -15 rev1  \n \n23 \n The FSN w ill allow the correct identification of the manufacturer ( by including the, if issued, SRN), the \ndevice or devices affected (by including the relevant UDIs) and the FSN will explain, in a clear manner, \nwithout understating the level of risk, the reasons fo r the FSCA. This includes a clear reference to the \ndevice deficiency and the associated risks for patients, users or other persons and will clearly indicate all \naction to be taken by the users.  \nManufacturers will report by the means of a trend report to Eudamed any statistically significant \nincrease in the frequency or severity of incidents that are not serious incidents or that are expected \nundesirable side -effects, when it could have a significant impact on the benefit -risk analysis and which \nhave led o r may lead to risks to the health or safety of patients, users or other persons that are \nunacceptable when weighed against the intended benefits.  \nManufacturers will, if they exist, follow national provisions in the field of vigilance specifically in but \nnot limited to the case of field safety corrective actions:  \n\uf0b7 The allowed languages used to communicate with users by means of the Field Safety Notice.  \nManufacturers are asked to check if templates exist (on European Commission website) on any of the \nreporta ble forms and make sure that all the necessary information according to these templates is \nprovided. This will be only applicable until Eudamed is available.  \nManufacturers should keep concerned economic operators informed of reported serious incidents and \nFSCA activities.  \nc) Non-conforming  products  \nIf a manufacturer has reasons to believe that a device which they have placed on the market or put into \nservice is not in conformity with the MDR they will immediately take the necessary corrective action to \nbring t hat device into conformity, to withdraw it or to recall it, as appropriate. The manufacturer will \ninform the distributors of the device in question and, if applicable, the authorised representative and \nimporters. If the device presents a serious risk, the manufacturer will immediately inform the competent \nauthorities of the Member States in which the manufacturer made the device available and, where \napplicable, the notified body that issued a certificate for the device, in particular, of the non -compliance \nand of any corrective action taken."}, {"title": "mdcg_2019_3_rev1_cecp_en.pdf.txt", "text": "Medical Devices       \nMedical Device  Coordination Group Document   MDCG  201 9-3 Rev.1   \nPage 1 of 4 \n  \n \n \n \n \nMDCG  2019 -3 Rev. 1 \n Interpretation of Article 54(2)b     \n          \n \n \n April 2020  \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commission document and it cannot be regar ded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  \n \n  Medical Devices       \nMedical Device  Coordination Group Document   MDCG  201 9-3 Rev.1   \nPage 2 of 4 \n  \nMDCG 2019 -3 Rev. 1 changes  \nAddendum on procedural aspects  New \n \n \nInterpretation of Article 54(2)b  \nArticle 54(2) of the MDR lays down three criteria that exempt devices from the pre -\nmarket clinical evaluation consultation procedure with the involvement of expert \npanels. In particular that article states that:  \n\u201cThe procedure referred to in paragraph 1 shall not be required for the devices \nreferred to therein:  \n(a)  in the case of renewal of a certificate issued under this Regulation;  \n(b)  where the device has been designed by modifying a device already marketed by \nthe same manufacturer for the same intended purpose, provided that the \nmanufacturer has demonstrated to the satisfaction of the notified body that the \nmodifications do not ad versely affect the benefit -risk ratio of the device; or  \n(c) where the principles of the clinical evaluation of the device type or category have \nbeen addressed in a CS referred to in Article 9 and the notified body confirms that the \nclinical evaluation of the manufacturer for this device is in compliance with the \nrelevant CS for clinical evaluation of that kind of device\u201d.  \nInterpretation of point (b) of Article 54(2) is unclear, notably in relation to the \napplication of the word \u201cmarketed\u201d.  In fact, while in point \u201ca\u201d the co -legislator \nexplicitly indicates that the certificates referred to are those issued under the new \nRegulation, in point \u201cb\u201d there is no indication of whether a \u201cdevice already marketed\u201d \nrefers to devices already marketed under the Directi ves or the Regulations.  \nThis has raised questions from the public and from Member States.  \nAs we are about to launch the procedures for the establishment of expert panels, \nclarification of this issue is extremely urgent, notably due to its impact on the fu ture \nworkload of panels and hence on relevant budget and workload estimations.  \nThe following considerations seem to indicate that the expression \u201cdevice already \nmarketed\u201d cannot be intended to refer to a device already marketed uniquely under \nthe new Regu lation : \n\uf0b7 If the co -legislators had decided to restrict the application of point \u201cb\u201d to devices \nmarketed uniquely under the MDR, they would have explicitly stated so, as they \ndid for point \u201ca\u201d;  \n\uf0b7 Article 54, together with other Articles (such as Article 61(6) and Article 120(3)), \nwas written at the end of the negotiation process with a view to smoothen the  Medical Devices       \nMedical Device  Coordination Group Document   MDCG  201 9-3 Rev.1   \nPage 3 of 4 \n  \n \nimplementation of the new Regulation. Therefore the interpretation of the \nexemption should be understood in line with the spirit and intention of the co -\nlegislators.  \n \nIt has to be noted that, in respect to devices that have been marketed already under \nthe relevant Directives, the word \u201cmodification\u201d shall be meant as limited only to those \nmodifications needed in order to comply with the new legal requiremen ts introduced \nby the MDR1 2. \n \n \nAddendum - Procedural aspects  \n \nTogether with the application to be lodged under the applicable conformity \nassessment procedure, the manufacturer will provide the notified body with:  \n\uf0b7 a statement that it has marketed the device  in question for the same intended \npurpose under the relevant Directive,  \n\uf0b7 copy of the last issued certificate(s) together with the certificate history, and  \n\uf0b7 a description of the modifications introduced to comply with the MDR  \nAs part of its technical documen tation assessment according to the MDR, the notified \nbody will verify that the \u201cmodifications\u201d, as referred to in the main document, do not \nadversely affect the benefit -risk ratio. In particular, the notified body will verify:  \n\uf0b7 that the device in question h ad a valid certificate under the Directives,  \n\uf0b7 in case the certificate has been withdrawn, suspended3 or expired, if there is \nan impact on compliance with the general safety and performance \nrequirements, and  \n\uf0b7 that there is no pending assessment of changes fo r the device or outstanding \nnon-compliance.   \nIn addition, the notified body will verify the description of modifications provided and \nassess if these modifications are limited only to those needed in order to comply with \nthe new legal requirements introdu ced by the MDR. Limitations of the intended \npurpose of the device should not trigger the consultation procedure in accordance to \nArt. 54.  \n                                                            \n1  These devices will anyhow be subject to all applicable new MDR requirements, including those ones related \nto the clinical evaluation, and will need to be assessed by notified bodies against these new (and higher) \nrequirements. This aspect together with the increased notified bodies\u2019 oversight foreseen under MDR should \nguarantee a high standard of safety for these products.  \n2  From a practical perspective, u nder the scenario where those products had to be subject to clinical evaluation \nconsultation procedure with the involvement of expert panels, as a result of the application of criteria set in \nAnnex IX 5c, in most if not all of the cases, the panel would de cide not to give an opinion. Therefore , a very \nsignificant additional workload and financial burden would be created for an extremely limited added value.  \n3    Certificates for which the rationale for withdrawal or suspension is linked to lack of complian ce with essential   \nrequirements may adversely affect the benefit -risk ratio of the device and will require a clinical evaluation \nconsultation procedure.  Medical Devices       \nMedical Device  Coordination Group Document   MDCG  201 9-3 Rev.1   \nPage 4 of 4 \n  \n \nIn case that any of the abovementioned conditions are not fulfilled the notified body \nwill follow the consultation procedure in accordance to Art. 54.  \nThe assessment of the above conditions will be documented by the notified body in \naccordance with Section 4.6 of Annex VII in the clinical evaluation assessment report \nthat will be made available to competent authorities  in accordance with Art. 54 (1) \nand (3).  \n \n \nClarifications in respect to the applicability of Art. 54(2)b with regard to devices \nalready marketed under the MDR are to be provided in a separate guidance."}, {"title": "mdcg_2019_11_guidance_qualification_classification_software.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document   MDCG  2019-11    \n \n \n \n  \n \n \nMDCG  2019-11  \n        Guidance on Qualification and Classification  \n        of Software in Regulation (EU) 2017/745 \u2013 MDR  \n        and Regulation (EU) 2017/746 \u2013 IVDR    \n           \n \n           October   2019 \n \n \n  \n    \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member States and it is chaired by a representative of the European Commission. The document is not a European Commission document and it cannot be regarded as reflecting the official position of the European Commission. Any views expressed in this document are not legally binding and only the Court of Justice of the European Union can give binding interpretations of Union law.  \n \n   \nPage 1 of 28 \n   \nGuidance on Qualification and \nClassification of Software in \nRegulation (EU) 2017/745 \u2013 MDR and \nRegulation (EU) 2017/746 \u2013 IVDR \n \n Guidance on \nQualification and \nClassification of \nSoftware  \nOctober 201 9  \nPage 2 of 28 \n  \n \n \nTable of Contents \n \n 1.\n Scope and purpose of this document 3  \n2. Definitions and abbreviations 3  \n3. Qualification 6  \n3.1. Introduction to qualification criteria 6  \n3.2. Medical Device Software (MDSW)  7  \n3.3. \u2018Software  driving or influencing the use of a medical device\u2019 8  \n3.4. Qualification criteria of MDSW as an in vitro  diagnostic medical device 10  \n4. Classification of MDSW per MDR 2017/745 12  \n4.1. Implementing Rules 12  \n4.2. Classification Rules 12  \n5. Classification and implemen ting rules per IVDR 2017/746 15  \n5.1. Implementing Rules: 15  \n5.2. Classification Rules: 15  \n6. Considerations on placing on the market  and conformity asse ssment of MDSW 16  \n6.1. Option 1: as a medical device in its own right 16  \n6.2. Option 2: as an integral component/part of a device 17  \n7. Modules 17  \n8. Consideration of changes to an MDSW 18  \n9. Annex I: Illustrative examples of qualifica tion of software used in the healthcare \nenvironment 18  \n10. Annex II - Qualification examples of Medical Device Software (MDSW) according to \nFigures 1 and 2 24  \n11. Annex III - Usability of the IMDRF risk classification framework in the context of the \nMDR  26 \n12. Annex IV \u2013 Classification examples 27  \n \n \n  \nPage 3 of 28 \n 1. Scope and purpose of this document \nThis document, which primarily targets medical software manufacturers, defines the criteria for the \nqualification of software falling within the scope of the new medical devices regulations1 and provides \nguidance on the application of classification criteria for software under Regulation (EU) 2017/745 \u2013 \nMDR and Regulation (EU) 2017/746 \u2013 IVDR.2 The guidance also provides information related to \nplacing on the market. The classification criteria (classification rules) are set out in Annex VIII of the \nMedical Devices Regulation (EU) 2017/745 (MDR) and Annex VIII of the In vitro Diagnostic Medical Devices Regulation (EU) 2017/746 (IVDR).  \nThe criteria specified in this document shall also apply to applications (commonly referred to as apps), \nmay they be operating on a mobile phone, in the cloud or on other platforms. \n2. Definitions and abbreviations \nIntended purpose : \nAccording to Regulation (EU) 2017/745 \u2013 MDR, \u201cIntended purpose\u201d means the use for which a \ndevice is intended according to the data supplied by the manufacturer on the label, in the instructions \nfor use or in promotional or sales materials or statements and as specified by the manufacturer in the \nclinical evaluation;3 \nAccording to Regulation (EU) 2017/746 \u2013 IVDR, \u201cIntended purpose\u201d means the use for which a \ndevice is intended according to the data supplied by the manufacturer on the label, in the instructions for use or in promotional or sales materials or statements or as specified by the manufacturer in the \nperformance evaluation;\n4 \nAccessory: \nAccording to Regulation (EU) 2017/745 \u2013 MDR, \u201cAcc essory for a medical device\u201d means an article \nwhich, whilst not being itself a medical device, is intended by its manufacturer to be used together \nwith one or several particular medical device(s) to specifically enable the medical device(s) to be used in accordance with its/their intended purpose(s) or to specifically and directly assist the medical \nfunctionality of the medical device(s) in terms of its/their intended purpose(s);\n5 \nAccording to Regulation (EU) 2017/746 \u2013 IVDR, \u201cAccessory for an in vitro diagnostic medical \ndevice\u201d means an article which, whilst not being itself an in vitro diagnostic medical device, is \nintended by its manufacturer to be used together with one or several particular in vitro diagnostic \nmedical device(s) to specifically enable the in vitro diagnostic medical device(s) to be used in \naccordance with its/their intended purpose(s) or to specifically and directly assist the medical \nfunctionality of the in vitro diagnostic medical device(s) in terms of its/their intended purpose(s);6  \nNote:  Software accessory may be driving or influencing the use of a medical device.  \nNote:  Manufacturers must describe in the technical documentation accessories of a medical device or \nan in vitro diagnostic medical device which are intended to be used in combination with it; and in case \n                                                 \n1 The use of \u201cThe Medical Devices Regulations\u201d from here on out refers to both Regulation (EU) 2017/745 \u2013 MDR and \nRegulation (EU) 2017/746 \u2013 IVDR. \n2 It shall be noted that the term \u201cstandalone software\u201d which was used in the text of the medical device directives, is no \nlonger used in the context of the Medical Device Regulation. The rationale of the change is that software should be qualified and classified depending on its intended purpose uniquely, regardless of its location. \n3 Article 2(12) of Regulation (EU) 2017/745 \u2013 MDR  \n4 Article 2(12) of Regulation (EU) 2017/746 \u2013 IVDR  \n5 Article 2(2) of Regulation (EU) 2017/745 \u2013 MDR \n6 Article 2(4) of Regulation (EU) 2017/746 \u2013 IVDR   \nPage 4 of 28 \n of medical devices they must include in the instructions for use information allowing the selection of \nthe corresponding software and accessories.7 \n \nPlacing on the market: \nAccording to Regulation (EU) 2017/745 \u2013 MDR, \u201cPlacing on the market\u201d means the first making available of a device, other than an investigational device, on the Union market;\n8 \n \nAccording to Regulation (EU) 2017/746 \u2013 IVDR, \u201cPlacing on the market\u201d means the first making \navailable of a device, other than a device for performance study, on the Union market;9 \nPutting into service: \nAccording to Regulation (EU) 2017/745 \u2013 MDR, \u201cPut ting into service\u201d means the stage at which a \ndevice, other than an investigational device, has been made available to the final user as being ready \nfor use on the Union market for the first time for its intended purpose;10 \n \nAccording to Regulation (EU) 2017/746 \u2013 IVDR, \u201cPutti ng into service\u201d means the stage at which a \ndevice, other than a device for performance study, has been made available to the final user as being ready for use on the Union market for the first time for its intended purpose;\n11 \nMedical device : \n\u201cmedical device\u201d means any instrument, apparatus, appliance, software , implant, reagent, material or \nother article intended by the manufacturer to be used, alone or in combination, for human beings for \none or more of the following specific medical purposes: \n- diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease,  \n- diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability, \n- investigation, replacement or modification of the anatomy or of a physiological or \npathological process or state,  \n- providing information by means of in vitro examination of specimens derived from the human \nbody, including organ, blood and tissue donations,  \nand which does not achieve its principal intended action by pharmacological, immunological or \nmetabolic means, in or on the human body, but which may be assisted in its function by such means.  \nThe following products shall also be deemed to be medical devices:  \n- devices for the control or support of conception;  \n- products specifically intended for the cleaning, disinfection or sterilisation of devices as \nreferred to in Article 1(4) and of those referred to in the first paragraph of this point.12 \nActive medical device:  \n\u201cactive device\u201d means any device, the operation of which depends on a source of energy other than \nthat generated by the human body for that purpose, or by gravity, and which acts by changing the \ndensity of or converting that energy. Devices intended to transmit energy, substances or other elements \nbetween an active device and the patient, without any significant change, shall not be deemed to be active devices. Software shall also be deemed to be an active device;\n13 \n \n                                                 \n7 Article 32.2(c), Annex I, Chapter III Section 23.4(f), Annex II Section 1.1(h) of Regulation (EU) 2017/745 \u2013 MDRArticle \n29.2(c) and  Annex II Section 1.1(m) of Regulation (EU) 2017/746 \u2013 IVDR  \n8 Article 2(28) of Regulation (EU) 2017/745 \u2013 MDR \n9 Article 2(21) of Regulation (EU) 2017/746 \u2013 IVDR \n10 Article 2(29) of Regulation (EU) 2017/745 \u2013 MDR \n11 Article 2(22) of Regulation (EU) 2017/746 \u2013 IVDR \n12 Article 2(1) of Regulation (EU) 2017/745 \u2013 MDR \n13 Article 2(4) of Regulation (EU) 2017/745 \u2013 MDR   \nPage 5 of 28 \n In vitro  diagnostic medical device: \n\u201cIn vitro diagnostic medical device\u201d means any medical device which is a reagent, reagent product, \ncalibrator, control material, kit, instru ment, apparatus, piece of equipment, software  or system, \nwhether used alone or in combination, intended by the manufacturer to be used in vitro for the \nexamination of specimens, including blood and tissue donations, derived from the human body, solely \nor principally for the purpose of providing information on one or more of the following:  \n- concerning a physiological or pathological process or state;  \n- concerning congenital physical or mental impairments;  \n- concerning the predisposition to a medical condition or a disease;  \n- to determine the safety and compatibility with potential recipients;  \n- to predict treatment response or reactions;  \n- to define or monitoring therapeutic measures.  \nSpecimen receptacles shall also be deemed to be in vitro diagnostic medical devices;14 \n \nSoftware: \nFor the purpose of this guidance, \u201csoftware\u201d is defined as a set of instructions that processes input data \nand creates output data. \nInput data : \nAny data provided to software in order to obtain ou tput data after computation of this data can be \nconsidered as input data. Input data examples (non-exhaustive): \n- Data given through the use of a human data-input device such as a keyboard, mouse, stylus, or \ntouch screen; \n- Data given through speech recognition; \n- Digital document: formatted for general purpose such as Word file or pdf file or jpeg image, \nformatted for medical purpose such as DICOM file or ECG records or Electronic Health \nRecord, unformatted document. Note that digital documents have to be differentiated from \nsoftware able to read such documents; \n- Data received from/transmitted by devices. \nOutput data : \nAny data produced by a software can be considered  as an output data. Output data examples (non-\nexhaustive): \n- Screen display data (such as layout with number, characters, picture, graphics, etc.); \n- Print data (such as layout with number, characters, picture, graphics, etc.); \n- Audio data; \n- Digital document (formatted for a general purpose such as Word file or pdf file or jpeg image, \nor formatted for medical purpose such as DICOM file or ECG records or Electronic Health \nRecord, unformatted document). \n- Haptic buzzing as an alternative to audio sound \nSoftware driving or influencing the use of a device  \nSoftware which is intended to drive or influence the use of a (hardware) medical device and does not  \nhave or perform a medical purpose on its own , nor does it create information on its own  for one or \nmore of the medical purposes described in the definition of a medical device or an in vitro  diagnostic \nmedical device. This software can, but is not limited to:  \n(a) operate, modify the state of, or control the device either through an interface (e.g., software, \nhardware) or via the operator of this device \n(b)  or supply output related to the (hardware) functioning of that device \nNote:  Software driving or influencing the use of a (hardware) medical device may be qualified as an \naccessory for a (hardware) medical device.  \n                                                 \n14 Article 2(2) of Regulation (EU) 2017/746 \u2013 IVDR   \nPage 6 of 28 \n Medical Device Software (MDSW) \nMedical device software is software that is intended to be used, alone or in combination, for a purpose \nas specified in the definition of a \u201cmedical device\u201d in the medical devices regulation15 or in vitro  \ndiagnostic medical devices regulation.16 \n3. Qualification \n3.1. Introduction to qualification criteria \nThe purpose of this section is to clarify what software is in itself subject to the medical devices \nregulations.  \nSoftware must have a medical purpose on its own to be qualified as a medical device software \n(MDSW). It should be noted that the intended purpose as described by the manufacturer of the \nsoftware is relevant for the qualification and classification of any device. \nIn order to be qualified as medical device software, the product must first fulfil the definition of \nsoftware according to this guidance and the definiti on of a medical device according to Article 2(1) of \nRegulation (EU) 2017/745 \u2013 MDR. To be qualified as an in vitro  diagnostic medical device software, \nthe product must additionally fulfil the definition of an in vitro  diagnostic medical device according to \nArticle 2(2) of Regulati on (EU) 2017/746 \u2013 IVDR.  \nWhere a given product does not fall under the definition of a medical device, or is excluded by the \nscope of the Medical Devices Regulations, other Community and/or national legislation may be \napplicable. Software that does not meet th e definition of a medical device or an in vitro diagnostic \nmedical device (i.e. software that is not MDSW) but is intended by the manufacturer to be an \naccessory for a medical device, or an in vitro  diagnostic medical device, falls respectively under the \nscope of the Regulation (EU) 2017/745 \u2013 MDR or Regulation (EU) 2017/746 \u2013 IVDR. \nSoftware can directly control a (hardware)  medical device (e.g. radiotherapy treatment software), can \nprovide immediate decision-triggering information (e .g. blood glucose meter software), or can provide \nsupport for healthcare professionals (e.g. ECG interpretation software).  \nIt is important to clarify that not all software used within healthcare is qualified as a medical device. \nFor example, \u201cSimple search\u201d, which refers to the retrieval of records by matching record metadata \nagainst record search criteria or to the retrieval of information does not qualify as medical device \nsoftware (e.g. library functions).  \nHowever, software which is intended to process, an alyse, create or modify medical information may \nbe qualified as a medical device software if the creation or modification of that information is \ngoverned by a medical intended purpose. For example, the software which alters the representation of \ndata for a medical purpose would qualify as a medical device software. (e.g. \u201csearching image for \nfindings that support a clinical hypothesis as to th e diagnosis or evolution of therapy\u201d or \u201csoftware \nwhich locally amplifies the contrast of the finding on an image display so that it serves as a decision \nsupport or suggests an action to be taken by the user\u201d). However, altering the representation of data for \nembellishment/cosmetic or compatibility purposes does not readily qualify the software as medical \ndevice software.  \nSoftware intended for non-medical purposes (excludi ng MDR Annex XVI devices), such as invoicing \nor staff planning, does not qualify as a medical device software. These software do not fall under the \nMedical Devices Regulations. \n                                                 \n15 Article 2(1) of Regulation (EU) 2017/745 \u2013 MDR \n16 Article 2(2) of Regulation (EU) 2017/746 \u2013 IVDR   \nPage 7 of 28 \n A task such as e-mailing, web or voice messaging, data parsing, word processing, and back-up is by \nitself not considered as having a medical purpose. \nAdditionally, software may run on different operating systems or in virtual environments. These \noperating systems or virtual environments do not impact the qualification criteria. \nIt must be highlighted that the risk of harm to patients, users of the software, or any other person, \nrelated to the use of the software within healthcare, including a possible malfunction is not a criterion \non whether the software qualifies as a medical device.  \n3.2. Medical Device Software (MDSW)   \nMedical device software is software that is intended to be used, alone or in combination , for a \npurpose as specified in the definition of a \u201cmedical device\u201d in the MDR or IVDR, regardless of \nwhether the software is independent or driving or influencing the use of a device. \nNote 1:  MDSW may be independent , by having its own intended medical purpose and thus meeting \nthe definition of a medical device or in vitro  diagnostic medical device on its own (i.e. alone ) \nMDSW that uses maternal parameters such as ag e, concentration of serum markers and information \nobtained through foetal ultrasound examination for evaluating the risk of trisomy 21. \nMDSW that receives measurements from transrectal  ultrasound findings, age, and in vitro diagnostic \ninstruments and calculates a patient\u2019s risk of developing prostate cancer. \nMass Spectrometry MDSW intended to analyse LC-MS/MS data to be used for microorganism \nidentification and detection of antibiotic resistance. \nMDSW smartwatch app, which is intended to send alarm notifications to the user and/or health \npractitioner  when it recognises irregular heartbeats for the purpose of detecting cardiac arrhythmia. \nNote 2:  If the software drives or influences a (hardware) medical device and also has a medical \npurpose, then it is qualified as a MDSW \nMelanoma image analysis software intended to drive a near-infrared laser light scanner. \nMDSW intended to measure and transmit blood glucose levels, calculate insulin dose required and \ndrive the insulin pump to administer the calculated dosage (closed loop insulin delivery system). \nNote 3:  Software may be qualified as MDSW regardless of its location (e.g. operating in the cloud, on \na computer, on a mobile phone, or as an additional functionality on a hardware medical device). \nMDSW that is intended to operate a point of care test from a remote location.  \nNote 4:  MDSW may be intended to be used by healthcare professionals or laypersons (e.g. patients or \nother users).17, 18 \nMDSW that provides insulin dose recommendations to  a patient regardless of the method of delivery \nof the prescribed dose, whether via an insulin pump, insulin pen or insulin syringe. \n                                                 \n17 Where MDSW is intended to be used by a lay person, the manufacturer shall apply safety and performance requirements \noutlined in MDR Annex I. 22 and 23.4 (w); or IVDR Annex I. 9.4 and 20.4.2. \n18 MDSW which can be considered as an IVD for self-testing shall be considered as a device intended to be used by \nlaypersons.   \nPage 8 of 28 \n Manufacturers must ensure that all regulatory requirements for placing on the market and conformity \nassessment have been fulfilled. As set out in Article 7 of MDR and IVDR, this also entails that any claims, relating to the intended medical purpose of their MDSW are supported by clinical evidence. If \nthis is not the case, the software would not meet the requirements of the regulations and therefore may \nnot be CE marked as a medical device, nor present said claims.  \n3.3. \u2018Software  driving or influencing the use of a medical device\u2019  \nIs software intended to drive or influence the use of a (hardware)  medical device and does not  have or \nperform a medical purpose on its own , nor does it create information on its own  for one or more of the \nmedical purposes described in the definition of a medical device or an in vitro  diagnostic medical \ndevice. This software can, but is not limited to:  \na) operate, modify the state of, or control the device either through an interface (e.g., software, \nhardware) or via the operator of this device \nb)  or supply output related to the (hardware) functioning of that device \nNote:  Software that is driving or influencing the use of a medical device is covered by the medical \ndevices regulations either as a part/component of a device or as an accessory for a medical device. \n(refer to Figure 2, box 2).  \nSoftware that is intended to be used to operate a clinical chemistry analyser. \nSoftware with built-in electronic controls for IVD quality control procedures. These quality control \nprocedures are intended to provide users with assurance that the device is performing within \nspecifications. \nDecision steps for qualification of software as MDSW (Figure 1) \nDecision step 1 : if the product is software according to Section 2 (Definitions and Abbreviations) of \nthis guidance, then it may be a medical device software, proceed to decision step 2; if the product is \nnot software according to the definition of this guidance, then it is not covered by this guidance but \nmay still be covered by the Medical Devices Regulations. \nDecision step 2 : if the product is an MDR Annex XVI device, or is an accessory for a medical \ndevice19, or is software driving or influencing the use of a medical device, then it must be considered \nas part of that device in its regulatory process or independently if it is an accessory. If it is not, proceed \nto decision step 3. \nDecision step 3 : if the software does perform an action on data, or performs an action beyond storage, \narchival, communication20, simple search, lossless compression (i.e. using a compression procedure \nthat allows the exact reconstruction of the original data) then it may be a medical device software \n(Refer to section 3.1 for more guidance on these software functions) proceed to step 4. \n \nDecision step 4 : is the action for the benefit of individual patients?  \nExamples of software which are not considered as being for the benefit of individual patients are those \nwhich are intended only to aggregate population data, provide generic diagnostic or treatment \npathways (not directed to individual patients), scientific literature, medical atlases, models and \ntemplates as well as software intended only for epidemiological studies or registers. \n \nDecision step 5:  Is the software medical device software (MDSW) according to the definition of this \nguidance? \n                                                 \n19 According to Article 2(2) of the Medical Devices Regulation or In Vitro  Diagnostic Medical Devices Regulation. \n20 Communication: The flow of information from one point, known as the source, to another, the receiver; Source: IEEE \n610.10-1994.   \nPage 9 of 28 \n  \n  \n \nPage 10 of 28 \n 3.4. Qualification criteria of MDSW as an in vitro  diagnostic medical \ndevice \nMedical Device Software (MDSW) fulfilling the definition of an in vitro  diagnostic medical device \nfalls under the in vitro diagnostic medical devices Regulation (EU) 2017/746.  Provided that MDSW is \nintended specifically by its manufacturer to be used together with an in vitro diagnostic  medical device \nto enable it to be used in accordance with its in tended purpose, this MDSW falls under the scope of the \nin vitro  diagnostic medical devices regulation and shall be treated as an In Vitro  Diagnostic MDSW \n(IVD MDSW) in its own right.  \nIn cases when software is driving or influencing the use of a (hardware) device, the software should be \nconsidered as falling under the respective regulation of the driven or influenced (hardware) device.  \nSoftware that analyses and interprets the optical density delivered by an ELISA reader, line or spot \npattern of a blot.  Such software takes raw data outputs and use clinical algorithms for diagnostic \nand/or prognostic purposes, in which case it qualifies as IVD MDSW. \n \n \nDecision steps for qualification of MDSW as either a medical device or an in vitro  \ndiagnostic medical device (Figure 2) \nDecision Step 1: Does the  Medical Device Software (MDSW) provide information within the scope \nof the in vitro  diagnostic medical device definition? \nMDSW which provides information according to Re gulation (EU) 2017/746 \u2013 IVDR Article 2(2) (a) \nto (f) should qualify as In Vitro  Diagnostic Medical Device Software (IVD MDSW) \n(a) concerning a physiological or pathological process or state (by investigation of this process or \nstate); or \n(b) concerning congenital physical or mental impairments  \n(c) concerning the predisposition to a medical condition or a disease;  \n(d) to determine the safety and compatibility with potential recipients;  \n(e) to predict treatment response or reactions;  \n(f) to define or monitoring therapeutic measures. \nA MDSW which falls under the definition set out in EU Article 2 (1) of Regulation (EU) 2017/745 \u2013 \nMDR should qualify as Medical Device Software (MD MDSW). In specific, the following \nconsiderations should apply on the prov ision of information by software on: \n(g) diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease \n(h) diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury or disability, \n(i) investigation, replacement or modification of the anatomy or of a physiological or \npathological process or state, \n(j) control or support of conception; \n(k) products specifically intended for the cleaning, disinfection or sterilization of devices as \nreferred to in Article 1(4) and Annex XVI products.  \nDecision Step 2 : Does the MDSW create information based on data obtained by in vitro  diagnostic \nmedical devices only?  \nIf the information provided is based on data obtained solely from  in vitro  diagnostic medical devices, \nthen the software is an in vitro  diagnostic medical device and is therefore an IVD MDSW. \nIf the data analysed is obtained from a combination of both in vitro  diagnostic medical devices and \nmedical devices, proceed to step 3.     \nPage 11 of 28 \n Decision Step 3 : Is the intended purpose substantially driven by data sources coming from in vitro  \ndiagnostic medical devices? If yes, then the appli cable legislation is Regulation (EU) 2017/746. If the \nintended purpose is substantially driven by data sources coming from medical devices, then the \napplicable legislation is Regulation (EU) 2017/745.  \n \nIn the condition where the intended purpose of the MDSW output data fulfils both the medical device \nand in vitro  diagnostic medical device definitions set out in the MDR and IVDR (refer to Decision \nStep 2), a weighting of the data sources based on the significance of the information21 in relation to \nfulfilling the intended purpose should be conducted to aid the manufacturer in determining which regulation to apply. \n \nAnnex II of this guidance offers some prescrip tive examples of how such a weighting may be \nperformed. \n \n \n \n                                                 \n21 A qualitative approach is intended to drive the weighting of data. The weighing aims to assess the contribution of each data \ntowards achieving the result.  \n \nPage 12 of 28 \n 4. Classification of MDSW per MDR 2017/745 \n4.1. Implementing Rules \nAll implementing rules in Annex VIII of Regulation (EU) 2017/745 shall be considered.  \nSpecial considerations on Implementing Rule 3.3 and 3.5:  \nThe first sentence of implementing rule 3.3  of Annex VIII clarifies the regime applicable to software \ndriving or influencing the use of a device:   \n\u2018Software, which drives or influences the use of a device, shall fall within the same class as the device\u2019  \nThe second sentence of implementing rule 3.3  of Annex VIII clarifies that the regime applicable to \nIndependent MDSW:  \n \u2018If software is independent of any other device, it shall be classified in its own right\u2019 \nThis rule should also be considered at least as an orientation for finding the correct (minimum) \nclassification of software which is placed on the market in combination with a (hardware) medical \ndevice. Therefore, Medical Device Software that both achieves its own intended purpose and also \ndrives or influences the use of a (hardware) device for a medical purpose is classified on its own, \nbased on the intended purpose achieved. In such a case, however, the risk class shall not be lower than \nthe risk class of the hardware medical device.  \nImplementing rule 3.5  of Annex VIII is relevant for all devices and states that  \n\u2018If several rules, or if, within the same rule, seve ral sub-rules, apply to the same device based on the \ndevice\u2019s intended purpose, the strictest rule and sub-rule resulting in higher classification will apply\u2019  \nMelanoma image analysis software intended to be used with a near-infrared laser light scanner , \nwhich is considered class IIa per Rule 10. The software \u201cdrives or influences the use of\u201d the near-\ninfrared laser light scanner as it is intended to take control of the scanner by letting it execute \nproprietary multi-exposure programs for the detection of melanoma. As such, implementing rule 3.3  \napplies. However, Rule 11 would also apply based on the intended medical purpose of the software \ne.g. cancer diagnosis. The MDSW would be classified as class III based on Rule 11 (see section \nClassification Rules) and per implementing rule 3.5  of Annex VIII. \n4.2. Classification Rules \nRules 9, 10 and 12 mainly categorise the risks related to the exchange of energy/substances between \nthe body and diagnostic or therapeutic active devices, taking into account the different healthcare \nsituations (condition of patients).  \nMDSW, in the majority of cases, does not (directly) relate to such risks. It relates to the consequences \nof indirect harm from failure to provide correct information.  \nTherefore, in line with Recital 5 of the Medical Device Regulation and international guidance from the \nIMDRF (International Medical Device Regulators Forum)22, Rule 11 was introduced into the MDR \nand is intended to address the risks related to the information provided by an active device, such as \nMDSW. Rule 11, in particular, describes and categorises the significance of the information provided \nby the active device to the healthcare decision (patient management) in combination with the healthcare situation (patient condition). \nAs software is defined as an active device, for the classification of active (hardware) devices, which \nalso includes MDSW providing information for patient management, Rules 9, 10, 11, 12, 13, 15 and \n                                                 \n22 IMDRF is a voluntary group of medical device regulators from around the world who have come together to build on the \nstrong foundational work of the Global Harmonization Task Force on Medical Devices (GHTF) and aims to accelerate international medical device regulatory harmonization and convergence.  \nPage 13 of 28 \n 22 of Annex VIII MDR 2017/ 745 should be considered. In line with implementation rule 3.5, the \nstrictest rule or sub-rule should hence apply. \nMDSW should be classified in the same way, rega rdless of the software's location or the type of \ninterconnection between the software and a (hardware) device.  \n4.2.1.  Rule 11 \u2013 Software for decisions with diagnosis or therapeutic purposes or \nsoftware intended to monitor  physiological processes  \nRule 11 states:  \nSoftware intended to provide information which is used to take decisions with diagnosis or \ntherapeutic purposes is classified as class IIa, except if such decisions have an impact that \nmay cause: \ndeath or an irreversible deterioration of a person's state of health, in which case it is in class \nIII; or \na serious deterioration of a person's state of health or a surgical intervention, in which case it \nis classified as class IIb.  \nSoftware intended to monitor physiological processes is classified as class IIa, except if it is \nintended for monitoring of vital physiological parameters, where the nature of variations of \nthose parameters is such that it could result in immediate danger to the patient, in which case \nit is classified as class IIb.  \nAll other software is classified as class I. \nThe text of Rule 11 can be divided into what are essentially three sub-rules that are applied depending \non the intended use/purpose of the MDSW: \n11a: (3 first paragraphs of Rule 11) intended to provide information which is used to take \ndecisions with diagnostic or therapeutic purposes; \n11b: (Paragraph 4 of Rule 11) intended to monitor physiological processes or parameters; \n11c: (Paragraph 5 of Rule 11) all other uses.  \nSub-rule 11a): \nThe wording \u201cintended to provide information which is used to take decisions with diagnosis or \ntherapeutic purposes\u201d describes, in very general terms, the \u201cmode of action\u201d which is characteristic of \nall MDSW.  Therefore, this sub-rule is generall y applicable to all MDSW (excluding those MDSW \nthat have no medical purpose). \nSub-rule 11a), states that MDSW (which is intende d to provide information which is used to take \ndecisions with diagnosis or therapeutic purposes) is classified as class IIa. \nThere are two exceptions from sub-rule 11a) that ar e mainly intended to apply a risk classification \nbased on the significance of the provided information and the potential impact of an (incorrect) \ndecision made using information from the MDSW.23 Accordingly, MDSW that is intended to provide \ninformation which is used to take decisions with diagnosis and therapeutic purposes, is at a higher risk \nclass where such decisions, if based on incorrect information from the MDSW, are reasonably likely to have an impact that may cause: \ni. death or an irreversible deterioration of a person's state of health, in which case it is in class III; \nii. serious deterioration of a person's state of health or surgical intervention, in which case it is \nclassified as class IIb. \n                                                 \n23 Compare IMDRF/SaMD WG/N12FINAL:2014 which states that there are two major factors that provide adequate \ndescription of the intended use of software: A. - Significance of  the information provided by the software to the healthcare \ndecision and B. - State of the healthcare situation or patient condition.   \nPage 14 of 28 \n The MDR contains several references to \u201cserious deterioration of a person\u2019s state of health\u201d and \n\u201csurgical intervention\u201d, notably in the vigilance or clinical investigation context. Further horizontal guidance could be provided in the future and will be available at: \nhttps://ec.europa.eu/growth/sectors/medical-devices/new-regulations/guidance_en    \nRule 11 was also introduced to mirror the regulatory guidance developed at international level and \nnotably in the context of the International Medi cal Device Regulators Forum (IMDRF). The IMDRF \nframework for risk categorisation of software as a medical device (SaMD) (\u201cIMDRF Risk \nFramework\u201d) categorises the risk of software based on the combination of the significance of the \ninformation provided by the software to the healthcare decision and the healthcare situation or patient condition. IMDRF also developed a table for assisting operators in identifying the appropriate risk \ncategory for their own product. \nSuch a table could provide operators placing MDSW on the EU market with some useful indications \non the risk class applicable to their products as a result of the application of Rule 11 of the MDR. For \nthis purpose, a table is provided in Annex III to this document which lists the IMDRF risk categories and the possible corresponding MDR risk classes accor ding to Rule 11 of the MDR. It must be noted \nthat this table does not take into account MDSW which is Class I.   \nSub-rule 11b): \nMDSW that is intended to monitor physiological processes will, under most circumstances, provide \n\u201cinformation which is used to take decisions with diagnosis or therapeutic purposes and hence fall under sub-rule 11a. Sub-rule 11b) should therefore be considered as a specific rule for MDSW \nintended only for monitoring purposes. Sub-rule 11b) was introduced to ensure that MDSW which has \nthe same intended purpose as (hardware) devices which would fall under rule 10, third indent, are in \nthe same risk class.  \nHowever, this sub rule applies to MDSW intended to be used for monitoring any/all physiological \nprocesses and not just vital physiological processes (equivalent to rule 10, third indent).  \nVital physiological processes and parameters include, for example, respiration, heart rate, cerebral \nfunctions, blood gases, blood pressure and body temperature. \nSub-rule 11c): \nSub-rule 11c) implies that all other MDSW is classified as class I. \n4.2.2.  Rule 12 \u2013 Active devices intended to administer and/or remove \nsubstances \nAs software devices cannot physically administer and/or remove substances, please refer to the \nimplementation rule 3.3 of Annex VIII for MDSW covered by this rule.  \n4.2.3.  Rule 13 \u2013 All other active devices \nTaking into consideration all implementing and classification rules applicable to active devices, if no \nother rule applies, all other active devices are class I. 24 \n4.2.4.  Rule 15 - Devices used  for contraception \nRule 15 applies to devices used for contraception or prevention of the transmission of sexually \ntransmitted diseases. Software used for contraception will be classified as class IIb. \n                                                 \n24 Specific implementation or classification rules for active Annex XVI devices (which might also include software) are \nexpected to be provided together with the relevant Common Specifications for those devices.   \nPage 15 of 28 \n 4.2.5.  Rule 22 \u2013 Closed loop systems \nActive therapeutic devices with an integrated or incorporated diagnostic function which significantly \ndetermines the patient management by the device, such as closed loop systems or automated external \ndefibrillators, are classified as class III.  \nSee also implementing rule 3.3 fo r MDSW covered by this rule. \nFurther horizontal Guidance on the application of MD classification and implementing rules can be \nfound at https://ec.europa.eu/growth/sectors/medical-devices/new-regulations/guidance_en . This is \nexpected to provide useful orientation in relation to the application of non-software specific \nclassification rules.   \n5. Classification and implementing rules per IVDR 2017/746 \n5.1. Implementing Rules: \nAll implementing rules in Annex VIII of Regulation (EU) 2017/746 shall be considered.  \nSpecial considerations on Implementing Rule 1.4 and 1.9:  \nImplementing rule 1.4  is only applicable for software which drives or influences the use of an in vitro  \ndiagnostic medical device. This rule should also be considered at least as an orientation for finding the \nright (minimum) classification of software which is placed on the market in combination with a \n(hardware) medical device.  \nAccording to the second sentence of implementing rule 1.4 , if the software is independent of any other \ndevice, it shall be classified in its own right.  \nExamples for applying this implementing rule under the in vitro  diagnostic medical devices regulation:  \n\u0081 Software that is exclusively intended to drive or influence the use of an instrument intended by \nthe manufacturer specifically to be used for in vitro diagnostic procedures is classified in the \nsame class as the instrument. \n\u0081 A software that is intended to operate (driving) a C-reactive protein (CRP) measuring \nanalyser from a remote location is classified in the same class as the analyser i.e. if the \nanalyser is a classified as class A then the software operating the analyser falls into Class A. \n\u0081 MDSW that integrates genotype of multiple genes to predict risk a disease or medical \ncondition developing or recurring; this is an independent IVD MDSW and is classified on its \nown.  \nImplementing rule 1.9  states that if several classification rules apply to the same device based on the \ndevices\u2019 intended purpose, the rule resulting in higher classification will apply. To classify In Vitro \nDiagnostic Medical Device Software (IVD MDSW) which is independent of any other device, see the \nMDCG Guidance on Classification of IVDs when available at \nhttps://ec.europa.eu/growth/sectors/medical-devices/new-regulations/guidance_en . \n5.2. Classification Rules:  \nIn determining the proper classification of MDSW  under the IVDR, the manufacturer shall consider \nall classification and implementing rules of Annex VIII of the IVD Regulation (EU) 2017/746. \nAs spelled out by Implementing Rule 1.1 of Annex VIII of Regulation (EU) 2017/746, the application \nof the classification rules shall be governed by the intended purpose of the MDSW.   \nPage 16 of 28 \n Guidance on the application of the IVD classification and implementing rules can be found at \nhttps://ec.europa.eu/growth/sectors/medical-devices/new-regulations/guidance_en25 \nExamples for the classification of MDSW under the IVDR: \n\u0081 Software intended to be installed on a fully automated enzyme-linked immunosorbent assay \n(ELISA) analyser, and intended to determine the Human HbA1c concentration in serum from \nthe results obtained with a Human HbA1c ELISA, intended to screen for and diagnose \ndiabetes and monitor diabetic patients, should be in class C per Rule 3(k). \n\u0081 Software within a PAP stain automated cervical cytology screening system, intended to \nclassify the PAP cervical smear as either normal or suspicious, should be in class C per Rule \n3(h). \n\u0081 Software for the interpretatio n of automated readings of line immunoassay for the \nconfirmation and determination of antibodie s to HIV-1, HIV-1 group O and HIV-2 in human \nserum and plasma, should be in class D per Rule 1. \n\u0081 Software that uses maternal parameters such as age, concentration of serum markers and \ninformation obtained through foetal ultrasound ex amination for evaluating the risk of trisomy \n21, should be in class C per Rule 3(l). \nClassification examples in Annex IV are provided for guidance purposes and aim to illustrate how \na particular rule may be applied to a device. The indicated classification in the example is not a confirmation of the final classification of the device, as other rules must also be considered.  \n6. Considerations on placing on the market and conformity \nassessment of MDSW \nThe type of interconnection between the MDSW and the device (e.g. embedded systems, wires, Wi-Fi, \nBluetooth) does not affect the qualification of the software as a device under the MDR and IVDR (e.g. \nwhether the software is incorporated in a device or is at a different location). However, MDSW can be \nplaced on the market in two different ways: as a medical device or in-vitro  diagnostic medical device \nin its own right or as an integral component or part of a hardware device. \n6.1.  Option 1: as a medical d evice in its own right \nMDSW may be placed on the market or put into service in its own right. \n\u0081 MDSW intended to be installed on a fully aut omated enzyme-linked immunosorbent assay \n(ELISA) analyser, and intended to determine the Human HbA1c concentration in serum from \nthe results obtained with a Human HbA1c ELISA. \n\u0081 MDSW app that provides a 10-year risk of cardiovascular disease from data input by a lay \nuser. \n\u0081 MDSW app that calculates anticoagulant dosage fo r patients in oral anticoagulant therapy, \nfrom INR test results input by IVD instrume nts and other manually entered patient data. \n\u0081 MDSW app that analyses digital images of stained HEp-2 cell substrates from a microscope, \nfor detecting antinuclear antibody (ANA) patterns to guide confirmatory testing useful in elucidating a specific clinical diagnosis or prognosis. \nConformity assessment:  \n                                                 \n25 Please note that at the time of the adoption of this document, the referenced Guidance on the application of IVDR \nclassification and implementing rules was under finalisation.   \nPage 17 of 28 \n MDSW placed on the market as a device or put into service in its own right shall undergo an \nappropriate regulatory process that shall take into consideration the qualification, classification and intended purpose of the MDSW. \n6.2. Option 2: as an integral component/part of a device \nMDSW may be placed on the market or put into service as an integral component/part of a device.  \n\u0081 MDSW contained within a blood gas analyser that enables a user to run tests on the \ninstrument. \n\u0081 MDSW that is part of a handheld hardware device intended for near-patient testing (POCT: \npoint of care testing) for the determinat ion of the blood glucose concentration. \n\u0081 A fully automated enzyme-linked immunosorb ent assay (ELISA) analyser, composed of \nhardware and MDSW, intended to determine the Human HbA1c concentration in serum from \nthe results obtained with a Human HbA1c ELISA. \n\u0081 MDSW that is part of a pulse oximeter intended to digitally filter the noise from low perfusion \nperformance and motion artefacts, to calculate the ratio of red light/infrared light and to use a \nlookup table based on Beer-Lambert law to convert the ratio into the oxygen saturation in a person\u2019s blood (SpO2). \nConformity assessment: \nMDSW that is placed on the market or put into se rvice solely as an integral component/part of a \n(hardware) device may not have to undergo its own regulatory process.\n26 In this case, the MDSW shall \nbe assessed through the regulatory process applied to the device as a whole, as it is placed on the \nmarket. \nApplying the classification rules to these hardware devices, which is de-facto  a combination of the \nhardware device and the MDSW, requires careful consideration of the intended purpose of the \nMDSW. This must also be analysed when later changes to the MDSW are done. \nNote:  MDSW could be independent under both scenarios described in 6.1 and 6.2, despite the \npresentation in which it is placed on the market. \n7. Modules \nSome medical device software may be segregated into a number of applications where each of these \napplications is correlated with a module. Some of  these modules have a medical purpose, some not. \nSuch modules may be intended to cover many needs, e.g.: \n\u0081 Collect and maintain administrative patient data; \n\u0081 Keep on file the medical history of the patient; \n\u0081 Invoicing and other accounting functions; \n\u0081 Provide a link to the social security system for reimbursement; \n\u0081 Provide a link to drug prescription systems (with possible link to drug dispensing outlets); \n\u0081 Provide expert system assistance for medical decision making (e.g. radiotherapy dose \nplanner). \n                                                 \n26 Note: MDSW that is intended specifically to replace a part or com ponent of a device and that significantly changes the \nperformance or safety characteristics or the intended purpose of the device shall be considered to be a device and shall meet the requirements laid down in this Regulation (see Article 23.2 (2)).\n  \nPage 18 of 28 \n This raises the issue as to whether the whole product can be CE marked when not all applications have \na medical purpose.   \nComputer programmes used in healthcare can have applications which consist of both medical device \nand non-medical device modules. \n \nThe modules which are subject to the Medical Devices Regulations (figure 1 and 2) must comply with \nthe requirements of the medical device regulations and must carry the CE marking. The non-medical \ndevice modules are not subject to the requirements for medical devices. It is the obligation of the manufacturer to identify the boundaries and the interfaces of the different modules.  \n \nThe boundaries of the modules which are subject to the medical device regulations should be clearly \nidentified by the manufacturer based on the intended use. \nIf the modules which are subject to the medical device regulations are intended for use in combination \nwith other modules of the whole software stru cture, other devices or equipment, the whole \ncombination, including the connection system, must be safe and must not impair the specified \nperformances of the modules which are subject to the medical device regulations.\n27 \n8. Consideration of changes to an MDSW \nManufacturers shall evaluate the potential impact of any changes to the function, intended use, \nessential design, and manufacturing characteristics on the software\u2019s qualification as MDSW and its \nclassification (including the classification of the combination of the MDSW with another medical \ndevice). \nIt is to be noted that a change to or the addition of functionality to a software may lead it to be \nqualified as MDSW, or a revision of the classificati on of the MDSW. Similarly, a module that is added \nto a software might be qualified as a MDSW on its own. \nWhen determining the risk class of a combinati on of a modified MDSW and a medical device, the \nintended purpose and functionality of that (new) combination must be considered. \nNote:  For all MDSW, the manufacturer shall ensure safety and performance throughout the lifecycle \nof the software, through a continuous process of clinical and/or performance evaluation and risk management.  \n \n \n \n9. Annex I: Illustrative examples of qualification of software \nused in the healthcare environment \nSoftware for a medical purpose is rapidly evolving. Thus, the list of examples provided below is not \nexhaustive. The examples have been drafted in light of today\u2019s state of the art, in order to give the reader a better understanding of the application of the principles set out in the guideline. \nThe Manual on borderline and classification in the Community regulatory framework for medical \ndevices contains many examples related to qualification of software and apps, under the current \n                                                 \n27 i.e. general safety and performance requirements 14.1 of EU MDR 2017/745 and 13.1 of EU IVDR 2017/746   \nPage 19 of 28 \n Directives28.  The Manual is currently under revision for adaptation to MDRs. In light of the \ntechnological progress, further examples will be regularly published in both the Manual and in this guidance.  \n \na) Hospital Information Systems \nHospital Information Systems mean, in this context, systems that support the process of patient \nmanagement. Typically they are intended for patient admission, for scheduling patient appointments, \nfor insurance and billing purposes. \nThese Hospital Information Systems are not qualified as medical devices. However, they may be used \nwith additional modules, as described hereafter. These modules might be qualified in their own right as medical devices. \n \nb) Decision Support Software \nIn general, these are computer based tools which combine general medical information databases and \nalgorithms with patient-specific data. They are intended to provide healthcare professionals and/or \nusers with recommendations for diagnosis, prognosis, monitoring and treatment of individual patients. \n \nBased on Figure 1, they are qualified as medical devices.  \n\u0081 Radiotherapy treatment planning systems\n29 are intended to calculate the dosage of ionizing \nirradiation to be applied to a specific patient . They are considered to control, monitor or \ndirectly influence the source of ionizing radiation and are qualified as medical devices. \n \n\u0081 Drug planning systems (e.g. chemotherapy) are intended to calculate the drug dosage to be \nadministered to a specific patient and therefore are qualified as medical devices. \n \n\u0081 Computer Aided Detection systems are intended to provide information that may suggest or \nexclude medical conditions are qualified as medical devices (MDSW). For example, such \nsystems would be able to automatically analyse x-ray images or interpret ECGs. \n \nc) Information Systems \nInformation Systems that are intended only to transfer, store, convert, format, archive data are not \nqualified as medical devices in themselves. However, they may be used with additional modules which maybe qualified in their own right as medical devices (MDSW). \nc.1.) Electronic Patient Record Systems \nElectronic patient record systems are intended to store and transfer electronic patient records. They \narchive all kinds of documents and data related to a specific patient. The electronic patient records \nshould not be qualified as a medical device, i.e. an electronic patient record that simply replaces a patient\u2019s paper file does not meet the definition of a medical device. The modules used with electronic \npatient record system modules that might be qualified in their own right as medical devices (MDSW) \nare for example: \n\u0081 An image viewer with functionality for diagnosis based on digital images; \n\u0081 A medication module \n                                                 \n28 http://ec.europa.eu/DocsRoom/documents/12867/a ttachments/1/translations/en/renditions/native   \n29 See EN 62083 \u201cRequirements for the safety and radiotherapy treatment planning systems\u201d   \nPage 20 of 28 \n c.1.1.) Clinical Information Systems \u2013 CIS / Patient Data Manag ement Systems \u2013 PDMS \nA CIS/PDMS is a software-based system primarily intended to store and transfer patient information \ngenerated in association with the patient\u2019s intensive care treatment (e.g. intensive care units).  \nUsually the system contains information such as patient identification, vital intensive care parameters and other documented clinical observations.  \nThese CIS/PDMS are not qualified as medical devices. \nModules that are intended to provide additional information that contributes to diagnosis, therapy and \nfollow-up (e.g. generate alarms) are qualified as medical devices. \nc.1.2.) Pre-hospital Electrocardiograph (ECG) System \nA system for managing pre-hospital ECG is a software-based system intended for ambulance services \nto store and transfer information from patients to a doctor at remote location. Usually the system \ncontains information about patient identification, vital parameters and other documented clinical \nobservations. These Pre-hospital Electrocardiograph (ECG) Systems are not qualified as medical \ndevices.  \nModules that create and provide new patient treatment information to the paramedics or to the doctor \nat a remote location to start the patient\u2019s treatment while the patient is being transported are qualified \nas medical devices.   \n \nc.1.3.) Picture Archive Communication System (PACS) \nThe Manual on Borderline and Classification in th e Community Regulatory Framework for Medical \nDevices addresses the qualification of PACS.\n30 The transposition of this Directive Guidance to the \nRegulations is currently underway and will be published at \nhttps://ec.europa.eu/growth/sectors/medical-devices/new-regulations/guidance_en  \nd) Communication Systems \nThe healthcare sector uses communication systems (e.g. email systems, mobile telecommunication \nsystems, video communication systems, paging, etc.) to transfer electronic information. Different \ntypes of messages are sent such as prescription, referrals, images, patient records, etc. \nMost of the communication systems handle types of messages other than medical information. This communication system is intended for general purpos es, and is used for transferring both medical and \nnon-medical information. \nCommunication systems are normally based on software for general purposes, and do not fall within \nthe definition of a medical device. \nCommunication system modules might be used with other modules that might be qualified in their own right as medical devices (MDSW). \n \nA software module generating alarms based on th e monitoring and analysis of patient specific \nphysiological parameters is qualified as a medical device (MDSW). \n \nd.1) Telemedicine systems \nTelemedicine Systems are intended to allow monitoring and/or delivery of healthcare to patients at \nlocations remote from where the healthcare professional is located. \n                                                 \n30 https://ec.europa.eu/docsroom/documents/35582/attachments/1/translations/en/renditions/native   \nPage 21 of 28 \n d.1.1.) Telesurgery \nTelesurgery is intended to conduct a surgical procedure from a remote location. Virtual reality \ntechnology may be used to support a remote surgeon to control a surgical robot performing the \nsurgical procedure. Telesurgery systems should be qualified as medical devices according to Figure 2 of this document.  \nRemote control software used in combination with telesurgery robots is a software that drives or \ninfluences the use of a medical device. Communication modules themselves are not medical devices. \nOther modules that are intended to influence the su rgery procedure are qualified as medical devices \n(MDSW). \ne) Web systems for monitoring of data \nA web system for the monitoring of clinical data typically interacts with a medical device (e.g. \nimplanted devices or homecare devices), and uses a transmitter to send the information over the \ninternet, a landline telephone or a mobile network. \nThe information is collected and stored on a web server usually run by an external party who is \ngenerally the manufacturer of the system. The information can be reached by authorized health \nprofessionals or the patient through an internet connection. \n\u0081 Monitoring of performance of medical devices: \nModules that are intended to monitor the medical performance of medical devices fall under \nthe medical device regulations. \nThis includes the clinical performance and failures that could affect medical performance of the device. One example of such a product is a web system for monitoring of active implants \nsuch as pacemakers or Intra Cardiac Defibrillators (ICDs). \n \n\u0081 Monitoring of non-medical performance of medical devices \nModules that are intended to perform administrative monitoring of non-medical performance \nof medical devices do not necessarily fall under the scope of the medical devices regulations. \nSoftware for the monitoring of medical devices in hospital systems for the purpose of \nmaintenance and repair.  \nf) In vitro  diagnostic medical device software \n \nf.1.) Laboratory Information Systems (LIS) and Work Area Managers (WAM) \nLaboratory Information System (LIS) and Work Area Managers (WAM) mean, in this context, \nsystems that support the process from patient sample to patient result. Typically, they have pre-\nanalytical functions for ordering, sorting and distribution of test samples. The main task is the management and validation of incoming information obtained from in vitro  \ndiagnostic medical device analysers connected to the system, such as calibration, quality control, \nproduct expiry and feedback (e.g. retesting of samples needed) through interconnections with various \nanalytical instruments (technical and clinical validation). \nFinally the post-analytical process allows communication of laboratory results, statistics and optional reporting to external databases. \nThe software normally supports the following functions: \n\u0081 Ordering of laboratory tests, samples with labels and sorting; \n\u0081 Technical and clinical validation, connection to analytic instruments; \n\u0081 Laboratory results and reports on paper, fax or electronic records that can be directly returned \nto e.g. the ordering clinic\u2019s patient record; \n\u0081 Analytical instruments can be interfaced with Hospital Information Systems (HIS), Electronic \nPatient Record Systems, Infectious control databases, etc.  \nPage 22 of 28 \n Note : software intended to modify the representation of available in vitro  diagnostic medical device \nresults is not considered an in vitro  diagnostic medical device, e.g. basic operations of arithmetic (e.g. \nmean, conversion of units) and/or plotting of results in function of time, and/or a comparison of the \nresult to the limits of acceptance set by the user. \nThe results are available, readable and understandable without the intervention of the software. \nLaboratory Information Systems (LIS) and Work Area Managers (WAM) are not qualified as \nmedical devices in themselves.  However, they may be used with additional modules. These modules \nmight be qualified in their own right as medical devices. \nA module whose intended purpose is to assess the criticality of tests required and to perform \nautomatic reprioritisation of the order based on patient data is qualified as a MDSW.  \nf.2.) Expert system \nMDSW which is intended to provide information within the scope of the in vitro diagnostic medical \ndevices definition by capturing and analysing together one or multiple results obtained for one patient \nby means of in vitro  examination of body samples (possibly combined with information from medical \ndevices and non-medical devices). \n\u0081 MDSW that integrates genotype of multiple genes to predict risk a disease or medical \ncondition developing or recurring; \n\u0081 MDSW that uses an algorithm to characterise viral resistances to various drugs, based on a \nnucleotide sequence generated by genotyping assays. This software serves to generate new information (virus resistance profile) from avai lable information on the genotype of the virus; \n\u0081 MDSW intended to be used in microbiology for the identification of clinical isolates and/or the \ndetection of antimicrobial resistances. \nRefer to Figure 2 of this guidance if data is obtained from both in vitro  diagnostic medical devices and \nmedical devices.  \nf.3.) Interpretation of raw data \nIn the case where MDSW is necessary to render raw data, readable for the user, obtained from an in \nvitro  diagnostic medical device by means of in vitro  examination of body samples, this MDSW is to \nbe considered driving or influencing the use of the in vitro  diagnostic medical device when it is \nspecifically intended to be used together with this in vitro  diagnostic medical device to enable it to be \nused in accordance with its intended purpose. \n \nMDSW intended for the analysis and interpretatio n of enzyme-linked immunosorbent assay (ELISA) \nreader optical density results, line patterns or spot patterns of a blot. \n \nf.4.) Home care monitoring, wired or mobile \nSoftware intended for archiving patient result s or for transferring results obtained from in vitro  \ndiagnostic medical devices from the home environment to the healthcare provider is not an in vitro  \ndiagnostic medical device. The results are available, readable and understandable by the user without \nthe intervention of the software. \n \nf.5.) Image Management System (IMS) \nAn IMS is a software-based system primarily intended to be networked with digital pathology \nsystems, e.g., whole slide scanners, scanning microscopes, as well as LIS. It does not contain controls \nfor the direct operation of the digital pathology syst ems, and is intended to access, display, annotate, \nmanage, store, archive and share collections of digitised patient images. IMS may be configured to  \nPage 23 of 28 \n provide limited or extensive capabilities to further visualise or analyse patient images acquired from \nnetworked digital pathology systems. \n \nAn IMS only used for viewing, archiving and transmitting images are not considered medical devices \nin themselves. However, these IMS may be used with additional modules that might be qualified in \ntheir own right as medical devices (MDSW). \n \nIMS that incorporate functions to support post-processing of images for diagnostics purposes, e.g., \nimage processing functions which alter image data or complex quantitative functions to aid in diagnosis, are qualified as MDSW. \n   \nPage 24 of 28 \n 10. Annex II - Qualification examples of Medical Device \nSoftware (MDSW) according to Figures 1 and 2 \nFigure 1 - Example 1: \nA software module which runs on an in vitro  diagnostic medical device instrument and tracks how the \nlaboratory is performing in real-time on key operational metrics such as test volumes, turnaround \ntimes, pending tests, and quality control. Its intent is to improve a laboratory\u2019s operations by providing \nreal-time monitoring of performance metrics that can drive change management and continuous improvement initiatives within the lab. The software is configurable so that customers can choose the \nmetrics on which they would like to focus. \n \nQualification: Step 1 is concluded with a \u201cyes\u201d as the software is a product which uses a set of \ninstructions (or algorithm) to process input data and create output data.  Step 2 determines that the software is not an MDR Annex XVI device, nor is it an accessory for a medical device, nor a software \ndriving or influencing the use of a medical device. Step 3 is answered \u201cyes\u201d since the software is \ndoing more than storage, archival, communication or simple search of information. Step 4 is answered \n\u201cno\u201d as the software does not perform this action for the benefit of individual patients.  The conclusion \nis that the software does not fall under the Medical Devices Regulations.  This is appropriate since the software is intended to be a Laboratory Information Systems (LIS), which is not considered a medical \ndevice. \n \nFigure 2 - Example 2:  \nMDSW intended to generate a risk score in order to trigger care processes to help reduce ICU \ntransfers, readmissions, adverse events and length of stay. The risk score by default includes \nrespiratory rate, heart rate, blood pressure and Sp O2, but a user can configure it to include other \nparameters, including in vitro  diagnostic medical device results. \n \nQualification:  In decision Step 1, the MDSW can be understood  to meet criteria (a), (f) and (h), it is \ntherefore answered \u201cyes\u201d. Step 2 is answered with a \u201cNo\u201d as an in vitr o diagnostic medical device \nresult may be included in the in the calculation. Step 3 directs the significance of the medical device \nderived information as driving the intended purpose, re sulting in the qualification of the software as an \nMD MDSW (as the data received from the in vitro  diagnostic medical device is not deemed decisive \nfor the overall calculation result (output) achieved by the MDSW) \n \nFigure 2 - Example 3: \nA MDSW algorithm intended to provide information on the statistical predisposition for Down \nsyndrome (Trisomy 21) and Edwards syndrome (Trisomy 18) in the first and second trimesters of \npregnancy. 31 The MDSW analyses input data from various in vitro  diagnostic medical device assays32 \nas well as, ultrasound measurements of the nasal bone or neck fold.  The MDSW  provides \nclinicians/obstetricians with a risk factor score for a foetus\u2019s likelihood of having genetic mutations in \nthe first or second trimester of pregnancy.  The risk score suggests whether or not additional diagnostic testing is needed to confirm the genetic mutations of Trisomy 21, Trisomy 18.\n33 \n \nQualification: Step 1 can be answered \u201cyes\u201d as the software bears a medical purpose and fulfils the \ndefinition of MDSW. The MDSW meets criteria (c) as it provides information according to the in vitro  \n                                                 \n31 The software can also detect neural tube defects (NTD) in the second trimester as well as the risk for Patau\u2019s syndrome \n(Trisomy 13). \n32 AFP (LKAP, L2KAP), Unconjugated Estriol (LKUE3, L2KUE3), hCG (LKCG, L2KCG), free \u03b2-hCG (LKFB, L2KFB), \nPAPP A (LKPC, L2KPC) \n33 or neural tube defects and Trisomy 13   \nPage 25 of 28 \n diagnostic medical devices definition. Decision step 2 is answered \u201cno\u201d as an imaging measurement is \nincluded in the calculation. Step 3 is answered \u201cyes\u201d as the intended purpose is substantially driven by in vitro  diagnostic medical device data resulting in the qualification of the software as an IVD MDSW \n(as the data received from the in vitro  diagnostic medical devices (markers) are deemed decisive for \nthe overall calculation result (output) achieved by the MDSW). \n \nFigure 2- Example 4:  \nA bioinformatics MDSW intended to analyse digi tal Next Generation Sequencing (NGS) raw data \ncoming from sequenced patient\u2019s cancer genomes. It allows the detection and visualisation of somatic genome alterations (such as substitutions, small insertions and deletions (indels), copy number \nalterations, and genomic rearrangements) across a selected number of genes. Additionally, it is also \ncapable of determining genomic signatures* (such as microsatellite instability [MSI] and/or tumour \nmutational burden [TMB]). The types of somatic genome alterations and genomic signatures detected \ndepend on the test chosen.  The MDSW assists the user in identifying and visualising genomic alterations and is intended to identify somatic genome alterations to support diagnosis and treatment \ndecisions.   \n \nQualification: Decision step 1 is concluded with a \u201cyes\u201d as the MDSW is intended for analysing \ncongenital data to provide information on the predisposition to a medical condition or disease, thus meeting criteria (b) and (c) laid out in the decision step. As the MDSW processes data coming only \nfrom in vitro  diagnostic medical devices into the calculation, then the software is qualified as an IVD \nMDSW according to Step 2.  \n \n \n   \nPage 26 of 28 \n 11. Annex III - Usability of the IMDRF risk classification \nframework in the context of the MDR 34 \nThe table below, which is intended for illustrative purposes only, may provide operators placing \nMDSW on the EU market with some useful indicative orientation on the risk class applicable to their \nproducts as a result of the application of Rule 11 a of the MDR.  \nNote:  MDR 2017/745 Sub-rule 11(a), point i., referr ing above to MDR class III, aligns with IMDRF \nrisk category IV . Sub-rule 11(a), point ii.,, referring above to MDR class IIb, aligns with IMDRF risk \ncategory III  products mentioned in section 7.2 of the mentioned IMDRF document. The IMDRF risk \ncategory II and IMDRF risk category I products are classified as MDR class IIa as per Rule 11. \nThis table does not take into account MDSW which is Class I.   \n \n  Significance of Information provided by the \nMDSW to a healthcare situation related to \ndiagnosis/therapy  State of Healthcare  \nsituation or patient condition   High \nTreat or  \ndiagnose  \n~ IMDRF 5.1.1  Medium  \nDrives clinical \nmanagement  \n~ IMDRF 5.1.2  Low \nInforms clinical \nmanagement  \n(everything else)  \nCritical situation \nor patient \ncondition  \n~ IMDRF 5.2.1  Class III \nCategory IV.i Class IIb \nCategory III.i Class IIa \nCategory II.i \nSerious situation \nor patient \ncondition  \n~ IMDRF 5.2.2 Class IIb \nCategory III.ii Class IIa \nCategory II.ii Class IIa \nCategory I.ii \nNon-serious \nsituation or \npatient condition  \n(everything else) Class IIa \nCategory II.iii Class IIa \nCategory I.iii Class IIa \nCategory I.i \nTable 1: Classification Guidance on Rule 11 \n \n \n \n                                                 \n34 Annex III and IV are not relevant for IVD MDSW. See sec tion 4.2 in order to classify IVD MDSW. MDCG Guidance on \nClassification of IVDs should also be considered.   \nPage 27 of 28 \n 12. Annex IV \u2013 Classification examples  \nThe examples are provided for guidance purposes only, to illustrate how a particular rule may be \napplied to a device. The indicated classification in  the example is not a confirmation of the final \nclassification of the device, as other rules might also be considered.  \nMoreover, the proposed classification reflects the specific intended purpose, or the healthcare context \nor situation, in which the device is used as described in the example itself. Any change to the intended \npurpose or the healthcare context/situation in which that same device is used might result in a different risk class. \n\u0081 MDSW intended to  perform diagnosis by means of image analysis for making treatment \ndecisions in patients with acute stroke should be classified as class III  under Rule 11(a)  \n- IMDRF Risk Category IV.i as the healthcare situation (stroke) is critical and the \nsignificance of the information is \u201ctreat or diagnose\u201d.   \n\u0081 Cognitive therapy MDSW that includes a diagnostic function which is intended to  feed back \nto the software to determine follow-up therapy , e.g. software adapts treatment of depression \nbased on diagnostic feedback, should be in class III per Rule 22 . When a specialist \ndetermines the necessary cognitive therapy base d on the outcome provided by the MDSW, the \nMDSW would be classified as class IIa per Rule 11(a).  \n- IMDRF Risk Category II.ii as the healthcare situation is serious and the significance \nof the information is to \u201cdrive clinical management\u201d. \n\u0081 Medical devices including MDSW intended to be used for continuous surveillance of vital \nphysiological processes in anaesthesia, intensive care or emergency care should be classified as class IIb per (Rule 11(b)) . \n\u0081 Medical devices, including MDSW intended to monitor physiological processes that are not \nconsidered to be vital, and devices intended to be used to obtain readings of vital physiological signals in routine check-ups incl uding monitoring at home should be classified \nas class IIa (Rule 11(b)).  \n\u0081 A mobile app intended to analyse a user\u2019s he artbeat, detect abnormalities and inform a \nphysician accordingly should be classified as class IIb per Rule 11(a) , if the information \nprovided by the software is intended to guide the physician in the diagnosis.  \n- IMDRF Risk Category III.i as the information drives clinical management. \n\u0081 Diagnostic MDSW intended for scoring depression based on inputted data on a patient\u2019s \nsymptoms (e.g. mood, anxiety) should be classified as class IIb under Rule 11(a) ,  \n- (IMDRF  Risk Category III.ii)  as the healthcare situation (depression) is serious and \nthe significance of the information is \u201cdiagnosis\u201d). \n\u0081 Ambulatory respiratory ventilation systems MD SW intended for long-term use (e.g. at home) \nthat alert the user/operator to any disconnection or deviation to the programmed respiratory \nvolume should be classified as class IIb per Rule 9 .  \n\u0081 Active devices, such as electronic thermometers and stethoscopes, which include MDSW \nintended for direct diagnosis may be classified as class IIa per Rule 10 , third indent since \nbody temperature and heart rate are considered decisive information for diagnosis \n(implementing rule 3.7), where the nature of the variations of these parameters would not \nresult in immediate danger to the patient.  \n\u0081 MDSW intended to rank therapeutic suggestions for a health care professional based on \npatient history, imaging test results, and patient characteristics, for example, MDSW that lists and ranks all available chemotherapy options for BRCA-positive individuals, should be \nclassified as class IIa per Rule 11(a)    \nPage 28 of 28 \n - IMDRF Risk Category II.i as it informs clinical management for cancer, a critical \ndisease. \n\u0081 MDSW app intended to support conception by calculating the user\u2019s fertility status based on a \nvalidated statistical algorithm. The user inputs health data including basal body temperature (BBT) and menstruation days to track and predict ovulation. The fertility status of the current \nday is reflected by one of three indicator lights: red (fertile), green (infertile) or yellow \n(learning phase/cycle fluctuation). This MDSW app should be classified as class I per Rule \n11c."}, {"title": "md_mfr_factsheet.pdf.txt", "text": "Factsheet for  \nManufacturers  \nof Medical Devices\nWhat you need to know!MEDICAL DEVICES  CHANGE OF LEGISLATION\nThis Factsheet is aimed at manufacturers of medical devices. \nFor a general overview of the impact of the In-Vitro   Medical \nDevices Regulation (IVDR) on manufacturers see the Factsheet \nfor manufacturers of in-vitro diagnostic medical devices. Refer -\nences to  Annexes and Articles in this factsheet refer to the MDR \n(2017/745/EU).\nThe new Medical Devices Regulation \n(2017/745/EU) (MDR) and the In-vitro \nDiagnostic Medical Devices Regulation \n(2017/746/EU) (IVDR) bring EU legislation \ninto line with technical advances, chang -\nes in medical  science, and progress in law \nmaking.\nThe new Regulations will create a robust, \ntransparent, and sustainable regulatory \nframework, recognised internationally, that \nimproves clinical safety and creates fair \n market access for manufacturers.\nIn contrast to Directives, Regulations do \nnot need to be transposed into national \nlaw. The MDR and the IVDR will therefore \nreduce the risks of discrepancies in inter -\npretation across the EU market.\nTransitional periods are planned to smooth \nthe application of the new Regulations. \nHowever, you should bear in mind that con -\nsultants, in-house professionals, and Notified \nBodies will all get busier as the deadline \ndraws closer. \nAct now to be ready on time!       Medical Devices Regulation  \n   (MDR) background\nThe MDR will replace the existing Medical Devices Directive (93/42/EEC) \n(MDD) and the Active Implantable Medical Devices Directive (90/385/EEC) \n(AIMDD). The MDR was published in May 2017, marking the start of a \nthree-year period of transition from the MDD and the AIMDD.\nDuring the transitional period the MDR will come into force gradually, start -\ning with the provisions related to the designation of Notified Bodies and \nthe ability of manufacturers to apply for new certificates under the MDR.\nThe transitional period will end on 26 May 2020, the \u201cDate of Application\u201d \n(DoA) of the Regulation. From that date the MDR will apply fully.\n1\nInternal market, \nIndustry,  \nEntrepreneurship  \nand SMEs\nRef. Ares(2018)3873669 - 20/07/20182To avoid market disruption and allow a smooth transition from \nthe Directives to the Regulation, several transitional provisions \nare in place (Article 120). Some devices with certificates issued \nunder the Directives (AIMDD/MDD certificates) may continue to \nbe placed on the market until 27 May 20241, and made avail -\nable until 27 May 20252 .\nDuring the transition phase, products certified under the Direc -\ntives and products certified under the Regulation will coexist on \nthe market. Both will have equal status under the law, and no \ndiscrimination in public tenders may take place.\n   What has changed?  \nIn terms of their impacts on manufacturers and products, the \nDirectives and the MDR largely share the same basic regulatory \nrequirements. No existing requirements have been removed, but \nthe MDR adds new requirements.\nCompared to the current Directives, the MDR places more em -\nphasis on a life-cycle approach to safety, backed up by clinical \ndata.\nThe MDR brings more stringent requirements for the designation \nof Notified Bodies, with increased control and monitoring by the \nnational competent authorities and the Commission.\nThe MDR reclassifies certain devices and has a wider scope. \nFor instance, the MDR explicitly covers all devices for cleaning, \nsterilising or disinfecting other medical devices (Article 2.1); re -\nprocessed single-use medical devices (Article 17)3; and certain \ndevices with no intended medical purpose (Annex XVI).\nThe MDR also covers internet sales of medical devices and med -\nical devices used for diagnostic or therapeutic services offered \nat a distance (Article 6).\nThe MDR introduces a clinical evaluation consultation procedure \nfor some Class IIb devices and for implantable Class III devices \nby an independent expert panel (Article 54).\nA new Unique Device Identification system (Article 27) will \nsignificantly enhance the traceability and the effectiveness of \npost-market safety-related activities.\nThe MDR will also provide increased transparency, with infor -\nmation on devices and studies being made public. The new Eu -\nropean Database for Medical Devices \u2013 Eudamed \u2013 will play a \ncentral role in making data available and increasing both the \nquantity and quality of data (Article 33).\n1  For definition see Article 2 paragraph 282\n2  For definition see Article 2 paragraph 27\n3  Reprocessing and further use of single-use devices may only take place where permitted by national law and only in accordance with this Article.  \n4  EEA: European Economic Area   What does this mean  \n   in practice?\nScope (Article 1)\nThe scope of the MDR has broadened, so as a manufacturer you \nmust check your product portfolios to find out whether more of \nyour devices fall within the scope of the Regulation compared \nto the Directives. Pay attention to products listed in Annex XVI, \nwhich will be covered by the Regulation once the respective Im -\nplementing Regulation setting out common specifications has \nbeen adopted. The list of products excluded from the scope can \nbe found in paragraph 6. Some products that combined a medi -\ncal device and an in-vitro diagnostic device or a medicinal prod -\nuct follow specific rules (see paragraphs 7, 8, 9).\nIt is now explicit that devices and services sold online fall under \nthe scope of this Regulation (Article 6).\nDefinitions (Article 2)\nThe definition of a medical device has been slightly modified \nand there are more definitions of terms in the Regulation than in \nthe Directives, in order to ensure a common understanding at EU \nlevel. Examples include: Unique Device Identifier (Definition 15), \nclinical data (Definition 48), clinical evidence (Definition 51), and \nserious incident (Definition 65).\nObligations of manufacturers\nThe obligations of the different actors and their relations are \nnow clearly stated in the Regulation.\nAccording to Article 10, manufacturers shall have systems \nfor risk management (paragraph 2) and quality management \n(paragraph 9); conduct clinical evaluations (paragraph 3); com -\npile technical documentation (paragraph 4); and apply a confor -\nmity assessment procedure (paragraph 6). Manufacturers are \nalso responsible for their devices once they are on the market \n(paragraphs 12, 13, 14). They must have systems in place to \ncover their financial responsibility for harm caused by defective \ndevices (paragraph 16).\nEvery manufacturer shall have a named person responsible for \nregulatory compliance (Article 15).\nManufacturers of some implantable devices will have to provide \nan implant card for the patient (Article 18).\nOnce they have completed all these obligations, manufacturers \nshall draw up a declaration of conformity (Article 19) and apply \nCE marking to their devices (Article 20).\nManufacturers outside the EU/EEA shall have a contract with an \nauthorised representative inside the EU/EEA4 (Article 11).3The obligations of authorised representatives (Article 11), \n importers (Article 13) and distributors (Article 14) are also \n clearly described.\nRisk classes of devices\nAs a manufacturer you must check your portfolio of products \nto determine whether some of your devices will be reclassified \nor will need to be scrutinised by a Notified Body. Determining \nthe risk class of a medical device is essential in specifying the \nsteps required for CE marking (Article 51), especially in terms \nof the choice of conformity assessment procedure and clinical \nrequirements.\nThe MDR sets out 22 rules for determining risk classes (Annex \nVIII), compared to 18 rules under the Directive. You should pay \nspecial attention to rules regarding: invasive devices, surgically \ninvasive devices and implantable devices (Section 5: Rules 5 to \n8); active devices (Section 6: Rules 9 to 13, for example, soft -\nware now falls under Rule 11); devices utilising tissues and cells \n(Rule 18); devices incorporating nanomaterials (Rule 19); and \ndevices composed of substances (Rule 21).\nNotified Bodies (Chapter IV)\nNotified Bodies have to be designated under the new Regula -\ntion. They will be required to meet more stringent criteria, par -\nticularly in terms of clinical competence. Notified Bodies can \napply to be designated from 26 November 2017. The process \nof designation, which might take 12 months or more, involves \nassessors from different national and European authorities. This \nmeans that the first Notified Bodies designated under the new \nRegulation might be available by the end of 2018.\nThe database of Notified Bodies (NANDO) can be found here.\nhttp://ec.europa.eu/growth/tools-databases/nando/\nAs a manufacturer you must verify whether your Notified Body \nwill be designated under the new Regulation and whether the \nscope of its designation will cover all your products. You must \nalso start working with your Notified Body to plan the timing \nof certification for your product portfolio, taking into account \nthe availability of your Notified Body, the need for additional \ndata on devices and the transitional provisions in the new \nRegulation.\nDevice identification\nA system of unique device identifiers (UDIs) will enhance the \nidentification  (Article 27)  and traceability (Article 25) of MDs. \nThis is a completely new feature of the Regulation.\nEach MD \u2013 and as applicable, each package \u2013 will have a UDI \ncomposed of two parts: a device identifier (UDI-DI) specific to a \ndevice, and a production identifier (UDI-PI) to identify the unit \nproducing the device.Manufacturers are responsible for entering the necessary data \non the European database (Eudamed), which includes the UDI \ndatabase, and for keeping it up to date.\nConformity assessment (Chapter V Section 2)\nThe assessment of the conformity of a device for CE marking \nvaries according to the risk class and specific features of certain \ndevices (Article 52). The intervention of a Notified Body is need -\ned for all Class IIa, IIb and III devices, as well as some specific \nClass I devices (see paragraphs 7a5, b6, and c7). The different \nroutes of assessment according to the class of the device are \ndescribed in Article 52 and the Annexes IX, X, XI. In some cases \nmanufacturers have some choice regarding the conformity as -\nsessment route.\nFor certain Class III and Class IIb devices there is a new clinical \nevaluation consultation procedure to be carried out by an inde -\npendent expert panel, based on the clinical evaluation assess -\nment report of the Notified Body (Article 54).\nAnnex I specifies the general safety and performance require -\nments, while Annexes II and III specify the makeup of the tech -\nnical documentation.\nThe scope of the Quality Management System (Article 10 para -\ngraph 9) now includes clinical evaluation and post-marketing \nclinical follow-up (PMCF). A clinical evaluation plan must pre -\ncede the clinical evaluation itself (Annex XIV, Part A).\nCommon specifications defining additional requirements may be \nput in place for certain devices (Article 9).\nClinical requirements (Chapter VI)\nThe new Regulation reinforces the requirements for clinical \nevaluation (Article 61), introducing some of the biggest changes \ncompared to the previous regime.\nAs under the Directives, it includes the collection of clinical data \nalready available in the literature as well as the setting up of \nany necessary clinical investigations. The concept of equiva -\nlence with other devices for which clinical data already exists \ncan still be used, but only in a limited number of situations, and \nthe new rules are tighter (Article 61 paragraphs 4, 5, 6).\nArticle 62 and Annex XV set out the new and more precise re -\nquirements for clinical investigations. With only certain excep -\ntions, implantable and Class III medical devices must now go \nthrough clinical investigations.\nFor all Class III devices, and for Class IIb devices intended to \nadminister a medicinal product (or remove it from the body), \nthe manufacturer has the option to consult a group of European \nexperts to obtain an upstream review of its intended clinical de -\nvelopment strategy (Article 61 paragraph 2).\n5 \u201cDevices placed on the market in sterile condition, to the aspects relating to establishing, securing and maintaining sterile conditions\u201d.\n6 \u201cDevices with a measuring function, to the aspects relating to the conformity of the devices with the metrological requirements\u201d.\n7 \u201cReusable surgical instruments, to the aspects relating to the reuse of the device, in particular cleaning, disinfection, sterilization,  \n maintenance and functional testing and the related instructions for use\u201d.4Summary of safety and clinical performance  \n(Article 32)\nFor Class III and implantable devices, manufacturers shall draw \nup a summary of their safety and clinical performance in a form \nthat intended users (and patients, if relevant) can understand. \nThis summary will form part of the technical documentation \nsent to the Notified Body\n   Timing your transition  \n                  to the new Regulation\nAs a manufacturer, the timing of your transition to the MDR is \nup to you.\nFrom 26 May 2020, all new certificates will have to be delivered \naccording to the Regulation. The certificates delivered under the \nDirectives can be valid until their date of validity for a maximum \nof four years (27 May 20248 at the latest). However, in the latter \ncase, the requirements of the new Regulation relating to post-mar -\nket surveillance, market surveillance, vigilance, and the registration \nof economic operators and devices shall apply from the Date of \nApplication (Article 120 paragraph 3).\nClass I devices (other than those that have a valid certificate \nunder the Directive) will have to conform to the new Regulation \nfrom 26 May 2020.\nClass I (except sterile devices, devices with a measuring func -\ntion and reusable surgical instruments) and Class IIa might be \neasiest to start with. Classes IIb and III will be more challenging \nbecause of the more stringent requirements for clinical data.\nAs a manufacturer, you can start now by making sure that:\n1. all your products are classified appropriately;\n2. all product documentation and evidence of compliance will \nbe available in a timely fashion and conforms with the \nMDR; and\n3. you have the necessary systems in place to handle clinical \nevaluation, quality management, post-market surveillance, \nand liability for defective devices.\nMore information\nFor more information on any of the above topics, please refer to \nthe Medical Devices section  on the DG GROW website.\nhttps://ec.europa.eu/growth/sectors/medical-devices_en         Frequently asked  \n   questions\nBelow you can find an extract from the FAQs of the Competent \nAuthorities for Medical Devices. For a complete list, see: \nhttp://www.camd-europe.eu/sites/default/files/media/docu -\nments/FAQ_MDR_180117_V1.0.pdf .\nWhen does the Medical Devices Regulation (MDR) \napply?\nThe MDR (EU) 2017/745 will apply from 26 May 2020 \u2013 the \n\u201cDate of Application\u201d (DoA).\nSome provisions of the MDR will come into force earlier (e.g. \nregarding Notified Bodies and the Medical Device Coordination \nGroup). Some will apply later (e.g. regarding UDI labelling).\nWhen do the existing Directive cease to apply?\nIn general, Directives 90/385/EEC and 93/42/EEC will be  \nrepealed on 26 May 2020 (the DoA). However, there are some \nexceptions, such as:\n\u2022 for the continued marketing of devices that comply with the \nDirectives (see below); and\n\u2022 to serve as a backup in case Eudamed is not fully functional \nby the DoA.\nWhat is the applicable legislation up to 26 May 2020?\nUntil the Date of Application, the laws and regulations adopted \nby Member States in accordance with the Directives will contin -\nue to apply. However, there are some exceptions.\nIs it possible to place devices on the market that \nare compliant with the MDR prior to the DoA?\nYes, you may certainly place MDR-compliant devices on the \nmarket before the end of the transitional period. This applies \nto devices in all risk classes, and includes, for example, cus -\ntom-made devices, systems and procedure packs.\nHowever, devices subject to the \u201cclinical evaluation consultation \nprocedure\u201d, which covers certain devices in Classes IIb and III, \nmay not be placed on the market before the Medical Device \nCoordination Group (MDCG) and the expert panels have been \nestablished.\nDepending on the risk class of the device, conformity assess -\nment may involve an appropriate Notified Body. This require -\nment may create further delays before such devices can be \nmarketed due to the delays in the availability of appropriate \nNotified Bodies for all technologies.\n8 There are some exceptions described in Article 120 paragraph 25As a manufacturer, which obligations of the Regulation \ndo I need to fulfil in order to place compliant devices \non the market before the DoA?\nYou should meet as many obligations as possible, bearing in \nmind that the complete MDR infrastructure, including Eudamed, \nis unlikely to be complete before the Date of Application.\nBoth the device and the manufacturer must comply with the \nMDR. You should assess the conformity of your device \u2013 a pro -\ncess that may require the involvement of a Notified Body. Other \nimportant points include:\n\u2022 Clinical evaluation\n\u2022 Risk management\n\u2022 Quality Management System (QMS)\n\u2022 Post-market surveillance\n\u2022 Technical documentation and other reports\n\u2022 Liability for defective devices.\nUntil Eudamed is fully operational, some parts of the Directives \nwill have to substitute for the corresponding requirements of \nthe Regulation. These include the registration of devices and \neconomic operators.\nA person responsible for regulatory compliance needs to be \navailable but not necessarily registered until Eudamed is \n operational.\nDo certificates issued by Notified Bodies  \nunder the existing Directives remain valid  \nafter the DoA?\nYes, AIMDD/MDD certificates will generally remain valid un -\ntil their indicated expiry dates. This applies to all the certifi -\ncates commonly issued by Notified Bodies, including the EC \nDesign- Examination Certificates, Certificates of Conformity, EC \nType  Examination Certificates, the EC Certificate Full Quality \n Assurance System, and the EC Certificate Production Quality \n Assurance.However, all certificates issued after 25 May 2017 will be void \nat the latest by 27 May 2024. After this date there will be no \nmore valid AIMDD/MDD certificates.\nIs it possible to have valid MDR and AIMDD/MDD \ncertificates in parallel until 27 May 2024?\nYes.\nCan manufacturers still place on the market/put \ninto service Directive-compliant devices after the \nend of the transition period?\nYes, under certain conditions there will be an option to con -\ntinue placing on the market/putting into service devices that \ncomply with the Directives until their existing certificates ex -\npire. This may avoid the immediate need for a new certificate \nunder the MDR.\nTo use this option, all the existing certificates will have to be val -\nid (including, for example, the QMS), the purpose and nature of \nthe device must not change, and you must follow the new MDR \nrules for registration, surveillance and vigilance.\nWhat is the \u201csell-off\u201d provision about? \nThe \u201csell-off\u201d provision is intended to limit the time during which \ndevices that are compliant with the Directives and have already \nbeen placed on the market may be made available. \nAny devices that are still within the supply chain and that have \nnot reached their final user as being ready for use, for example \na hospital, on 27 May 2025 are no longer marketable and must \nbe withdrawn. \nOnce a Directive-compliant device has been made available to \nthe final user by the deadline, the further making available of \nthis device is not subject to/covered by the Regulation.\n\u00a9 European Union, [2018]  Reuse is authorised provided the source is acknowledged.\nThe reuse policy of European Commission documents is regulated by Decision 2011/833/EU (OJ L 330, 14.12.2011, p. 39).\nISBN: 978-92-79-89634-7    DOI: 10.2873/614436\nET-03-18-102-EN-N"}, {"title": "cnd_general_principles_en.pdf.txt", "text": "Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 1 of 13 \n The CND Nomenclature  \n\u2018Classificazione Nazionale Dispositivi medici\u2019  \n \n \nTable of Contents  \n1. Background and General Principles  ................................ ................................ ................................ ...... 2 \n2. The CND structure  ................................ ................................ ................................ ................................ .. 4 \nAnatomic Categories \u2013 by anatomical area of use:  ................................ ................................ ...................  6 \nFunctional Categories \u2013 by intended use or clinical method:  ................................ ................................ .... 6 \nSpecial Categories \u2013 by other criteria:  ................................ ................................ ................................ .......  6 \nGroups: the second hierarchical level  ................................ ................................ ................................ ........  7 \nType: the third hierarchical level (expands into several levels of detail (1\u00b0, 2\u00b0, 3\u00b0, 4\u00b0 and 5\u00b0))  ...........  7 \n3. External links  ................................ ................................ ................................ ................................ ...........  8 \n \n \nThe purpose of this document is to provide information regarding the basic principles and the \nstructure of the Italian  \u201cClassificazione Nazionale Dispositivi medici\u201d (CND) . In March 2019, an d \naccording to the criteri a set out by the Medical Device  Coordination Group1 (MDCG) , the CND \nwas selected as the basis for the future European M edical Device Nomenclature  (EMDN ). The \nEMDN  will support the functi oning of EUDAMED  as stated by the MDCG and in accordance with \nArticles 23 of Regulation (EU) 2017/745 \u2013 MDR and Regulation (EU) 2017/746.  \n \n \n  \n                                                           \n1 (MDCG 2018 -2) \u2013 Future EU medical device nomenclature: Description of requirements  Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 2 of 13 \n 1. Background and General Principles2 \nIn 2005, the Italian Ministry of Health set out that the  CND would be the  official Italian medical \ndevice  classification and  nomenclature. Since then, t he CND has been  implemented not only in  Italy, \nbut also  in Portugal and Greece.  \nAbout 15.000 manufacturers3 from various countries have used the CND for the registration of \nmedical devices and in vitro  diagnostic medical devices in the Italian database. The distribution of \nmanufacturers of medical devices and in vitro  diagnostic  medical  devices per countr y is reported \nbelow in Figure 1. \n \n \n   Fig. 1 Distribution of manufacturers of medical devices per countr y \n \nThe CND nomenclature  is one of the tools used in the  governance of the medical device sector  and \nis characteri sed by its refined and hierarchical structure . It aims to support the improvement of \npatient safety and the quality of health systems by enabling information to be communicated in a \nstandard ised manner . \n \nUpdates and maintenance of CND:  \n                                                           \n2 The principles and rules presented thereafter are the ones historically established/followed when building the CND nomenclature u p \nto the last update in 2018. This is without prejudice to the new rules that will govern the EMDN  which will be  established by th e \nMDCG.  \n3 Source NSIS: data updated on 10 August 2019  31,6%  \n15,2%  \n10,2%  9,8%  \n3,9%  3,6%  2,7%  2,5%  2,0%  18,5%  \n0,0%5,0%10,0%15,0%20,0%25,0%30,0%35,0%Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 3 of 13 \n The construction of the CND , its subsequent updates and maintenance have been  based  on three  \nfundamental principles.  \nA) Participative approach:  \nFor the update and maintenance of a qualitative nomenclature, highly differentiated and \nqualified expertise is required. As the  medical device sector is acknowledged  for its \nheterogeneity and complex ity, a broad participation of all stakeholders (economic operators and \nhealthcare professional from NHS - at all levels of its organisation ) is essential.   \n \nB) Qualified validation of proposals :  \nNomenclature and Classification proposals are technically validated based on  assessment s of \nactual need . Factors taken into  consideration are: \n\uf0b7 other existing nomenclature and classification systems available at international level  \n\uf0b7 consumption and expense information  \n\uf0b7 assessment with sector experts from the different disciplines  \n \nC)  Formal adoption and free public availability:  \nThe CND system , which represents the basis of the whole information system on medical \ndevices is formally approved and thus constitutes an offici al reference, freely available to all \nstakeholders.  \n \nMore information on previous  updates of the CND up to 2018 can be found in Annex I of this \ndocument.  \n \nThe following pr oducts are currently not included in the CND : \n\uf0b7 Medicinal products  \n\uf0b7 Cosmetics products  \n\uf0b7 Human blood and its derivatives;  \n\uf0b7 Organs, tissues and cells of human origin, products including human tissues and cells and \nproducts derived therefrom.  \n\uf0b7 Organs, tissues and cells of animal origin except medical devices manufactured using \nanimal devitalized tissues o r devitalized products derived from animal tissue.  \n\uf0b7 Individual Protection Devices  Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 4 of 13 \n 2. he CND structure   \nThe CND is characterised by its alphanumeric  structure that  is established  in a multi -level \nhierarchical tree . It clusters medical devices in  three main levels:  \n\uf0b7 Category:  the first hierarchical level  \n\uf0b7 Group:  the second hierarchical level  \n\uf0b7 Type:  the third hierarchical level  (which  if necessary, expands into several levels of detail \n(1\u00b0, 2\u00b0, 3\u00b0, 4\u00b0 e 5\u00b0))  \n \n \n \nEach medical device is classified by an alphanumeric code consisting of a letter referring to the \n\u201cCategory\u201d, a couple of numbers referring to the \u201cGroup\u201d and a series of other couples of numbers \nreferring to the \u201cType\u201d (whose amount depends on the level o f detail) up to a maximum of 7 levels . \n \n \nEach level isidentified by:\n\u2022an alphanumeric code (max 13 digits )\nA ## ## ## ## ## ##\nLevel 1: \nC ategoriesLevel 2: \nGroupsLevel from 3 to 7:\nTypesMedical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 5 of 13 \n Categories:  the first hierarchical level  \nThe first hierarchical level of the CND is defined  as a \u201cCategory\u201d.  There are 22 categories, each \nidentif ied by a letter of the alphabet:  \n \nEach \u201cCategory \u201d includes devices regulated under Directive 93/42/EEC, 90/385/EEC or 98/79/EC \nor following a dedicated prescription from reimbursement rules in Italy. These \u201ccategories\u201d are used \nfor the same specific apparatus, anatomical district or organ or as a replace ment of them \n(anatomical categories), or devices characterised by similar use, intended use or clinical m ethod \n(functional categories).  \nConsidering these criteria and the ramified tree structure with different detail level, the following \nAnatomic (8), Fun ctional (9) and Special (5) Categories have been defined:  \n \nMedical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 6 of 13 \n Anatomic Categories \u2013 by anatomic al area of use:  \n\u2022 B \u2013 HEMATOLOGY AND HEMOTRANSFUSION DEVICES  \n\u2022 C \u2013 CARDIOCIRCULATORY DEVICES  \n\u2022 F \u2013 DYALISIS DEVICES  \n\u2022 G \u2013 GASTROINTESTINAL DEVICES  \n\u2022 N \u2013 DEVICES FOR NERVOUS AND MEDULLAR SYSTEMS  \n\u2022 Q \u2013 DENTAL, OPHTALMOLOGIC AND ENT DEVICES  \n\u2022 R \u2013 RESPIRATORY SISTEM AND ANAESTHESIA DEVICES  \n\u2022 U \u2013UROGENITAL APPARATUS  DEVICES  \n \nFunctional Categories \u2013 by intended use or clinical method:   \n\u2022 A \u2013  DEVICES FOR ADMINISTRATION, COLLECTING AND PICKING  \n\u2022 D \u2013 DISINFECTANTS, ANTISEPTICS AND P ROTEOLYTICS FOR MEDICAL \nDEVICES  (regulated by Italian Legislative Decree No. 46/97  and European Directive \n93/42/EEC ) \n\u2022 H \u2013 SUTURE DEVICES  \n\u2022 K \u2013 ENDOTHERAPY AND ELECTROSURGICAL DEVICES  \n\u2022 L \u2013 REUSABLE SURGICAL INSTRUMENT S \n\u2022 M \u2013 DEVICES FOR GENERIC AND SPECIALISTIC MEDICATION  \n\u2022 S \u2013 STERILIZATION DEVICES  \n\u2022 T \u2013 PROTECTION DEVICES AND INCONTINENCE AIDS ( regulated by Italian \nLegislative Decree No. 46/97  and European Directive 93/42/EEC ) \n\u2022 V \u2013 MEDICAL DEVICES - VARIOUS  \n \nSpecial Categories \u2013 by other criteria : \n\u2022 J \u2013 ACTIVE -IMPLANTABLE DEVICES : MDs  regulated by Directive 385/90 EEC   \n\u2022 P \u2013 IMPLANTABLE PROSTHETIC DEVICES AND OSTEOSYNTHESIS DEVICES : \nnon-active implantable MDs  \n\u2022 Y \u2013 SUPPORTS OR TECHNICAL AIDS FOR DISABLED PERSONS  \n\u2022 W \u2013 IN VITRO DIAGNOSTIC DEVICES MDs regulated by Directive 98/79  EEC  \n\u2022 Z \u2013 MEDICAL EQUIPMENT AND RELATED ACCESSORIES AND MATERIALS  \n Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 7 of 13 \n Groups : the second hierarchical level  \nThe second  hierarchical level s are  called \u201cGroup s\u201d. There are 146 anatomical/functional Medical \nDevices Gr oups  4, which  represent the various differentiations that distinguish devices contained in \nthe Categories. They are identified by two -digit nu mbers from 01 to 99 for each Category.  \nNumber \u201c90\u201d identifies the gr oups of devices having various characteristics that are not related to \nexisting gro ups. Number \u201c99\u201d  \u201cAltri \u2013 Others\u201d is reserved to medical d evices that are not included \nin already existing Groups and will be categori sed in later updates.  \nType: the third hierarchical level (expands into several levels of detail (1\u00b0, 2\u00b0, 3\u00b0, \n4\u00b0 and 5\u00b0)) \nThe \u201cType\u201d represents the third hierarchical level . If necessary, it expands into several level s of \ndetail (1\u00b0, 2\u00b0, 3\u00b0, 4\u00b0 and 5\u00b0). The group of every type includes medical devices characteri sed by a \nhigh affinity of use, intended use or s imilar clinical method. In case of doubt, the peculiar \ncharacteristics of the medical device under examination should be considered for a proper \ncollocation or search proces s (i.e. the anatomic -functional characteristics and/or the intended use \ndeclared by the manufacture r). \nAs explained, the term \u201cot hers\u201d marked with the code \u201c99 \u201don the first detail level is suitable for \ndevices not included i n existing types. The \u201c99\u201d  types will be submitted for later updates. Th e code \nreserved to the generic term \u201cothers\u201d must be used by users only if it is not possible to classify the \nmedical device in existing typologies .  This type is subject  to continuous checks and monitoring.  \nRegarding accessories, e very accessory follows the CND classification code of the medical device \nthat it is associated with , according to the intended use  given by the manufacturer . If an accessory \ncan be used with multiple medical devices belonging to several group s, it must be placed  in the \nprevalent type.  \n \n  \n                                                           \n4 Updated as of the Italian Ministerial Decree of 13 March 2018.  Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 8 of 13 \n 3. External links  \n \nFor more information, please  consult the Italian Ministry website at: \nhttp://www.salute.gov.it/portale/temi/p2_6.jsp?lingua=italiano&id=328&area=dispositivi -\nmedici&menu=classificazione  \n      \nThe fo llowing documents  may also be of use : \n\uf0b7 National Classification of Medical Devices (CND) - as modified by Ministerial Decree \n13.03.2018 ( PDF format)  \n\uf0b7 National Classification of Medical Devices (CND) - as modified by Ministerial Decree \n13.03.2018 (XLSX format)  \n\uf0b7 English translation of National Classification of Medical Devices Codes (as modified by \nMinister ial Decree 13.03.2018 -pdf, format).  \n\uf0b7 English translation of National Classification of Medical Devices Codes (as modified by \nMinisterial Decree 13.03.2018 -XLSX format).  \n\uf0b7 Search code and description of the CND  \n\uf0b7 Search in alphabetical order  \n \n  Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 9 of 13 \n Annex I \u2013 CND updates up to 2018  \nThe periodical updating process of the CND was schematically subdivided into four main phases:  \n \n\uf0b7 Phase 1:  \nCollection of proposals  This phase is open to all stakeholders who submit proposals for \nthe definition of new classifications or for the revision of existing \nones.  \n\uf0b7 Phase 2:  \nPreliminary technical \nevaluation and elaboration \nof the proposal.  The MoH MD Technical Team (MDTT) analyses th e collected \nproposals, the existing systems and the contents of the medical \ndevices database to identify elements useful for classification.  \n\uf0b7 Phase 3:  \n \u201cWidespread validation\u201d \nof the proposal.  The proposal is formally evaluated in three steps:  \nA) the regional levels of the NHS involving clinical professionals \nin technical sessions  \nB) Technical Health Committee - medical devices section of the \nMinistry of Health  \nC) State - Regions Conference   \n\uf0b7 Phase 4:  \nFormal adoption of the \nproposal  Finally, the proposal is approved by formal MoH act and \npublished on the Italian Official journal as well as the website of \nthe Italian MoH  \n \n \nMost of the inputs adopted for updating purposes are listed below:  \n\uf0b7 The analysis of the terminal typologies \"90\" and \"99\":  \nImplemented and consolidated, it originates from the analysis of information within the Italian \ndatabank and consider s data from  all the medical device s registered and classified in the CND \nterminal types with code \" 90\" ( - various) and \"99\" ( - other) of specific categories or groups \nidentified. In fact, the classification system had already foreseen ab origine that medical devices \nthat are not placed in a specific \u201ctypology\u201d are classified in the generic typologies in dicated \nwith the codes 90 and 99.  \n\uf0b7 Manufacturer requests:  \nWhen a manufacturer is unable to classify a medical device in an appropriate way inside the \nCND terminal level, a specific request for the introduction of a new CND class is required, with \na communic ation to the MoH of a rationale and the technical characteristics and / or intended \nuse that differentiate the device from the specific terminal classes already represented in the \nCND.  \n\uf0b7 The analysis of CND coming from vigilance system:  Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 10 of 13 \n Market surveillance and the vigilance system are part of the institutional activities of the MOH. \nThe lack of classificatory level can emerge in order to identify products that need particular \nattention for public health.   Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 11 of 13 \n \uf0b7 The analysis of consumption by the NHS:  \nThe revision of the CND made through the processing of the consumption data of the \nMonitoring Database is based on identification of medical devices with great economic \nrelevance or price variability.  \n\uf0b7 The analysis coming from HTA Report s: \nHealth Technology Assessment documents are periodically published by the Ministry of Health. \nThese reports are considered when evaluating  the revision of the CND.  \nThe following principles were considered in the revision of the CND:  \n\uf0b7 the number of levels in the CND structure can be inc reased up to a maximum of seven, by \ncoherently applying the homogeneity of the classification rules and of the coding system \ndefined for the first CND structure.  \n\uf0b7 for the definition of a new CND branch the number of manufacturers manufacturing the medical \ndevices that will be placed in the new typology of the CND should be more than 1;  \n\uf0b7 significant characteristics of medical devices detected by NHS professionals should be \nevaluated  \n\uf0b7 the proposal of relocation of medical devices placed in class 90 or 99 should  be consistent.  \n\uf0b7 for the definition of a new CND branch significant differences of price between similar medical \ndevices could be considered if necessary:  \n\uf0b7 for the definition of a new CND branch an assessments related to the use of medical devices is \nconside red (quantity and number of users in NHS);  \n \nFor each update proposal of the CND, the information associated to the devices registered in the \nItalian database were analysed and, if necessary, the information detect ed by the \u201cConsumption \nMonitoring Database\u201d were processed.  \n \n \n \n \n  Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 12 of 13 \n Annex II \u2013 CND VERSIONS  \nArt. No. 57 of the Italian Law n\u00b0 289 of the 27 December 2002 stated the  requirement of the  \nestablishment of a Commission on Medical Devices (CUD) as a technical advisory board to the \nMinistry of H ealth. The CUD has the task of defining and updating the repertoire of medical \ndevices and classifying all medical devices in specific classes and sub -classes.  \nThe CUD d efined the first version of the Classificazione Nazionale dei Dispositivi Medici (CND) \non July 2005 (Italian Ministerial Decree of 22 Sept .2005). In Vitro  Diagnostic Medical Devices \n(regulated by European Directive No. 98/79 EEC and Italian Legislative De cree No. 332/2000) \nwere not  included in the first version of the Classification , although they belong to a class of \nMedical Devices.  \nThe Italian Financial Law of 2006 (Law No. 266 of the year 2005, art. 1, par. 409) established that \nthe CND has to be appr oved by a decree of the Minister of Health in agreement with the State -\nRegions Conference.  \nThe CUD considered it appropriate to review and update the CND with the inclusion of in vitro  \ndiagnostic medical devices before proceeding with the State -Regions Con ference . Therefore,  on 20 \nFebruary 2007 , and after a revision of the classification, the Health Minister decreed  the approval of \nthe Classificazione Nazionale dei Dispositivi Medici (CND) drawn up by the CUD. The \nclassification refers to the medical device s regulated by Italian legislative decrees N\u00b0. 507/92, N\u00b0. \n46/97, N\u00b0. 332/2000 and subsequent amendments.  \nIn 28 March2013, the Italian D.P.R. n.44, replaced the Commission on Medical Devices (CUD) \nwith the Technical Committee section F on medical devices.  \nThe Classification represented the first step towards the establishment of the Italian Repertoire of \nthe Medical Devices.  \nAccording to the art. N\u00b0 2 of The Italian Financial Law No. 266, the Technical Committee section F  \n(previously CUD) , review the CND a nd make  the necessary changes and updates. Every update is \napproved by a Ministerial Decree:  \n \n1. Decree of the Italian Ministry of Health (13 Mar 2008) regarding Modification and update of \nClassificazione Nazionale dei Dispositivi Medici (CND) published in th e Official Gazette - GU \nNo. 125 of 29/05/2008. Links:  \nhttp://www.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_2_file.pdf   Medical Devices                January 2020  \nDG Health and Food Safety  \nDirectorate Health systems, medical products and innovation  \nUnit Medical Devices  \nPage 13 of 13 \n www.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_3_file.xls   \n2. Decree of the Italian Ministry of Health (12 Feb 2010) regarding Modification and update  of \nClassificazione Nazionale dei Dispositivi Medici (CND) published in the Official Gazette - GU \nNo.119 of 24/05/2010. Links:  \nhttp://www.salute.gov.it/imgs/C_1 7_pagineAree_328_listaFile_itemName_5_file.pdf   \nwww.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_7_file.xls   \n3. Decree of the Italian Ministry of Heal th (7 Oct 2011) regarding Modification and update of \nClassificazione Nazionale dei Dispositivi Medici (CND) published in the Official Gazette - GU \nNo.259 of 7/11/2011.Links:  \nhttp://www.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_9_file.pdf   \nwww.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_10 _file.xls   \n4. Decree of the Italian Ministry of Health (29 July 2013) regarding Modification and update of \nClassificazione Nazionale dei Dispositivi Medici (CND) published in the Official Gazette - GU \nNo. 258 of 04/11/2013). Links:  \nhttp://www.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_16_file.pdf   \nwww.sa lute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_17_file.xlsx   \n5.  Decree of the Italian Ministry of Health (8 J une 2016 ) regarding Modification and update of the \nClassificazione Nazionale dei Dispositivi Medici (CND )  published in the Official Gazette G.U. \nSerie Generale, n. 242 del 15/10/2016).  \n6. Decree of the Italian Ministry of Health (13 march 2018) regarding Mod ification and update of \nthe Classificazione Nazionale dei Dispositivi Medici (CND ) published in the Official Gazette \nG.U. Serie Generale, No. 116 del 21/05/2018). Links:  \nhttp://www.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_15_file.pdf   \nwww.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_18_file.xlsx"}, {"title": "mdcg_2019_2_gui_udi_dev_en.pdf.txt", "text": "Medical Devices       \nMedical Devices Coordination Group Document   MDCG  201 9-2   \nPage 1 of 3 \n  \n \n \n \n \nMDCG  201 9-2    \n Guidance on application of UDI rules to  \n device -part of products referred to in Article \n 1(8), 1(9) and 1(10) of Regulation 745/2017  \n                 \n \n \n February 2019  \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commission document and it cannot be regarded \nas reflecting the official position of the European  Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  Medical Devices       \nMedical Devices Coordination Group Document   MDCG  201 9-2   \nPage 2 of 3 \n  \n1. Scope  \nArticle 1(8),1(9), 1(10) of the Medical Device Regulation (EU) 2017/745 (MDR) set \nthe basic criteria to determine whether and to what extent the relevant legislation on \nmedical devices, medicinal products, human tissue and cells apply to certain \nproducts c ontaining a medical device part. In particular,  \n\u201c8. Any device which, when placed on the market or put into service, incorporates, as \nan integral part, a substance which, if used separately, would be considered to be a \nmedicinal product as defined in poin t 2 of Article 1 of Directive 2001/83/EC, including \na medicinal product derived from human blood or human plasma as defined in point \n10 of Article 1 of that Directive, and that has an action ancillary to that of the device, \nshall be assessed and authorised  in accordance with this Regulation.  \nHowever, if the action of that substance is principal and not ancillary to that of the \ndevice, the integral product shall be governed by Directive 2001/83/EC or Regulation \n(EC) No 726/2004 of the European Parliament an d of the Council, as applicable. In \nthat case, the relevant general safety and performance requirements set out in Annex \nI to this Regulation shall apply as far as the safety and performance of the device part \nare concerned.  \n9. Any device which is intende d to administer a medicinal product as defined in point \n2 of Article 1 of Directive 2001/83/EC shall be governed by this Regulation, without \nprejudice to the provisions of that Directive and of Regulation (EC) No 726/2004 with \nregard to the medicinal produ ct.  \nHowever, if the device intended to administer a medicinal product and the medicinal \nproduct are placed on the market in such a way that they form a single integral \nproduct which is intended exclusively for use in the given combination and which is \nnot reusable, that single integral product shall be governed by Directive 2001/83/EC \nor Regulation (EC) No 726/2004, as applicable. In that case, the relevant general \nsafety and performance requirements set out in Annex I to this Regulation shall apply \nas far  as the safety and performance of the device part of the single integral product \nare concerned.\u201d  \n10. Any device which, when placed on the market or put into service, incorporates, as \nan integral part, non -viable tissues or cells of human origin or their de rivatives that \nhave an action ancillary to that of the device shall be assessed and authorised in \naccordance with this Regulation. In that case, the provisions for donation, \nprocurement and testing laid down in Directive 2004/23/EC shall apply.  \nHowever, if the action of those tissues or cells or their derivatives is principal and not \nancillary to that of the device and the product is not governed by Regulation (EC) No \n1394/2007, the product shall be governed by Directive 2004/23/EC. In that case,  the \nrelevant general safety and performance requirements set out in Annex I to this \nRegulation shall apply as far as the safety and performance of the device part are \nconcerned\u201d.  \n Medical Devices       \nMedical Devices Coordination Group Document   MDCG  201 9-2   \nPage 3 of 3 \n  \n2. Application to UDI rules to the device part of products referred to in \npoint 1 that are governed by the medical device Regulations  \nEXAMPLES:  \n- Catheters coated with heparin or an antibiotic  \n- Soft tissue fillers incorporating local anaesthetics  \n- Implantable infusion pump  \n- Spacer devices for use with metered dose inhalers  \n- Bone void  filler with an antibiotic  \n- Bone void filler with animal growth factors, where the action of the growth \nfactors is demonstrated to be ancillary to that of the physical filler  \nIf a product referred to in point 1 is assessed and authorised in accordance with  the \nMedical device regulations, the device part will be subject to all UDI -related \nobligations.  \n3. Application to UDI rules to the device part of combination products that \ndo not fall under the medical device Regulations  \nEXAMPLES:  \n- Non-reusable autoinjectors  containing a medicinal product as integral part  \n- Nebulizers precharged with a specific medicinal product  \n- Patches for transdermal drug delivery  \n- Wound dressings impregnated with an antibiotic, where the primary intended \npurpose is to administer the antibioti c to the wound  \n- Bone void filler with animal growth factors, where the action of the growth \nfactors cannot be demonstrated to be ancillary to that of the physical filler  \nIn general terms, if a product referred to in point 1 is governed by the medicinal \nproduct or tissue and cell legislation, the device part is required to comply only with \nthe relevant general safety and performance requirements set out in Annex I to the \nRegulation on medical devices. This cannot be interpreted as meaning that the \nrelevant o bligations related to UDI, as laid down in Chapter III and Annex VI of the \nRegulation on medical devices, apply to the medical device part or the package of \nthe relevant combination. For this reason, the medical device part is not mandatorily \nrequired to c omply with any UDI -related obligation. This also means that a UDI is not \nneeded on the package that combines the medicinal product and the medical device1 2. \n                                                           \n1  However,  if the medical device part bears a UDI on its label, that should not be deemed as being in contrast with the \napplicable medical device legislation  \n2  For products such as prefilled syringes which are made on the b asis of a UDI direct part marked (MDR compliant) \nsyringe it shall be noted that, while UDI rules do not apply to the device part of the integral product, the direct mark \nUDI on the syringe shall not be removed unless that mark compromises the safety and pe rformance of the integral \nproduct."}, {"title": "mdcg_2018_4_udi_core_spp_en.pdf.txt", "text": "Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -4   \nPage 1 of 3 \n  \n \n \n \n \nMDCG  2018 -4 \nAnnex: UDI database  \nDefinitions/Descriptions and formats  \n of the UDI core elements for systems  \n or procedure packs  \n               \n October  2018  \n \n \n  \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission . \nThe document is not a European Commission document and it cannot be regarded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  \n \n  Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -4   \nPage 2 of 3 \n  \nIn accordance with Article 29(2) and Annex VI, Part B of the MDR, in the case of \nsystems and procedure packs, the system or procedure pack producer shall \nprovide to the UDI database the UDI -DI and all of the following information1: \n \n1. quantity per package configuration (meaning the quantity of systems or \nprocedure packs in a package, whenever applicable)  \n2. the Basic UDI -DI as referred to in Article 29 (MDR) and any additional UDI -\nDIs, \n2a. Indication of s pecific medical purpose of the system or procedure pack  \n3. the manner in which the system or procedure pack is controlled (expiry date \nor manufacturing date, lot number, serial number),  \n5. name and address of the system or procedure pack producer (as indic ated \non the label),  \n6. the SRN of the system or procedure pack producer  \n8. The medical device nomenclature code as provided for in Article 26 (MDR)2 \n9. risk class (to be intended as the highest risk class of the device components \nof the system or procedure  pack),  \n10. if applicable, name or trade name,  \n11.A. name or, if applicable, system or procedure pack model associated with \nthe BASIC UDI -DI in the statement drawn in accordance with Article 22.1 of \nthe MDR  \n11.B. reference or catalogue number, or product n umber found on the system \nor procedure pack label or accompanying packaging to identify a system or \nprocedure pack  \n13. additional product description,  \n14. if applicable, storage and/or handling conditions of the system or \nprocedure pack (as indicated on th e label or in the instructions for use),  \n15. if applicable, additional trade names of the system/procedure pack,  \n18. labelled sterile (y/n) (meaning that the system or procedure pack in its \nentirety is labelled as sterile),  \n19. need  for sterilisation before use (y/n)  \n22. URL for additional information, such as electronic instructions for use \n(optional),  \n23. if applicable, critical warnings or contra -indications  \n \n                                                            \n1 Please note that format and definition of all UDI data elements are  provided at \nhttps://ec.europa.eu/docsroom/documents/28669   \n2 Applicability of this data element to systems and procedure packs is to be determined at the time of \ndesignation of the future EU nomenclature for medical devices (foreseen end of 2018/beginning 2019).  Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -4   \nPage 3 of 3 \n  \n24. status of the system or procedure pack (on the market, no longer placed \non the market, recalled, field safety corrective action initiated).  \n \nWhenever a label is referred to, the label of the entire system/procedure pack shall \nbe meant, in accordance with Article 22(5) of Regulation 745/2017.  \n \n \n,"}, {"title": "faq_udi_en.pdf.txt", "text": "Introduction to the new \nUDI system and the \nobligations of operators\nThe existing regulatory framework on medical \ndevices dates back to the 1990s and consists of \nthree Directives. Two new Regulations (Regulation \n(EU) 745/2017 on medical devices and Regulation \n(EU) 746/2017 on  In Vitro  diagnostic medical devices) \nwere adopted in April 2017 and entered into force on \n25 May 2017. The general application dates of the \ntwo Regulations are 26 May 2021 for medical devices \nand 26 May 2022 for In Vitro  diagnostic medical \ndevices, though different timelines apply for certain \nspecific provisions. \nThese Regulations introduce an EU identification sys -\ntem for medical devices based on a Unique Device \nIdentifier (UDI).\n1The UDI system will facilitate easier traceability of medical \ndevices, significantly enhance the effectiveness of the post-mar -\nket safety-related activities for devices and allow for better \nmonitoring by competent authorities. It will also help to reduce \nmedical errors and to fight against falsified devices. The use of \nthe UDI system finally should also improve purchasing and waste \ndisposal policies and stock-management by health institutions \nand other economic operators.\n1  IMDRF/UDI WG/N7FINAL:2013  UDI Guidance Unique Device Identification (UDI) of Medical Device s\n2  IMDRF/UDI WG/N48 FINAL: 2019 Unique Device Identification system (UDI system) Application Guide - DOCX (12.5Mb)The new system will be applied to all medical devices except \ncustom-made and performance study/investigational devices and \nis substantially based on internationally recognised principles, \nnotably by using definitions that are compatible with those used \nby major trade partners.1,2MEDICAL DEVICES  CHANGE OF LEGISLATION\nWhat you need to know! \nUnique Device  \nIdentification (UDI) System  \nunder the EU medical devices Regulations \n2017/745 and 2017/746European \nCommission\nHealth and Food \nSafety 2Article 27 of Regulation (EU) 2017/745 (\u2018MDR\u2019) and Article 24 of \nRegulation (EU) 2017/746 (\u2018IVDR\u2019) lay down that the UDI system \nshall consist of:\na. the production of a UDI that comprises a UDI device identifier \n(\u2018UDI-DI\u2019) specific to a manufacturer and a device, providing \naccess to the information, and a UDI production identifier \n(\u2018UDI-PI\u2019) that identifies the unit of device production and \nif applicable the packaged devices, as specified in Part C \nof Annex VI;\nb. the placing of the UDI carrier on the label of the device or \non its packaging or in case of reusable devices on the device \nitself (direct marking);\nc. the storage of the UDI by economic operators, health insti -\ntutions and healthcare professionals, in accordance with the \nconditions laid down in paragraphs 8 and 9, respectively, of \nthe Articles;\nd. the establishment of an electronic database for Unique \nDevice Identification (the \u2018UDI database\u2019), which is part of \nthe Eudamed database, in accordance with Article 28 of MDR \nand Article 25 of IVDR.\nIn accordance with the new rules, any manufacturer shall thus \nassign a unique UDI to a device and to all higher levels of packag -\ning before placing that device on the market except custom-made \nmedical devices and performance study/investigational devices. \nThe UDI carrier shall be placed on the label of the device and on all \nhigher levels of packaging and in case of reusable devices on the \ndevice itself (direct marking). The manufacturer shall also ensure \nthat the information \u2013 related to the device in question - referred \nto in Part B and Part A, Section 2, of Annex VI of the relevant \nRegulation, is correctly submitted to the European Database on \nMedical Devices (Eudamed) as required by Article 27(3) of MDR \nand Article 24(3) of IVDR. The manufacturer shall also maintain \nunique UDIs for its devices.\nNOTE: Timelines related to those obligations are indicated under \nquestion 6 of this document.\nWithin the EU, the manufacturer shall assign to their devices, \ntogether with a UDI, also a Basic UDI-DI, which is not yet required \nby other jurisdictions. The Basic UDI-DI is the main key in Eudamed \nand relevant documentation (e.g. certificates, declaration of \nconformity, technical documentation and summary of safety \nand clinical performance) and will also be the access key for \ndevice-related information entered in the database.\nUDI issuing entities designated by the European Commission \noperate a system for the assignment of UDI in the EU.3\n3  Issuing entities have been designated on 6 June 2019 via the Commission Implementing Decision (EU) 2019/939 .Frequently Asked  \nQuestions and Answers\n1. What is the UDI?\nThe UDI is a series of numeric or alphanumeric characters that \nis created through a globally accepted device identification and \ncoding standard. It allows the unambiguous identification of a \nspecific medical device on the market. The UDI is comprised of the \nUDI-DI and UDI-PI. The unique identifier may include information \non the lot or serial number and be able to be applied anywhere \nin the world.\nThe production of a UDI comprises the following:\n\u2022 A UDI device identifier (\u2018UDI-DI\u2019) specific to a device, providing \naccess to the information laid down in Part B of Annex VI.\n\u2022 A UDI production identifier (\u2018UDI-PI\u2019) that identifies the unit \nof device production and if applicable the packaged devices, \nas specified in Part C of Annex VI.\n2. What is the Basic UDI-DI?\nThe Basic UDI-DI is the main access key for device-related \ninformation in the Eudamed database and it is referenced in \nrelevant documentation [e.g. certificates (including certificate of \nfree sale), EU declaration of conformity, technical documentation \nand summary of safety and (clinical) performance)].\nIt is intended to identify and connect devices with the same \nintended purpose, risk class and essential design and manufac -\nturing characteristics.\nIt is independent/separate from the packaging/labelling of the \ndevice and it does not appear on any trade item.\nAny Basic UDI-DI shall identify the devices (group) covered by \nthat Basic UDI-DI in a unique manner.\nMDCG 2018-1 v3  guidance provides additional information on \nBasic UDI-DI.\n3. Which products are subject to the UDI system?\nThe UDI system should apply to all devices, except custom-made \nand performance study/investigational devices.34.  Who is responsible for placing the UDI carrier \non the device itself, on the label and on the \npackage of a device?\nThe manufacturer is responsible for complying with all UDI related \nrequirements. This includes the assignment of the UDI (and Basic \nUDI-DI), the UDI (and Basic UDI-DI) registration in the Eudamed \ndatabase and the placement of the UDI carrier on the label of \nthe device or on its packaging or, in case of reusable devices, on \nthe device itself (direct marking).\n4.1 What happens in the case of Article 16 of the MDR and \nIVDR? Which obligations do economic operators have \nregarding UDI when assuming obligation incumbent \non manufacturers per Article 16 of the MDR and IVDR?\nAny distributor, importer or other natural or legal person that \nassumes the obligations incumbent on manufacturers in accord -\nance with Article 16(1), assumes all the relevant responsibilities \nrelated to UDI, including UDI labelling. \nThe distributor or importer carrying out the operations described \nin Article 16(2) (providing translation or repackaging of devices) \nshall ensure that: \n\u2022 the activities are performed by means and under conditions \nthat in no way compromise the readability of the UDI carrier \nand its information identifying the actual device. \n\u2022 the specific procedures are part of the distributor\u2019s or import -\ner\u2019s quality management system.\nA dedicated guideline with additional information on this aspect \nis available at the MDCG 2018-6 guidance document .\n5.  What is the procedure for systems and procedure \npacks to undergo a UDI registration?\nSystems and procedure packs shall undergo a UDI registration, \nas described in Article 29(2) of MDR.\nBefore placing on the market a system or procedure pack pursuant \nto Article 22(1) and (3), that is not a custom-made device, the \nsystem or procedure pack producer shall assign to the system or \nprocedure pack, in compliance with the rules of the issuing entity, \na Basic UDI-DI and shall provide it to the Eudamed database \ntogether with the other relevant core data elements listed in the \nMDCG 2018-4 guidance document .6.  What is the mandatory deadline for a device \nto comply with the UDI requirements?\nThe obligation for UDI assignment applies as from the date \nof application of the two new Regulations, i.e. 26 May 2021 for \nmedical devices and 26 May 2022 for In Vitro  diagnostic medical \ndevices.\nThe obligation for submission of UDI data in the EUDAMED \ndatabase  applies from 26 November 2022 for medical devices \nand 26 November 2023 for in vitro  diagnostic medical devices \n(provided that EUDAMED is fully functional before the date of \napplication of the respective Regulation; otherwise, this obligation \napplies 24 months after EUDAMED has become fully functional)\nHowever, manufacturers will be in a position to voluntarily comply \nwith registration obligations as from 26 May 2021 for medical \ndevices and 26 May 2022 for  In Vitro  diagnostic medical devices.\nIt shall be noted that, provided that Eudamed is fully functional, \nat any time after 26 May 2021 for medical devices and 26 May \n2022 for In Vitro  diagnostic medical devices, the full registration \nof devices (Article 29 of MDR and Article 26 of IVDR) remains a \npre-condition for the possible registration of their relevant serious \nincident in Eudamed.\nThe MDCG 2019-4  guidance document provides more information \non this subject.\nThe obligation for placing the UDI carrier applies according \nto the following timelines:\nDevice as per\nRegulation (EU) 2017/745  (MDR)Implantable  \ndevices and \nClass III devicesClass IIa and\nClass IIb \ndevicesClass I  \ndevices\nPlacing UDI-carriers  \non the labels of devices\nMDR Article 123(3)(f), Article 27(4)26 May  \n202126 May  \n202326 May  \n2025\nDirect marking of the  \nreusable devices\nMDR Article 123(3)(g), Article 27(4)26 May  \n202326 May  \n202526 May  \n2027\nDevice as per\nRegulation (EU) 2017/746 (IVDR)Class D \nIVDsClass C and B \nIVDsClass A \nIVDs\nPlacing UDI-carriers on the  \nlabels of devices\nIVDR Article 113(3)(e), Article 24(4)26 May \n202326 May  \n202526 May \n2027\nNOTE: Devices which are compliant with the Regulations may be placed on \nthe market ahead of the general application date of 26 May 2021 (MDR) and \n26 May 2022 (IVDR). For more information on this aspect, please consult  \nFAQ - MDR Transitional Provisions  and FAQ - IVDR Transitional Provisions .47.  Are devices, which are compliant with the \nMedical Device Directives (MDD and AIMDD) \nand placed on the market after the applica -\ntion date of the Regulations (legacy devices), \ncontinue to be subject to UDI requirements?\nIn order to facilitate the transition to the new system, the new \nRegulations give manufacturers the possibility to place products \non the market after the general application dates of the new \nRegulations (and until 26 May 2024 at the latest) by virtue of \nvalid Directive certificates.4\nThese legacy devices are not subject to UDI obligations but they \nshould be registered in the Eudamed database. Timelines for \nregistration as described under question 6 also apply to these \nproducts. More information on the operational aspects of the \nregistration of legacy devices is available at the MDCG 2019-5 \nguidance document .\n8.  What is the role of the UDI issuing entities? \nWho designates them?\nThe issuing entities operate a system for the assignment of UDIs.\nFollowing a call for applications launched at the end of 2018, the \nCommission has designated the following entities:\na. GS1 AISBL\nb. Health Industry Business Communications Council (HIBCC)\nc. International Council for Commonality in Blood Banking \nAutomation (ICCBBA)\nd. Informationsstelle f\u00fcr Arzneispezialit\u00e4ten (IFA) GmbH\nFor more information, please refer to the relevant implementing \nact designating the entities: Commission Implementing Decision \n(EU) 2019/939  of 6 June 2019 designating issuing entities \ndesignated to operate a system for the assignment of Unique \nDevice Identifiers (UDIs) in the field of medical devices. \n4 For additional information on the general conditions for legacy devices to be placed on the market after the general application dates of the new  \n Regulations, see the MDR and IVDR transitional FAQs  published by the CAMD Transitional Task-force  9.  How should a UDI appear on the label or  \npackage of a device?\nThe UDI Carrier [Automated Identification for Data Capture (AIDC) \nand human readable interpretation (HRI) representation of the \nUDI] shall be on the label or on the device itself and on all higher \nlevels of device packaging.\nIn the event of significant space constraints on the unit of use \npackaging, the UDI carrier may be placed on the next higher \npackaging level.\nHigher levels of packaging shall have their own unique UDI. \nPlease note that shipping containers shall be exempted from \nthe requirement.\nThe UDI must appear in a plain-text version/human readable \ninformation (HRI) and in a form that uses AIDC technology. AIDC \nmeans any technology that conveys the unique device identifier \nor the device identifier of a device in a form that can be entered \ninto an electronic patient record or another computer system via \nan automated process. The HRI consists of legible characters that \ncan easily be read by people.\nIf there are significant constraints limiting the use of both AIDC \nand HRI on the label, only the AIDC format shall be required to \nappear on the label.\nFor devices intended to be used outside healthcare facilities, such \nas devices for home care, the HRI shall, however, appear on the \nlabel even if this results in there being no space for the AIDC.\nFor other specific requirements related to the UDI carrier, please \nconsult Section 4 of Annex VI Part C of the two Regulations.\nFor single-use devices of classes I and IIa medical devices and \nclass A and class B IVD medical devices packaged and labelled \nindividually, the UDI carrier shall not be required to appear on \nthe packaging but it shall appear on a higher level of packaging, \ne.g. a carton containing several (individually packaged) devices. \nHowever, when the healthcare provider is not expected to have \naccess, in cases such as in home healthcare settings, to the \nhigher level of device packaging, the UDI shall be placed on the \npackaging (of the individual device).\nFor devices exclusively intended for retail point of sale, the UDI-\nPIs in AIDC shall not be required to appear on the point of sale \npackaging. \nIf the UDI carrier is readily readable or, in the case of AIDC, \nscannable, through the device\u2019s packaging, the placing of the UDI \ncarrier on the packaging shall not be required.510.  Are there any requirements for the PI  \n(Production Identifier) information?\nIf a lot number, serial number, software identification or expiry \ndate appears on the label, it shall be part of the UDI-PI. If there \nis also a manufacturing date on the label, it does not need to be \nincluded in the UDI-PI. If there is only a manufacturing date on \nthe label, this shall be used as the UDI-PI.\nThe different types of UDI-PIs include serial number, lot number, \nsoftware identification and manufacturing date and/or expiry date. \nThe UDI-PI characteristics such as the lot or serial number shall \nbe defined by the manufacturer. However:\n\u2022 For active implantable devices, the UDI-PI shall include at \nleast the serial number; for other implantable devices, the \nserial number or lot number. \n\u2022 A configurable device UDI-PI shall be assigned to each indi -\nvidual configurable device.\nIt is important to note that no UDI-PI information can be included \nin the UDI database.\n11.  What changes in the medical device would \nrequire a new UDI-DI?\nA new UDI-DI shall be required whenever there is a change that \ncould lead to misidentification of the device and/or ambiguity \nin its traceability. In particular, a new UDI-DI shall be required in \nthe case of any change of the following elements: name or trade \nname, device version or model, labelled as single use, packaged \nsterile, need for sterilisation before use, quantity of devices \nprovided in a package, critical warnings or contra-indications and \nCMR/Endocrine disruptors.\nA UDI-DI shall be associated with one and only one Basic UDI-DI.\nAdditional information on this aspect is available at  MDCG \n2018-1 v3 guidance document .12.  What are the obligations of economic operators \nand health institutions in relation to UDI?\nAccording to the two medical devices Regulations, manufacturers \nshall be responsible for the UDI assignment and placement of the \nUDI carrier, the initial submission and updates of the identifying \ninformation and other device data elements in the Eudamed \ndatabase. Manufacturers shall update the relevant database \nrecord within 30 days of a change being made to an element, \nwhich does not require a new UDI-DI.\nDistributors and importers shall verify that, where applicable, a \nUDI has been assigned by the manufacturer.\nAll economic operators and health institutions shall store and \nkeep preferably by electronic means the UDI of the devices, which \nthey have supplied or with which they have been supplied if \nthose devices belong to class III implantable devices. Please note \nthat the Commission may decide to adopt implementing acts to \nexpand the scope of devices for which economic operators shall \nstore and keep the UDI.\n13.  Is the software subject to UDI rules?\nThe UDI shall be assigned at the system level of the software.\nOnly software that is commercially available on its own and \nsoftware that constitutes a device in itself shall be subject to \nthat requirement.\nThe software identification shall be considered the manufacturing \ncontrol mechanism and shall be displayed in the UDI-PI.\nUDI requirements for software are laid down in Annex VI Part C \nof the two medical device Regulations.\nA dedicated guideline with additional information on this aspect \nis available at MDCG 2018-5 guidance document .614.  Direct marking of reusable devices. Are there \nexemptions?\nDevices that are reusable shall bear a UDI carrier on the device \nitself.\nThe UDI carrier for reusable devices that require disinfection, ster -\nilisation or refurbishing between patient uses shall be permanent \nand readable after each process performed to make the device \nready for the subsequent use throughout the intended lifetime \nof the device.\nThe UDI carrier shall be readable during normal use and throughout \nthe intended lifetime of the (reusable) device.\nThe requirements shall not apply to the device in case of the \nfollowing circumstances:\n\u2022 any type of direct marking would interfere with the safety \nor performance of the device;\n\u2022 the device cannot be directly marked because it is not tech -\nnologically feasible.\n15.  Is there an adjudication process for ad-hoc \nexemptions foreseen for medical devices?\nAn adjudication process to allow for ad-hoc exemptions is not \nenvisaged in the EU. All devices are therefore subject in principle \nto UDI requirements, with the only exceptions explicitly stated in \nthe Regulation.However, the UDI Expert Group will analyse requests for adap -\ntation of UDI requirements to certain specific device types and \nrecommend the Medical Device Coordination Group (MDCG) to \nissue dedicated guidelines, where necessary.\n16.  What are the UDI and device data sets to be \nprovided in Eudamed?\nDedicated guidelines containing information on this aspect \nare available at https://ec.europa.eu/health/md_sector/\nnew_regulations/guidance .\nGuidance\nFurther information on EUDAMED is available at  https://ec.europa.\neu/health/md_eudamed/overview_en .\nNOTE: The Commission intends to expand this document on a regular \nbasis based on the assessment of most frequently asked questions and/\nor of other specific needs.\nET-02-18-963-EN-N\nFunded under the Third EU Health Programme\nISBN:XXXXX    DOI: XXXXX01/08/2020\n\u00a9 European Union, [2018] Reuse is authorised provided the source is acknowledged.\nThe reuse policy of European Commission documents is regulated by Decision 2011/833/EU (OJ L 330, 14.12.2011, p. 39).https://ec.europa.eu/health/\nmd_sector/overview_en"}, {"title": "mdcg_2019_1_budi_rules_ie_en.pdf.txt", "text": "Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2019 -1   \nPage 1 of 2 \n  \n \n \n \n \nMDCG  201 9-1    \n MDCG guiding principles for issuing entities \n rules on Basic UDI -DI \n                \n \n \n January 2019  \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commissio n document and it cannot be regarded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law. \n Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2019 -1   \nPage 2 of 2 \n  \n \nIn order to ensure, to the maximum possible extent, the quality of the code value \nentered in Eudamed, the Basic UDI -DI requirements on format should be as close as \npossible to the ones for the UDI -DI. In particular,  \n\uf0b7 the Basic UDI -DI code value sha ll have maximum 25 characters, so that it \ndoes not differ too significantly from the maximum length of the UDI -DI as \nestablished by the issuing entities;  \n\uf0b7 a check digit/character must be part of the Basic UDI -DI, based on an \nalgorithm defined by the issuin g entity. This algorithm shall be provided by the \nissuing entities to the Commission and to the manufacturers."}, {"title": "MDCG 2018-1 v3 Guidance on basic UDI-DI and changes to UDI-DI.pdf.txt", "text": "1 \n Medical Device       \nMedical Device Coordination Group Document    MDCG 2018-1 v3   \n \n \n \n \n       \n   MDCG 2018-1 v3  \nGuidance on BASIC UDI-DI  \n      and changes to UDI-DI            \n \n             March 2020 \n \n  \n \nThis document has been endorsed b y the Medical Device Coordinat ion Group (MDCG) established by \nArticle 103 of Regulation (EU) 2017/745. The MDCG is composed o f representatives of all Member \nStates and it is chaired by a representative of the European Co mmission. \nThe document is not a European Commission document and it canno t be regarded as reflecting the \nofficial position of the European Commission. Any views express ed in this document are not legally \nbinding and only the Court of Justice of the European Union can  give binding interpretations of Union \nlaw.   \n2 \n Guidance on BASIC UDI-DI and changes to UDI-DI \nIntroduction \nThe new Medical Device Regulations (EU) 2017/745 and (EU) 2017/746 introduce a \nUnique Device Identification (UDI) system for medical devices.  \nMain provisions related to the establishment of the UDI system are contained in \nChapter III and Annex VI of the two medical device Regulations.  \nThe main features of the UDI system and relevant obligations for operators will be \nprovided in a dedicated Q/A paper to be published by the Commission in spring 2018.  \nThis guidance is intended to provide a clarification on the notion of Basic UDI-DI, its \nuse in relevant documentation and the factors triggering UDI-DI changes.   \n----------------------------- \nThe Basic UDI-DI \nThe Basic UDI-DI is the main key in the database and relevant documentation (e.g. \ncertificates, declaration of conformity, technical documentation and summary of safety and clinical performance) to connect devices with same intended purpose, risk class and essential design and manufacturing characteristics.  \nIt is independent/separate from the packaging/labelling of the device and it does not \nappear on any trade item.  \nAny Basic UDI-DI shall identify the devices (group) covered by that Basic UDI-DI in a \nunique manner. \nLink with between Basic UDI -DIs and certificates or declaration of conformity \nIn accordance with Annex XII of the medical device Regulations, the scope of the \ncertificates shall unambiguously identify the device or devices covered. The scope of EU technical documentation assessment certificates, EU type-examination certificates and EU product verification certificates shall include, together with the Basic UDI-DI, a clear identification, including the name, model and type, of the device or devices, the intended purpose, as included by the manufacturer in the instructions for use and in relation to which the device has been assessed in the conformity assessment procedure and the risk classification. \nEach of the abovementioned certificates shall identify and cover all devices \nassociated with the same Basic UDI-DI, that is referred to in that certificate.  \nThe association between different Basic UDI-DIs, where applicable, shall be \nidentified through the technical dossiers.  \nIn accordance with Annex IV of the two Regulations, the declaration of conformity \nshall contain the Basic UDI-DI and the product and trade name, product code,  \n3 \n catalogue number or  other unambig uous reference allowi ng identif ication and \ntraceability of the device covered by the EU declaration of conformity. \nChanges of UDI-DI \nA new UDI\u2014DI shall be required whenever there is a change that could lead to \nmisidentification of the device and/or ambiguity in its traceability. In particular, a new UDI-DI shall be required in the case of any change of the following elements: name or trade name, device version or model, labelled as single use, packaged sterile, need for sterilization before use, quantity of  devices provided in a package, critical \nwarnings or contra-indications (e.g. containing latex or DEHP), CMR/Endocrine disruptors\n1 2. \n A UDI-DI shall be associated with one and only one Basic UDI-DI.  \n \n  \nRegarding changes to the specific data elements listed below\n3, the following \nconsiderations should be noted: \n1. Is the Device Directly Marked (Yes/No) \nThe database design will force the creation of a new UDI-DI only if there is a change \nfrom Yes to No and not vice versa for this data element.  \n \n2. Manner in which production of the device Is controlled (expiry date or \nmanufacturing date, lot number, serial number, software identification)  - Type of UDI-PI  \nAs long as there is no change to the la bel, a change to this data element will not \nrequire the allocation of a new UDI-DI. \n                                                           \n1  It should be noted that a new regulatory decision classifying  an existing product as CMR/Endocrine \ndisruptor might not result in a new UDI-DI for products already  containing that substance. The decision on \nwhether to assign a new UDI-DI should be based on the conformit y assessment of the product with regard \nto the impact of the information provided and the significance of the change. \n2  Specific attention shall be paid to the fact that changes of colour or language might also require a new UDI-\nDI when those changes might lead to misidentification of produc t or change the product \nsafety/performance. For example:  \nA- Change of colour coding of e.g. connectors, latex-free surgi cal gloves, blood tubes  \nB- Two identical self-testing de vices, that exist in parallel a nd cannot be substitute d due to local labelling \nrequirements (IVD Article 10(10) of Regulation 746/2017), requi res different UDI-DIs \nSpecifications of EU designated issuing entity should be used a s a reference source to identify other \npossible examples.  \n3 Please refer to Guidance UDIWG 2018-1 on \"UDI database. Defini tions, descriptions and formats of the UDI \ncore elements\u2019  available at https://ec.europa.eu/docsroom/documents/28669   \n4 \n  \nWARNING: This guidance does not address requirements for reprocessed devices, \nsystems or procedure packs, software, Annex  XVI, nor for cases of parallel trade or \nown brand labelling. Specific requirement s for those products are addressed in \nspecific guidance."}, {"title": "mdcg_2018_5_software_en.pdf.txt", "text": "Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -5   \nPage 1 of 3 \n  \n \n \n \n \nMDCG  2018 -5 \nUDI Assignment to Medical Device Software  \n  \n \n            \n October  2018  \n \n \n  \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commission document and it cannot be regar ded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  \n \n  Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -5   \nPage 2 of 3 \n  \nSpecific consideration on UDI rules for software  \nUDI Assignment to Medical Device Software  \n \n- Scope of UDI requirements for software  \nIn accordance with Annex VI, Part C of the Medical Device Regulation (EU) 2017/745 \n(MDR) and the In -Vitro Diagnostic Medical Device Regulation (EU)  2017/746 (IVDR), \nonly software which is commercially available on its own as well as software which \nconstitutes a device in itself shall be subject to UDI requirements.   \n \n- Basic UDI -DI \nIn line with the general Guidance on Basic UDI -DI and changes to UDI -DI1, the Basic \nUDI-DI connects software with same intended purpose, risk class and essential \ndesign and manufacturing characteristics.  \n \n- Changes to UDI -DI \nin accordance with Annex VI Part C, Section 6.5 of the MDR and Section 6.2 of the \nIVDR, a new UDI -DI is required whenever there is a modification that changes the \noriginal performance, the safety of the software or the interpretation of data . Such \nmodifications include new or modified algorithms, database structures, operating \nplatforms, architecture, user i nterfaces and new channels for interoperability . Such \nchanges would be considered \u201csignificant.\u201d  \nThe Guidance on Basic UDI -DI and changes to UDI -DI2, defines standard rules on \ntriggers that entail the creation of a new UDI -DI. It lays down that a new UDI \u2014DI \nshall be required whenever there is a change that could lead to misidentification of a \ndevice and/or ambiguity in its traceability. In particular, a new UDI -DI shall be \nrequired in the case of any change of the following device related elements: name or \ntrade name, device version or model, labelled as single use, packaged sterile, need \nfor sterilization before use, quantity of devices provided in a package, critical \nwarnings or contra -indications (e.g. containing latex or DEHP3), CMR4/Endocrine \ndisruptors , colour, language. Not all those data elements are however applicable to \nsoftware.  \n                                                            \n1 The Guidance is available at https://ec.europa.eu/docsroom/documents/28667   \n2 The Guidance is available at https://ec.europa.eu/docsroom/documents/28667   \n3 DEHP stands for Bis(2 -ethylhexyl) phthalate  \n4 CMR stands for carcinogenic, mutagenic, or toxic for reproduction  Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -5   \nPage 3 of 3 \n  \nIt can therefore be concluded that, in the specific case of software,  \n- Any change of the Basic UDI -DI5 \n- Any changes which impact the original performance, safety, or the \ninterpretation of data6 \n- A change to the name or trade name, version or model number, critical \nwarnings or contra -indications, user interface language  \nwould require a new UDI -DI.   \nThis is to guarantee the traceability and correct identification of the med ical device \nsoftware.  \n \n- Minor software revisions  \nIn accordance with Annex VI, Part C, point 6.5.4 of the MDR and Annex VI, Part C, \npoint 6.2.4 of the IVDR, minor software revisions require a new UDI -PI and not a new \nUDI-DI. Minor software revisions are generally associated with bug fixes, usability \nenhancements that are not for safety purposes, security patches or operating \nefficiency. Minor software revisions shall be identified by a defined manufacturer -\nspecific form of identification.  \n- Evaluation of ch anges to software by the manufacturers  \nAs part of their maintenance and post -market surveillance activities, manufacturers \nshould evaluate the possible impact of any changes to the function of software on the \nsoftware\u2019s qualification as medical device soft ware, its classification, its intended \npurpose and essential design and manufacturing characteristics, as that could trigger \na new Basic UDI -DI.   \nLikewise, any changes shall be assessed in defining the need of a new UDI -DI. \nUDI Placement Criteria  \nUDI plac ement criteria for software are laid down in Annex VI, Part C, point 6.5.4 of \nthe MDR and Annex VI, Part C, point 6.2.4 of the IVDR.  Additional considerations on \nthis aspect will be provided in future guidance.  \n                                                            \n5 This is a general rule. As indicated in the Guidance on Basic UDI -DI and changes to UDI -DI (available at \nhttps://ec.europa.eu/docsroom/documents/28667 ), \"a UDI-DI shall be associated with one an d only one Basic \nUDI-DI\u201d.  \n  \n6 Annex VI, Part C, point 6.5.2 of the MDR and Annex VI, Part C, point 6 .2.2 of the IVDR"}, {"title": "mdcg_2018_7_languages_en.pdf.txt", "text": "Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -7   \nPage 1 of 3 \n  \n \n \n \nMDCG  2018 -7 \nProvisional considerations regarding language \n issues associated with the UDI database  \n (Annex VI, Part A Section 2 and Part B of the \n Medical Device Regulation (EU) 2017/745 (MDR) \n and the In -Vitro Diagnostic Medical Device \n Regulation (EU) 2017/746 (IVDR ))            \n  \nOctober  2018  \n \n \n  \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commission document and it cannot be regarded \nas reflecti ng the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  \n \n  Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -7   \nPage 2 of 3 \n  \nGeneral principles  \nIn consideration of the following:  \n- In accordance with Article 28(3) MDR and Article 25(3) IVDR, the core data \nelements to be provided to the UDI database shall be accessible to the public,  \n- Annex VI Part C of the MDR and IVDR on the UDI System requires explicitly in its \nsection 5.10 that the user interface of the UDI database shall be available in all \nofficial languages of the Union and that  the use of free - text fields shall, however, be \nminimized in order to reduce translations,   \n-  one of the main declared purposes of th e European database on medical devices \n(Eudamed) as per Recitals 43 -46 and Article 33(1a) of the MDR and Recitals 40 -43 \nof the IVDR is to enable the public (including the healthcare professionals) to be \nadequately informed about devices placed on the marke t, \nit is essential that the information in the UDI database is publicly available and easily \nunderstandable by any European citizen.   \n \nUse of free -text and translation  \nAmong the UDI core data elements of Part B of Annex VI of the MDR and IVDR, only \nthree data elements (\"Additional product description\", \"Storage and handling \nconditions\" and \"Critical warnings or contra -indications\") are expected to have a free -\ntext format, while a fourth data element (nomenclature term) is associated with a text \nallowing to  understand the meaning of the associated code (description).  \nAs to the nomenclature, ideally, all the terms/description associated with the \nnomenclature codes should be translated in the different Union official languages. \nHowever, it could be also consi dered having terms available only in English, \nparticularly taking into account that the nomenclature will have a code. Appropriate \nbudget and legal verifications will be made on this matter, in the context of the \ndesignation procedure for the new nomenclat ure.   \nAmong the three data elements that use free -text, one is an optional field: \"Additional \nproduct description\". It should be provided in English as well as in the languages of \nthose countries where the device is made available. A data field will be av ailable for \neach relevant language.  \nFor the data elements \"Storage and handling conditions\" and \"Critical warnings or \ncontra -indications\", relevant information (as per Annex I Section 23.2 of the MDR and \nAnnex I Section 20.2 of the IVDR: (k) \"any special s torage and/or handling \nconditions\" and (m) \"warning or precautions to be taken\") should be provided in  Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -7   \nPage 3 of 3 \n  \nEnglish as well as in the languages of those countries where the device is made \navailable. It shall be noted that, as laid down in the provisional guid ance related to \nformats and definitions of UDI data elements, only storage/handling conditions and \ncritical warnings or contra -indications, that are required to be on the label, shall be \ntransmitted to the UDI database. With respect to those two data eleme nts, the \npossibility to use (in EUDAMED) \u2013 as an alternative option - symbols and/or list of \nreference that can categorise and provide enough information understandable by \nanyone is currently being explored.  \n \nIndication of hazardous substances (only appli cable for MDR)  \nFor CMR substances, the Commission intends to explore the feasibility for \nEUDAMED to provide the list of official CMR1 substances (from CLP Regulation2) \navailable in the ECHA3 database. The CAS number4, EC number and/or official \nchemical nam e could be used to identify those substances.  \nWith regard to endocrine disruptor substances, pending verification that an official \ndatabase managed by the Commission containing these substances is available, a \nsolution is currently being explored.  \nInform ation to be provided is known by the economic operator in charge of the \nsubmission as it shall be displayed on the device label (Annex I Section 23.2 (f) of the \nMDR).  \n \n                                                            \n1 CMR stands for carcinogenic, mutagenic, or toxic for reproduction  \n2 Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (the 'CLP \nRegulation')  \n3 The European Chemicals Agency  \n4 A CAS Registry Number, also referred to as CASRN or CAS Number, is a unique numerical identifier assigned by \nthe Chemical Abstracts Service (CAS) to every chemical substance described in the open scientific literature"}, {"title": "mdcg_2018_6_art16_en.pdf.txt", "text": "Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -6   \nPage 1 of 2 \n  \n \n \n \nMDCG  2018 -6 \nClarifications of UDI related responsibilities in \n relation to Article 16 of the Medical Device \n Regulation (EU) 2017/745 and the  \n In-Vitro Diagnostic Medical Device  \n Regulation (EU) 2017/746  \n            \n October  2018  \n \n \n  \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commission document and it cannot be regarded \nas reflecting the official position of the European  Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  \n \n  Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -6   \nPage 2 of 2 \n  \nRelevant obligations arising from Article 16(1)  \nAny distributor, importer or other natural or legal person that assumes the obligations \nincumbent on manufacturers in accordance with Article 16(1), assumes all the \nrelevant responsibilities related to UDI, including UDI labelling.  \nThis means that those e conomic operators must also apply for registration as \nManufacturers, receive a Single Registration Number (SRN), apply for the \nappropriate conformity assessment procedure and feed and provide UDI -product \nregistration.  \nHowever, in accordance with the provis ion of Article 16(1)a, when a distributor or \nimporter enters into an agreement with a manufacturer whereby the manufacturer is \nidentified as such on the label, the manufacturer is responsible for meeting the \nrequirements placed on manufacturers in this Reg ulation, including the relevant UDI \nobligations.  \n \nRelevant obligations arising from Article 16(2) to 16(4)  \nThe distributor or importer carrying out the operations in Article 16(2) shall ensure \nthat: \n-  the activities mentioned in points  (a) and  (b) of par agraph  2 are performed by \nmeans and under conditions that in no way compromise the readability of the UDI \ncarrier and its information identifying the actual device.  \n- the specific procedures are part of the distributor's or importer\u2019s quality \nmanagement sy stem."}, {"title": "mdcg_2018_2_nomenclature_en.pdf.txt", "text": "This document has been endorsed by the Medical Device Coordination Group (MDCG) \nestablished by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of \nrepresentatives of all Member States and it is chaired by a representative of the European \nCommi ssion.  \n \nThe document is not a European Commission document and it cannot be regarded as \nreflecting the official position of the European Commission. Any views expressed in this \ndocument are not legally binding and only the Court of Justice of the European  Union can \ngive binding interpretations of Union law.  \n \n1 \n  \nMDCG 2018 -2 \nFuture EU medical device nomenclature   \nDescription of requirements                                                                                                                                                                                                                                             \n \nIntroduction  \n \nAccording to Article 26 of the Regulation 745/2017 on medical devices and Article 23 \nof Regulation 746/2017  on in-vitro diagnostic medical device , the Commission is \nrequired to make available a medical device nomenclature to support the functioning \nof the future  EUDAMED . \n \nThis document intends to provide a detailed description of requirements and criteria \nthat the future nomenclature is expected to fulfil. This is expected to serve as a \nreference basis throughout the decision process and will also ensure th at all legal \nand technical issues associated with the future EU medical device nomenclature are \nproperly mapped.  \n \n \n1. Description of legal requirements  \n \nIt arises from the text of the new Regulations (namely Article 26 of Regulation \n745/2017 and Article 23 of Regulation 746/2017) that t he future EU medical device \nnomenclature  will have to comply with certain defined requirements . \n \nFirst of all, t he future nomenclature shall be available free of charge to \nmanufacturers and other natural o r legal persons required by the  Regulation to use \nthat nomenclature, this meaning that no manufacturer or natural/legal person should \nbe subject to fee or suffer from any discrimination, compared to other operators, in \nrelation to the use of the nomenclature under the new Medical Device Regulations.  \n \nIt shall be therefore ensured that relevant names and codes are accessible (in full) in \nEUDAMED to all operators that are requested to provide the relevant UDI \nsubmissions.  \n \nProvisions in Chapter III and Annex VI of the new Regulations, and in particular  the \ncombination of Article 28( 3) of the Regulation 745/2017 on medical devices and \npoint 8 of part B of Annex VI , provide that moreover names and codes are publicly \navailabl e in the UDI database (in EUDAMED ).  \n \nBy virtue of Article 26, t he Commission shall a lso endeavour to ensure that the  \nnomenclature is available to other stakeholders free of charg e, where reasonably This document has been endorsed by the Medical Device Coordination Group (MDCG) \nestablished by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of \nrepresentatives of all Member States and it is chaired by a representative of the European \nCommi ssion.  \n \nThe document is not a European Commission document and it cannot be regarded as \nreflecting the official position of the European Commission. Any views expressed in this \ndocument are not legally binding and only the Court of Justice of the European  Union can \ngive binding interpretations of Union law.  \n \n2 \n practicable. The public availability of terms and codes in EUDAMED is in itself an \nideal vehicle to provide sufficient access of all stakeholders .   \n \nFinally the nomenclature shall be internationally recognised at the time of the date of \napplication of the Regulations. In this context, global harmonisation principles and \norientations followed and adopted by  the International Medical Device Regulators \nForum  (IMDRF)  and the World Health Organisation , are taken into particular \naccount .  \n \nWithout prejudice to the fulfilment of requirements d escribed in previous paragraphs, \nthe European Commission and the Competent Authorities  from EU Member States  \nshall benefit from the full access to the most up to date nomenclature system  and its \nhierarchies  free of charge . They shall not be charged  for any service received from \nthe nomenclature provider, which is necessary for them to exert their supervisory \nrole over the nomenclature and the fulfilment of their obligations under the new \nRegulations.   \n \n2. Description of other relevant criteria  \n \nIn order for the system to leverage further the potential of the future EU \nnomenclature, some other essential requirements that the nomenclature shall fulfil  \nhave been identified .  \n \nWhile those requirements are not explicitly mentioned in the texts of the two  \nRegulation s, they are  essential to guarantee the good functioning of the future \nEUDAMED  and to the fulfilment of some of the regulatory objectives set in the new \nRegulation s, namely facilitating effective market surveillance  operations  and \nfacilitating  device traceability throughout the supply chain.  \n \nPolicies/rules for update, removal  and creation of names  and descriptions  in the \nnomenclature are to be sound and must reflect regulators \u2019 and the wider healthcare \neconomy needs . An EU regulatory team on no menclature  composed of regulators , to \nbe established possibly  as an MDCG sub -group , will review, determine (preferably \nwithin a global perspective) and validate those rules prior to designation decision and \nwill continue to hold an advisory role on these matters . On a  periodic basis, in \naccordance with a pre -defined procedure, and in consultation with the nomenclature \nprovider, that group shall also provide feedback and advice on the governance  of \nterms and descriptions, based, inter alia, on the requests received from economic \noperators and other stakeholders.  \n \nIn the context of activities mentioned in the previous paragraph, it shall be aimed to \nensure that the terminology structure used for it should not be unnecessarily  granular  \nand should not contain names that are only used by only a few  economic operators This document has been endorsed by the Medical Device Coordination Group (MDCG) \nestablished by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of \nrepresentatives of all Member States and it is chaired by a representative of the European \nCommi ssion.  \n \nThe document is not a European Commission document and it cannot be regarded as \nreflecting the official position of the European Commission. Any views expressed in this \ndocument are not legally binding and only the Court of Justice of the European  Union can \ngive binding interpretations of Union law.  \n \n3 \n or stakeholders , unless it is proven to be advantageous to regulators or the wider \nhealthcare economy.  \n \nThe structure and design of the future nomenclature should facilitate the \nestablishment of lin ks with the codes defining N otified Bodies  competence \n(designation scope) , the scope of medical device s QMS  (Quality Management \nSystem)/QA (Quality Assurance)  certificates , and product portfolio s in the mandate  \nof Authorised Representatives .   \n \nThe nomenclature should have hierarch ies by which terms and codes could be \nmeaningfully grouped  into categories and subcategories   \n \nThe future nomenclature system shall adequately support the functioning of the \nEUDAMED database and the functioning of the new Regulations as a whole. In this \ncontext, EUDAMED shall make available the most updated names/codes related \ninformation, to the be nefit of operators and general public. Therefore, the \nnomenclature provider will need to have procedures and services in place that shall \nallow E UDAMED  to be kept up -to-date at any time.  When setting the procedure, in \nparticular the frequency, related to the periodic review of nomenclature terms and \ndescriptions , this shall be taken into account.  \n \nFor enforcement purposes , in relation to its obligations vis -\u00e0-vis the Commission and \nthe EU economic operators, the nomenclature provider  shall have a legal entity in \neither one of the EEA countries  or Switzerland  or Turkey1 with an exception being \nforeseen for international organisations in which the EU is one of the members .   \n \nSystem/processes shall be in place to periodically  review the terminology structure \nand content to incorporate learning from ongoing experience with real -world use of \ndevice nomenclature (ex. EUDAMED, GUDID, registries)  as well as from \ntechnological  innovation . \n \nAvailability of names and descriptions in all the official EU langu ages is recognised \nas of being of high importance.  \n \nAll copyright s associated with the nomenclature shall be secured.  \n                                                       \n1 Indication of these countries is based on current situation with the applicable directives on medical devices \nas a result of the combination of the legal text of those Directives and relevant currently applicable \ninternational agreements . this list of countries might be subject to change in the context of the new m edical \ndevice framework."}, {"title": "12 MDCG 2020-12 Guidance on transitional provisions for consultations of authorities on devices.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-12  \n \nPage 1 of 6 \n  \n \n \n \nMDCG 2020-12 \n  \n         Guidance on transition al provisions for \n       consultations of authorities on devices \n       incorporating a substance which may be \n       considered a medicinal product and which  \n       has action ancillary to that of the device,  \n       as well as on devices manufactured using  \n       TSE suscep tible animal tissues   \n             \n \n           June 2020 \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member States and it is chaired by a representative of the European Commission.The document is not a European Commission document and it cannot be regarded as reflecting the official position of the European Commission. Any views expressed in this document are not legally binding and only the Court of Justice of the European Union can give binding interpretations of Union law. \n  Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-12  \n \nPage 2 of 6 \n  \nGuidance on transitional provisions for consultations of author ities on \ndevices incorporating a substa nce which may be considered a \nmedicinal product and which has action ancillary to that of the  device, \nas well as on devices manufacture d using TSE susceptible animal  \ntissues \n \nI. Consultations for a substance which may be considered a medicin al product \nand which has action ancillary to that of the device (including  human blood \nderivatives) \n \nConsultation procedure under the MDD and AIMDD \nAccording to Annex I section 7.4 of Directive 93/42/EEC on medical devices (the MDD), and Annex \nI section 10 of Directive 90/385/EEC on active im plantable medical devices (the AIMDD), for \ndevices containing a substance which, if used separately, would be considered to be a medicinal \nproduct and which is liable to act upon the body with an action ancillary to that of the device, the \nnotified body is required, having verified the usefulness of the substance as part of the medical device \nand taking account of the intended purpose of the device, to seek a scientific opinion from one of the competent authorities designated by the Member St ates or the European Medicines Agency (EMA) on \nthe quality and safety of the  substance in the medical device, including the clinical benefit/risk profile \nof the incorporation of the substance into the device. Similarly, where changes are made to that \nsubstance, particularly relating to its manufacturing process, the notified body is required to consult \nwith the same authority in order to confirm that the quality and safety of that substance are maintained \nand to ensure that the changes have no negative impact on the established benefit/risk profile of the \naddition of the substance in the medical device. This consultation on changes is referred to as supplementary consultation in this guidance document.  \n \nThere is an equivalent consultation requirement for medical devices containing a human blood \nderivative with ancillary action. In this case the notified body is required to consult the EMA only. \n \nTransitioning from MDD and AIMDD to MDR \n \nRegulation (EU) 2017/745 on medical devices (the MDR)  establishes a similar requirement in Article \n52 (9) (Annex IX section 5.2 and Annex X Section 6): fo r devices incorporating, as an integral part, a \nsubstance which, if used separately, may be considered to be a medicinal product\n1 and which has an \naction ancillary to that of the device (hereafter referred to in this document as the ancillary substance), \nthe notified body is required, having verified the usefulness of the substance as part of the medical \ndevice and taking account of the intended purpose of the device, to consult a medicinal products \nauthority designated by a Member State or the EMA2 on the quality and safety of the substance, \nincluding the benefit or risk of the incorporation of the substance into the device. The notified body is \n                                                           \n1 including a medicinal product derived from human blood or human plasma \n2 only the EMA in the case of medicinal products derived from human blood or human plasma, or those falling \nexclusively within the scope of Regulation (EC) 726/2004  Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-12  \n \nPage 3 of 6 \n required to do so both for the initial conformity assessment of the device (this consultation is referred \nto as initial in this guidance document) and for an y subsequent changes to the ancillary substance, in \nparticular in relation to its manufacturing process (the consultation on changes is referred to as a \nsupplementary consultation, by analogy to the M DD/AIMDD). A competent auth ority designated by a \nMember State in accordance with Directive 2001/83/EC or the EMA (hereafter referred as medicinal products authority in this document) consulted has 210 days since the receipt of all the necessary \ndocumentation to provide its opinion in the case of an initial consultation, or 60 days for a \nsupplementary consultation. Unlike the MDD and AIMDD, the MDR also states that the notified \nbody may not deliver the certificate if the opinion is unfavourable (Annex IX 5.2 (e) and (f)).  \n This document provides guidance on fulfilling th is requirement for the first time under the MDR for \ndevices which already underwent a consultation with a medicinal products authority according to \nAnnex I 7.4 of the MDD or Annex I 10 of the AIMDD. \n \nConsultation for ancillary substances under the MDR for devices which have undergone the \nconsultation under the MDD or AIMDD \n \nIn order for the notified body to issue the first certificate for a given device under the MDR, a full \nconformity assessment covering all requirements has to be carried out even if the device has been \ncertified under the MDD (Q&A IV.1 MDCG 2019-6). For devices containing ancillary substances, this includes the consultation of the medicinal products authority as per Article 52 (9) of the MDR.  \n \nFor some devices, there may be no change to the device, the ancillary substance and its manufacturing \nprocess since the last consultation of the me dicinal products authority  under the MDD/AIMDD. \nNevertheless, there may be changes in the documentation of the device due to the new requirements \nof the MDR, for example in clinical evaluation, which have a bearing on the quality, safety or \nusefulness of the ancillary substance. There may also be changes in the assessment of the device and its documentation by the notified body under the MDR. Lastly, the medicinal products authority may \nhave new information on the substance, leading to a modified or different opinion.   \n \nFor the first consultation under the MDR, the notified body is required to submit the full \ndocumentation package to the medicinal products authority as described in dedicated guidance. The notified body is free to approach any medicinal products authority at its discretion, not necessarily the \none consulted under the MDD/AIMDD. This should in clude the last opinion of the medicinal products \nauthority under the MDD/AIMDD (whether initial or supplementary), as well as a consolidated list of \nchanges, if any, in the following:  \n\u0081 the ancillary substance, \n\u0081 its manufacturing process,   \n\u0081 the way the substance is incorporated into the device, \n\u0081 design, manufacturing of the device which could influence the quality, safety or usefulness of \nthe ancillary substance, and/or \n\u0081 the parts of the technical documentation related to the above aspects.  \nIf there were no changes to some or any of the above, the package may be accompanied by a \ndeclaration by the notified body to this effect, stating the elements that have remained identical. If \nthere have also been no changes to the assessment of this documentation by the notified body, this \nmay be included in the declaration. Should there be only administrative changes to the above (e.g. \nchanges of names or addresses, changes in document layout, etc.), these should be clearly detailed in the declaration.  \n \nThe medicinal products authority may consider the depth of its review given the extent of the changes \nsince the previous consultation under the MDD/AIMDD. It is at the discretion of the medicinal Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-12  \n \nPage 4 of 6 \n products authority to issue its opinion in less than 210 days. If many elements concerning the \nsubstance remain identical, the medicinal products authority is highly recommended to expedite its \nreview.   \n \nThe medicinal products authority may contact the authority consulted on this device under the MDD/AIMDD, who may, at its discretion, confirm the opinion provided in the previous consultation \nand/or share any additional information. The final opinion for the consultation under the MDR and its \nissuance according to the stipulated timeline remains the responsibility of the medicinal products \nauthority to which the notified body submitted the request under the MDR.  \n  \nNote on \u201cliability to act upon the body\u201d  \n \nIt should be noted that Annex I 7.4 of the MDD refers to devices in which the substance is liable to \nact upon the body . In the MDR (Article 52(9), referring to Article 1(8), and Section 5.2 of Annex \nIX), this is no longer the case. Therefore, for al l those devices where the \"liability to act upon the \nbody\" was used by the manufacturer as a justification not to follow the consultation, the consultation \nmust take place under the MDR.  In those cases where there are doubts on the applicability of the \nconsultation, independently of any considerations concerning the classification of the device, the \nnotified body should seek the scientific opinion as described in Annex IX Section 5.2 (b) of the MDR.    \nRelevant text from MDD and MDR  \nMDD \u2013 Annex I Section 7.4 [emphasis added] \nWhere a device incorporates, as an integral part, a substance which, if used separately, may be \nconsidered to be a medicinal product as defined in Article 1 of Directive 2001/83/EC and which is \nliable to act upon the body  with action ancillary to that of the device, the quality, safety and \nusefulness of the substance must be verified by an alogy with the methods specified in Annex I to \nDirective 2001/83/EC. \n \nFor the substances referred to in the first paragraph, t he notified body shall, having verified the \nusefulness of the substance  as part of the medical device and taking account of the intended purpose \nof the device, seek a scientific opinion from one of the competent authorities designated by the \nMember States or the European Medicines Agency (EMEA)  acting particularly through its \ncommittee in accordance with Regulation (EC) No 726/2004 (1) on the quality and safety of the \nsubstance including the clinical benefit/risk profile of the incorporation of the substance into the \ndevice . When issuing its opinion, the competent authority or the EMEA shall take into account the \nmanufacturing process and the data related to the usefulness  of incorporation of the substance into \nthe device as determined by the notified body. \n \nWhere a device incorporates, as an integral part, a human blood derivative, the notified body shall, \nhaving verified the usefulness of the substance  as part of the medical device and taking into account \nthe intended purpose of the device, seek a scientific opinion from the EMEA , acting particularly \nthrough its committee, on the quality and safety of the substance including the clinical benefit/risk \nprofile of the incorporation of the human blood derivative into the device . When issuing its opinion, \nthe EMEA shall take into account the manufacturing process and the data related to the usefulness of \nincorporation of the substance into the device as determined by the notified body. \nWhere changes are made to an ancillary substance incorporated in a device, in particular related to \nits manufacturing process, the notified body shall be informed of the changes and shall consult the \nrelevant medicines competent authority (i.e. the one involved in the initial consultation), in order to confirm that the quality and safety of the ancillary substance are maintained. The competent authority Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-12  \n \nPage 5 of 6 \n shall take into account the data related to the usef ulness of incorporation of the substance into the \ndevice as determined by the notified body, in order to ensure that the changes have no negative \nimpact on the established benefit/risk profile of the addition of the substance in the medical device. \n \n \nMDR \u2013 Annex IX 5.2 b \n \n(a) Where a device incorporates, as an integral part, a substance which, if used separately, may be \nconsidered to be a medicinal product within the meaning of point 2 of Article 1 of Directive \n2001/83/EC, including a medicinal product derive d from human blood or human plasma and \nthat has an action ancillary to that of the device, the quality, safety and usefulness of the \nsubstance shall be verified by analogy with the methods specified in Annex I to Directive \n2001/83/EC. \n \n(b) Before issuing an EU technical documentation assessment certificate, the notified body shall, \nhaving verified the usefulness of the substance  as part of the device and taking account of the \nintended purpose of the device, seek a scientific opinion from one of the competent authorities \ndesignated by the Member States in accor dance with Directive 2001/83/EC or from the EMA , \neither of which to be referred to in this Section as \u2018the medicinal products authority consulted\u2019 \ndepending on which has been consulted under this point, on the quality and safety of the \nsubstance including the benefit or risk of the incorporation of the substance into the device . \nWhere the device incorporates a human blood or plasma derivative or a substance that, if used \nseparately, may be considered to be a medicinal product falling exclusively within the scope of \nthe Annex to Regulation (EC) No 726/2004, the notified body shall seek the opinion of the EMA.  \n \n(c) When issuing its opinion, the medicinal products authority consulted shall take into account the \nmanufacturing process and the data relating to the usefulness  of incorporation of the substance \ninto the device as determined by the notified body. \n \nII. Consultations for medical device s containing TSE susceptible an imal tissue \nunder the MDR, where such a consultation took place under the M DD or \nAIMDD \n \nArticle 5(4) of Regulation (EU) 722/2012 requires that for all medical devices, including active \nimplantable medical devices, manufactured utilising tissues of animal origin which are susceptible to \ntransmissible spongiform encephalopathy (TSE), the notified body must, through their competent \nauthority, carry out a consultation of the other competent authorities and the Commission. \nUnder the MDR, this requirement rema ins unchanged (Annex IX Section 5.3.2). \nIn order to fulfil the requirements of the MDR, during the first certification under the MDR, the \nnotified body is required to submit the full summary evaluation report as stated in Regulation (EU) \n722/2012 to the competent authorities. If there have been no changes to the documentation required \nfrom the manufacturer as per Regulation (EU) 722/2012, the summary evaluation report may be \naccompanied by a declaration by the notified body to this effect, stating the elements that have remained identical. If there have also been no changes to the assessment of this documentation by the \nnotified body, this may also be included in th e declaration. Should there be only administrative \nchanges to the above (e.g. changes of names or addresses, changes in document layout, etc.), these \nshould be clearly detailed in the declaration.  Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-12  \n \nPage 6 of 6 \n  \nAs stated in Article 5(5) of Regulation (EU) 722/2012, the competent authorities and the Commission \nmay agree on shortening the time periods for the consultation. If many elements of the summary evaluation report remain identical, it is highly recommended to expedite the review. \nRelevant text from Regulation (EU) 722/2012 \nArticle 5 (4) and (5) 4. Before issuing an EC design-examination certificate or an EC type-examination certificate, the \nnotified bodies shall, through their competent authority, hereinafter \u2018coordinating competent \nauthority\u2019, inform the competent authorities of th e other Member States and the Commission of their \nassessment carried out pursuant to paragraph 2 by means of a summary evaluation report in \naccordance with Annex II to this Regulation.  \n5. The competent authorities of the Member States may submit comments on the summary evaluation \nreport referred to in paragraph 4 within the following deadlines:  \n(a) in relation to medical devices using starting materials for which a TSE certificate of suitability as \nreferred to in paragraph 3 has been submitted, within four weeks from the date on which the notified \nbody informed the coordinating competent authority pursuant to paragraph 4;  \n(b) in relation to medical devices using starting materials for which a TSE certificate of suitability has \nnot been submitted, within 12 weeks from the date on which the notified body informed the \ncoordinating competent authority pursuant to paragraph 4.  \nThe competent authorities of the Member States  and the Commission may agree on shortening the \ntime periods set out in points (a) and (b)."}, {"title": "mdcg_2018_8_crf_transfer_en.pdf.txt", "text": "Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -8   \nPage 1 of 2 \n  \n \n \n \n \nMDCG  2018 -8 \nGuidance on c ontent of the certificates,    \n voluntary certificate transfers  \n                 \n \n \n November 2018  \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical  Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commissi on document and it cannot be regarded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union  law. \n Medical Devices       \nMedical Devices Coordination Group Document   MDCG  2018 -8   \nPage 2 of 2 \n  \n \nIn the meeting of 30 November 2018, MDCG endorsed the below positions. These \npositions will be part of a more comprehensive guideline related to notified bodies, \ncurrently under development.  \n \nContent of the certificate under MDR / IVDR Annex XII, Chapter II, section 10  \nCertificates do not need to include reference to relevant common specifications or \nharmonised standards as long as such information on all examinations and tests \nperformed is traceable and available from e.g. report(s) which are ment ioned in the \ncertificate.  \n \nVoluntary certificate transfer under MDR Article 58 / IVDR Article 53  \nWhile MDR Article 58(1) / IVDR Article 53(1) sets out the requirements for a transfer \nagreement, it does not specify the conformity assessment activities to be  performed \nby the incoming NB. The incoming NB may decide not to carry out full conformity \nassessment activities according to Article 52 MDR / Article 48 IVDR, as long as it \ndoes have sufficient information in respect to the conformity activities performed  by \nthe outgoing NB.  \nFor quality management system certificates, the incoming NB needs to perform \nappropriate on -site audit(s) and assessments to ensure that the manufacturer in \nquestion applies the approved QMS and the post -market surveillance plan prior to \nthe issue of any certificate. In respect to the assessment of technical documentations \non a sampling basis, the oncoming NB shall review the previous assessment results \ntogether with a sample of a  technical documentation and draw up or amend a \nsampling plan. For product certificates (Annex IX Chapter II/Annex X), new \ncertificates without a  comprehensive (initial) review may be issued as long as the \ndocumentation received does not identify ongoing existing or other concerns.  \nThe incoming NB assumes full responsibility for the new certificates issued following \nthe transfer."}, {"title": "mdcg_2019_14_MDR_codes.pdf.txt", "text": "1 \n Medical Device       \nMedical Device Coordination Group Document   MDCG  2019-14    \n \n  \n \n \n \nMDCG  2019-14  \n        Explanatory note on MDR codes   \n           \n \n           December   2019 \n \n \n  \n    \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission. \nThe document is not a European Commission document and it cannot be regarded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European Union can give binding interpretations of Union law.  \n   \n2 \n Explanatory note on MDR codes \n \n1 Introduction \nCommission Implementing Regulation 2017/2185 establishes the codes for the designation of notified \nbodies in medical devices under Regulation (EU) 2017/745 and in vitro  diagnostic medical devices \nunder Regulation (EU) 2017/746.  These codes are primarily used by designating authorities to define \nthe notified body scope of designation but they are also used by the notified body to:  \n1) describe the individual qualification of the NBs staff members 2) describe the qualification required for assessing a device  \nThese codes may be very broad and, furthermore, unequivocal authorisation of personnel to codes \nand the assignment of codes to a device is not always straightforward. However, the notified body\u2019s system needs to ensure, in all cases, that the authorisation of personnel and team allocation for the conformity assessment of a device ensures adequate knowledge and expertise.  \n \n2 Scope \nThe lists of codes and corresponding types of devices established by the above mentioned \nRegulation takes into account various device types which can be characterised by design and intended purpose, manufacturing processes and technologies used, such as sterilisation and the use of nanomaterials.  \nThese lists of codes should be used in a way that provides for a multi-dimensional application to all \ntypology of devices. This will ensure that notified bodies as well as the staff assigned to conformity assessment are fully competent for the devices they are required to assess. \nThis guidance is intended to explain the different level of codes and how they should be used, \nincluding the use of conditions with a view to ensure a harmonised use of the codes especially for the allocation of resources to conformity assessment activities.  \n \n \n3 \n 3 Assignment of codes to devices within the conformity \nassessment procedure \nWhen a manufacturer lodges an application with a notified body, the type of devices and technologies \nsubject to conformity assessment activities are to be indicated. Usually, at the application review stage (as defined in section 4.3 of Annex VII MDR), notified bodies will verify the assignment of codes provided by the manufacturer or will assign these codes to the devices themselves. This verification is carried out in order to ensure that the notified body is able to assess the application based on its designation, and that it has available resources to carry out the relevant conformity assessment \nactivities (feasibility evaluation). The final assignment is made by the NB.  \nAfter this application review, and signing of the contract, the notified body will allocate appropriately \nqualified and authorised personnel to carry out audit activities or product reviews.  \nThe following table presents an overview of the different types of codes and a summary of the main \ncharacteristics of each of them for the assignment to specific devices and the allocation of resources. \nType Code Assignment of codes to the \ndevice Relevance for allocation of \nconformity assessment team \nMDA / MDN Codes reflect design and \nintended  purpose of \ndevice Exactly 1 code per device. \n \nThe codes should be selected \naccording to their hierarchical order in Regulation 2017/2185. If more than 1 MDA/ MDN code is applicable, the one that is highest in the list should be selected.  Allocation of personnel involved in \nthe review of technical \ndocumentation (e.g. product \nreviewers) or in audits concerning product related aspects. \nMDS Horizontal codes that \nreflect the specific \ncharacteristics of the device  0 to several per device \n \nAssign all codes applicable to the \ndevice.  Select once an MDN/MDA code has been assigned.  Allocation of personnel involved in \nthe review of technical \ndocumentation (e.g. product \nreviewers of sterilisation validation).   \nMay also be applicable to staff \nperforming audits concerning  \ncertain special processes (e.g. \nsterilization).* \nMDT  \nHorizontal codes that describe technologies or processes  1 to several per device \n Assign the codes which describe the main production technologies or processes.  \n \nSelect once an MDN/MDA code has been assigned. Allocation of personnel involved in \naudits (e.g. site auditors involved in the auditing of metal processing). \n* Note: Assessment of these codes could be performed by Product reviewers or Site auditors depending on their competence  \n \n3.1 MDN / MDA-codes \nMDA / MDN-codes reflect the design and intended purpose of the device and hence are mostly \nrelevant for the allocation of personnel involved in the review of technical documentation.  In some \nspecific cases, the NB may assign product reviewers to assess product performance and safety aspects during an audit. This means that if there are product related issues to be audited and the auditors do not possess the required qualification, product reviewers who are qualified for the device in question should be part of the audit team.  \nThe NB needs to ensure that the personnel allocated to the project are competent to assess for the \ndevices and technologies under assessment . Special attention should be paid in situations such as \nthe one described in example 4 of this section.   \n4 \n The MDA / MDN codes may either specify a field of medical application (e.g. MDA 0309 Active non-\nimplantable ophthalmologic devices) or the physical or technological principle of the device (e.g. MDA \n0302 Active non-implantable devices utilising non-ionizing radiation or MDA 0315 Software). \nTherefore, there are cases where more than one specific code might apply to a device (e.g. surgical \nlaser for refractive surgery of the eye ). Also, where there is a broad intended purpose, several codes \nmay apply. \nHaving these issues in mind, when drafting the Regulation 2017/2185, the codes were put in order \nsuch that the MDA/MDN codes that require very specific technological knowledge and experience are highest in the code lists. Therefore, in cases where more than one MDA/MDN code apply, the code highest in the list is to be selected. This approach ensures consistent assignment of codes (and therefore consistent assignment of suitably qualified staff) to devices. \nExample 1: A surgical laser for refractive surgery of the eye is assigned to MDA 0302 Active \nnon-implantable devices utilising non-ionizing radiation and not to MDA 0309 Active non-\nimplantable ophthalmologic devices because, even though both codes are specific for the device, since MDA 0302 is higher in the list. \nExample 2: A screw for orthopaedic surgery is assigned to MDN 1102 Non-active osteo- and \northopaedic implants and not to 1104 Non-active soft tissue and other implants, because MDN 1102 is higher in the list. \nDevices may be composed of different \u201ccomponents\u201d which, if they were products on their own, would \nbelong to different MDA/MDN codes\n(1). In such cases, the intended purpose or the main physical or \ntechnological principle of the device should be considered (Example 3).  Nonetheless, the notified body needs to ensure that the assigned staff is qualified to assess all components of the device.  \nExample 3: A medical devices is composed of a suture anchor (a bone screw attached to a \nsurgical suture to reattach ruptured tendons) as well as a single use deployment instrument \nand a single use bone drill. The components are provided sterile in a blister, are covered by the same technical documentation and are not available individually (e.g. are not medical devices on their own). This product is assigned to MDN 1102 Non-active osteo- and orthopaedic implants and not to MDN 1208 Non-active non-implantable instruments because the implanted component of the device is associated with the intended purpose rather than the deployment instrument and the drill.  \nNote that, given the complexity and the diversity of medical devices, in exceptional cases deviations \nfrom the guidance given above may be necessary when assigning codes to devices in order to ensure \nsuitably qualified staff in the conformity assessment. In such cases, a brief rationale shall be documented (see Example 4).  \nExample 4: A heater-cooler unit (HCU) for cardiac surgery is a device through which blood \ncirculates, and which changes the circulating blood\u2019s temperature in order to achieve hypo- or hyperthermia. Both the codes MDA 0303 Active non-implantable devices utilising hyperthermia/hypothermia and MDA 0306 Active non-implantable devices for extra-corporal circulation, administration or removal of substances and haemapheresis are specific to the \ndevice. Since MDA 0303 Active non-implantable devices utilising hyperthermia/hypothermia is \na code that describes physical or technological characteristics higher in the list, according to the rule explained above MDA 0303 should be chosen. Nonetheless, the notified body assigns the device to the code MDA 0306 Active non-implantable devices for extra-corporal circulation, administration or removal of substances and haemapheresis and documents that \nthe risks associated with the HCU are such that the staff having experience in this code is \nmore suitable to assess the device.  \nIt is important to note that Stand-alone software (i.e. software that is not part of a physical medical \ndevice) should be assigned to MDA 0315 since assessment of software requires very specific knowledge (see annex VII 3.2.2 5\nth indent MDR) and also that  non-implantable cardiovascular \n                                            \n1 This description does NOT refer to procedure packs or systems according to MDR Article 2 (10) and (11) since those are \ncombinations of individual CE-marked products that have been subjected to separate conformity assessments.  \n5 \n catheters, guidewires, introducers, filters and related tools shall fall under MDN 1203 (instead of MDN \n1201 or MDN 1202). \n \n3.2 MDS codes \nMDS codes are horizontal codes that are applicable to devices with specific characteristics. All codes \nthat are applicable need to be assigned to a device in order to ensure that the review team possesses \nthe full set of qualifications necessary for the conformity assessment. The MDS-codes are mainly relevant for the allocation of personnel involved in the review of technical documentation. This is because, generally, the auditing aspects linked to MDS codes have their corresponding MDT code for \nthe relevant technology (e.g. MDS 1001 Devices incorporating medicinal substances  vs MDT 2007  \nDevices which require knowledge regarding the production of pha rmaceuticals ). However, MDS \ncodes may also be applicable to staff performing audits concerning  certain special processes (for \nexample MDS 1005 for staff auditing ethylene oxide sterilization processes). \nExample 1: A partially resorbable, sterile surgical implant that contains an antibiotic to prevent \npost-surgical infection will need to be assigned to the following MDS codes:  \n1) MDS 1005 - Devices in sterile condition: because it is provided sterile,  \n2) MDS 1008 - Devices utilising [...] being wholly or mainly absorbed or locally dispersed \nin the human body [\u2026]:  because it is absorbed, and  \n3) MDS 1001 - Devices incorporating medicinal substances: because it contains an \nantibiotic. \nExample 2: An infusion pump should be assigned to MDS 1009 - Devices incorporating \nsoftware/utilising software/controlled by software [\u2026] because the infusion pump is controlled \nby software. \n3.3 MDT codes \nMDT codes relate to the technologies and processes that are used in the manufacturing and making available of the devices. MDT codes are relevant for the allocation of site auditors. \nAssignment of MDT codes should be done taking into consideration production of the device itself as \nwell as for critical upstream production steps. This means that, even  though many codes could be \napplicable when taking into consideration the processes involved in the entire supply chain of a medical device, these should not be considered for the use of MDT codes (e.g. for an electronic \nmedical thermometer, at one point, metal processing, plastic processing, non-metal mineral processing, chemical processing, manufacture in clean rooms, manufacturing using electronic components, labelling and packaging are necessary to assemble the device from raw materials).  \nExample 1: An electronic medical thermometer for layman\u2019s use should be assigned to the \nfollowing MDT codes:  \n1) MDT 2010 Devices manufactured using electronic components including \ncommunication devices because the product is assembled from electronic \ncomponents and  \n2) MDT 2011 Devices which require packaging, including labelling because the device is \npacked and labelled. \nExample 2: A sterile animal derived bone graft substitute is manufactured using several steps. \nIn the first step, the raw animal bone undergoes a sequence of chemical treatments to remove organic components. In a second step, the remaining mineral bone component is subjected to a heat treatment, then ground and sieved to obtain particles of defined sizes. The material is packed, labelled and sterilized. Therefore the following MDT codes should be assigned:  \n6 \n 1) MDT 2008 Devices manufactured in clean rooms and associated controlled \nenvironments, because the manufacturing of the implant after the heat treatment is conducted in clean rooms,  \n2) MDT 2009 Devices manufactured using processing of materials of human, animal, or \nmicrobial origin because the implant is made from animal bone \n3) MDT 2011 Devices which require packaging, including labelling because the implant \nis packed and labelled. \nNote: MDT 2006 Devices manufactured using chemical processing and MDT 2003 \nDevices manufactured using non-metal mineral processing (e.g. glass, ceramics) \nwere not applied since the chemical treatment and (bone) mineral processing are already considered within the scope of processing of animal materials.  \nExample 3: A calcium phosphate bone cement is provided as a sterile powder composed of a \nmixture of calcium salts and a vial with sterile saline.  The following MDT codes should be assigned: \n1) MDT 2008 Devices manufactured in clean rooms and associated controlled \nenvironments, because the manufacturing of the implant is in a controlled environment,  \n2) MDT 2006 Devices manufactured using chemical processing, because the main risks \nin manufacturing are related to the testing and mixing of the components, \n3) MDT 2011 Devices which require packaging, including labelling because the implant \nis packed and labelled. \nExample 4: A manufacturer of cross-linked hyaluronic acid implants has no in-house \nmanufacturing. The finished, labelled implant is bought from a supplier. The implant raw \nmaterial (hyaluronic acid) is produced by fermentation using bacteria. The following MDT \ncodes should be assigned: \n1) MDT 2008 Devices manufactured in clean rooms and associated controlled \nenvironments, because the manufacturing of the implant is in a controlled environment,  \n2) MDT 2005 Devices manufactured using bi otechnology, because the main risks in \nmanufacturing are related to the production and cross-linking of the hyaluronic acid. \n3) MDT 2011 Devices which require packaging, including labelling because the implant \nis packed and labelled. \nNote that, despite the fact that the manufacturer itself does not physically manufacture the \ndevice, the MDT codes concerning the manufacturing steps are assigned to the device since they are relevant when auditing suppliers / subcontractors. \n4 Competence description: conditions (including limitations) \nConditions should be established by the notified body for individual codes in cases where the qualification of the staff authorised to a certain code is not sufficient to cover the entire spectrum of the devices within this code.  The designating authority could also apply conditions to the notified \nbody's designation where the notified body does not have sufficient competence to cover a given \ncode or could seek designation for conformity assessment of only certain devices within a code. \nConditions, including limitations, should be formulated in an unambiguous way (see example 1). \nFurthermore, since the technical codes basically mirror the competence system of the notified body, the conditions and limitations should concern device characteristics (see example 2). \nExample 1: \u201cMDN 1101 Non-active cardiovascular, vascular and neurovascular implants. \nCondition: heart valves\u201d. This condition is unsuitable since it is not clear whether the notified body is restricted to assessment of heart valves or whether those products are excluded from  \n7 \n the scope of designation. Therefore, the condition should be \u201cexcluding heart valves\u201d or \n\u201cincluding only heart valves\u201d. \nExample 2: \u201cMDN 1102 Non-active osteo- and orthopaedic implants. Condition: excluding \nclass III devices\u201d. The scope of designation is intimately linked to the qualification of the staff \nthat the notified body needs to have available. Conditions serve to exclude the devices for \nwhich the notified body does not have competent staff and/or suitable procedures; therefore, they need to be expressed in a way that they relate to knowledge and experience of staff and/or procedures. The condition \u201cexcluding class III devices\u201d does not allow this and therefore it is unsuitable. In this case, the designating authority has to determine, based on the qualification of the notified body\u2019s staff, which devices are included in the scope. This \nmight result, for example, in the following condition: \u201cincluding only orthopaedic plates and \nscrews; excluding implants that are applied in or on the spine\u201d. \nFurther examples of conditions are illustrated in the final column of the table below. Considerations of \nthe conditions should be based on the demonstrated competence of the applicant body\n. \n   \n8 \n  \n5 Specific clarifications linked to individual codes  \nThe devices included in the third and fourth columns are only a few examples of the devices covered in the relevant code. The t hird \ncolumn is not intended to provide an exhaustive list of devices included in each code. \n \nMDA \nCODE Active implantable devices Devices covered and Specific \nConsiderations1 Examples of \nconditions \nMDA 0101 Active implantable devices for stimulation / inhibition / monitoring Implanted defibrillator \nSpinal cord stimulator \nImplantable cardiac pacemakers \nImplantable bladder stimulators Excluding brain stimulation \nMDA 0102 \n Active implantable devices delivering drugs or other substances Implanted drug delivery pump \n  \nMDA 0103  Active implantable devices supporting or replacing organ functions Artificial heart \nCochlear implants \n \n  \nMDA 0104 \n Active implantable devices utilising radiation and other active implantable \ndevices Prostate radioactive seed implant \n \n  \n  \n                                            \n1 The assessment also should consider Section 5.1 of Annex IX applies as well as Validation of SSCP acc. Article 32 .   \n9 \n MDA \nCODE Active non-implantable devices for imaging, monitoring and / or \ndiagnosis Devices covered and Specific \nConsiderations Examples of conditions \nMDA 0201 \n Active non-implantable imaging devices utilising ionizing radiation X-ray computer tomography equipment  \nGamma cameras \nFluoroscopy equipment \nPET scanner Restricted to X-ray and gamma \ncameras \nMDA 0202  Active non-implantable imaging devices utilising non-ionizing radiation MRI computer tomograph \n  \nMDA 0203 \n Active non-implantable devices for monitoring of vital physiological \nparameters Blood pressure monitor \nMedical thermometer \nPulse oximeter \nApnoea monitors  \nIntensive care patient monitoring system \nSpirometers \nElectrocardiographs \nElectroencephalographs \n  \nMDA 0204 \n Other active non-implantable devices for monitoring and / or diagnosis Ocular tonometer \nAudiometers \nRetinal cameras  \n   \n10 \n MDA \nCODE Active non-implantable therapeutic devices and general active \nnon-implantable devices Devices covered and Specific \nConsiderations Examples of conditions \nMDA 0301 \n Active non-implantable devices utilising ionizing radiation \n Radioactive sources for cancer after \nloading therapy \nTherapeutic cyclotrons and linear \naccelerators   \nMDA 0302 \n Active non-implantable devices utilising non-ionizing radiation Surgical laser for refractive surgery of the \neye \nLaser for pain treatment \n \n Including only microwave and \nmagnetotherapy medical devices \nMDA 0303  Active non-implantable devices utilising hyperthermia / hypothermia Medical heating blanket \n \nWarming and cooling blankets \nBlood warmers \nParaffin bath  \nMDA 0304  Active non-implantable devices for shock-wave therapy (lithotripsy) Extracorporeal shock wave lithotripsy \ndevice \n \n  \nMDA 0305  Active non-implantable devices for stimulation or inhibition \n Automated external defibrillator \nDevice for the transcranial magnetic brain \nstimulation \nDevice for transcutaneous electrical nerve \nstimulation (TENS) \nMuscle stimulators \nElectrical acupuncture \nExternal bone growth stimulators \n  \n   \n11 \n MDA \n0306 \n Active non-implantable devices for extra- corporal circulation, administration or \nremoval of substances and haemapheresis Haemodialysis machine and equipment \nCardiopulmonary bypass pump \nInfusion pumps \nFeeding pumps \nJet injectors for vaccination \nBlood pumps for heart-lung machines \nAnaesthesia machines  \nMDA \n0307 \n Active non-implantable respiratory devices \n Medical ventilator \nHyperbaric chambers \nNebulisers  \nMDA \n0308 \n Active non-implantable devices for wound and skin care \n Water jet for wound debridement \n  \nMDA \n0309 \n Active non-implantable ophthalmologic devices \n Aspiration pump for opthalmological use \n(removal of crystalline residue)  \nMDA \n0310 \n Active non-implantable devices for ear, nose and throat  \n Hearing aids \n \nMDA \n0311 \n Active non-implantable dental devices \n Powered dental surgical unit and hand \npieces \nSurgical suction device for dental use \nUltrasonic scalers  \nChairs with equipment \n  \nMDA \n0312 \n Other active non-implantable surgical devices \n RF electrosurgical generator \nElectrosurgical instrument Cauterization \ndevices. \nPowered surgical drills and saws    \n12 \n MDA \n0313 \n Active non-implantable prostheses, devices for rehabilitation and devices for \npatient positioning and transport  Hospital beds \nPatient hoists \nElectric Wheelchairs \nActive limb prostheses \nExoskeletons  \nMDA \n0314 \n Active non-implantable devices for processing and preservation of human cells, \ntissues or organs including in vitro fertilisation (IVF) and assisted reproductive \ntechnologies (ART) IVF cryopreservation systems \nblood bank refrigerator  \nMDA \n0315 \n Software  \n Radiotherapy planning system. \n \nMDA \n0316 \n Medical gas supply systems and parts thereof \n Medical gas supply system in a hospital \nGas manifold and line pressure regulator \nfor medical regulators \nMedical gas supply pipeline systems   \nMDA \n0317 \n Active non-implantable devices for cleaning, disinfection and sterilisation Sterilizers like autoclaves etc \nWasher disinfector for medical devices.  \nMDA \n0318 \n Other active non-implantable devices \n  \n \n   \n13 \n MDN \nCODE Non-active implants and long term surgically invasive devices Devices covered and Specific \nConsiderations Examples of conditions \nMDN \n1101 \n Non-active cardiovascular, vascular and neurovascular implants Cardiac vascular stent \nPeripheral vascular stent \nArtificial heart valve \nCardiac Valve Prostheses, Vascular and \nneurovascular grafts, shunts, vascular \nstents, cardiovascular patches \nSutures for cardiovascular surgery \nFor biological heart valves MDS 1003 \nshould be applied. For drug eluting stents - \nMDS 1001 should be appliedIncluding only cardiac stents \nMDN \n1102 \n Non-active osteo- and orthopaedic implants \n Artificial spinal disc \nSpinal cage \nBone graft substitute for orthopaedic \nindications \nProsthetic joint replacements (i.e knee, hip \nimplants) \nBone cement \nHyaluronic acid implant for intra-articular \nuse \nOrthopaedic nails, screws,plates \nBone graft substitute for maxillofacial \nindications \nsutures, suture anchors, staples for \northopedic surgery \nspacers, ligament reconstruction products \n \nFor antibiotic bone cements- MDS 1001 \nshould be applied \nFor absorbable substances MDS 1008 \nshould be applied   \n14 \n MDN \n1103 \n Non-active dental implants and dental materials \n Dental implant  \nDental fillers \nRoot canal filler \nAbutments   \n   \n15 \n MDN \n1104 \n Non-active soft tissue and other implants \n Hyaluronic acid dermal fillers \nIntraocular lenses \nIntrauterine dispositive- IUD \nBreast implant \nHernia mesh \nUrethral stent implants \nSutures (not falling within the above codes) \nEyelid implants \n \nBariatric surgery devices: Intragastric \nBalloons, Gastric Bands, Anti-Reflux \nimplants. \nLung Volume Reduction devices: Coils, \nValves, Sealants. Biliary and Pancreatic \nstents \n \nFor contraceptive intrauterine devices \ncontaining copper or silver \u2013 MDS 1001 \nshould be applied \n Excluding breast implants \nMDN \nCODE Non-active non-implantable devices Devices covered  and specific \nconditions Examples of conditions \nMDN \n1201 \n Non-active non-implantable devices for anaesthesia, emergency and intensive \ncare Device for pleural drainage \nMasks, tubes for the administration of \ngases. \nEndotracheal tube \nTracheostomy tubes Endotracheal tube \nintroducers   \n16 \n MDN \n1202 \n Non-active non-implantable devices for administration, channelling and removal \nof substances, including devices for dialysis Intravenous line \nHypodermic needle \nSyringe tubing, bags for injection or \ntransfusion \nDialysis filter \nDialysis solution \nEpidural catheters, Urinary Catheter \nAmnioscopic needles  \n \nMDN \n1203 \n Non-active non-implantable guide catheters, balloon catheters, guidewires, \nintroducers, filters, and related tools Vascular filter catheter \nEmbolectomy catheter  \nCardiovascular guidewires and catheters \nNeurovascular catheters \ncentral venous catheter.  \nMDN \n1204 \n Non-active non-implantable devices for wound and skin care \n Wound dressing \nCotton wool \nGauze dressings \nBandages \nSutures for dermal wound closure (of less \nthan 30 days) \nSurgical gloves \nFor dressings incorporating an \nantimicrobial agent -  MDS 1001 should be \napplied \nMDN \n1205 \n Non-active non-implantable orthopaedic and rehabilitation devices Orthoses \nCrutches \nWheelchairs   \n17 \n MDN \n1206 \n Non-active non-implantable ophthalmologic devices \n Contact lenses \nEye drops \nInstrument for ophthalmologic surgery \nSolutions for contact lenses.  \nMDN \n1207 \n Non-active non-implantable diagnostic devices  Thermal expansion thermometer  \nMDN \n1208 \n Non-active non-implantable instruments \n Instruments for general use in surgery: \nForceps, clamps, scalpels, dental \ninstruments \n  \nMDN \n1209 \n Non-active non-implantable dental materials \n Etching solution for dental use \nBraces \nDental cements (when not considered long \nterm surgically invasive) \nDental impression materials  \nMDN \n1210 \n Non-active non-implantable devices used for contraception or prevention of the \ntransmission of sexually transmitted diseases Condom \nContraceptive diaphragms  \nMDN \n1211 \n Non-active non-implantable devices for disinfecting, cleaning and rinsing Solutions for disinfecting medical devices  \nContact lens care, catheter lock solutions \n  \nMDN \n1212 \n Non-active non-implantable devices for processing and preservation of human \ncells, tissue or organs including in vitro fertilisation (IVF) and assisted \nreproductive technologies (ART) Freezing solution for egg cells \nEmbryo transfer catheters \nArtificial insemination probes \nMedia, substances or mixture of \nsubstances intended for washing, \nseparating, sperm immobilizing, \ncryoprotecting solutions. \n   \n18 \n MDN \n1213 \n Non-active non-implantable devices composed of substances to be introduced \ninto the human body via a body orifice or the dermal route   \nMDN \n1214 \n General non-active non-implantable devices used in health care and other non-\nactive non-implantable devices Ultrasound gels   \n   \n19 \n MDS \nCODE Devices with specific characteristics Devices covered  and specific \nconditions Examples of conditions \nMDS \n1001 \n Devices incorporating medicinal substances \n Devices incorporating medicinal products \nincluding herbal substances and human \nblood derivatives are included in this code.   \nMDS \n1002 \n Devices manufactured utilising tissues or cells of human origin, or their \nderivatives Section 5.3.1 of Annex IX applies   \nMDS \n1003 \n Devices manufactured utilising tissues or cells of animal origin, or their \nderivatives Section 5.3.2 of Annex IX applies \nDevices manufactured utilising tissues or \ncells of animal origin, or their derivatives, \nwhich are non- viable or rendered non-\nviable, unless such devices are intended to \ncome into contact with intact skin only   \nMDS \n1004 \n Devices which are also machinery as defined in point (a) of the second \nparagraph of Article 2 of Directive 2006/42/EC of the European Parliament and \nof the Council1   \nMDS \n1005 \n Devices in sterile condition  Including aseptic processing, \nethylene oxide gas sterilisation \n(EOG), low temperature steam, \nformaldehyde sterilisation, moist \nheat sterilisation, radiation (gamma, \nx-ray, electron beam), sterilisation \nwith hydrogen peroxide, sterilisation \nwith liquid chemical sterilising \nagents, thermic sterilisation with dry \nheat \n                                            \n1 Directive 2006/42/EC of the European Parliament and of the Council of 17 May 2006 on machinery, and amending Directive 95/16/E C (recast) (OJ L 157 \n9.6.2006, p. 24).  \n20 \n MDS \n1006 \n Reusable surgical instruments \n Reusable surgical instruments according to \nart. 52 (7) c) MDR   \nMDS \n1007 \n Devices incorporating or consisting of nanomaterial  \n   \nMDS \nCODE Devices with specific characteristics Devices covered  and specific \nconditions Examples of conditions \nMDS \n1008 \n Devices utilising biologically active coatings and / or materials or being wholly or \nmainly absorbed or locally dispersed in the human body or are intended to \nundergo a chemical change in the body Section 5.4 of Annex IX applies for devices  \nintended to be introduced into the human \nbody via a body orifice or applied to the \nskin and devices  at are systemically \nabsorbed by the human body in order to \nachieve their intended purpose   \nMDS \n1009 \n Devices incorporating software / utilising software / controlled by software, \nincluding devices intended for controlling, monitoring or directly influencing the \nperformance of active or active implantable devices   \nMDS \n1010 \n Devices with a measuring function \n    \nMDS \n1011 \n Devices in systems or procedure packs \n   \nMDS \n1012 \n Products without an intended medical purpose listed in Annex XVI to Regulation \n(EU) 2017/745    \n21 \n MDS \n1013 \n Class III custom-made implantable devices  \n   \nMDS \n1014 \n Devices incorporating as an integral part an in vitro  diagnostic device \n   \n   \n22 \n MDT \nCODE Devices for which specific technologies or processes are used Examples of device manufacturing technologies \nMDT \n2001 Devices manufactured using metal processing \n 3 d printing, Casting, Welding \n3d printing (metal), turning (metal), anodization, passivation, polishing, surface \nmodification, laser tube cutting, honing \nMDT \n2002 Devices manufactured using plastic processing \n Injection molding, Extrusion, Bonding \npolymer compounding, 3d printing (plastics), thermoforming, blow moulding, turning \n(plastics) \n \nMDT \n2003 Devices manufactured using non-metal mineral processing (e.g. glass, \nceramics) Ceramic sintering, ceramic compounding,  \n \nMDT \n2004 Devices manufactured using non-metal non-mineral processing (e.g. textiles, \nrubber, leather, paper) Weaving, knitting  \nMDT \n2005 Devices manufactured using biotechnology \n Fermentation using cell cultures, enzymatic production processes, purification and \nmodification of biomolecules  \nMDT \n2006 Devices manufactured using chemical processing  \n Compounding, buffering  \nMDT \n2007 Devices which require knowledge regarding the production of pharmaceuticals production, handling and incorporation into a device of substances which, if used \nseparately, can be considered to be a medicinal product  \nMDT \n2008 Devices manufactured in clean rooms and associated controlled environments  \nMDT \n2009 Devices manufactured using processing of materials of human, animal, or \nmicrobial origin Handling, dissection, storage, processing, inactivation and sterilization of human \nand animal tissues   \n \nMDT \n2010 Devices manufactured using electronic components including communication \ndevices  \nMDT \n2011 Devices which require packaging, including labelling \n   \n23 \n MDT \n2012 Devices which require installation, refurbishment \n Installation of devices at the point of use by or under the manufacturer\u2019s \nresponsibility  \nMDT \n2013 Devices which have undergone reprocessing"}, {"title": "QA requirements for notified bodies V2 01102019.pdf.txt", "text": "Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 1 of 14 \n  \n \n \n \n  \nMDCG  2019-6 v2  \nQuestions and answers: \nRequirements relating to notified bodies \n \n \n Version 2 - October 2019 \n \n \n This document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission. \nThe document is not a European Commission document and it cannot be regarded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  \n \n  Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 2 of 14 \n  \nIntroduction This document presents questions and answers on requirements relating to notified \nbodies under Regulation (EU) 2017/745 on medical devices (MDR) and Regulation \n(EU) 2017/746 on in vitro  diagnostic medical devices (IVDR). The issues covered by \nthis document have been identified in the context of joint assessments, and the \ndocument may be updated from time to time as new issues are identified. \nI. ORGANISATIONAL AND GENERAL REQUIREMENTS \nI.1. Are CABs obliged to follow guidance endorsed by the Medical \nDevices Coordination Group (MDCG)? \nGuidance documents are by definition not compulsory. However, all guidance \ndocuments endorsed by the MDCG reflect the interpretation of the EU law jointly agreed by the authorities which are in charge of interpreting and applying the EU law. Hence notified bodies should be encour aged to apply these guidance documents \n(also taking into consideration Section 1.6.2 of Annex VII to the MDR/IVDR\n1). \nFurthermore, it is to be noticed that the European Court of Justice often refers to guidance documents when developing its rulings. Hence Notified Bodies have an interest, also in terms of liabilit y risk, to follow that guidance.  \nI.2. What is the meaning of \u201clegal  personality\u201d under Section 1.1.1 of \nAnnex VII\n2? \nThe CAB needs to have legal personality, meaning that it has to exist as a legal \nentity. To that end, it must be registered as legal entity, also called \"legal person\". The wording of the MDR/IVDR does not exclude that only a part of a legal entity undertakes conformity assessment activities in the field of medical devices. In this case, where the CAB is part of a wider legal entity, the documentation provided should be clear as to where the CAB sits within that legal entity. In case the entire legal entity is the CAB, the documentation to be provided refers to the legal entity as such. It is always this legal entity as such which is designated (and not its organisational part). \nI.3. What is the meaning of \u201corgan isation\u201d as described in 1.1.2 of \nAnnex VII? \nThe term of \"organisation\" as described in 1.1.2 refers to the whole organisation (e.g. \ncorporate group) to which the CAB belongs including the CAB's legal entity. The concept of \"organisation\" should be based not only on ownership rights (e.g. shares), but also functional/hierarchical links, such as voting/management/other control rights. One typical example of organisation is a holding company owning different companies (i.e. separate legal entities), one of them being or containing the CAB.  \n                                                           \n1 1.6.2. The notified body shall take into consideration guidance and best practice documents.  \n2 Unless specified otherwise, a reference to Annex VII means a reference to both Annex VII of the MDR and Annex VII of the \nIVDR.  Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 3 of 14 \n I.4. Does the term \u201corganisational structure\u201d as per 1.1.5 refer only to \nhierarchical relationships? \nIf a notified body is part of a larger organisation, both hierarchical (i.e. mother and \ndaughter companies of the CAB) and horizontal relationships (e.g. sister companies where there is a common mother company) between the notified body and other entities belonging to that organisation are covered by the term \"organisational structure\".  \nThe organisational structur e of the CAB will vary depending on the complexity of the \nlegal entity and the organisation to which it belongs. For instance, in the case of holding companies, the CAB could provide a matricial organisational chart with dual reporting relationships (i.e. functional and managerial). In this case, hierarchical and reporting lines should be clear and should match the information provided in job descriptions for the activities related to the MDR/ IVDR certification. \nI.5. Is a 3-year competitor clause for consultants covered in the MDR / \nIVDR requirements? \nThe MDR/IVDR does no longer define the timelines for clearance of consultants that \nwere defined in Section 1.3b of Annex I to the Implementing Regulation (EU) 920/2013, except in case that the person worked for the same company or the group (Section 1.2.4 of Annex VII). However, the requirements under the Implementing Regulation (EU) 920/2013 on the management of impartiality for consultants are included in sections 1.2.2, and 1.2.3 (c), (d) and (e) of Annex VII. Therefore, it is expected that CABs will have similar measures in place under both regimes.   It is essential that competitors, authorised representatives and suppliers are also included in the identification, analysis and resolution of potential conflicts of interests.  \nI.6. May CAB provide pre-certification services?  \nPre-certification services are not allowed before an application is lodged by the \nmanufacturer (e.g. review of clinical data or assessment of the quality management system aside from regulatory standards such as ISO 13485) and therefore these services have to take place under the scope of the application.  \nEvery activity carried out once an application has been submitted will be considered \npart of the conformity assessment activities and therefore if the manufacturer withdraws its application after this process has started, the notified body has to inform the other notified bodies through Eudamed according to Article 53(2) of the MDR / 49(2) of the IVDR. Whenever these activities consist in providing solutions to the manufacturer, they fall under the definition of consultancy and therefore the notified body impartiality policy and procedure(s) will need to cover that these pre-certification activities could be seen as consultancy. The CAB has to implement in their policy and/or procedures how it prevents that pre-certification activities carried out as part of the conformity assessment activities are falling into consultancy. \nServices provided by the CAB that could fall under the definition of conformity \nassessment activities are not allowed outside of an application as they would be regarded as consultancy (e.g. gap analysis, check of MDR/IVDR readiness, use of mock-up files produced instead of \u201creal\u201d TD assessments). Nevertheless, general Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 4 of 14 \n training activities that are not client specific and that relate to regulation of devices or \nto related standards are allowed. \nI.7. Can the CAB accept applications prior to being notified? \nNo, applications under the MDR / IVDR cannot be accepted before the designation of \nthe CAB became valid, i.e. the day after the notification is published in NANDO. \nI.8. How are the conditions on remune ration to be assessed within the \nmeaning of 1.2.5 of Annex VII? \nThe MDR/IVDR establishes that remuneration cannot depend on the results of the \nassessments. Both direct and indirect correlations between results of the assessments and remuneration are prohibited. Hence an individual examination is needed. Special care has to be applied with regard to bonuses. Bonuses on the basis of general objectives, even when not directly linked to the result of the individual conformity assessments, might still be problematic if they indirectly \ncorrelate to the average result of assessments. In the context of a joint-assessment, sampling of contracts or agreements covering remuneration (sheets) should take place. The sampling should cover different grades of influence, e.g. project handlers, final reviewers/decision makers, or head of the CAB / medical devices' certification.  \nI.9. Are declarations of absence of conflict of interests sufficient to \nensure compliance with legal re quirements for impartiality? \nNo, declarations are not sufficient in isolation to ensure compliance. CABs should \ndefine their own system to comply with the legal requirements for independence and \nimpartiality, but a system based on analysis of risk and control measures should be \ngenerally in place. This system will usually  include a comprehensive risk analysis of \nthe CAB's activities, its staff (including top- level management) and the activities of its \norganisation or related bodi es. Risks posed to impartialit y from each individual should \nbe assessed with regard to past employment, consultancy services and financial interests. For instance, shares in companies certified by the notified body or in competitors of these companies (investment  funds can be seen differently) as well as \nrelatives of the person under analysis. Also, the risks linked to subcontractors/suppliers (1.2.1) of the manufacturer need to be assessed.  \nSection 2.4 of Annex VII also requires, as part of this system, a \u201cmulti-level\u201d \nstatement. Firstly, a general one, listing any existing or prior association with clients or devices or processes under assessment. This general one needs to be renewed from time to time (e.g. annually). In addition, there is a need for a written statement and verification by the notified body within each conformity assessment project.  \nAny involvement in processes (e.g. design, risk management, manufacturing \nprocesses) being related with the devices and quality management systems for economic operators covered by the application/designation needs to be seen as consultancy. Other activities not specifically linked with the product will be also regarded as consultancy (e.g. internal audi ts to manufacturers or client specific \ntraining).  Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 5 of 14 \n I.10. Does a CAB that is part of a larger organisation need \nindividual liability insurance? \nThe CAB is responsible for taking out liability insurance and therefore there must be \nevidence that the legal entity is covered by a liability insurance that fulfils the legal \nrequirements. The contract with the insurance company can be signed by other legal entity of a larger organisation (i.e. mother company) provided that the contract gives the CAB the individual right to  be protected against liabilit y claims. The notified body \nmust be able to invoke that right directly towards the insurance company, and not only indirectly via the company which has signed the contract (this is important e.g. in case of insolvency of the signing company or  in case of unwillingness or inability of \nthe signing company to effectively invo ke the insurance contract towards the \ninsurance company). Furthermore, the signing legal entity must involve the notified body in any change of insurance conditions affecting the medical devices conformity assessment activities of the CAB so that the notified body has the possibility to react if it considers that the coverage is insufficient. \nAny change on the liability insurance which may affect the compliance of the notified \nbody with the requirements set out in Annex VII should be communicated by the body to the authority responsible for notified bodies in accordance with articles 44 (1) of the MDR / 40(1) of the IVDR.  \n \nII. QUALITY MANAGEMENT SYSTEM \n \nIII. RESOURCES REQUIREMENTS \nIII.1. Is a complete re-author ization of existing personnel \nnecessary to document satisfaction of the new qualification criteria under section 3 of Annex VII?  \nYes, all personnel that will be used to per form conformity assessment tasks under \nthe MDR/IVDR shall be authorized under the new criteria. For the satisfaction of the work experience criteria, the CAB can accept previous experience in a notified body but it cannot automatically grandfather authorisations (i.e. transfer authorisations) granted by other notified body or by the same notified body under the Directives. However, the experience in a notified body needs to be extensive and traceable and always specific to the tasks to be carried out and the specific technology or product \n(specific codes) in order to satisfy the MDR/IVDR qualification criteria. In addition, comprehensive and objective evidence of such previous experience in a notified body in the relevant scope shall be part of the personnel files.    \nIII.2. What is the meanin g of \u201cpermanent ava ilability of sufficient \npersonnel\u201d within Section 3.1.1 of Annex VII?  \nIn respect to the availability of personnel, MDR / IVDR Annex VII Section 3.1.1 do not \nestablish the number of auditors / reviewers per code to ensure permanent availability of sufficient personnel. As a ve ry minimum, it is considered that notified \nbody should have one person available and authorised per applied-for scope code Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 6 of 14 \n and role as per Section 3.2 of Annex VII at the time of the joint assessment. \nNevertheless, it is recommended that the notified body has two product reviewers/auditors authorised per code to ensure a sufficient capacity to allow fulfilment of other related requirements such as rotation of personnel. When this is not the case, an observation may be raised at the joint assessment in order to flag that for certain codes the available resources are limited.   \nThe notified body is expected to have 2 auditors / reviewers available and authorised \nper applied-for scope in order to fulfil the legal requirements under Section 3.1.1 of Annex VII at the moment of its re-assessment joint assessment.   \nIII.3. What is the meaning of \u201cpossess or have access to all \nequipment and facilities\u201d needed to perform its tasks within the meaning of Section 3.1.1 of  Annex VII of the MDR? \nThis question refers to the requirements in relation to possessing or having access to \nsufficient equipment and facilities to properly perform the conformity assessment activities within the CAB's applied-for scope. It is expected that the CAB would have internal testing facilities or access to testing subcontractor(s) (e.g. by a framework agreement) for device tests in support of the codes for which it seeks designation under Annex X and Annex XI(B).  \nIn order to be designated under Annex X and XI(B), the CAB's personnel needs to \nhave the technical knowledge to identify and select all the tests needed; the CAB must have implemented detailed procedures ensuring the identification of the  relevant tests; and have access to at least some of the tests to be performed within the scope of designation. In particular, for each MDA or MDN code for which the CAB applies under Annex X or XIB it should identify at least the basic tests to be performed and the corresponding testing fac ilities (internal or subcontracted). The \nCAB should be able to demonstrate how t he facilities available are linked to the \ncodes the CAB applies for.  \nNevertheless, the CAB is not expected to hav e testing equipment and facilities (either \nin house or a framework agreement) covering all possible tests within a code under \nAnnex X or XI(B) or as part of surveillanc e or unannounced audits as some of the \ntests are very specific or rarely used. For these purposes, the CAB should have procedures in place in order to find additional subcontractors whenever needed or to define under which circumstances the CAB will perform witness testing (i.e. when the \ntest equipment needed is very specialised)\n \nIII.4. What is the meaning of \"two  years' professional experience\" \nin cases where the experience h as been gained within a CAB \nunder section 3.2.5 of Annex VII? \nAccording to MDR/IVDR Annex VII 3.2.5 product reviewers have to demonstrate two \nyears\u2019 professional experience in the design, manufacture, testing or use of the device or technology to be assessed or related to the scientific aspects to be assessed. Experience related to the scientific aspects to be assessed could include, Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 7 of 14 \n but not be limited to, extensive experience in conformity assessment activities in a \nspecific type of device or technology gained within a CAB3 . \nIn such case, when professional experience \u2013 based on a relevant background \neducation \u2013 is to be proven by activities only within a CAB, this experience should have been gained during at least two years. As a guideline if one individual has carried out at least five full technical documentation assessments of devices in the relevant code (or aspects to be assessed) or under the equivalent code under the Directives, during at least 2 years, this can be accepted as a valid work experience within the meaning of 3.2.5 of Annex VII.  Nevertheless, based on the assessment of the educational background and specific work experience of the individual, the CAB has always to analyse if additional assessments must be performed (i.e. under supervision). \nIn addition, in situations where the objective evidence for the experience gained \nduring technical file reviews is insufficient (e.g. if the staff was authorised for the code \nin a different CAB without detailed supporting evidence), as a guideline, the technical documentation assessments on the code (or aspects to be assessed) to which the individual wishes to be authorised have to be carried out under close supervision of an experienced product reviewer (e.g. mirror review\n4).  At least five of these \nassessments should be related to a full assessment. In addition to technical documentation assessments or product tests,  product-related audit activities can be \nconsidered as work experience as long as  they are not used solely and they are \nadequately documented and assessed by the authorising personnel of [or within] the CAB.  \nIn all of the cases above, the CAB has to analyse individual training needs (e.g. on \nrelevant standards) especially when the work experience was gained a few years ago in the past or when the individual has experience related to a very similar technology. Before authorisation, the authorising personnel needs to ensure that all the qualification criteria under 3.2.5 of Annex VII are fulfilled and their satisfaction fully documented (including an adequate justification in the exceptional cases where the criteria cannot be fully demonstrated as established in 3.3.1 of Annex VII) and that the knowledge is state-of-the-art. \nFor codes (MDR/IVDR) comprising a broad range of devices, the CAB has to ensure \nthat the individual has carried out technical documentation assessments in different devices covered by the code or the authorisation to the code is to be granted with appropriate limitations. \nIII.5. Does the CAB need to defi ne qualification criteria for \nmonitoring and maintenance of competences in accordance with Section 3.5 of Annex VII? \n                                                           \n3 As defined in section 6.2.2. of NBOG BPG 2017-2 \n4 Mirror review is to be understood as a review carried out simultaneously by two product reviewers of the notified body, one \nbeing on training and the other one being an experienced product reviewer on that code. Once the review is finalised from the two reviewers, the most experienced will assess and document the quality of the review carried out by the person in training.\n Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 8 of 14 \n Yes. The CAB\u2019s personnel competence needs to be maintained and therefore \nreviewed at regular intervals. For this purpose, the authorising personnel5 (as per \n3.2.3 of Annex VII) needs to define qualification criteria for monitoring and maintenance of competence of its entire staff (internal and external, as well as \nsubcontractors), involved in conformity assessment activities. Such \"re-qualification\" \nor \"maintenance\" criteria will be used as a basis for re-authorisation of personnel to \ncodes and roles.  \nIn respect of monitoring of competence, such criteria should be defined for personnel \ninvolved in conformity assessment activities, at least for personnel with relevant clinical expertise, product reviewers, site auditors and final reviewer / decision-maker, \nand authorising personnel. \nIII.6. What is the meaning of the term \u201cemployed\u201d in MDR Article \n36(1) / IVDR Article 32(1)? \nThe personnel referred to in Article 36(1) MDR / Article 32(1) IVDR carries out the \nkey functions within the notified body, and therefore the Regulations expressly \nrequire that this personnel is employed by the notified body. This requirement is estimated to be complied with when the contractual relationship between the notified \nbody and the individual meets at the minimum the following criteria: \n\u0081 direct employment contract between the notified body and the employee \nsetting out the rights and obligations of the latter; \n\u0081 control and supervision over the activities of the employee by the notified body \n\u0081 direct reporting obligations of the employee towards the notified body; and  \n\u0081 a direct paid remuneration by the notified body to the employee for the work \ncarried out, accompanied by the payment of any relevant taxes and social security contributions. \nAny reference to \u201cinternal activities\u201d sha ll be intended as activities being carried out \nby personnel employed by the Notified Body. \nN.B. Whenever needed and appropriate, any action from the Notified Bodies aimed \nat ensuring compliance with those requirements should be taken throughout the designation period as soon as possible and completed at the latest by the time of \ntheir first re-assessment. \nIII.7. What is the meaning of \u201cpe rmanent availability of personnel \nwith relevant clinical expertise\u201d in accordance with sections 3.2.4 and 3.1.1 of Annex VII? \nWith regard to \u201cpersonnel with relevant clinical expertise\u201d, in order to fulfil the tasks \ncovered in Section 3.2.4 of Annex VII it is expected that the CAB has at least one \n\"internal clinician\" who, where possible, has to be employed by the CAB. This does \n                                                           \n5 Short term used in NBOG BPG 2017-2 to refer to \"personnel responsible for establishing qualification criteria and for \nauthorising other personnel to perform specific conformity assessment activities\" according to Section 3.2.3 of Annex VII.  Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 9 of 14 \n not preclude the possibility to subcontract su ch a role, provided that the notified body \nproduces a justification as to why it is not possible to employ the person(s).  In any case, when the CAB does not have the possi bility of employing that person(s), it \nshould at least ensure that she/he is fully integrated throughout the conformity \nassessment and the decision-making process, which means that the person is \ninvolved in the CABs assessment and decision-making process in the same way as an employed staff. However, it should be noted that when the internal clinician is a subcontractor even if this person will suppo rt the final review and decision making \nprocess as indicated in 3.2.4 (e.g. in case an external clinical expert has been \ninvolved making a recommendation to the final reviewer or decision maker) they cannot be authorised as final reviewer or decision maker as these personnel should be employed by the notified body itself as required in Art. 36 of the MDR and Art. 32 \nof the IVDR.  \nAccordingly, all \u201cinternal clinicians\u201d are integrated, whereas some internal clinicians \nare not employed. Given that the term \"internal clinician\" is widely spread and it has \nbeen used to defined personnel carrying out tasks established in Section 3.2.4 of \nAnnex VII it is assumed that when the term \"internal clinician\" is used, it could refer \neither to an employee of the CAB or not. \n \nIV. PROCESS REQUIREMENTS \nIV.1. Do devices certified under the Directives need to be subject \nto a full conformity assessment under the new Regulations if the manufacturer applies for certifi cation under the MDR / IVDR?  \nThe conformity assessment activities described under Article 52 / Article 48 apply to \nany certificate issued under the new regulations. As no exceptions were established under the regulations for the migration or transfer of MDD/AIMDD/IVDD certificates to the MDR / IVDR the general provisions should apply. Therefore, all devices to be certified under the MDR / IVDR should be subject to an initial certification according to the applicable annex. The notified body should ensure that all requirements under the MDR / IVDR are fulfilled. It may not restrict its procedures to gap audits or gap file reviews.  \nIt should be noted that MDD/AIMDD/IVDD certificates will remain valid until their \nexpiration date and at the latest on 27 May 2024 as long as conditions laid down in Article 120(3) of the MDR and 110 (3) of the IVDR  are complied with.  \nIV.2. What should be the criter ia for auditing suppliers and \nsubcontractors? \nThe MDR/IVDR established  that the audit of the manufacturer pr emises must include \nan audit on the premises of subcontractors and/or suppliers if appropriate. Therefore, the notified body should have criteria for auditing these actors on the basis of their criticality. At the very least, the criteria defined in Section 4.5.2(b) of Annex VII should Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 10 of 14 \n be applied (i.e. the control over the supplier/subcontractor and its influence on the \nconformity of the device is essential whereas the sole existence of a certificate against ISO 13485 is not sufficient).  \nIV.3. What is the meaning of \"examinations and tests\" to be \nincluded in a certificate in accordance with Section 10 of Annex XII of the MDR / IVDR?\n6 \nCertificates do not need to include reference to relevant common specifications or \nharmonised standards as long as such information on all examinations and tests performed is traceable and available from e.g. report(s) which are mentioned in the certificate.  \nIV.4. What are the applicable requirements for voluntary \ncertificate transfer under MDR Article 58 / IVDR Article 53?  \nWhile MDR Article 58(1) / IVDR Article 53(1) sets out the requirements for a transfer \nagreement, it does not specify the conformity assessment activities to be performed by the incoming NB.  \nhe incoming NB may decide not to carry out full conformity assessment activities \naccording to Article 52 MDR / Article 48 IVDR, as long as it does have sufficient information in respect to the conformity ac tivities performed by the outgoing NB. \nFor quality management system certificates, the incoming NB needs to perform \nappropriate on-site audit(s) and assessments to ensure that the manufacturer in question applies the approved QMS and the post-market surveillance plan prior to \nthe issue of any certificate. In respect to the assessment of technical documentations \non a sampling basis, the oncoming NB shall review the previous assessment results together with a sample of a technical documentation and draw up or amend a sampling plan.  \nFor product certificates (Annex IX Chapter II/Annex X), new certificates without a \ncomprehensive (initial) review may be issued as long as the documentation received does not identify ongoing existing or other concerns. \nThe incoming NB assumes full responsibility for the new certificates issued following \nthe transfer. \nIV.5. What are the applicable requirements for OBL \nmanufacturers? \nThe MDR / IVDR does not distinguish between OBL\n7 and other manufacturers. There \nare just \"manufacturers\" and therefore OBL manufacturers must comply with the legal requirements, as any other manufacturer\n8.  \n                                                           \n6 See also Q&A IV.8  \n7 OBL\u201d (own brand label manufacturer) is a term used in the fiel d that describes manufacturer that are supplied with the finish ed medical \ndevice by their supplier, who often is called \u201cOEM\u201d (original e quipment manufacturer). Neither of both are defined in the MDR (or ever \nwere defined in the Directives).  Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 11 of 14 \n IV.6. What is the role of the intern al or integrated clinician in the \nnotified body\u00b4s assessment and decision-making process?   \nThe internal or otherwise integrated clinici an is responsible to identify when specialist \ninput is required for the assessment of the clinical evaluation as defined in Section 3.2.4 of Annex VII of the MDR and IVDR. This decision will be made by the internal \nor integrated clinician on a case-by-case basis, based on the products covered by the applications lodged by the manufacturer and the clinical expertise available. The internal clinician or integrat ed clinician will be responsible fo r this process in all cases \nwhere the conformity of the device to the requirements of annex I is achieved also by clinical data. In cases where demonstration of conformity to requirements of Annex I based on clinical data is not deemed appropriate (in accordance with Article 61(10)) the internal or integrated clin ician will also examine the ju stification provided in order \nto assess its adequacy.  The internal or otherwise integrated clinicians will decide if the review of clinical evaluation is to be carried out by themselves, to be delegated to other qualified staff or if it necessitates the input of external clinical experts. This process is also defined in Section 4.3 of Annex IX of the MDR and Section 5.4 of NBOG\u2019s best practice guide 2017-2 as endorsed by the MDCG. \nSection 3.2.4 of Annex VII defines that there must be a clinician who is either internal \n(= employee) or otherwise integrated into the CAB's assessment and decision-making process. To be regarded as integrated, a clinician (who is not an employee) must have access to all the information, required to perform its activities, circulating in the CAB and must be involved in the internal processes in the same way as an employee, the only difference to an employee being that there is no employment contract, but a service contract and therefore this person should not be considered final reviewer or decision-maker as per 3.2.7 of Annex VII.  \nIn addition to this, the internal or otherwise integrated clinician will clinically judge the \nopinion provided by  any external expert (including verificati on of comparability and \nconsistency of the assessments of clinical evaluations conducted by clinical experts) \nand will be responsible to make a recommendation to the decision maker on the adequacy of the clinical evaluation. \nIV.7. What is the meaning of  allocation of resources under \nSection 4.4 of Annex VII? \nAllocation of resources is to be understood as the allocation of appropriately \nauthorised and qualified perso nnel and means (including eq uipment and facilities) for \na given project (application), as stated in second paragraph of Section 4.4 of Annex VII \"appropriate resources including personnel\". Section 4.4 of Annex VII describes the assignment of tasks within a project to \u201cindividuals\u201d, starting with the individual responsible for ensuring that the assessment of that application is conducted in accordance with the relevant procedures and for ensuring that the appropriate resources including personnel are utilised for each of the tasks of the assessment \n                                                                                                                                                                                     \n8 Including but not limited to having: full and permanent access  to the technical documentation; (ability for) post-market surv eillance \nincluding post market clinical follow-up; sufficient technical competence; and control of the quality system (control of the d esign, \nmanufacture and/or final verificat ion and testing of the device s). Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 12 of 14 \n (often referred to as project leader) and following with the identification of individual \npersonnel that will carry out each task of a given project.  \nThe assessment of the resources needed for each application is a key function that \nhas to be fulfilled as part of the internal activities of the CAB as indicated in Section 4.1 of Annex VII and any changes on such allocation should be documented. \nIV.8. How can a CAB ensure that information on \"examinations \nand tests\" in accordance with Section 10 of Annex XII of the MDR / IVDR is available to all interested parties (as referred to in Section IV.3 of this document)? \nAccording to Annex XII information on tests and examinations performed as part of \nthe conformity assessment activities need to be included on the  certificates issued by notified bodies. This information might be of interest for competent authorities and third parties.   \nIf the certificates do not include explicitly references to relevant common \nspecifications, harmonised standards or other standards or referential but include a reference to the relevant report(s), the CAB should ensure that competent authorities and interested parties can have access this information on request.  For example, the certificate may  include a sentence like \"information on examinations and tests as per Annex XII, section 10 is available on reques t\" and possibly provide a contact (e.g. e-\nmail). \nIV.9. Which changes need prior approval by the CAB? \nThe Regulations - in Annex VII and in the specific conformity assessment annexes \n(i.e. Annex IX, X and XI) -establish the need for the manufacturer to notify certain planned changes.  Section 4.9 of Annex VII contains general requirements for notified bodies in respect to changes.  \nFor manufacturers, the specific conformity assessment annexes (i.e. Annex IX, X and \nXI) detail such requirements e.g. asking for plans for \u201cany\u201d changes (e.g. MDR Annex IX, 5.2 f), 5.3.1 d) or Annex X 5.2), for  changes could affect the safety and performance of the device or the conditions prescribed for use of the device (e.g. MDR Annex IX 4.10) or for \u201csubstantial\u201d changes only (e.g. MDR / IVDR Annex IX 2.4). With regard to the latter, the CAB needs to make clear in its communication to the manufacturer (e.g. in the terms and conditions) what it considers as \u201csubstantial changes\u201d to the quality management system or the device-range covered. \nIn order to fully comply with all the relevant requirements the CAB must have \ndocumented procedures defining how different changes need to be notified and assessed prior to their implementation and how the assessment will be documented. In particular, the CAB will define in its procedures when the approval of such changes will take the form of a supplement of the previously issued certificate. \nIV.10. What is the frequency of surveillance audits according to \nthe Regulations? \nAccording to the Regulations (Section 3.3 of Annex IX and Section 7 of Annex XI), \nsurveillance audits have to be carried out at least every 12 months. This means that Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 13 of 14 \n the audit planning defined in Section 4.5.2 and 4.10 of Annex VII will need to take \ninto consideration that surveillance audits have to be scheduled on at least an annual basis with a maximum of 12 months after the previous surveillance audit was carried out The first surveillance audit should be scheduled  taking as a reference the certification decision date. \nIV.11. What is the meaning of the last sentence in Section 4.5.1 of \nAnnex VII with regard to the need  for notified bodies  to take into \nconsideration standards and guidance even if the manufacturer does not claim compliance? \nCABs need to consider all the availabl e guidance, common specifications and \nharmonised standards to carry out its assessments.  This means, that CABs will have \nto consider this documentation when developing its own procedures and processes (including checklists and report templates) and when assessing the manufacturers \nQMS (e.g. by taking into consideration EN ISO 13485) and technical documentation.  \nFor instance, in order to assess if the solutions adopted by the manufacturer are \nstate of the art and in line with expectations, the CAB need to use the available guidance documents and standards. It should be noted that non-conformities will not \nbe raised against standards or guidance but need to be phrased against legal \nrequirements. For instance, Annex I Chapter I Section 1 of the Regulation which states that \u201cdevices shall be safe and effective [\u2026] taking into account the generally acknowledged state of the art\u201d can be used when the technical documentation does \nnot follow standards or guidance. \nIV.12. What are the applicable requirements for re-certification?   \nConformity assessment activities to be carried out in case of renewal of \ncertificates/re-certification are laid down in Article 56(2) of the MDR / Article 51(2) of \nthe IVDR, where the Regulations establish that the notified body can extend the validity of the certificate for further periods based on a re-assessment in accordance with the applicable conformity assessment procedures (i.e. as described in annexes \nIX-XI). In addition, Section 4.11 of Annex VII states that the notified body must use \nthe same methods and principles for the decision on re-certification as for the initial \ncertification decision.   \nWhile for EU Technical documentation assessment certificates and EU type \nexamination, Section 4.11 of Annex VII establishes a targeted conformity assessment (i.e. focusing in certain elements of the technical documentation review), this is not \nthe case for the quality management system certificates.  \nThe notified body will ensure that all relevant Regulation requirements for conducting \naudits (i.e. those covered in Section 4.5.2 of Annex VII, and sections 2.2 and 2.3 of Annex IX) are assessed in its entirety at le ast once after issuin g the certificate and \nbefore its expiry date.  In addition, prior to the renewal of a QMS certificate, it is \nrequired that the notified body will assess the results of the surveillance audits carried Medical Devices       \nMedical Device Coordination Group Document   MDCG  2019-6 v2 \n  (01/10/2019)    \nPage 14 of 14 \n out during the period of validity of the certificate in accordance with section 4.10 of \nAnnex VII, also including any unannounced audits and all audits carried out at \nsubcontractors and suppliers.   \nThis review must include the manufacturer\u00b4s system for vigilance, post-market \nsurveillance, PMCF and risk management as well as all open non-conformities   Furthermore, re sults of the notified body\u00b4s ev aluation of additio nal scientific and \nclinical data and clinical evaluations and post-market information as well as the \noutcome of latest technical documentation assessments on sampling basis and product tests have to be considered. \n \nV. OTHER REQUIREMENTS \nV.1. Are activities described under arti cles 16 and 17 of the Medical \ndevices Regulation (MDR) and Article 16 of the in vitro medical devices Regulation (IVDR) will be covered during joint assessments? \nConformity assessment bodies (CABs) can i ssue certificates following the process \ndescribed in articles 16 and 17 of the MDR and Article 16 of the IVDR but these are not considered conformity assessment activities covered by Chapter IV and Annex VII of the Regulations and therefore w ill not be part of joint assessments. \nV.2. What is the meaning of \u201cpublicly available\u201d as regards the list of \nstandard fees of a notified body under Article 50 MDR / Article 46 IVDR?  \nWhenever the Regulations require certain information to be made \u201cpublicly available\u201d, \nthat implies that a member of the public can access this information at any point in time, without the need for additional steps. In view of the public functions carried out by notified bodies, this requirement supports transparency of their activities. \nNot only Article 111 MDR / Article 104 IVDR re fer to different type of fees (i.e. fees \nlevied by Member States), but also it uses different wording. It cannot therefore be used to support the interpretation of Article 50 MDR / Article 46 IVDR. Moreover, public availability of fees levied by Member States will usually result from the official publication of national laws setting out such fees (therefore, there will be no need to request information on such fees)."}, {"title": "mdcg_2020_4_nb_audits_covid-19_en.pdf.txt", "text": "Medical Device       \nMedical Device  Coordination Group Document   MDCG  20 20-4   \nPage 1 of 6 \n  \n \n \n \n \nMDCG  20 20-4 \nGuidance on temporary extraordinary  \n measures related to medical device Notified \n Body audits during COVID -19 quarantine orders \n and travel restrictions  \n             \n \n April  2020 \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commission document and it cannot be regarded \nas reflecting the official position of the European  Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  Medical Device       \nMedical Device  Coordination Group Document   MDCG  20 20-4   \nPage 2 of 6 \n  \n \n1.  Introduction  \nIn the context of the current COVID -19 global outbreak as well as the rapid spread of \nthe virus across various regions of the globe, the resulting travel and quarantine \nrestrictions have significantly affected the ability of notified bodies to conduct \nmandatory on -site audits under the medical devices legislation. Theref ore, in the \ninterest of public health, this document has been developed to outline temporary \nextraordinary measures for notified bodies to follow in this interim period  in order to \nallow continued  availability of safe medical devices to the market and as sist in the \nprevention of  the risk of medical device shortages. In this context,  it is considered \nthat alternative solutions to carrying out on -site audits by notified bodies under the \nmedical devices Directives1 should be allowed under specific circumst ances, \nincluding the possibility to perform remote audits under certain conditions.  \nThis guidance takes immediate effect and is valid for the whole period of duration of \nthe pandemic COVID -19 as declared by the World Health Organisation.  \n2.  Scope  \nThis guida nce is intended to cover the following audits notified bodies are requested \nto carry out as part of medical devices conformity assessments:  \n\uf0b7 surveillance audits under the medical devices Directives,  \n\uf0b7 audits conducted for re -certification purposes under the medical devices \nDirectives,  \n\uf0b7 in cases where a manufacturer submits a change notification to a notified body \nthat would typically require on -site audit or verification,  \n\uf0b7 in cases where a manufacturer terminates (voluntarily or involuntarily) its \ncontract with a notified body and enters into a contract with another notified \nbody in respect of the conformity assessment of the same device(s).  \nAlthough this guidance applies to the medical device Directives only, for Regulations \n(EU) 2017/745 (MDR) and 2017/746  (IVDR) in the event that the availability of \ndevices is affected by COVID -19 restrictions the principles in this guidance may \napply.  \n \n \n                                                           \n1Directive 90/385/EEC, the AIMDD; Directive 93/42/EEC, the MDD; Directive 98/79/EC, the IVDD.  Medical Device       \nMedical Device  Coordination Group Document   MDCG  20 20-4   \nPage 3 of 6 \n  \nThe temporary extraordinary measures proposed in this guidance should not apply to \nunannounced audits, or, to special a udits which require on -site assessment (such as \nthe verification of implementation of specific corrective actions which can only be \nassesed on -site). This does not prevent the use of the alternative measures for these  \ntypes of audits in cases where doubt has been raised on the conformity / safety  of a \ndevice and it is not in the interest of public safety to wait  until the end of the \nrestrictions put in place due to the COVID -19 pandemic.  \nIn general, initial certification audits or audits to extend the s cope of certification \nunder the Directives should not be performed using these temporary extraordinary \nmeasures. However, notified bodies may apply these extraordinary measures on a \ncase -by-case basis for such audits in cases where devices are considered r elevant to \nensure medical care, especially if clinically necessary during the period of COVID -19 \nrestrictions.  \n3.  Proposed temporary alternative extraordinary measures and \narrangements to on -site audits  \nNotified bodies may introduce temporary alternative extraordinary measures in place \nof on -site conformity assessment audits that have been impacted by COVID -19 \nrestrictions and that are within the scope of section 2 above.  \nNotified bodies should have documented procedures detailing the alternative \ntemporary measures to be utilised and should define the criteria for implementing \nsuch measures (e.g. procedure for \u201cforce majeure\u201d). The relevant procedures should \nalso take into account the technologies to be used during such audits and also \naddress the impact of the alternative measures on the audit duration.  \nThese temporary alternative extraordinary measures may include the following \nprinciples and arrangements:  \n\uf0b7 Postponement of  on-site surveillance audits under the Directives in line with \ndocumented procedures of the notified body for force majeure.  \n\uf0b7 On-site audits may be replaced by remote audits using the most advanced \navailable Information and Communication Technologies as ap propriate in \naccordance with legislation on information security and data protection.  \n\uf0b7 Assessment of all relevant and required documents/records off -site by the \nnotified body.  \n\uf0b7 To take into account existing recent results from  MDSAP audits (or other \napprop riate audits) in lieu of Directive audits, where available  \n\uf0b7 To consider published international guidance such as those issued by the \nInternational Accreditation Forum (IAF) e.g. on how to use information and  \n \n \n Medical Device       \nMedical Device  Coordination Group Document   MDCG  20 20-4   \nPage 4 of 6 \n  \ncommunication technologies2 and for alternat ive auditing methods in \nextraordinary circumstances3. \n4.  Eligibility criteria and procedural aspects  \nTo be eligible for these temporary alternative extraordinary measures the audits must \nbe covered within the scope of section 2 above.  \nThe possibility to make use of temporary alternative extraordinary measures to on -\nsite audits should be carefully assessed and documented by notified bodies on a \ncase -by-case basis and performed using a risk -based approach. In particular, when \ndetermining the possibility to use t hese alternative measures, the risk assessment \nshould take into account the experience gained with a manufacturer. For example,  \nmanufacturers who have a history of a high number and/or critical non -compliances \nrelated to production/operational control  ma y have an impact on the appropriateness \nto conduct such temporary measures. However, in these cases an alternative \nmeasure could be performed as a temporary measure to assess the progress of the \nmanufacturer and should be be supplemented by an on -site audi t once travel \nrestrictions are lifted.  \nIn order to assess which alternative extraordinary measure (as outlined in section 3 \nabove) is most appropriate, the notified body should review their files relating to the \nstatus and operations of the manufacturer re lated to the audit in question, for \nexample the activities conducted at the site to be audited,  its quality management \nsystem, and its level of compliance from previous audits. Following this review, a risk \nanalysis should be made as to whether or not the  audit could be performed with \nalternative measures. Where a postponement cannot be justified, the notified body \nshould assess which alternative extraordinary measure should be performed (e.g. \nremote audit; off -site document review; conference calls with r elevant personnel of \nthe manufacturer).  \nFor remote audits, both the notified body and the manufacturer must have the \nrequired information and communication technologies or tools available and \nestablished (e.g. web conferences with document sharing, use of  web cams for \naudits of production lines). Confidentiality of intellectual property aspects shall be \nsafeguarded.   Notified bodies should clearly document and communicate any such \nrequirements for their audits with their auditees, along with the required \ndocumentation to be shared before and within such audits, including the necessary \ndata protection and cybersecurity measures . The technological capability of the  \nmanufacturer to ensure that such an audit can be accomplished should be verified by \nthe notified body in advance of the audit.  \n \n                                                           \n2 Requirements on how to use information and communication technologies to support and maintain the \nintegrity of the audit/assessment process may be found in International Accreditation Forum document IAF MD \n4 (Mandatory Document for the Use of Information and Communication Technology (ICT) for \nAuditing/Assessment Purposes).  \n3 ID3:2011  (IAF Informative Document For Management of Extraordinary Events or Circumstances Affecting \nABs, CABs and Certified Organizations)  Medical Device       \nMedical Device  Coordination Group Document   MDCG  20 20-4   \nPage 5 of 6 \n  \nDesignating Authorities may request to observe/witness such remote audits  via \ninformation and  communication technologies or to ols available and established.  \nWhen establishing the audit plan, the notified body should adjust the duration for \nreview of the areas on the audit plan, along with the overall duration of the audit, in \ncoordination with the manufacturer in order to make ef fective use of these alternative \nextraordinary measures. The audit plan should also clearly indicate which alternative \nextraordinary measures will be used and what will be conducted remotely. When \nissuing their audit reports the notified body should also c learly indicate that the audit \nwas conducted remotely and the method(s) used for such audits should also be \nspecified.  \nRemote surveillance audits should cover all of the surveillance tasks that can be \nverified remotely, including an off -site review of all  documents that would normally be \nassessed on -site.  \nFollowing such an alternative extraordinary measure the notified body should review \nand adjust the audit programme for each manufacturer to ensure that all required \nelements are assessed during the certi fication cycle.   \n5.  Decisions taken on certification  \nRemote audits undertaken for re -certification purposes should cover all of the \nmandatory re -certification tasks that can be verified remotely. Subsequent to a \nsucccessful remote audit a notified body may r e-issue the certification with the \ncondition that such audits should be followed up by an on -site verification audit at the \nnext available opportunity to verify the elements that could not be assessed remotely \n(the timeline for the on -site verification aud it should be justified by the notified body). \nAt the request of the notified body, the manufacturer may provide the notified body \nwith records (e.g. product release documentation) on an ongoing or regular basis,. If \nthe re -certification remote audit is uns uccessful, the certification should be \nsuspended or should expire as appropriate.   \nRemote audits conducted by the incoming notified body in the context of cases \nwhere a manufacturer terminates its contract with a notified body and enters into a \ncontract with another notified body in respect of the conformity assessment of the \nsame device (s), should also cover all of the tasks that can be verified remotely to \nallow the incoming notified body to ensure a proper assessment of the conformity of \nthe device. If the remote audit is unsuccessful (as per the notified body\u2019s procedures \nfor unsucces sful audits), the incoming notified body should not issue the certification.  \nIn the exceptional circumstance of the issuance of  an initial or extended scope \ncertificate under these alternative extraordinary measures (as per section 2 Scope \nabove), the no tified body should consider the clinical risk / benefit of their decision \nand should clearly document their rationale for these decisions. At the request of the \ndesignating authority the notified body should inform the national authority of any \nsuch decisi ons and provide any supporting documentation.  Medical Device       \nMedical Device  Coordination Group Document   MDCG  20 20-4   \nPage 6 of 6 \n  \n \nNote: A  task force established in March 2020 under the MDCG NBO working group \nis tasked with the development of guidance to define the operational implementation \ndetails of this guidance document."}, {"title": "Guidance on significant changes &amp; annexes.pdf.txt", "text": "1 \n Medical Device       \nMedical Device Coordination Group Document    MDCG 2020 - 3    \n \n \n \n       \n   MDCG 2020 -3 \nGuidance on significant changes regarding  \n   the transitional provision under Article 120  \n       of the MDR with regard to devices covered  \n       by certificates according to MDD or AIMDD            \n \n             March 2020  \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) established by \nArticle 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member States \nand it is chaired by a representative of the European Commission.  \nThe document is not a European Commission document and it ca nnot be regarded as reflecting the \nofficial position of the European Commission. Any views expressed in this document are not legally \nbinding and only the Court of Justice of the European Union can give binding interpretations of Union \nlaw. \n \n    \n2 \n  \nGuidance on  significant changes  regarding the \ntransitional provision under Article 120 of the \nMDR with regard to devices covered by \ncertificates  according to MDD or AIMDD1 \n \n1 Introduction  \nArticle 120( 2) and 120( 3) of the  Medical Device Regulation  (EU) 2017/745 (MDR) states that \ndevices which  have a valid certif icate issued by a notified body under the Active Implantable \nMedical Devices Directive 90/385/EEC  (AIMDD) or the Medical Devices Directive 9 3/42/EEC \n(MDD) may be placed on the market or put into service after th e date of application of the MDR \nunder certain conditions  and no later than  26 May 2024.  \nQuestions 8 and 9 of the CAMD Transition Sub Group  guidance : \u201cFAQ \u2013 MDR Transitional \nprovisions, V1.0 of 17. January 2018\u201d2 state that the certificates  covered by MDR Article 120(3) \ninclude \u201call certificates which are commonly issued by notified bodies with reference to the \nCouncil Directives MDD and AIMDD\u201d . \nConditions referred to in the first paragraph require that no  significant change s in design or \nintended purpose  of a device  be performed  after the date of application of the MDR . Therefore, it \nis important for manufacturers and notified bodies to get clarity on the significant changes to be \nconsidered under  MDR Art icle 120(3).  \nIt is also important that the AIMDD and MDD certificates remain valid following changes that are \nnot significant with regard  to design or intended purpose , provided that the required surveillance \nis carried out  by the notified body that issued the certificate. See also Question 17 of the above \nmentioned CAMD guidance2. \n2 Scope  \nThis guidance document is intended to provide clarification on the changes to a device that \nshould be considered a \u201csignificant change in design or a significant change in the intended \npurpose\u201d under  MDR Art icle 120(3). Assessment s should  be made on a case -by-case basis.  \n                                                           \n1 The principles  outlined in this guidance can be applied also for class I devices requiring the involvement of a \nnotified body for the first time.  \n2 https://www.camd -europe.eu/wp -content/uploads/2018/05/FAQ_MDR_180117_V1.0 -1.pdf    \n3 \n This guidance document does not elaborate on the process for manufacturers\u2019 submission and  \nnotified bodies\u2019  assessment of such changes as these should be part of the conformity \nassessment process  and surveillance  defined by the relevant notified body under the MDD or \nAIMDD. It is expected that manufacturers adjust their change not ification procedures, i.e. their \nprovisions to inform their notified body on changes, in accordance with the principles outlined in \nthis guidance until the date of application of the MDR. The adjusted procedures will be subject to \nnotified body assessment within their surveillance activities according to MDR Art. 120(3).   \n3 Changes to Directive  certificate s \nIt is important to highlight that no issuing of new MDD/AIMDD certificates, including modified,  \namended  or supplemented certificates , is allowed under MDR Article 120(3).  In particular, i f the \nmanufacturer wishes to make a  \u201csignificant chang e in design or intended purpose\u201d under MDR \nArticle 120(3), the implementation of such a  change would  prevent the manufacturer from \ncontinuing to place that device on the market  under the Directives . \n4 Assessment of changes' significance  in accordance with MDR \nArticle 120(3)  \nIn line with agreed arrangements for notification of changes between the manufacturer and the \nnotified body  according to the AIMDD/MDD  (e.g. contractual relationships, approved  procedures)  \nchanges and their implementation will be verified by the notified body as part of the surveillance \nactivities, or following a manufacturer\u2019s  submission for prior approval . The outcome of this \nverification will determine whether a certificate in accordance with AIMDD/MDD remains valid \naccording to Article 120 MDR. To use this derogation from Article 5 MDR manufacturers are not \nallowed to make s ignificant change s in design or a significant changes in the intended purpose. \nIn case of doubt whether a change is significant they should ask their notified body .  \nFor instance, administrative changes of organisations are considered in principle as non -\nsignificant. This includes changes of the manufacturer\u2019s name , address or legal form  (legal entity \nremains) or changes of the authorised representative.  \nFurthermore, all changes not having an impact on the design or the intended purpose of the \ndevice can be regarded as not significant  in the meaning of MDR Article 120(3) .  This is the case \nfor example of relocation or addition of new manufacturing sites, including when it affects \nsubcontractors  or suppliers , or of certain changes of the quality management system, provided \nthat the conditions for which the conformity assessment certification was granted are maintained. \nNevertheless, such changes continue to be subject to the agreed notification procedure identified \nin the first paragraph of the current secti on. T he manufacturer should always remain responsible \nfor providing evidence that all the above -mentioned changes do indeed neither  affect the design \nnor the intended purpose.     \n4 \n On the other hand, when the change is likely to affect the design or the inten ded purpose of the \ndevice, the significance of such a change must be assessed on a case -by-case basis.  \nTo facilitate a harmonised judgement of the significance of changes flowcharts (see Annex) have \nbeen developed.  \nIf a change is not a significant chang e in design or intended purpose  under MDR Article 120(3), \nthe implementation of such a change  is therefore  allowed during the transitional period. Acc. to \nsection 3 the certificate should not be amended.  \nThe notified body that issued the AIMDD or MDD certif icate may confirm in writing (after having \nreviewed manufacturer\u2019s description of the (proposed ) change) that the implementation of the \nchange does not represent a significant change in design or intended purpose under MDR Article \n120(3) and that the relat ed AIMDD or MDD certificate remains valid after the date of application \nof the MDR, but no longer than its expiry date or 26 May 2024, whichever comes first. Such \nwritten confirmation corrects or complements information on an existing certificate but does not \nrepresent the issuance of a \u201csupp lemented certificate\u201d as this is prohibited as mentioned in \nSection 3 . In case of requests from authorities the manufacturer should number such letters \nreceived from the notified body and submit them together with the certificate.   \nIn relation to class I medical devices requiring the involvement of a notified body for the first time, \nmanufacturers of such devices must be able to justify their decision when the changes are \nconsidered to be non -significant. The justificat ion shall be documented and made available when \nrequested.  \nThis guidance document provides in its Annex several flowcharts based on NBOG\u2019s Best \nPractice Guide 2014 -3: \u201cGuidance for manufacturers and Notified Bodies on reporting of Design \nChanges and Change s of the Quality System\u201d . In particular, Chart C , which is specific to \nsoftware, draws inspiration  from Annex VI, Part C, section  6.5 of the MDR to identify \nmodifications that are considered as significant change in (software) design.  \nThe assessment of a proposed change by using the main flowchart and any of the applicable  \nsub-charts in the Annex, is intended to assist  manufacturers and notified bodies  in deciding  \nwhether or not a change is to be considered significant in the design or intended purpose of the \ndevice under MDR Art icle 120(3).  \nThe flowcharts are divided into a main chart and five sub -charts (A to E) . There are six \ncategorical questions in the main chart that are linked to  one or more sub -charts with more \ndetailed questions . The change is considered a non -significant change of design or intended \npurpose per MDR Art icle 120(3)  if the answer to every  question in a sub -chart leads to \u201c non-\nsignificant change \u201d also when returnin g to the main chart. On the contrary, if any  sub-chart   \n5 \n delivers the result \u201csignificant change\u201d , the change being assessed is a \u201c significant chang e in \ndesign or intended purpose\u201d  of a device according to the MDR Article 120(3).  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n   \n6 \n Annex  \nDesign Changes and Changes of the Intended Purpose  \nWhich may be Considered \u201cSignificant\u201c When Interpreting the \nFirst Sentence of MDR Art. 120(3)   \n     Main Chart   \nChange of an existing Medical Device  \ncertified under MDD or AIMDD  \nChange of the  \nIntended Purpose?  \nSoftware change?  \nChart A  \nChart B  \nChart C  \nYes  \nYes  \nYes  \nNo \nNo \nIf non -significant  \nIf non -significant  \nIf non -significant  \nA \nB \nC \nChange of the  \ndesign or  \nperformance  \nspecification?  \nNo \nNo \nX \nDesign change related  \nto corrective  \nactions*?  \n*assessed and  \naccepted by the  \nrelevant Competent  \nAuthority acc. to  \nCAMD FAQ no 17  \nYes    \n7 \n Design Changes and Changes of the Intended Purpose  \nWhich may be Considered \u201cSignificant\u201c When Interpreting the \nFirst Sentence of MDR Art. 120(3)   \nMain Chart (ctd.)  \n \n \n \n \n \n \n \n \nChange of a  \nMaterial*?  \nChange  \nof terminal  \nsterilization method of  \ndevice or packaging design  \nwith impact to the  \nsterilisation?  \nChart D  \nChart E  \nThe change is considered a  \nnon \n- \nsignificant change  \nper MDR Art. 120(3)  \nYes  \nYes  \nNo \nNo \nNo \nIf non -significant  \nD \nE \n*The termmaterial  \nincludesany  \nsubstance  \n( \nsynthetic, natural,  \nbiological, chemical,  \nphysical, medicinal,  \n...) \n that is used to  \nmake or compose  \nthe device    \n8 \n Design Changes and Changes of the Intended Purpose  \nWhich may be Considered \u201cSignificant\u201c When Interpreting the \nFirst Sentence of MDR Art. 120(3)   \nChart A  \n \nFromMain  Chart:  \nChange of the IntendedPurpose*  \nThe changeisconsidered  \nsignificantper MDR Art. 120(3)  \nExtension  \nor change of the  \nIntended Purpose?  \nNew user or  \npatient population?  \nChange of  \nclinical use**?  \nYes  \nYes  \nYes  \nNo \nNo \nNo \nLimitation of the  \nIntended  \nPurpose?  \nReturn toMain Chart  \nQuestionX  \nYes  \nNo \nA1 \nA2 \nA3 \nA4 \n** Example:  \n- \nChange in the  \nanatomical site;  \n- \nChange in the access  \nsite or deployment  \nmethods;  \n*  Labellingchangesshouldbe  \nassessedtoensuretheyarenot  \npotentiallysignificantwhen  \nlinkedtothe intendeduse(e.g.  \ncontraindicationsandwarnings).   \n \n \n \n Design Changes and Changes of the Intended Purpose  \nWhich may be Considered \u201cSignificant\u201c When Interpreting the \nFirst Sentence of MDR Art. 120(3)   \n \nChart B  \n \n \nFromMain Chart:  \nChange of theDesignorPerformance Specification*  \nYes  \nNo \nNo \nB1 \nChange  \nof built -in control  \nmechanism, operating  \nprinciples, source  \nof energyor  \nalarms  \n? \nYes  \nNo \nReturn toMain Chart  \nQuestionC (or move directly to E  \nif Chart D was previously used)  \nYes \nB3 \nThe changeisconsidered  \nsignificantper MDR Art. 120(3)  \nbetakeninto  \n not \n * Itshall  \naccounthowthe changeis  \nachieved. A changein specification  \nmaybetriggeredby, but isnot  \nlimited to, changeof hardwareor  \nsoftware, includingchangeof a  \ncomponent.  \nDoes the  \nchange require  \nfurther clinical or  \nusability data to support  \nsafety and perfor - \nmance?  \n** \nDo new risks  \nrequire control measures  \nor are existing risks  \nnegatively  \naffected?  \nB2 \n** Compare  \nMEDDEV 2.7/1 rev.4  \nforfurtherguidance   \n \n \n \n Design Changes and Changes of the Intended Purpose  \nWhich may be Considered \u201cSignificant\u201c When Interpreting the \nFirst Sentence of MDR Art. 120(3)   \nChart C  \n \n \n \n \n \nFromMain Chart:  \nSoftware Change  \nNew or modified  \narchitecture or database  \nstructure, change of  \nan algorithm?  \nRequired  \nuser input replaced  \nby closed loop  \nalgorithm  \n? \nYes  \nYes  \nNo \nNo \nNew or major  \nchange of operating  \nsystem or any  \ncomponent?  \nNo \nYes  \nC1 \nC2 \nC3 \nNew diagnostic or  \ntherapeutic feature,  \nor new channel of  \ninter-operability  \n? \nYes \nC4 \nNo  \n \n \n \n Design Changes and Changes of the Intended Purpose  \nWhich may be Considered \u201cSignificant\u201c When Interpreting the \nFirst Sentence of MDR Art. 120(3)   \n \nChart C (ctd.)  \n \n \n \n \nThe changeisconsidered  \nsignificantper MDR Art. 120(3)  \nYes \nNo \nReturn toMain Chart  \nQuestionD  \nC5 \nNo \nNew user interface or  \npresentation of data*?  \n*\u201cPresentationof data\u201c  \ngoesbeyondthe  \nappearanceof theuser - \ninterface whichmayinclude  \nnewlanguages, layoutsor  \ngraphicsandisconsidered  \na minor change.  \nItisconnectedtomedical  \ndatawhicharepresentedin  \na newformatorby a new  \ndimensionormeasuring  \nunit.  \nYes \n*Minor changeswithout  \nimpacttodiagnosisor  \ntreatmentdeliveredmay  \ninclude:  \n- \ncorrectionof an error  \nwhichdoesnot posea  \nsafetyrisk(bugfixes),  \n- \nSecurity update (e.g.  \ncyber -security  \nenhancements,  \nlongevitycalculations),  \n- \nappearanceof the user  \ninterface,  \n- \noperatingeffeciencies.  \n- \nChangestoenhancethe  \nuserinterfacewithout  \nchangesin performance  \nMinor Change*?  \nC6  \n \n \n \n Design Changes and Changes of the Intended Purpose  \nWhich may be Considered \u201cSignificant\u201c When Interpreting the \nFirst Sentence of MDR Art. 120(3)   \n \nChart D  \n \n \n \n \n \n \nFromMain Chart:  \nChange of a Material*  \nChange to a  \nmaterial of human/animal  \norigin including addition of  \nnew materials?  \nNo \nYes  \nChange  \nto a material  \ncontaining a MS**  \nortothe MS  \nitselfor, a change which may  \nimpact the quality, safety or  \nefficacy of a MS  \n*** \n? \nYes  \nNo \nD1 \nD2 \n**MS: Substancewhich,  \nif used separately, would  \nbe considered to be a  \nmedicinal substance  \n***Including a change in  \nits manufacturing process,  \nwhich result in changes to  \nthe existing specification  \nof the medicinal  \nsubstance.  \n* These relate to changes  \ninvolving existing  \ningredients and materials.   \n \n \n \n Design Changes and Changes of the Intended Purpose  \nWhich may be Considered \u201cSignificant\u201c When Interpreting the \nFirst Sentence of MDR Art. 120(3)   \n \nChart D (ctd.)  \n \n \n \n \n \nIngredient  \nnew \n ormaterial from  \nuppliermeetsexisting  \n s \nspecification?  \nThe changeisconsidered  \nsignificantper MDR Art. 120(3)  \nNo \nYes  \nYes \nChanged  \ningredientor  \nmaterial fromexisting  \nsuppliermeetsexisting  \nspecification?  \nNo \nReturn toMain Chart  \nQuestionE  \nD3 \nD4 \nChange tobeassessedin  \naccwithChart B   \n \n \n \n Design Changes and Changes of the Intended Purpose  \nWhich may be Considered \u201cSignificant\u201c When Interpreting the \nFirst Sentence of MDR Art. 120(3)   \nChart E  \n \n \nFromMain Chart:  \nChange of terminal sterilization method  \nof device or packaging design  \nwith impact to the sterilization  \nDesign Change  \nwhich affects or  \nchanges the sterility  \nassurance**?  \nYes  \nNo \nNo \nYes  \nChange in  \npackaging design which  \naffects functionality, safety,  \nstability or  \nseal integrity?  \nE2 \nE3 \nShelf-life change  \nvalidated by protocols  \napproved by the notified body  \n***? \nThe changeisconsidered  \nsignificantper MDR Art. 120(3)  \nThe change is considered a  \nnon-significant change  \nper MDR Art. 120(3)  \nNo \n Yes  \nE4 \n** Guidance on assessing  \nchanges for their impact on  \nthe effectiveness of the  \nsterilization process is  \nprovided in the respective  \nsterilization standards such  \nas: \n\uf0a7 \nEN ISO 11135 (Ethylene  \nOxide),  \n\uf0a7 \nEN ISO 11137 -1  \nRadiation),  \n ( \n\uf0a7 \nEN ISO 17665 -1 (Moist  \nHeat),  \n\uf0a7 \nEN ISO 13408 -1 (Aseptic  \nProcess).  \nChange* of  \nterminal sterilization  \nmethod?  \nNo \nYes  \nE1 \n* Includes change from  \nnon-sterile to sterile or a  \nchange to the sterilisation  \nmethod. Changes of cycle  \nparameters under the  \napproved quality  \nmanagement system are  \nnot deemed as significant in  \nthe meaning of Art. 120(3)  \nMDR  \n***In principle, an increase  \nin shelf life can be  \nconsidered non -significant  \n( \ne.g. the increase is made  \nfollowing the completion of  \na real time test whose  \nmethod and end -point was  \nvalidated and previously  \nassessed by the notified  \nbody)."}, {"title": "md_application-transitional-provisions-certificates_en.pdf.txt", "text": "Medical Device       \nMedical Device  Coordination Group Document   MDCG  201 9-10 rev.1   \nPage 1 of 2 \n  \n \n \n \n \nMDCG  201 9-10 rev. 1  \n Application of transitional provisions concerning     \n validity of certificates issued in accordance to \n Directives 90/385/EEC and 93/42/EEC     \n            \n \n October  2019   \n July 2020 rev. 1 \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is \ncomposed of representatives of all Member States and it is chaired by  a \nrepresentative of the European Commission.  \nThe document is not a European Commission document and it cannot be regarded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only  the Court of Justice of the European \nUnion can give binding interpretations of Union law.  \n \n  Medical Device       \nMedical Device  Coordination Group Document   MDCG  201 9-10 rev.1   \nPage 2 of 2 \n  \nMDCG 2019 -10 revision 1 changes  \nMDR postponement dates: from 2020 to 2021  \nApplication of transitional provisions concerning validity \nof certificates issued in accordance to Directives \n90/385/EEC and 93/42/EEC1 \nAccording to Article 120(2) of Regulation (EU) 2017/475 on Medical Devices (the MDR), certificates \nissued in accordance with Directives 90/385/EEC and 93/42/EEC  (the Directives ) will remain valid \nuntil 26 May 2024 at the latest. However, Article 120(3) establishes specific conditions that such \ncertificates, and the related devices thereof, have to comply with.  In particular, it is required that the  \nnotified body that issued the certificate \u2013 under a valid designation \u2013 continues to be responsible for \nthe appropriate surveillance activities with respect to all of the applicable requirements related to \nthe devices it has certified and that it has the possibility to take any necessary measure in relation to \nthose. \nIt has to be noted that, as reported in FAQ n.17 of the MDR transitional provision document \npublished by the  CAMD Transition Sub Group, the contract between the manufacturer and the \nnotified body who issued the certificate under the relevant Directive  shall include provisions allowing \nthe appropriate performance of such surveillance activities.  \nIn order to allow manufacturers to take advantage of Art. 120( 2) and Art. 120(3) of the MDR, it needs \nto be ensured that Authorities  responsible for notified bo dies have the right to and do monitor those \nnotified body\u2019s activities to the extent appropriate and necessary. For this purpose, Article 120(3) \nand Article 122(1) of the MDR provide the necessary legal basis for Member States to establish the \nnecessary le gal empowerments2 by means of National law to carry out the needed  monitoring \nactivities in relation to Notified Bodies. All this is regardless of whether the Notified Body has applied \nor not to be designated under the MDR  and/or it has a still valid desig nation under the Directives \nduring the validity of certificates issued in accordance to the Directives . \nConcerning information published in the NANDO database, in accordance to Article 120(1) of the \nMDR, any publication of a notification in respect of a no tified body in accordance with the Directives \nwill become void  as from 26 May 2021 .  Therefore, NANDO will only be used in relation to the  \nDirectives for information purposes after 25 May 2021 . NANDO will therefore list those notified \nbodies  that have bee n designated under the Directives with a clear  message that they are not able to \nissue new certificates but only  allowed to carry out  surveillance activities for valid certificates in the \ntransitional period, as established in  Article 120 of the MDR.  \n                                                           \n1  This document specifically refers to transitional provisions laid down in Regulation (EU) 2017/745  but can \nbe applied by analogy to Regulation (EU) 2017/746.  \n2  It should be noted that  relevant legal empowerments might be already available by means of National law \nwhich build on different EU pieces of legislation."}, {"title": "md_2020-14-guidance-mdsap_en.pdf.txt", "text": "1 \n  \nMedical Devices \nMedical Device Coordination Group Document                             MDCG 2020-14         \n \n \n \n \n \n \nMDCG 2020-14 \n  \nGuidance for notified bodies on the use of \nMDSAP audit reports in the context of \nsurveillance audits carried out under the \nMedical Devices Regulation (MDR)/ In Vitro  \nDiagnostic medical devices Regulation (IVDR)  \n \n \nAugust 2020 \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) established by Article 103 of Regulation (EU) 2017/745.  The MDCG is composed of representatives of all Member States and a representative of the European Commission chairs it. The document is not a European Commission document and it cannot be regarded as reflecting the official position of the European Commission. Any views expressed in this document are not legally binding and only the Court of Justice of the European Union can give binding interpretations of Union law. \n  2 \n Guidance for notified bodies on the use of MDSAP audit \nreports in the context of surveillance audits carried out under \nthe Medical Devices Regulation (MDR)/ In Vitro  Diagnostic \nmedical devices Regulation (IVDR) \n \nBackground \nIn fulfilling the EU\u2019s commitment to encourage notifi ed bodies to make use of audit reports from the \nMedical Device Single Audit Program (MDSAP) in a manner that is compatible with EU legislative \nrequirements, the Medical Device Coordination Group (MDCG) endorsed this guidance which has been developed by a group of experts comprised of interested Member State representatives, notified \nbody associations and stakeholders.  \nScope \nThe purpose of this document is to provide guidance to notified bodies on how to take into account MDSAP Medical Device Regulatory Audit Reports\n1 (from hereafter \u201cMDSAP audit reports\u201d) issued \nby MDSAP auditing organisations2 when performing surveillance audits under Regulation (EU) \n2017/745 \u2013 Medical Devices Regulation (MDR) and Regulation (EU) 2017/746 \u2013 In Vitro  Diagnostic \nmedical devices Regulation (IVDR). This is of particular use when a manufacturer has undergone an \nMDSAP audit and wishes to present this audit report (including the associated attachments) in context \nof the regular surveillance audits performed in accordance to the MDR or IVDR.  \nGeneral regulatory considerations \nUnder the MDR/IVDR, most conformity assessme nt procedures consist of both the quality \nmanagement system audit and the assessment of a device\u2019s safety and performance. Notified body\u2019s \nconformity assessment activities, which are a prerequisite for the manufacturer\u2019s declaration of \nconformity, when concluded successfully result in a conformity assessment certificate, a pre-market requirement for most classes of medical devices and IVDs. In that regard, notified bodies designated \nunder the MDR/IVDR fulfil roles, which correspond to combined functions of both MDSAP auditing \norganisations and MDSAP participating regulatory authorities.\n3 Therefore, the roles performed by \nnotified bodies and MDSAP auditing organisations differ as the latter solely perform quality \nmanagement system audits which are then utilised by regulatory authorities in their evaluation of a \nproduct\u2019s safety and performance for the purpose of issuing a marketing authorisation.   \n \n                                                      \n1 MDSAP audits are recorded using the Medical Device Regulatory Audit Report form (MDSAP AU F0019.1). Final \nMDSAP audit reports are signed in section 18 of the form. \n2 Auditing Organization: An organization that audits a medical  device manufacturer for conformity with quality management \nsystem requirements and other medical device regulatory re quirements. Auditing Organizati ons may be an independent \norganization or a Regulatory Authority which perform regulatory audits. (IMDRF/MDSAP WG/N3 FINAL:2016) \n3 Regulatory Authority: A government body or other entity that exercises a legal right to control the use or sale of medical \ndevices within its jurisdiction, and that may take enforcemen t action to ensure that medical products marketed within its \njurisdiction comply with legal requirements. (GHTF/SG1/N78:2012, cited from IMDRF/MDSAP WG/N3 FINAL:2016)  3 \n Requirements of  the MDR/IVDR \nThe MDR/IVDR clearly state that all manufacturers need to have a quality management system in \nplace so as to ensure that devices manufactured in se ries are in conformity with the requirements of the \nrespective regulation and that experience from the use of devices is taken into account in the \nproduction process (MDR Recital 32/IVDR Recital 31). This becomes an explicit requirement for \nmanufacturers to establish, document, maintain, keep up to date and continually improve quality management systems so that to ensure compliance with the Regulations (MDR Article 10 (9)/IVDR \nArticle 10(8)). \n Notified bodies are charged with the assessment of quality management systems of devices in \naccordance with MDR Article 52 and IVDR Article 48. Specifically, notified bodies are responsible \nfor auditing and certifying manufacturers\u2019 quality management systems (MDR/IVDR Annexes IX and XI and Annex VII section 4.5 ), following up with  appropriate surveillance audits (MDR/IVDR Annex \nIX section 3 and Annex VII section 4.5.1, 4.10) as well as conducting unannounced audits \n(MDR/IVDR Annex VII section 4.5.1). Notified bodies are also responsible for the development of their appropriate procedures for conformity assessments according to the MDR /IVDR.  \n \nThe MDR/IVDR specifically state that notified bodie s\u2019 audit programmes should clearly identify the \nnumber and sequence of activities required to demonstrate complete coverage of a manufacturer\u2019s \nquality management system (MDR/IVDR Annex VII 4.5.2) and that surveillance audits need to be \ncarried out on at least an annual basis (MDR/IVDR Annex VII section 4.10 and Annex IX section 3.3). For each surveillance audit identified in the audit programme, the objectives, criteria and scope of \nthe surveillance audit are defined in an audit plan which adequately addresses and takes into account \nspecific requirements for the devices, technolog ies and processes involved (MDR/IVDR Annex VII \nsection 4.5.2(a) \u2013 third bullet point). Surveillance audits are expected to gather sufficient information \nto verify the proper implementation of the quality management system and ensure that it continues to \ncomply with the requirements of the MDR/IVDR. \n \nWhen and how to take MDSAP audit reports into account \nIt is important to stress that the MDR/IVDR remain applicable in their entirety. The use of MDSAP audit reports within the EU legislative framework is possible only where the MDSAP audit covers similar or equivalent MDR/IVDR requirements. Designated notified bodies maintain the full authority \nover their judgement, conclusion and final decision about the conformity of quality management \nsystems to the relevant provisions of the MDR/IVDR and the safety and performance of medical devices and IVDs intended to be placed on the market in the EU. \n \nGiven that surveillance audits, their periodicity and EU auditors\u2019 competencies are mandated by law, yearly surveillance audits need to be maintained. Ho wever, it could be possible to take into account \nthe scope and outputs of manufacturers\u2019 recent MDSAP audit reports as an input for developing \nsurveillance audit programmes. The taking into account of MDSAP audit reports could define in a more precise manner the activities to be performed during a surveillance audit. For example, the \npositive quality management system conformity appraisal through MDSAP might lead to a reduction 4 \n of the focus on aspects already covered by MDSAP audit reports. The notified body may then focus \ntheir surveillance audit on specific MDR/IVDR requirements which are either not covered or only \npartially covered by the MDSAP audit report. Non-exhaustive list of examples (alphabetical order):  \n- clinical evaluation/performance evaluation process (including post-market \nclinical/performance follow-up),  \n- EU authorised representative contractual provisions,   \n- EU UDI assignments within the quality management system,  \n- manufacturer financial coverage in respect of potential liability,  \n- person responsible for regulatory compliance qualification and role,  \n- records control,  \n- system for risk management,  \n- vigilance and post market surveillance activities, including the associated corrective actions \nand preventive actions. \n \nSimilarly, non-conformities identified in recent MDSAP audit reports can trigger the notified body to pay particular attention to those aspects in the MDR/IVDR planned surveillance audit.  \n \nIt is important to highlight the following details: \n- The taking into account of MDSAP audit reports is not applicable to initial quality \nmanagement system audits required for the issuing of EU QMS certificates. Notified bodies \ndesignated under the MDR/IVDR would always need  to conduct these audits in their entirety.  \n- The taking into account of MDSAP audit reports is not applicable to MDR/IVDR \nunannounced audits.  \n- Reports of MDSAP unannounced audits or special audits should not be taken into account in \nthe narrowing of focus in MD R/IVDR surveillance audits. \n- Regular surveillance audits would still take place on a yearly basis. However, the positive \nQMS conformity appraisal through an MDSAP audit may lead to a limitation of the surveillance focus from aspects already covered by the MDSAP audit reports. \n- When MDSAP audit reports are considered as input to the planning of an MDR/IVDR \nsurveillance audit, these reports should be taken into account in their complete form, including all associated attachments. Both positive and negative statements about the conformity of the \nmanufacturer should be incorporated in the planning of the MDR/IVDR audit. \nIf there is concern about the functioning of the quality management system, for instance due to \ninformation gathered through the assessment of vigilance cases or post market activities, previous \nsurveillance audits  or technical documentation assessments, a complete surveillance audit should be \ncarried out.  \nNotified bodies may wish to determine and establish additional guidance in order to support their \nprocedures for evaluating MDSAP audit reports.  Such guidance could for example specify the content details of MDSAP audit reports considered acceptable (i.e. may be taken into consideration) in the \nnotified body assessment programme and what modifications may be done to the notified body \nassessment programme after the taking into consider ation of the MDSAP audit report (to ensure that 5 \n any specific assessment items that are not covered in the MDSAP audit reports are performed by the \nnotified body). \n The notified body shall remain fully responsible for its decision, to whether or not, and to what extent, \nan MDSAP audit report can be taken into account. \n The Annex to this guidance identifies and analyses aspects within MDSAP audit reports that are \nrelevant in relation to the EU requirements. Part I focuses on providing an explanation of where to find \nrelevant information in MDSAP audit reports that could be used to a greater or lesser extent as supporting evidence for MDR/IVDR quality management system requirements. Part II provides \nexamples on how correlations between MDR requirem ents to sections of MDSAP audit reports may \nbe established in the notified bodies\u2019 additional guidance or procedures. Although the examples in Part II focus on MDR requirements, the same methodology could be applied for the IVDR. \n \n \n 6 \n Annex  \n \n \nPart I \u2013 Explanation of relevant information in MDSAP audit report \n \nThe following table shows where information with relevance for MDR/ IVDR quality management system audits can be found in MDSAP audit reports and \nhighlights specifics that should be understood by notified bodies when taking into account such information.   \nA comprehensive description of MDSAP audit report content can be  found in MDSAP AU P0019 MDSAP Me dical Device Regulatory Audit Reports and MDSAP \nAU G0019 Medical Device Regulatory Audit Report Form Guidelines\n4  \n \nSections of MDSAP audit report Relevant information  \nSection 1 \u2013 Audit Information Name of MDSAP auditin g organisation, audit dates and duration, audit team \nSection 2 \u2013 Audited Facility Audited facility name and address. \nIn case of a multi-site audited organization, a separate audit report is generally required for each audited \nfacility.  This means, the audited facility described in Section 2 is not necessarily the manufacturer \nresponsible for the overall product.  Also see Section 4. \nSection 3 \u2013 Certification Schemes, Scopes & Criteria, Audit Types Certification schemes with scope of certification, audit type and audit criteria. \nIn some cases, a list of medical devices covered in the scope is attached to the audit report. \nThe \u201cCE marking\u201d scheme may be referenced, but this is not mandatory.   \nFor unannounced audits, it is important to understand that they are commonly performed to verify \neffectiveness of corrective actions on non-conformities, and their content is not the same as that of \nunannounced audits under MDR/IVDR.  \n                                                      \n4 Both documents are available in the \u201cMDSAP Documents\u201d / \u201cMDSAP Audit Procedures and Forms\u201d section of the MDSAP program homepag e (https://www.fda.gov/medical-devices/cdrh-\ninternational-programs/medical-device-single-audit-program-mdsap , accessed on 2020-03-25). \n 7 \n Sections of MDSAP audit report Relevant information  \nSection 4 \u2013 Certification Holder and Multi-\nsite Organization Relationship between audited facilities and reference to other audited facilities included in the audit. \nCertification Holder is the main facility shown on the title page of the certificate. \nCampus is a group of facilities that can be described in one audit report by derogation from general requirement of \nseparate audit reports for each facility.  \nRelated sites are other audited facilities that are described in separate audit reports. \nCorporate Information describes the use of multiple names and identities by the organization and its significant \nrelationships of the manufacturer with related companies in the context of the audited QMS and its associated \nactivities and devices. \nSection 5 \u2013 Audit Objectives Additional audit objectives applying  to schemes other than MDSAP may be included, but this is not mandatory. \nSection 6 \u2013 Audited Facility Description Regulatory Roles of th e audited facility are indicated separately for each MDSAP parti cipating country.  It may \nadditionally include the roles in other countries, such as Europe, but this is not mandatory. \nActivities at the Audited Facility describe what is actually done at the audited site. \nActivities not included in the Scope of Certification are activities performed at the facility which are not required \nto be listed in the MDSAP certificate. \nSection 7 \u2013 Critical Suppliers Critical suppliers of the audited facility that are relevant to the scope of audit, including pr oducts or services \nobtained from them and indication whether this audit extended to visit a supplier. \nInstead of a detailed description in this section, the list may be attached to the report. \nSection 8 \u2013 Audit History Outcomes of previ ous audits that have been taken into consideration in preparation for this audit. \nSection 9 \u2013 Exclusion and Non-\nApplications of requirements in the QMS Exclusion and non-application of ISO 13485 requir ements in the QMS of the audited facility. \nSection 10 \u2013 Outcome of Pre-Audit \nActivities Outcome of the preceding documentation review and/or stage 1 audit, if applicable.   \nInstead of detailed description in this section, additional records may be attached to the report. 8 \n Sections of MDSAP audit report Relevant information  \nSection 11 \u2013 Audit Findings Sections 11.1-11.7 describe audit findings and ev idence related to ISO 13485 and country-specific \nrequirements.  Please refer to MDSAP Audit Model and details of requirements5 for more information. \nSection 11.7A is only included, if the critical suppliers we re visited as part of the audit, to describe the audit \nfindings made at the visited supplier locations. \nSection 11.8 may include findings according to scheme s other than MDSAP, but this is not mandatory. \nSection 12 \u2013 Non-conformities List of non-conformities, references to which are made in Section 11.  \nGrade is a numeric classification of significance of non-conformity between 1 and 5 according to \nGHTF/SG3/N19:2012 - Quality Management System - Medical Devices \u2013 Non-conformity Grading System \nfor Regulatory Purposes and Information Exchange \nSection 13 \u2013 Significant Deviations from the Audit Plan Circumstances that lead to deviations from the audit plan and obstacles experienced by the audit team during the \naudit. \nSection 14 \u2013 Follow-up of Past Non-conformities Results of audit team\u2019s evaluation of effectiveness of ac tions taken in response to non-conformities identified \nin prior audits with the possible status Closed, Superseded of Left Open. \nA record with the details of this evaluation may be attached to the report. \nSection 15 \u2013 Summary of Major Changes to \nthe Audited Facility Summary description of major changes since previous audit, especially those changes not described in \nSection 11. \nSection 16 \u2013 Conclusions Extensive conclusion of the audit, including the statement on the conformity of the QMS with the audit \ncriteria and recommendations of the audit team. \nSection 17 \u2013 Attachments List of records th at are considered as part of the audit report, including those referenced in Section  6 (list of \nmedical devices), Section 7 (list of critical suppliers), Section 10 (outcome of pre-audit activities), Section 11.2 \n(review of sampled technical documentation), Section 14 (updated non-conformity report relative to past non-\nconformities). \nSection 18 \u2013 Audit Report Approval Date and signature of review and approval of the final audit report. \n                                                      \n5 The MDSAP Audit Model can be found in the \u201cMDSAP Documents\u201d / \u201cMDSAP Audit Procedures and Forms\u201d section of the MDSAP program homepage ( https://www.fda.gov/medical-\ndevices/cdrh-international-programs/medical-device-single-audit-program-mdsap , accessed on 2020-03-25). 9 \n Part II \u2013 Examples on how correlations between MDR requirements to sections of MDSAP audit reports may be established  \n \nThe following examples of established correlations between MDR qua lity management system requirements and the MDSAP Audit Model  show how certain \noverlapping requirements may be covered in MDSAP audit reports, and what specific MDR requirements are not covered. The referen ces direct to MDSAP audit \nprocesses and tasks that overlap with MDR requirements and are linked to same or similar ISO 13485 requirements.  \n \nIt is recommended that notified bodies develop more detailed gu idance for determining the extent  in which MDR/IVDR quality mana gement system requirements \ncorrelate to those covered in MDSAP audit reports. Any such fully  developed correlation should be revised in the event of a pub lication of changes to any basic \ncriteria document including EN ISO 13485, MDSA P Audit Model and MDR/IVDR, or any documen t utilised to establish correlation, su ch as CEN/TR 172236. \n \nThe examples provided in the below table cover only the following  three blocks of MDR requirements: Clinical evaluation, Suppli er controls, and Post-market \nsurveillance. \n \nMDR requirement Sections of MDSAP audit report addressing this topic(s) Particular MDR requirements \nnot covered in an MDSAP audit \nClinical evaluation \nMDR Article 10, paragraph 3 \nMDR Annex IX, Chapter I, 2.1, indents 10-11 \nMDR Annex XI, Part A, 6.1 indent 17 Section 11.5 \u2013 Design and Development, Task 11 Specifics of Article 61 and Annex \nXIV Part A \nClinical evaluation plan and \nprocedures to keep up to date the \nclinical evaluation plan \nSupplier controls \nMDR Article 10, paragraph 9 (d) \nMDR Annex IX, Chapter I, 2.2 paragraph 2 b) \nindent 3 Section 11.1 \u2013 Management, Task 5 \nSection 11.3 \u2013 Measurement, Analysis and Improvement, Tasks 2, 7, 13 Section 11.5 \u2013 Design and Development, Tasks 1, 7, 8, 16 \nSection 11.6 \u2013 Production and Service Controls, Tasks 7, 14, 19, 21, 22 \nSection 11.7 \u2013 Purchasing, all tasks  Annex II 3. (c) \n                                                      \n6 CEN/TR 17223:2018 Guidance on the relationship between EN ISO 13485: 2016 (Medical devices \u2013 Quality management systems \u2013 Requ irements for regulatory purposes) and European Medical \nDevices Regulation and In Vitro  Diagnostic Medical Devices Regulation. \n7 MDR Annex XI, Part A, 6.1 indent 1 refers back to MDR Annex IX, Chapter I, 2.1 10 \n MDR requirement Sections of MDSAP audit report addressing this topic(s) Particular MDR requirements \nnot covered in an MDSAP audit \nPost-market surveillance \nMDR Article 10, paragraph 10 \nMDR Annex IX, Chapter I, 2.1 indent 8-9 MDR Annex XI, Part A, 6.1 indent 1\n8 \nMDR Annex XI, Part B, 13 Section 11.3 \u2013 Measurement, Analysis and Improvement, Task 12, 14, \n15 \nSection 11.4 \u2013 Medical Device Adverse Events and Advisory Notices \nReporting, Tasks 1, 2 Specific requirements on the PMS \nsystem incl. PMS plan, PMS report, \nPSURs, and PMCF plan (Articles 83-86 and Part B of Annex XIV as \nwell as obligations resulting from \nthe provisions on vigilance \n(Articles 87 to 92) \n \n \n \n                                                      \n8 MDR Annex XI, Part A, 6.1 indent 1 refers back to MDR Annex IX, Chapter I, 2.1"}, {"title": "mdcg_2019_13_sampling_MDR_IVDR.pdf.txt", "text": "1 \n Medical Device       \nMedical Device Coordination Group Document                           MDCG  2019 -13   \n \n \n \n \n \n \n \nMDCG  2019 -13 \n        Guidance on sampling of MDR Class  IIa / Class IIb  \n        and IVDR Class B / Class C devices  \n        for the assessment of the technical documentation\n              \n \n           Decem ber   2019  \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) \nestablished by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of \nrepresentatives of all Member States and it is chaired by a representative of the \nEuropean Commission.  \nThe document is not a European Commission document and it cannot be regarded as \nreflecting the official  position of the European Commission. Any views expressed in this \ndocument are not legally binding and only the Court of Justice of the European Union \ncan give binding interpretations of Union law.  \n   \n2 \n Guidance on s ampling of MDR Class IIa /  \nClass IIb and IVDR Class B /  Class C devices \nfor the assessment of the technical \ndocumentation  \n1 Introduction  \nRegulation (EU) 2017/745 on medical devices (MDR) and Regulation  (EU) \n2017/746 on in vitro  diagnostic medical devices (IVDR)  establish the \nrequirements for sampling of Class IIa / Class IIb and Class B /  Class C devices \nfor the assessment of the technical documentation.  \nArticle 52(4) and (6) of the MDR and Article 48( 7) and ( 9) of the IVDR est ablish \nthe need to assess the technical documentation of at least one representative \ndevice per generic device group  (for Class IIb and Class C) and for each \ncategory of devices  (for Class IIa and Class B) prior to issuing the certificate.   \nSection 2.3 and 3.4 of Annex IX of both Regulations (and section 10 of Annex XI  \nof the MDR ) defines that the quality management system assessment has to be \naccompanied by the assessment of technical documentation for devices selected \non a representative basis . \nSection  4.5.2(a) of Annex VII of both Regulations1 requires the notified body to \ndraw up and keep up to date, a sampling plan for the assessment of technical \ndocumentation as referred to in Annexes II and III prior to the audit .  \nSection 4.5.2(b) of Annex VII requires the notified body to assess t he technical \ndocumentation as preparation for the audit (s). This assessment is expected to be \nfinalised in due time of such  audit (s). \n \n2 Scope  \nThis guidance is intended to define  the requirements of sampling for Class IIa \nand Class IIb devices  under the MDR and Class B and Class C devices under \nthe IVDR for the purpose of assessing the technical documentation .   \nThis guidance defines and further elaborates  on the sampling criteria and use of \nsuch criteria for drawing up  and maintaining a sampling plan.  \nIn addition, th is guidance clarifies th e tasks to be performed by the notified body \nincluding the  applicability of Chapter II of Annex IX of both Regulations and the \nextent of  the technical documentation assessment.   \nSee Section 5.3 for exemptions for specific types of devices.  \n \n                                                      \n1 Hereafter referred to as \u201cAnnex VII\u201d  for both, the MDR and the IVDR.    \n3 \n 3 Definitions  \nThe Regulations do not contain definitions of certain terms applicable to \nsampling , and in some instances  certain definitions given cannot be used on an \noperational level. Therefore , only for th e purpose of this  guidance  the \nfollowing definitions apply : \n \n3.1. Category  of devices : category  of devices  should be understood as the \nrelevant M DA/MDN codes (MDR) or IV R code s (IVDR)  according to \nRegulation (EU) 2017/2185 on the codes for the designation of notified \nbodies .  \n \n3.2. Generic device group2:  is to be understood : \n\uf0b7 in respect of the MDR3,4 as the 4th level of the European \nNomenclature  on Medical Devices (EMD N) 5, 6 (i.e. combination of \none letter plus 6 digits ), and  \n\uf0b7 in respect of the IVDR as the 3rd level of the EMD N (i.e. \ncombination of one letter plus 4 digits respectively)  in combination \nwith the most appropriate  IVP code.  \n \n3.3. Device  range:  device range is to be understood as all \u201cdevice \ncategories\"  for Class IIa and Class B devices and all \u201cgeneric device \ngroups \u201d for Class IIb and Class C devices  covered in a certificate .   \n \n3.4. Device : device should be understood as the device(s) associated with \none Basic UDI -DI7.  \n \n3.5. QMS certificates:  QMS certificates are EU q uality management system \ncertificates  (MDR and IVDR) , EU quality assurance certificates  (MDR) \nand EU production quality assurance certificates  (IVDR)  issued by \nnotified bodies as a result of conformity assessments .  \n \n                                                      \n2 \"A set of devices having the same or similar intended purposes or a commonality of technology allowing \nthem to be classified in a generic manner not reflecting specific characteristics\" (Art. 2 (7) MDR  and \nArt. 2(8) IVDR).  \n3 In cases, where the 4th level for the MDR do es not exist the notified body should use the next higher \nlevel . \n4 If the notified body considers that  for a particular device level 4  for the MDR/level 3 for the IVDR is not \nsufficiently specific to define a generic device group, it can use the next lower level if available.  \n5EMDN  nomenclature  can be found currently at : \nhttp://www.salute.gov.it/imgs/C_17_pagineAree_328_listaFile_itemName_15_file. pdf \n6 In case where more than one EMDN  code applies to one device, only the most appropriate  one of these \nEMD N codes will be assigned for sampling purposes. The technical documentation related to that \nparticular device will be assessed in its entirety.  \n7 As defined in MDCG 2018 -1 v2 Guidance on BASIC UDI-DI and changes to UDI -DI.  \n4 \n 4 Sampling criteria  \nThe Regulation s establish minimum requirements for sampling prior to issuing \nthe certificate and during its validity.  The notified body will ensure that these \nrequirements  will be complied with when drawing up a sampling plan.  In \naddition, other considerations have to be observed in order to ensure an \nadequate coverage of devices on a representative basis.  \n4.1. Quantitative Sampling Criteria  \n \n4.1.1.  Sampling prior  to issuing a QMS certificate  \nThe Regulations establish the need for the notified body to assess technical \ndocumentation for a number of  devices prior to issu ing the QMS certificate :  \n- For Class IIb and Class C the technical documentation of at least one \nrepresentative device per generi c device group  (as per Article 52(4) of the \nMDR and Article 48( 7) of the IVDR ).  This means that the notified body \nshou ld asses s how many generic device groups as per 3.2 are covered in \nthe application  (how many nomenclature's 4th levels for MDR /  3rd levels  \nin combination with applicable IVP  codes  for the IVDR8), select per group  \nat least one representative device covered by a Basic UDI -DI and assess \nthe technical documentation  for the device(s) selected .   \n- For Class IIa and Class B the technical documentation of at least one \nrepresentative device per category  of devices  (as per Article 52(6) of the \nMDR and Article 48( 9) of the IVDR ).  This means that the notified body \nshould asses how many categories of devices as per section 3.1, (how \nmany  MDA/M DN or IVR codes ), are covered by the ma nufacturer\u2019s \napplication, select per category at least one representative device covered \nby a Basic UDI -DI (MDA/MDN or IVR code ) and assess the technical \ndocumentation  for the device(s) selected . \nThe outcome of these assessments is an essential input for the final review \naccording t o Annex VII section 4.7 of the R egulations  prior to issuing of the \ncertificate .  \n4.1.2.  Sampling during surveillance  \nAfter issuing the certificate, the notified body will continue to assess technical \ndocumentation in line with the sampling plan. Section 3.5 of Annex IX of both \nRegulations indicates that surveillance assessment shall also include an \n                                                      \n8 Generic device groups for Class C devices will consist on an EMDN  + an IVP code. Therefore, when \ndifferent products are covered under the same EMDN  but corresponds to different IVP codes, the \nnotified body will assign the most appropriate IVDP code to each device.    \n5 \n assessment of the tech nical documentation9 which means that at least one \ntechnical documentation must  be reviewed each year .  \nIn addition, notified bodies will ensure that the entire device range is covered \nduring the period of validity of the certificates  as required by Section 4.5.2 (a) of \nAnnex VII . This means that at least one device per each category, in case of \nClass IIa and Class B  devices , and at least one device per each generic device \ngroup, in case of Class IIb and Class C devices, should be samp led and the \nrelevant technical documentation assessed between the issue of a certificate \nand its expiry date.  \nFurthermore, in addition to  the above -mentioned criteria , the number of samples  \nto be assessed need to be selected on a representative basis ( as per Annex VII \n4.5.1 9th indent MDR, An nex IX 2.3  3rd paragraph MDR / IVDR,  and An nex VII \n4.5.1 8th indent IVDR). Therefore, in developing the sampling plan (see section \n6), the notified body should also ensure that the number of devices sampled is \nproportionate to the total number of devices contained in the certificate. For this \npurpose, it is expected that 15%10 of devices from  each category and from each \ngeneric device group covered in the certificate will be sampled during its validity  \n\u2013 taking into account the maximum validity of 5 years . \nIn cases where the certificate contains very few devices and the technical \ndocumentation s of these have been already reviewed, it is expected that during \nsurveillance audit s the notified body will focus on the review of the technical \ndocumentation related to post -market surveillance in accordance with Annex III .  \nNormally, the devices to be sampled after the certificate has been issued would \nbe spread evenly during the validity of the certificate. However, the notified body \nmight decide to perform different number s of reviews in a given year for different \nreasons (e.g. workload , vigilance concern ) as long as throughout the surveillance \nperiod all initially determined assessments are performed . Such an approach is \nacceptable as long as the minimum requirements mentioned in the first \nparagraph of this section are complied with.  \n4.2. Qualitative  Sampling Criteria  \nSection 2.3 of Annex IX of both Regulations establishes qualitative criteria to be \nused when drawing up sampling plans. While s ome of these criteria such as \nsimilarities in design, technology and manufacturing and sterilisation methods \nmay be covered already by the fact that devices belong to the same category or \ngeneric device group , all the criteria defined in Section 2.3 of Annex IX including  \nnovelty of the technology  intended purpose  or the results of any previous \nrelevant assessments such as with regard to physical, chemi cal, biological or \nclinical properties must be individually considered when prioritising the review of \none device over another.  This prioritisation should take into account the inherent \nrisk of  the different devices included in the relevant category  of devices  / generic \n                                                      \n9 The follow -up of change notifications according to Section 4.9 of Annex VII (e.g. \u201cthe device range \ncovered\u201d in Annex IX section 2.4), and other surveillance activities as laid down in Section 4.10 of \nAnnex VII are to be carried out in addition to sampling during surveillance . \n10 For the first certification cycle under the MDR/IVDR the 15% may be decreased to a minimum of 5%.   \n6 \n device group which means that , for instance, novel devices, will usually  be \nprioritised over well -known technologies (unless there are specific concerns over \nthe latter).  Additional criteria may be also taken into consideration by the  notified \nbody11. As required by the Regulation, the notified body must  document its \nrationale for the samples taken , in particular, mentioning what specific criteria \nhave been taken into account.  \nIt should be noted, that as long as there are devices that have  not been sampled , \neach device should only be sampled once  during the period of validity of the \ncertificate  unless vigilance cases or other information which  have been brought \nto the notified body \u2019s attention will require it .  \n \n5 Assessment of the technical documentation  \n \n5.1. Depth of the assessment  \nThe depth and extent of the technical documentation assessment of Class IIa / \nIIb and Class B / Class C devices will be the same as the  depth of assessment \ncarried out for Class III and Class IIb implantable  and Class D devices .  \nThis means that the technical documentation of a device shall be assessed \nagainst all General Safety and Performance Requirements (Annex I) and \nrequirements of Annex II and III. Records of the assessment shall be prepared \nwhich allow  a third party to understand the functionality of the device and all \naspects of the assessment including judgements made by the assessor . \nIt should be taken into account that every device (i.e. Basic UDI -DI) might include \ndifferent variants, models or sizes. In that case, the review of the technical \ndocumentation will also include the assessment of how the differences among \nthese have been addressed in the technical documentation and whether all of \nthem are in line with the relevant requirements.  \n5.2. Applicability of Chapter II, Section 4 of Annex IX   \nTaking into account the wording of article s 52(4) and 52(6) of the MDR and \nArticle 48(7) and 48(9) of the IVDR, as combined with annex es VII and IX, the \ntasks to be carried out by the notified body as part of the conformity assessment \nactivities described in Chapter II , Section 4  of Annex IX comprise t he complete \nreview of the technical documentation  in accordance with Annexes II and III .  \nIn addition, the manufacturer  will grant access to the technical documentation as \nreferred to in Section 2.2 of Annex IX and the  notified body will  provide the \nmanufacturer with a report on the technical documentation assessment. For \nClass IIa / IIb and Class B / Class C the notified body will neither require  an \napplication nor issue an EU technical documentation assessment certificate  (see \n5.3 for exceptions) .  \n                                                      \n11 For instance, where controls or calibrators are specifically intended to be used in conjunction with a  \nspecific IVD device, these controls or calibrators will preferably be assessed alongside that device   \n7 \n 5.3. Additional requirements for s pecific types of devices under the MDR \nand the  IVDR  \nFor class IIb  implantable devices12, Article 52(4) second subparagraph  of the \nMDR establish es the need to review the technical documentation in accordance \nwith the complete Section 4 of Annex IX for every device,  therefore  an \napplication as well as the issuance of an EU technical documentation \nassessment certificate  are req uired . They are exempt from sampling.  \nAccording to Article 54 , Class IIb active devices intended to administer and/or \nremove a medicinal product falling into rule 12 of Annex VIII are subject to the \nclinical evaluation consultation procedure  prior to issuing of the certificate . These \ndevices can be subject to sampling  but according to Article s 54(3) and 55 the \nnotified body must ensure that at least the clinical evaluation assessment report \n(CEAR) for each device  is uploaded in Eudamed prior to issuing the QMS \ncertificate.   This means that the sampling will not apply to the clinical evaluation \nas it has to be assessed for every device.  \nArticle 48  (7, 8 and 9) and Section 5 of Annex IX of the  IVDR establish  that class \nB and C devices for self -testing, near-patient testing  and companion diagnostics \nare exempt from sampling . The manufacturer will lodge an application as per \nsections 5.1  (a) and 5.2 (a) of Annex IX of the IVDR , and , as described in section \n5.1 (c-e) and 5.2 ( a-e), the notified bod y will review the technical documentation \nof all the devices covered in the certificate  and will issue an EU technical \ndocumentation assessment certificate.   \n5.4. Reporting  \nThe technical documentation assessment of Class IIa / IIb and Class B /  Class C  \ndevices and its reporting should follow the principles established in Annex VII \nand the applicable provisions of the conformity assessment annexes  and should \nuse or be similar to those procedures and checklists developed by the notified \nbody for the assessment of Class III / IIb implantable devices  and Class D \ndevices .  \nIn order to fulfil the legal requirements, the reporting requirements established in \nSection 4.6. of Annex VII will apply.  \n \n6 Drawing up and keeping up to date a sampling plan  \nAccording to Section 4.5.2(a) of Annex VII  the notified body shall draw up and \nkeep up to date a sampling plan . This plan should contain at least the devices  \ncovered by the certificate, their Basic UDI -DI, the generic device group (in case \nof Class IIb ), the generic device group plus the IVP code (in case of  Class C \ndevices) or the category of devices (in case of Class IIa / Class B devices) , the \nidentifier of the respective technical documentation , the (planned) assessment \ndates and the status of such asse ssments .  \n                                                      \n12 Except fo r sutures, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips \nand connectors,  which are subject to sampling   \n8 \n  \nThe notified body should update the sampling plan whenever needed on the \nbasis of the criteria defined in this guidance  as well as on the basis of its post -\ncertification activities laid down in Section 4.10 of Annex VII. In particular, the \noutco me of the screening of relevant sources of scientific and clinical data and \npost-market information relating to the scope of their designation , or the review of \nvigilance data should be taken into account.  \nIf the manufacturer makes a change in the product range during the period of \nvalidity of the certificate, the notified body should review the sampling plan \naccordingly. When a dding new devices to the scope of the certificate which do \nnot fall into the alrea dy covered generic device groups / categories  of devices , \nthe initial sampling criteria (section 4.1) apply.  \nIf the manufacturer applies for re -certification, the notified body should update \nthe sampling plan with the samples to be assessed during the upc oming \ncertification period according to the principles laid down under section 4.1.2 \nSampling during surveillance and keep the sampling plan up to date as \ndescribed above."}, {"title": "11 MDCG 2020-11 Guidance on the renewal of designation and monitoring of notified bodies under Directives 90385EEC and 9342EEC.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-11  \n \n \n1 \n  \n \n \n \n \n \n \nMDCG 2020-11 \n  \nGuidance on the renewal of designation and \nmonitoring of notified bodies under Directives \n90/385/EEC and 93/42/EEC to be performed in \naccordance with Commission Implementing \nRegulation (EU) 2020/666 amending Commission \nImplementing Regulation (EU) 920/2013   \n             \n \nMay 2020 \n \n \n  \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission. The document is not a European \nCommission document and it cannot be regarded as reflecting the official position of \nthe European Commission. Any views expressed in this document are not legally \nbinding and only the Court of Justice of the European Union can give binding \ninterpretations of Union law. \n \n  Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-11  \n \n \n2 \n Guidance on the renewal of designation and monitoring of \nnotified bodies under Directives 90/385/EEC and 93/42/EEC \nto be performed in accordance with  Commission \nImplementing Regulation (EU) 2020/666 amending \nCommission Implementing Regulation (EU) 920/2013  \n \n1. Introduction \nThe COVID-19 pandemic has created extraordinary circumstances that demand substantial \nadditional resources, as well as a continued availability of vitally important medical devices, \nthat could not reasonably have been anticipated at the time of adoption of Medical Devices \nRegulation (EU)  2017/745 (hereafter referred to as \u2018MDR\u2019). In order to allow Member States, \nhealth institutions and economic operators to prioritise the fight against the COVID-19 \npandemic it was considered necessary to defer the application of certain MDR provisions by \none year (i.e. until 25 May 2021)1. To ensure the continuous presence of a functioning \nregulatory framework for medical devices it was necessary to also defer by one year the date \nof repeal of the Medical Devices Directives 90/385/EEC and 93/42/EEC (hereafter referred to \nas \u2018the Directives\u2019). \nThe deferral of the date of repeal has a consequential impact on the designations of certain \nnotified bodies under the Directives, including their ability to carry out their obligations and \nbe operational until 25 May 2021. The current COVID-19 pandemic also affects the way in \nwhich designating authorities are able to perform the required appropriate surveillance and \nmonitoring activities over notified bodies. To take account of these extraordinary \ncircumstances, the Commission and the Member States, on 18 May 2020, adopted \nCommission Implementing Regulation (EU) 2020/666 amending Commission Implementing \nRegulation (EU) 920/2013 as regards the renewal of designations and the surveillance and \nmonitoring of notified bodies (hereafter referred to as \u2018the Implementing Regulation\u2019)2. The \namendment provides for a derogation from certain requirements on the renewal of \ndesignations of notified bodies and for alternative surveillance and monitoring activities that \ndesignating authorities should carry out.  \nIn particular, in the interest of health and patient safety, and, to ensure consistency among the \nactivities performed by designating authorities, this guidance document has been developed to \noutline common criteria for the renewal of designations of notified bodies under the \nDirectives until 25 May 2021. In addition, this document intends to provide clarification on \nthe appropriate activities performed by designating authorities over notified bodies in order to \nensure an adequate level of surveillance in accordance with Article 5 paragraph 1, third \nsubparagraph, of the Implementing Regulation. \n                                              \n1 OJ L 130, 24.4.2020, p. 18\u201322. \n2 OJ L 156, 19.5.2020, p. 2\u20135  Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-11  \n \n \n3 \n 2. Scope \nThis guidance covers the following activities performed by designating authorities under \nexceptional circumstances, as referred to in Article 4(6) of the Implementing Regulation: \n\uf0b7 renewal of designation under the Directives of notified bodies whose designation \nexpires in the period from 26 May 2020 to 25 May 2021; \n\uf0b7 surveillance activities to be performed by designating authorities in accordance with \nthe Implementing Regulation under COVID-19 related restrictions, notably \nquarantine orders and travel restrictions. \nThis guidance does not apply to the procedure for the initial designation of a notified body \nunder the Directives nor to the procedures for extensions of the scope of a notified body nor \nthe lifting of limitations to the scope of a notified body3. \n3. Renewal of designation of a notified body until 25 May 2021 \nWhen deciding upon the renewal of the designation as a notified body in accordance with \nArticle 4(6) of the Implementing Regulation, designating authorities should perform an \nappropriate assessment of the continuous competence of the notified body and its ability to \naccomplish the tasks for which it has been designated. \nDesignating authorities should base their decision to renew a designation on a review of \ndocuments, resources and activities, which lay ground for the verification of the criteria for \ndesignation as set out in the Directives and in Annex I to the Implementing Regulation. \nThis review should include in particular the following: \n\uf0b7 assessment of relevant quality management system procedures, forms and records, in \nparticular qualification criteria, procedures for selection and authorisation of persons \ninvolved in conformity assessment activities, procedures to ensure independence, \nobjectivity and impartiality of the notified body\u2019s activities; \n\uf0b7 assessment of an appropriate number of the notified body\u2019s reviews of the \nmanufacturer\u2019s technical documentation, including clinical evaluations; \n\uf0b7 assessment of an appropriate number of the notified body\u2019s personnel files; \n\uf0b7 discussion of the results of the assessments of quality management documents and \nrecords with responsible personnel, including management responsible for the \nimplementation and update of the quality management system as well as the notified \nbody\u2019s assessors responsible for product review, including clinical evaluation, final \nreview and decision-making processes; \n\uf0b7 review of the outcome of the most recent on-site surveillance assessments and \nobserved audits  as well as of recent extraordinary assessment activities conducted by \nthe designating authority \n                                              \n3 See Article 11 of Directive 90/385/EEC and Article 16 of Directive 93/42/EEC. Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-11  \n \n \n4 \n When performing the above-mentioned review, the designating authority could also consider, \nif relevant, the outcome of the most recent joint assessment carried out in accordance with \nArticle 3 of the Implementing Regulation as well as joint assessments recently carried out in \naccordance with the MDR. \nIn order to ensure a sufficient assessment the selection of the appropriate number of \nmanufacturer\u2019s technical documentation reviews and personnel files to be reviewed should \ntake into account the volume of the activities performed by the notified body, its scope of \ndesignation and any relevant vigilance data. The designating authority should be able to \njustify the number and type of files selected. The designating authority should ask the notified \nbody to implement appropriate measures to correct any non-conformities found during the \nreview \nNormally, the renewal should include an on-site assessment. However, when exceptional \ncircumstances prevent a designating authority from carrying out such an on-site assessment, \nalternative assessment measures should be used. Principles and arrangements of alternative \nmeasures described in Section 5 of this document concerning surveillance activities may \napply. \nThe results of the assessment performed by the designating authority should be documented \nand the final decision on the renewal of a designation should be substantiated. \n4. Notification and information to be provided to the Commission \nIn accordance with Article 4(6) of the Implementing Regulation, any decision by a Member \nState on the renewal of a designation as a notified body should be notified to the Commission \nand the other Member States through the New Approach Notified and Designated \nOrganisations information system (NANDO)  on or before the date of designation expiry. In \nline with the ordinary procedure, this should take place by means of submitting an update of \nthe existing notification under the relevant Directive. \nThe Commission may request further information relating to a decision taken by a designating \nauthority on the renewal of a designation. In particular, designating authorities should make \navailable, upon request from the Commission, the reports describing the assessments \nperformed in relation to the renewal of the designation and the relevant outcome as described \nin Section 3 of this guidance. This should clearly document the basis for the renewal decision \ndetailing the elements reviewed by the designating authority to substantiate the decision, \nincluding the results of any surveillance and monitoring activities as described in Section 5 of \nthis guidance. Relevant notified body\u2019s documentation should also be made available to the \nCommission on request. \n5. Surveillance activities to be performed under exceptional circumstances \nIn the context of the current COVID-19 pandemic, the resulting travel and quarantine \nrestrictions may significantly affect the ability of designating authorities to conduct their Medical Device       \nMedical Device Coordination Group Document                               MDCG 2020-11  \n \n \n5 \n mandatory surveillance and monitoring activities such as on-site assessments and observed \naudits of their notified bodies. Therefore, in accordance with Article 5(1) of the Implementing \nRegulation, in order to ensure an adequate level of surveillance, designating authorities should \nat least assess an appropriate number of notified body\u2019s reviews of the manufacturer\u2019s \ntechnical documentation, including clinical evaluations, and of personnel files, in addition to \ncarrying out alternative surveillance measures. These alternative measures may include the \nfollowing principles and arrangements: \n\uf0b7 on-site surveillance assessments may be replaced by remote surveillance assessments \nusing the most advanced available Information and Communication Technologies as \ndeemed appropriate in accordance with Union legislation on information security and \ndata protection; \n\uf0b7 assessment of all relevant and required documents/records off-site. \nIn order to ensure a sufficient assessment, the selection of the appropriate number of notified \nbody\u2019s reviews of the manufacturer\u2019s technical documentation, including clinical evaluations, \nand personnel files to be reviewed, should take into account the volume of the activities \nperformed by the notified body, its scope of designation and any relevant vigilance data. The \ndesignating authority should be able to justify the number and type of files selected."}, {"title": "mdcg_2019_5_legacy_devices_registration_eudamed_en.pdf.txt", "text": "Medical Device       \nMedical Device  Coordination Group Document   MDCG  201 9-5   \nPage 1 of 4 \n  \n \n \n \n \nMDCG  201 9-5 \n Registration of legacy devices in EUDAMED  \n               \n \n April  2019  \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commission document and it cannot be regar ded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  \n \n  Medical Device       \nMedical Device  Coordination Group Document   MDCG  201 9-5   \nPage 2 of 4 \n  \nThis document deals with registration of devices, which can continue to be placed on \nthe market under Directive certificates by virtue of Article 120(3) of Regulation \n745/2017 (MDR), and Article 110(3) of Regulation 746/2017 (IVDR) after the relevant \nMDRs application dates. Those products are, for the purpose of this document, \nreferred to as \u201clegacy devices\u201d1. All following considerations, which are made in \nrelation to the MDR shall apply to the IVDR, mutatis mutandis.  \nArt 120(3) of the MDR lays down that t he requirements of the MDR relating to post -\nmarket surveillance, market surveillance, vigilance, registration of economic \noperators and of devices shall apply to legacy devices placed on the market after the \napplication date of the MDR in place of the corr esponding requirements of the \nDirectives.   \nThe MDR is not explicit in requiring that these \u201clegacy devices\u201d are subject to relevant \nUDI obligations. The MDR device registration requirements (Annex VI Part A Section \n2 and Part B that are complementary) mak e the Basic UDI -DI and UDI -DI the access \nkeys for device -related information in the future Eudamed, which is reflected in the \ndatabase design. Therefore, any registration of a device is normally possible in \nEudamed only if a proper Basic UDI -DI and UDI -DI are assigned to the device and \nregistered in the database together with the other device -related data.   \n \nIn light of this, taking all views heard into account, and considering that Article 120(3):  \n- Refers to legacy devices to be registered in line with MDR  provisions,  \n- Lacks any explicit reference to UDI obligations for legacy devices   \nthe MDCG considers it appropriate to adapt the Eudamed design to allow the \nregistration of legacy devices in Eudamed in the absence of a (Basic) UDI -DI.  \nThis is intended to prevent any technical constraint to the applicability of Art 120(3) \nfor legacy device registration in Eudamed.  \nA comprehensive description of the technical implications is provided in the Annex.   \n                                                           \n1 It shall be noted  that, in other contexts, the term \u201clegacy devices\u201d might be used with a different meaning.  Medical Device       \nMedical Device  Coordination Group Document   MDCG  201 9-5   \nPage 3 of 4 \n  \n \nAnnex  \nBasic considerations related to functioning of future registration of legacy \ndevices in Eudamed  \n1. Legacy devices \u2013 covered by a valid Directive certificate - that will continue to \nbe placed on the market after the MDR date of application should be \nregistere d in Eudamed without a Basic UDI -DI and UDI -DI. The registration \ndeadlines for those devices is clearly the one referred to in Article 123(3)(e):  \n18 months after the date of application (provided that Eudamed is fully \nfunctional on time)2.  \n2. However, in ca se of serious incident or field safety corrective action to be \nreported during the 18 months referred to in point 1, where the legacy devices \nhave not been registered in Eudamed yet, they must be registered at the \nmoment of the serious incident/field safet y corrective action reporting.   \n3. Point 1 will be applicable only to the devices that are not already registered as \nMDR devices.  \nNOTE: All the Directive -compliant devices which have been placed on the market \nahead of the general application dates and will not continue to be placed on the \nmarket afterwards, should be registered in Eudamed (without a Basic UDI -DI and \nUDI-DI) only if a serious incident report and/or a field safety corrective action report \n(with the field safety notice) occurs after the applica tion date.  \n \n \nTechnical implementation in Eudamed  \n4. Legacy devices that will be registered in Eudamed will need two other \nunique access keys (IDs) to replace the Basic UDI -DI and UDI -DI for the \nsake of the workability of Eudamed .  \n5. For this purpose, a Eudamed DI will be assigned to the device instead of the \nBasic UDI -DI and a Eudamed ID will be assigned by Eudamed instead of the \nUDI-DI allowing the system to work and to keep the design of Eudamed as \nclose as possible to the MDR design. These Eudamed DI and Eudamed ID will \nbe unique for a given legacy device.  \n6. The Eudamed DI could be either entirely generated by Eudamed or the \nmanufacturer could partly assign the DI code. On the other hand, the \nEudamed ID will be always automatically and fully generated b y Eudamed  \n                                                           \n2  It should be noted that all class I devices that are not sterile and/or with a measuring function under the \nDirectives, are not eligible for any grace period. When placed on the market after the MDR date of \napplication, they will have to be MDR compliant and be registered in EUDAMED  as MDR devices.   Medical Device       \nMedical Device  Coordination Group Document   MDCG  201 9-5   \nPage 4 of 4 \n  \n \nfrom the Eudamed DI. The proposed rules for the assignment (still under \ndiscussion) are that Eudamed DI start with character \"B\", where Eudamed ID \nwill start with character \"D\" (only difference between Eudamed DI and \nEudamed ID). Beside this f irst character, the Eudamed DI/ID will include the \nSRN of the manufacturer, a number (assigned by the manufacturer or \nEudamed) and a check digit.  \n7. The relationship between the Eudamed DI and a Eudamed ID will be one to \none.  \n8. Furthermore, the registration o f the legacy devices will require the \nmanufacturer to enter the directive certificate identification (NB number, \ncertificate number, revision number and expiry date) since they will not be \nregistered in Eudamed by the NBs.  \nIn case a legacy device has been already registered in Eudamed and that same \ndevice becomes at any point in time an MDR compliant device, that MDR device \nshould be considered as a new device requiring a new registration (due to the \nchange in the applicable  legislation) with a Basic UDI -DI and UDI -DI in Eudamed. \nHowever, only a UDI -DI should be entered, if another device with the same Basic \nUDI-DI has already been registered. Eudamed should facilitate this (copy) process \nand allow the linking between the  MDR  device and the corresponding legacy device ."}, {"title": "mdcg_2019_4_devices_registration_eudamed_en.pdf.txt", "text": "Medical Device       \nMedical Device  Coordination Group Document   MDCG  201 9-4   \nPage 1 of 2 \n  \n \n \n \n \nMDCG  201 9-4 \nTimelines for registration of device  \n data elements in EUDAMED  \n                 \n \n April  2019  \n \n \n  \n \n \n \n \nThis document has been endorsed by the Medical Device Coordination Group \n(MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is \ncomposed of representatives of all Member States and it is chaired by a \nrepresentative of the European Commission.  \nThe document is not a European Commission docum ent and it cannot be regarded \nas reflecting the official position of the European Commission. Any views expressed \nin this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law.  \n Medical Device       \nMedical Device  Coordination Group Document   MDCG  201 9-4   \nPage 2 of 2 \n  \n\u201cWith regard to timelines for device registration, the text of the MDR presents an \ninconsistency. On the one hand, Article 123(3)(d) lists the full Article 29 as being \napplicable from the application dates or, if EUDAMED is not functional on time, six \nmont hs after the date of publication of the notice referred to in Article 34(3). On the \nother hand, Article 123(3)(e) grants an additional 18 -month transitional period for \nobligations contained in Article 29(4).  \nTaking into account:  \n- the declared will of the c o-legislator to grant an 18 -month additional \ntransitional period for device registration and registration of certificates,  \n- the logical correspondence and complementary character of device data \nelements in Part A (Section 2) and Part B of Annex VI,  \n- the nee d to ensure that information on devices in EUDAMED is not displayed \nto public in a partial or misleading nature,  \nthe obligation for registration in EUDAMED of device data elements listed in \nboth part A, Section 2, and Part B of Annex VI, shall be applicabl e as from the \ntimelines indicated in Article 123(3)(e) (meaning from 18 months after the \ngeneral application date or, if EUDAMED is not fully functional on time, from 24 \nmonths after the date of publication of the notice referred to in Article 34(3)).  \nThis is without prejudice to the fact that the obligation related to the operation of \nassignment of Basic UDI \u2014DI and UDI -DI to devices remains applicable as from the \ngeneral application dates.  \nThis is also without prejudice to the fact that at any time after the general application \ndate, for MDR compliant devices, the full registration of devices (Article 29) remains a \npre-condition for the possible registration of their relevant serious incident in \nEUDAMED  \nThese considerations apply mutatis mutandis  to the IV DR\u201d."}, {"title": "2020-15-position-paper-actor-registration-module_en.pdf.txt", "text": "Medical Devices \nMedical Device Coordination Group Document                                                  MDCG 2020-15       \n \n  \n \n \nMDCG 2020-15 \n  \nMDCG Position Paper on the use of the \nEUDAMED actor registration module and \nof the Single Registration Number (SRN) \nin the Member States  \n \nAugust 2020 \n \n  \n \nThis document has been endorsed by the Medical Device Coordinat ion Group (MDCG) \nestablished by Article 103 of Regulation (EU) 2017/745.  \nThe MDCG is composed of representatives of all Member States an d a representative of the \nEuropean Commission chairs it. The document is not a European C ommission document and \nit cannot be regarded as reflecting the official position of th e European Commission. Any \nviews expressed in this document are not legally binding and on ly the Court of Justice of the \nEuropean Union can give binding interpretations of Union law.   Medical Devices \nMedical Device Coordination Group Document                                                  MDCG 2020-15       \n \n MDCG Position Paper \non the use of the EUDAMED actor registratio n module and of the Single Registration \nNumber (SRN) in the Member States \n \nArticle 33 of Medical Devices Regulation (EU)  2017/745 of the European  Parliament and of \nthe Council of 5 April 2017 (her eafter: \u2018MDR\u2019) sets out that the Commission, after consulting \nthe MDCG, shall set up, maintain and manage the European database on medical devices (EUDAMED). EUDAMED shall be composed of  multiple electronic systems (so called \n\u2018modules\u2019), including an elect ronic system on registration of economic operators, also \nreferred to as the actor registration module .  \nIn accordance with Article 30(1) MDR, the actor registration module shall allow for the \ncreation of a unique single registration number (\u2018SRN\u2019)  referred to in Article 31(2) and to \ncollate and process information that is necessary and proportionate to identify the manufacturer (including producer s of system/procedure packs)  and, where applicable, the \nauthorised representative and the importer. As such, the actor registra tion module forms a pre-\nrequisite for the use of the other EUDAMED  modules and facilitates a secure way of \naccessing EUDAMED. The responsibility to assign  SRNs to economic operators lies with the \nMember States. To that end, Artic le 31(2) stipulates that, after having verified and validated \nthe data entered by an economic operator, the competent authority of a Member State shall obtain an SRN from the actor registration m odule and approve the issuing of it to the \nrequesting manufacturer, authorised representative or importer. \nOn 30 October 2019, the Commission published a notice by which it concluded that the full \nfunctionality of EUDAMED require s the availability and full opera tion of all six modules in \naccordance with the technical specifications and confirmed by an audit as referred to in Article 34. The notice foresees the launch of a fully functional EUDAMED for May 2022. \nHowever, at its meeting of 12 March 2020 th e MDCG agreed that the Commission makes \navailable to Member States each EUDAMED module on a gradual basis as soon as it is \noperational. \nIn line with the MDCG decision referred to above, the Commissi on has confirmed its \nreadiness to deploy the actor registration module as of 1 December 2020. The members of \nthe MDCG  strongly encourage the use of the actor registration module by all relevant \nactors on their territories,  including the use of the single registration number  by actors as \nstipulated in the MDR (e.g. indicating the SRN on certificates). \nThe members of the MDCG agree that double registration requirements for actors should \nbe avoided as much as possible . Therefore, actors that obtai n an SRN should be considered \nin compliance with the actor registration requirements (for manufacturers, authorised \nrepresentatives, importers, system/procedure pack producers) to the extent that national laws accommodate for this. In such cases, thos e actors should follow the obligations and \nrequirements of the MDR related to both the registration of relevant actors (via the actor \nregistration module) and the us e of their SRN as required."}, {"title": "05 MDCG 2020-5 Guidance on Clinical Evaluation - Equivalence.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document   MDCG  2020-5  \n \n  \n \n \n \nMDCG 2020-5 \n  \n Clinical Evaluation - Equivalence \nA guide for manufacturers and notified bodies \n               \n \n April 2020 \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) \nestablished by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of \nrepresentatives of all Member States and it is chaired by a representative of the \nEuropean Commission.The document is not a European Commission document and it \ncannot be regarded as reflecting the official position of the European Commission. Any \nviews expressed in this document are not legally binding and only the Court of Justice \nof the European Union can give binding interpretations of Union law. \n   \nPage 2 of 20 \n  \n \n \n \n \n \n \n \nClinical Evaluation - Equivalence  \nA guide for manufacturers and notified bodies  \n   \nPage 3 of 20 \n 1 Table of contents \n \n1. Introduction .......................................................................................................... 4 \n2. Scope ................................................................................................................... 5 \n3. Equivalence ......................................................................................................... 5 \n3.1 Technical characteristics ............................................................................... 5 \n3.2 Biological characteristics ............................................................................... 6 \n3.3 Clinical characteristics ................................................................................... 9 \n4. Demonstration of equivalence ............................................................................ 10 \n5. Use of data from similar devices ........................................................................ 14 \n6. Clinical data identification ................................................................................... 15 \nAnnex I \u2013 Equivalence table ..................................................................................... 16 \n \n   \nPage 4 of 20 \n 1. Introduction \n \nThis guidance document is not legally binding. It has been put together following \ncontribution from national competent authorities, industry and relevant stakeholders \nand it should therefore be recognised as best practice.  \nThe Regulation (EU) 2017/745 on medical devices1, hereafter referred to as the MDR \n(medical device regulation), provides a possibility to use clinical data related to an \nequivalent device in the clinical evaluation required for a device under conformity \nassessment2. \nWhilst carrying out a clinical investigation is the most direct way to generate clinical \ndata concerning the safety and performance of medical devices for the purpose of CE \nmarking, clinical data can also be sourced from3 \n\uf02d clinical investigation(s) or other studies reported in scientific literature, of a \ndevice for which equivalence to the device in question can be demonstrated, \n\uf02d reports published in peer reviewed scientific literature on other clinical \nexperience of either the device in question or a device for which equivalence to \nthe device in question can be demonstrated \n \nEquivalence shall be demonstrated according to the MDR requirements4. \nThe European Commission has published a guide on clinical evaluation under the \ndirectives 93/42/EEC and 90/385/EEC; MEDDEV 2.7/1 rev. 45. This MEDDEV guide \nshould be used also during the process of demonstrating equivalence under the MDR. \nHowever, it has been recognised that some of the requirements set out in MEDDEV \n2.7/1 rev. 4 are not fully aligned with the MDR and that further guidance to address the \ndifferences would be of benefit to industry and other stakeholders. Only the text of the \nMDR is legally binding. In cases of divergence between the MEDDEV 2.7/1 rev. 4, this \nMDCG guidance and the MDR, the MDR shall take precedence. \nThis MDCG guidance does not introduce any new requirements. \nThe demonstration of equivalence does not remove the requirement to always conduct \na clinical evaluation in accordance with the MDR. It is the demonstration of \nequivalence6 that allows the manufacturer to let clinical data from an equivalent device \nenter the clinical evaluation process of the device in question for the purpose of \nconfirmation of conformity with relevant general safety and performance \n                                                             \n1 Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices \nhttp://eur-lex.europa.eu/legal-content/EN/TXT/?uri=OJ:L:2017:117:TOC   \n2 MDR, Article 61 and Annex XIV Part A. \n3 MDR, Article 2 (48) 2nd and 3rd indent. \n4 MDR, Annex XIV, Part A (3). \n5 MEDDEV 2.7/1 revision 4, Guidelines on medical devices, clinical evaluation: A guide for manufacturers and \nnotified bodies under directives 93/42/EEC and 90/385/EEC \nhttps://ec.europa.eu/growth/sectors/medical-devices/current-directives/guidance_en   \n6 MDR, Annex XIV, Part A (3).  \nPage 5 of 20 \n requirements7. There may also be other sources of clinical data than from an \nequivalent device8 to include in the process of clinical evaluation. \n2. Scope \nThis MDCG guidance covers the demonstration of equivalence, based on data \npertaining to an already existing device on the market9, for the purpose of CE-marking \nunder the MDR.  \nOne of the purposes of this document is to highlight the differences between the MDR \nand the MEDDEV 2.7/1 rev.4 specifically with regards to equivalence. It is also \nintended to provide additional guidance and support a harmonised approach to the \ndemonstration of equivalence across the EU. \nIn addition, non-exhaustive guidance and references have been provided with respect \nto device considerations for medical devices incorporating an ancillary medicinal \nproduct.  \nThis MDCG guidance also covers products without an intended medical purpose listed \nin Annex XVI of the MDR. \n3. Equivalence  \nThe MDR requires10 that technical, biological and clinical characteristics are \nconsidered when demonstrating equivalence to another device. Whilst these general \ncharacteristics are described in the MEDDEV 2.7/1 rev. 4 Appendix 1 and are aligned \nwith the MDR requirement, there are differences in the criteria that are set out for each \nof the three characteristics. Differences in criteria between the MDR and the MEDDEV \n2.7/1 rev. 4 are highlighted below and are accompanied by some explanatory text.  \n3.1 Technical characteristics \n \nMDR, Annex XIV Part A (3) MEDDEV 2.7/1 rev 4, Appendix A1 \nThe device is of similar design;  \nis used under similar conditions of use ;  \nhas similar specifications and properties including \nphysicochemical properties such as intensity of \nenergy, tensile strength, viscosity, surface \ncharacteristics, wavelength and software \nalgorithms ;  \nuses similar deployment methods, where relevant;  \nhas similar principles of operation and critical \nperformance requirements. - be of similar design, and \n- used under the same conditions of use , and \n- have similar specifications and properties (e.g. \nphysicochemical properties such as type and intensity \nof energy, tensile strength, viscosity, surface \ncharacteristics, wavelength, \nsurface texture, porosity, particle size, nanotechnology, \nspecific mass, atomic inclusions such as \nnitrocarburising, oxidability), and \n- use similar deployment methods (if relevant), and \n- have similar principles of operation and critical \nperformance requirements \n \n                                                             \n7 MDR, Article 61 (1) and (3 (a)). \n8 MDR, Article 2 (48) 1st and 4th indent. \n9 Whether the \u2018market\u2019 is presumed to be the EU market or not is related to requirements in Article 61. See \nsection 4 (d) and (e) in this document for further guidance. \n10 MDR, Annex XIV Part A (3).  \nPage 6 of 20 \n (a) The MDR requires that technical characteristics shall be taken into \nconsideration for the demonstration of equivalence including that the device in \nquestion and the device presumed to be equivalent are \u201cused under similar \nconditions of use\u201d. MEDDEV 2.7/1 rev. 4, however, specifies use under the \nsame conditions with regard to technical characteristics11. The conditions of use \nshall be similar to the extent that there would be no clinically significant \ndifference in the safety and clinical performance between the device in question \nand the device presumed to be equivalent. For further guidance on the \nassessment of \u2018similar\u2019, see also section 4 of this document.  \n \n(b) Different examples are given for specifications and properties of the device \nwhen considering technical characteristics across the two definitions. These are \nexamples only and are to be considered as such. They must not be interpreted \nas an exhaustive list of specifications and properties of technical characteristics \nwhen considering equivalence to another device. Note however that the MDR \nspecifically points out that software algorithms  shall be similar in the device \npresumed to be equivalent. This includes software algorithms in software driving \nor influencing the use of a device, and in software intended to be used alone12. \nIt is the functional principle of the software algorithm, as well as the clinical \nperformance(s) and intended purpose(s) of the software algorithm, that shall be \nconsidered when demonstrating the equivalence of a software algorithm. It is \nnot reasonable to demand that equivalence is demonstrated for the software \ncode, provided it has been developed in line with international standards for \nsafe design and validation13 of medical device software. \n \nSoftware solely intended for the configuration of a device (e.g. presentation on \na graphical user interface etc), and not related to any medical purpose14  (e.g. \ndiagnosis, treatment etc), does not need to be similar when considering \nequivalence as long as it can be justified to not negatively affect the usability, \nsafety or clinical performance. \n3.2 Biological characteristics  \n \nMDR, Annex XIV Part A (3) MEDDEV 2.7/1 rev. 4, Appendix A1 \nThe device uses the same materials or substances in \ncontact with the same human tissues or body fluids \nfor a similar kind and duration of contact and \nsimilar release characteristics of substances, \nincluding degradation products and leachables  \n Use the same materials or substances in contact with \nthe same human tissues or body fluids. \nExceptions  can be foreseen for devices in contact \nwith intact skin and minor components of devices; in \nthese cases risk analysis results may allow the use of \nsimilar materials taking into account the role and \nnature of the similar material. \n                                                             \n11 \u201cConditions of use\u201d with regard to technical characteristics may e.g. be environmental factors such as \nmagnetic fields, temperature, moisture, conditions during transport of device in use etc.  \nSee section 3.3 in this document regarding use for the same clinical condition or purpose. \n12 See MDCG 2019-11 Guidance on Qualification and Classification of Software in Regulation (EU) 2017/745 - \nMDR and Regulation (EU) 2017/746 \u2013 IVDR. \n13 E.g. IEC 62304 Medical device software \u2013 Software life cycle processes, and IEC 82304-1 Health software \u2013 \nPart 1: General requirements for product safety. \n14 MDR, Article 2(1).  \nPage 7 of 20 \n (a) Manufacturers must consider the additional text in the MDR and adequately \nspecify all applicable characteristics. The exceptions, outlined in the MEDDEV \n2.7/1 rev 4, to not use the same materials are NOT acceptable under the MDR. \n \nThe MDR requires that biological characteristics shall be taken into \nconsideration for the demonstration of equivalence, i.e. the device uses the \nsame materials or substances  in contact with the same human tissues or body \nfluids for a similar kind and duration of contact, and with similar release \ncharacteristics of substances, including degradation products and leachables, \nas the presumed equivalent device. The distinction between \u201csame materials or \nsubstances\u201d and \u201csimilar release characteristics of substances\u201d is made to \naccount for the fact that processing, design and the use environment may \nintroduce small changes even when the raw materials are the same.  \n \nProcessing can make materials more susceptible to degradation by changing \nproperties of the material and/or by inducing different stresses. For example, \nsmall changes in pH or oxidative stress can increase or decrease release \ncharacteristics. For this reason, it is the final device that shall be assessed. \n \n(b) The principles outlined in ISO 10993 series of standards for the biological \nevaluation of medical devices can be adopted, in particular the ISO 10993-1 for \na risk-based approach to biological evaluation15 and also for material \ncharacterization.  \n \nIn addition, the ISO 10993-18 which covers chemical characterization of \nmaterials can be adopted to specify the identity of materials and to estimate the \ntype and quantity of leachables from the final device.  Annex C of this standard \naddresses biological equivalence. The ISO 10993-17 includes principles on the \ntoxicological risk assessment of leachables. Leachables may include \ndegradation products or other substances from the materials or substances that \nthe device is made of, but also other constituents for example residuals from \nthe manufacturing process or sterilisation, any contaminations etc. Therefore, \nfor the consideration of equivalence, it is the properties and characteristics of \nthe final device that shall be taken into account. \n \nFor degradable materials, ISO 10993, Parts 13, 14 and 15 address the \nidentification and quantification of degradation products. Note, that there may \nbe further parts in the ISO 10993 series of standards that are relevant for the \ndevice in question.  \n \n(c) The MDR has additional requirements16 for devices that are composed of \nsubstances or of combinations of substances  that are intended to be \nintroduced into the human body, and that are absorbed by or locally dispersed \n                                                             \n15 ISO 10993-1 Biological evaluation of medical devices \u2013 Part 1: Evaluation and testing within a risk \nmanagement process, and collateral standards in the 10993 series. \n16 MDR, Annex I, (12.2).  \nPage 8 of 20 \n in the human body. For the consideration of equivalence, the substances shall \nbe the same. \n \nThose devices are not medicinal products, but for the conformity assessment \nthey shall comply with the relevant requirements laid down in Annex I to \nDirective 2001/83/EC17 for the evaluation of absorption, distribution, \nmetabolism, excretion, local tolerance, toxicity, interaction with other devices, \nmedicinal products or other substances and potential for adverse reactions. This \nmeans that for the demonstration of equivalence under the MDR, those aspects \nshall also be taken into consideration. \n \nNote that the requirement18 that the notified body shall seek a scientific opinion \nfrom a competent authority for medicinal products or the EMA, for the device or \nits products of metabolism, that are systemically absorbed by the human body \nin order to achieve their intended purpose, on the compliance with the relevant \nrequirements laid down in Annex I to Directive 2001/83/EC, always applies for \nthe device under evaluation even if equivalence has been demonstrated under \nthe MDR. \n \n(d) The demonstration of equivalence may also concern medical devices with an \nancillary medicinal substance , for example drug-eluting stents or heparin-\nbonded central venous catheters.  \n \nThe MDR requires19 that biological characteristics shall be taken into \nconsideration for the demonstration of equivalence, including that the device in \nquestion and the device presumed to be equivalent, use \u201cthe same materials or \nsubstances in contact with the same human tissues or body fluids\u201d. This applies \nalso to the medicinal substance and any related excipients/coatings.  \n \nExcipients/coatings may potentially have a significant effect for example on the \nrelease characteristics of the medicinal substance intended only for a local \neffect from a stent, and thereby a significant effect on the clinical performance. \n \nIn all cases, concerning the device under evaluation, the notified body shall20   \n\uf02d verify the usefulness of the substance as part of the device, taking \naccount of the intended purpose of the device, and \n\uf02d seek a scientific opinion from a competent authority for medicinal \nproducts or the EMA to ensure that the quality, safety and benefit/risk of \nusing the ancillary medicinal product, including whether the \nmanufacturing process have been adequately assessed. \n \n                                                             \n17 Directive 2001/83/EC relating to medicinal products for human use. \n18 MDR, Annex IX, Chapter II, 5.4 (b). \n19 MDR, Annex XIV Part A (3)  second indent. \n20 MDR, Annex IX, Chapter II, 5.2. (b) and (c).  \nPage 9 of 20 \n Note that medical devices with an ancillary medicinal substance are class III \ndevices21. In cases where a manufacturer intends to claim equivalence to a \ndevice not manufactured by him, the MDR requires that the two manufacturers \nhave a contract in place that explicitly allows the manufacturer of the second \ndevice full access to the technical documentation on an ongoing basis22 . \n \nManufacturers cannot claim equivalence of a device with an ancillary medicinal \nsubstance to a device without an ancillary medicinal substance and vice versa. \nFor example, the manufacturer of a heparin coated catheter shall not claim \nequivalence to a drug-free catheter even if both catheters are otherwise \nidentical23 . See also section 4 of this document.  \n \nSimilarly, manufacturers shall not claim equivalence of the ancillary medicinal \nsubstance to a \u2018standalone\u2019 medicinal substance. \n \n3.3 Clinical characteristics \n \nMDR, Annex XIV Part A (3)  MEDDEV 2.7/1 rev . 4, Appendix A1  \nThe device is used for the same clinical condition or \npurpose , including similar severity and stage of \ndisease, at the same site in the body, in a similar \npopulation, including as regards age, anatomy and \nphysiology;  \nhas the same kind of user ;  \nhas similar relevant critical performance in view of the \nexpected clinical effect for a specific intended \npurpose. - used for the same clinical condition (including when \napplicable similar severity and stage of disease, same \nmedical indication ), and \n- used for the same intended purpose, and \n- used at the same site in the body, and \n- used in a similar population (this may relate to age, \ngender, anatomy, physiology, possibly other aspects), \nand \n- not foreseen to deliver significantly different \nperformances (in the relevant critical performances such \nas the expected clinical effect, the specific intended \npurpose, the duration of use , etc.) \n \n(a) The MDR additionally requires that, for manufacturers to compare clinical \ncharacteristics, the device shall have the same kind of user . The MDR clearly \npoints out that a user means any healthcare professional or lay person who \nuses a device24, and that a lay person means an individual who does not have \nformal education in a relevant field of healthcare or medical discipline25. \nManufacturers must therefore take into consideration whether the intended \nuser\u2019s competence or knowledge can have any implication for the safety, clinical \nperformance and outcome when considering equivalence between the device \nin question and the presumed equivalent device. For example, a device \nintended for professional use and a device intended for home use, but for the \nsame clinical condition or purpose, may have a different safety and performance \nprofile due to the environment in which they are intended to be used.  \n                                                             \n21 MDR, Annex VIII, Rule 14. \n22 MDR, Article 61 (5). \n23 MDR, Annex XIV Part A (3). \n24 MDR, Article 2 (37). \n25 MDR, Article 2 (38).  \nPage 10 of 20 \n  \n(b) The MDR does not explicitly state that the medical device needs to be used for \nthe same medical indication, gender and duration of use  as the equivalent \ndevice. However, it is understood that in general, this is covered by the MDR \nrequirement that both devices should be used for the same clinical condition \nor purpose  including similar severity and stage of disease and also have similar \nrelevant critical performance which is also outlined in the MEDDEV 2.7/1 rev. 4. \nThis is supported by the definitions in the MDR of the \u2018intended purpose\u201926, and \nthe ability of the device to achieve its intended purpose by the \u2018clinical \nperformance\u201927 including measurable \u2018clinical benefit\u201928.  \n4. Demonstration of equivalence   \n \nMDR, Annex XIV Part A (3) MEDDEV 2.7/1 rev. 4, Appendix A1 \nThe characteristics listed in the first paragraph shall be \nsimilar to the extent that there would be no clinically \nsignificant difference in the safety and clinical \nperformance of the device. Considerations of \nequivalence shall be based on proper scientific \njustification .  \n For assuming equivalence, \n- all three characteristics (clinical, technical, biological) \nneed to be fulfilled; \n- similar means that no clinically significant difference \nin the performance and safety of the device would be \ntriggered by the differences between the device under \nevaluation and the device presumed to be equivalent. \n \nThere are a number of prerequisites that shall be fulfilled for the demonstration of \nequivalence: \n(a) The overall considerations of equivalence shall conclude whether the listed \ntechnical, biological and clinical characteristics in the MDR29 are similar to the \nextent that there would be no clinically significant difference in the safety and \nclinical performance of the device. Note that some of the listed characteristics \nin the MDR shall be the same, not only similar. The corresponding wording from \nMEDDEV 2.7/1 rev. 4 is presented for information above. Consideration must \nbe given to the characteristics mentioned above and a gap analysis should be \nconducted by the manufacturer to evaluate any clinically significant \ndifference(s). \nModifications30 of a device may be implemented for a variety of reasons. If the \ndifferences have been introduced to address specific safety and/or performance \nissues it shall be duly justified, that there would be no clinically significant \ndifference in the safety and clinical performance other than the intended \nimprovements related to the specific issue that triggered the modification / \ndifference. For all modifications and concomitant claims of equivalence, there \nmust be no additional risks or potential of negatively altered performance related \nto the introduced modifications. \n                                                             \n26 MDR, Article 2 (12). \n27 MDR, Article 2 (52). \n28 MDR, Article 2 (53). \n29 MDR, Annex XIV Part A (3). \n30 MDR, Article 61 (4).  \nPage 11 of 20 \n See a template example of an Equivalence table in the Annex I of this document. \n \nA manufacturer of a medical device shall not claim equivalence to a product \nwithout an intended medical purpose listed in the MDR Annex XVI. \n \n(b) Manufacturers may identify more than one equivalent device to the device under \nevaluation, but each device shall be equivalent to the device under evaluation \nin all the listed technical, biological and clinical characteristics31. Equivalence to \neach device shall be fully investigated, described and demonstrated in the \nclinical evaluation report.  \nThis means that manufacturers shall not use different parts of different devices \nto claim equivalence to the device under evaluation. The MEDDEV 2.7/1 rev. 4 \nis in line with this approach. \nIn exceptional cases, a deviation from this principle may be considered. There \nmay be device systems comprised of several more or less \u201cstand alone\u201d \ndevices, where it may be justified to consider equivalence of a device in the \nsystem to a presumed equivalent device in a device system already on the \nmarket (by the same manufacturer) provided that all technical, biological and \nclinical characteristics are same/similar32, and that the devices in the system do \nnot affect the safety and performance of each other. This should be duly \ninvestigated and documented both on the level of potential interference between \nthe devices in the system, as well as on the overall safety and clinical \nperformance of the device system. \n \n(c) Regarding the clinical evaluation, the MDR requires33 that the manufacturer \nshall specify and justify the level of clinical evidence necessary to demonstrate \nconformity with the relevant general safety and performance requirements. That \nlevel of clinical evidence shall be appropriate in view of the characteristics of the \ndevice and its intended purpose34. In addition, considerations of equivalence \nshall be based on proper scientific justification35.  \n \nThis implies that technical, biological and clinical characteristics shall be duly \ninvestigated and documented. The manufacturer is expected to fully identify and \ndisclose any differences between the two devices.  \n \nPre-clinical data for the consideration of equivalence should allow a scientifically \nsound evaluation of technical and biological characteristics. Examples of data \nsources: \n                                                             \n31 MDR, Annex XIV Part A (3), the requirement refers to only \u201ca device\u201d and \u201cthe device\u201d. \n32 MDR, Annex XIV Part A (3). \n33 MDR, Article 61 (1) second paragraph. \n34 MDR, Article 61 (1) second paragraph  \nIt may under certain circumstances be justified to demonstrate conformity without support of clinical data, see \nMDR, Article 61 (10), but note that this is not applicable for implantable devices or class III devices. \n35 MDR, Annex XIV Part A (3) \nFor guidance see also MEDDEV 2.7/1 rev 4, Annex A6, Appraisal of clinical data - examples of studies that lack \nscientific validity for demonstration of adequate clinical performance and/or clinical safety.  \nPage 12 of 20 \n \uf02d data from the technical documentation of a manufacturer\u2019s own \npresumed equivalent device (specifications, test-results, \nchemical/physical/biological analyses, data from pre-clinical \ninvestigations etc) \n\uf02d data published in the scientific literature, e.g. animal or other pre-clinical \ndata \nThe assessment of whether any differences in characteristics would result in \nclinically significant difference in safety and clinical performance shall also be \nduly substantiated and based on proper scientific justification. This assessment \nmay be supported by e.g. clinical data from the scientific literature, common \nspecifications (CS)36, harmonised standards or other established technical \nspecifications. \nFurthermore, for the assessment of safety, a risk-based approach37 is expected, \nboth for the identification of characteristics that may affect safety as well as for \nthe final assessment of equivalence regarding safety. \n \nIt is important for the consideration of equivalence that pre-clinical data and any \nclinical data relate to the actual device under evaluation, and to a defined \ngeneration/version of the actual device considered for equivalence, bearing in \nmind that there may be significant differences between different generations of \nthe other device.   \n \nIf a manufacturer is not able to demonstrate sufficient levels of access to the \ndata38 relating to the presumed equivalent device and needed for the \nconsideration of equivalence, equivalence claims cannot be made for the \npurpose of conformity assessment. \n \n(d) The MDR notes specific requirements in addition to the demonstration of \nequivalence in order not to perform a clinical investigation which must be taken \ninto account. \n \nA manufacturer of implantable devices and class III devices  shall perform \nclinical investigations except if the device has been designed by modifications \nof a device already marketed by the same manufacturer  and equivalence can \nbe demonstrated according to the MDR39. In this context, a marketed device is \nconsidered to be a device already placed on the market and CE marked with \nrespect to either the MDR or the directives 93/42/EEC or 90/385/EEC. The CE \nmarking should still be valid, should be based on an updated clinical evaluation, \nand the benefit/risk ratio for this device should be favourable. \n \n                                                             \n36 MDR, Article 2, (71) \u2018common specifications\u2019 (CS) means a set of technical and/or clinical requirements, other \nthan a standard, that provides a means of complying with the legal obligations applicable to a device, process or \nsystem. \n37 ISO 14971 Medical devices \u2013 Application of risk management to medical devices, and also other related \nstandards as applicable e.g. ISO 10993-1 and ISO 10993-18. \n38 MDR, Annex XIV Part A (3) last paragraph. \n39 MDR, Article 61 (4), and Annex XIV (3).  \nPage 13 of 20 \n For a manufacturer of implantable devices and class III devices  claiming \nequivalence to an already marketed device not manufactured by him , in \naddition to the requirements in MDR Article 61(4), the manufacturer must have \na contract in place that allows full access to the technical documentation on an \nongoing basis40. Furthermore, the MDR also requires that the original clinical \nevaluation of the equivalent device has been performed in compliance with the \nrequirements of the MDR. This implies that the presumed equivalent device is \ncertified under the MDR. As such, it will not be possible to claim equivalence to \na device certified with respect to the Directives 93/42/EEC or 90/385/EEC. \n(e) For devices other than implantable devices and class III devices  and where \nthe manufacturer wants to claim equivalence, MDR Article 61 (3) is applicable. \nThis requirement does not specify whether the device is presumed to be \nmarketed within the EU. Therefore, it will be possible to claim equivalence to a \ndevice certified with respect to the Directives 93/42/EEC or 90/385/EEC or the \nMDR.  \nHowever, exceptions can be considered, and equivalence claimed to a device \nthat is not CE-marked, provided all relevant MDR requirements regarding \nequivalence and clinical evaluation can be met. This includes  \n\uf02d that the manufacturer shall have sufficient levels of access to the data \nrelating to devices with which they are claiming equivalence41 . In the \ncircumstance that the presumed equivalent device is from another \nmanufacturer, there is no MDR requirement of a contract between the \nmanufacturers for regulating the access to the technical documentation. \n\uf02d that clinical investigations were conducted in accordance with \ninternational guidelines42  \n\uf02d that the clinical data meet the requirements of the MDR, and a \njustification is provided whether the clinical data are transferrable to the \nEuropean population.  \nThe regulatory status of the presumed equivalent device should be disclosed. \nSee MEDDEV 2.7/1 rev. 4 Appendix A1 for further guidance.  \n \n(f) In case of products without an intended medical purpose  listed in MDR \nAnnex XVI clinical investigations shall be performed for those products unless \nreliance on existing clinical data from an analogous medical device is duly \njustified43. An analogous device, in this context, is understood as a medical \ndevice which is similar in terms of functioning and risks profile and has a medical \npurpose44. To duly justify reliance on existing clinical data from an analogous \n                                                             \n40 MDR, Article 61 (5). \n41 MDR, Annex XIV Part A (3) the last sentence. \n42 MDR, Recital (64) \nClinical investigation of medical devices for human subjects \u2013 Good clinical practice (ISO 14155), and \nWorld Medical Association Declaration of Helsinki on Ethical Principles for Medical Research Involving Human \nSubjects. \n43 MDR, Article 61 (9). \n44 MDR, Recital (12).  \nPage 14 of 20 \n medical device, the principles of demonstration of equivalence45 should be \napplied with the acceptance that the device under evaluation will only have an \naesthetic or another non-medical purpose whereas the analogous device has a \nmedical purpose. The general requirement to demonstrate a clinical benefit46 \nshall be understood as a requirement to demonstrate the performance of the \ndevice.  \n \nIn addition, since the common specifications (CS) for the products without an \nintended medical purpose may have requirements related to the clinical \nevaluation regarding safety47 these requirements must be taken into \nconsideration when demonstrating equivalence and concluding whether there \nwould be no clinically significant difference in the safety48. \n \nThere shall be no significant difference in the safety and performance between \nthe product and the presumed analogous medical device.  \n5. Use of data from similar devices \nThe term \u2018similar devices\u2019 may be understood as devices belonging to the same \ngeneric device group. The MDR defines this49 as a set of devices having the same or \nsimilar intended purposes or a commonality of technology allowing them to be \nclassified in a generic manner not reflecting specific characteristics. \nIn cases where equivalence cannot be demonstrated under the MDR, the data from \nsimilar devices may be useful for a variety of other purposes, for example: \n1. Ensuring that the risk management system is comprehensive by identifying \nrelevant hazards and clinical risks. \n2. Understanding the state of the art, the natural course of disease and \nalternative available treatment options. \n3. Helping to define the scope of the clinical evaluation, by identifying any design \nfeatures in similar devices that pose special performance or safety concerns. \n4. Provide input for clinical investigation design or post-market clinical follow-up \ndesign, and the post-market surveillance system. \n5. Identification of relevant and specified clinical outcome parameters for the \nintended clinical benefits, based on the published clinical data pertaining to the \nsimilar device(s). \n6. To define minimum requirements for a quantified clinical benefit that is \nconsidered clinically relevant, and/or to identify acceptable occurrence rates of \nrisks and adverse events. \n                                                             \n45 MDR, Annex XIV Part A (3). \n46 MDR, Article 61 and Annexes XIV and XV. \n47 MDR, Article 1 (2). \n48 MDR, Annex XIV Part A (3). \n49 MDR, Article 2 (7).  \nPage 15 of 20 \n 6. Clinical data identification \nA clinical evaluation of the device under assessment shall be made according to the \nMDR50. All the clinical data, both favourable and unfavourable shall be identified. This \napplies to clinical data from both the device in question and the device for which \nequivalence can be demonstrated. If the data meet the definition of clinical data as \ndefined in the MDR51, the data shall then progress to data appraisal and analysis in \norder to evaluate whether the clinical data are providing sufficient clinical evidence for \nthe purpose of confirmation of conformity with the relevant general safety and \nperformance requirements (GSPR)52.  \nFor identifying, appraising and analysing available clinical data from the scientific \nliterature to establish clinical evidence53, manufacturers will find facilitative guidance in \nsections 8-10 of MEDDEV 2.7/1 rev. 4.  \nIn the event that the data do not meet the MDR definition of clinical data these are not \nclinical data and cannot be subject to data appraisal, analysis and evaluation for the \npurpose of providing clinical evidence for the confirmation of conformity with the \nrelevant GSPR.  \n \n  \n                                                             \n50 MDR, Annex XIV Part A. \n51 MDR, Article 2 (48). \n52 MDR, Annex I. \n53 MDR, Article 2 (51).  \nPage 16 of 20 \n Annex I \u2013 Equivalence table \nA table, such as the table below, may be used to clearly demonstrate equivalence and \nto identify the supporting data on a device by device basis. The items in the first column \nof the table are examples only and are to be considered as such. They must not be \ninterpreted as an exhaustive list of specifications, properties, parameters and/or \naspects for demonstrating equivalence to another device. \nThe manufacturer should identify differences and place emphasis on the differences \nbetween the two devices rather than the similarities. Considerations shall include the \npotential additive effect of multiple small differences. For further considerations of \nequivalence, see sections 3 and 4 in this document.  \nScientific justifications shall be provided for the different characteristics when claiming \nno clinically significant difference in the safety and clinical performance of the device. \nWhere more than one device is assessed for equivalence, the table should be \ncompleted separately for each presumed equivalent device. The documentation of the \ndemonstration of equivalence shall be included in the clinical evaluation report. \n Medical Device       \nMedical Device Coordination Group Document   MDCG  2020-5  \n \n  \nEquivalence table \nfor the comparison of a device with a presumed equivalent marketed device for the purpose of demonstrating equivalence \n1. Technical \ncharacteristics  \n(add a separate row \nfor each of the \nassessed \ncharacteristics)  Device 1  (under clinical evaluation)  \nDescription of characteristics and  \nreference to specifying documents Device 2 (marketed device) \nDescription of characteristics and  \nreference to specifying documents  Identified differences or  \nconclusion that there are no differences in the \ncharacteristic \nDevice is of similar \ndesign   1.1 \nUsed under similar \nconditions of use \n   1.2 \nSimilar specifications \nand properties \nincluding \nphysiochemical \nproperties such as \nintensity of energy, \ntensile strength, \nviscosity, surface \ncharacteristics, \nwavelength and \nsoftware algorithms    1.3 \nUses similar \ndeployment methods \nwhere relevant   1.4 \nHas similar principles \nof operation and   1.5  \nPage 18 of 20 \n critical performance \nrequirements \nScientific justification why there would be no clinically significant difference in the safety and clinical performance of th e device, OR  \na description of the impact on safety and or clinical performance \n(use one row for each of the identified differences in characteristics, and add references to documentation as applicable) Clinically \nsignificant \ndifference \nYes / No  \n1.1  \n1.2  \n1.3  \n1.4  \n1.5  \n2. Biological \ncharacteristics   \n(add a separate row \nfor each of the \nassessed \ncharacteristics)  Device 1 \nDescription of characteristics and  \nreference to specifying documents Device 2 (marketed device) \nDescription of characteristics and  \nreference to specifying documents  Identified differences or  \nconclusion that there are no differences in the \ncharacteristic \nUses the same \nmaterials or \nsubstances in contact \nwith the same human \ntissues or body fluids     (The characteristic must be the same for the \ndemonstration of equivalence) \n2.1 \nSimilar kind and \nduration of contact \nwith the same human \ntissues or body fluids \n   2.2 \nSimilar release \ncharacteristics of \nsubstances including \ndegradation products \nand leachables   2.3 \nScientific justification why there would be no clinically significant difference in the safety and clinical performance of the device, OR  \na description of the impact on safety and or clinical performance \n(use one row for each of the identified differences in characteristics, and add references to documentation as applicable) Clinically  \nsignificant \ndifference \nYes / No   \nPage 19 of 20 \n 2.1  \n2.2  \n2.3  \n3. Clinical \ncharacteristics   \n(add a separate row \nfor each of the \nassessed \ncharacteristics)  Device 1 \nDescription of characteristics and  \nreference to specifying documents Device 2 (marketed device) \nDescription of characteristics and  \nreference to specifying documents  Identified differences or  \nconclusion that there are no differences in the \ncharacteristic \nSame clinical \ncondition or purpose, \nincluding similar \nseverity and stage of \ndisease   3.1 \nSame site in the body \n   (The characteristic must be the same for the \ndemonstration of equivalence) \n3.2 \n \nSimilar population, \nincluding as regards \nage, anatomy and \nphysiology    3.3 \nSame kind of user \n   (The characteristic must be the same for the \ndemonstration of equivalence) \n3.4 \nSimilar relevant \ncritical performance in \nview of the expected \nclinical effect for a \nspecific intended \npurpose \n   3.5 \nScientific justification why there would be no clinically significant difference in the safety and clinical performance of the device, OR \na description of the impact on safety and or clinical performance \n(use one row for each of the identified differences in characteristics, and add references to documentation as applicable) Clinically \nsignificant \ndifference \nYes / No   \nPage 20 of 20 \n 3.1  \n3.2  \n3.3  \n3.4  \n3.5  \nSummary  \nIn the circumstance that more than one non-significant difference is identified, provide a justification whether the sum of differences may affect the safety and clinical \nperformance of the device."}, {"title": "10-1 MDCG 2020-10-1 Guidance on safety reporting in clinical investigations.pdf.txt", "text": "Page 1 of 16 1 \n   \n \n \n \nMDCG 2020-10/1 \nSafety reporting in clinical investigations \nof medical devices under the  \nRegulation (EU) 2017/745  \n \n May 2020 \n \n \n  \n \n \n  \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) established by Article 103 of Regulation (EU) \n2017/745. The MDCG is composed of representatives of all Member States and it is chaired by a representative of the European \nCommission. \nThe document is not a European Commission document and it cannot be regarded as reflecting the official position of the Europea n \nCommission. Any views expressed in this document are not legally binding and only the Court of Justice of the European Union ca n \ngive binding interpretations of Union law.    \nPage 2 of 16 MDCG 2020-10/1 \nSafety reporting in clinical investigations of medical devices under the Regulation (EU) 2017/745\n \nMay 2020 \n \nTable of contents \n1 INTRODUCTION .................................................. ............................................................... ............................................................... ........................................................ 3  \n1.1 SAFETY REPORTING IN THE ABSENCE OF EUDAMED  .............................................................. ............................................................... ............................................................... ..... 3  \n2 SCOPE ......................................................... ............................................................... ............................................................... ............................................................... . 4 \n2.1 CLINICAL INVESTIGATIONS OF MEDICAL DEVICES  .............................................................. ............................................................... ............................................................... ......... 4  \n2.2 MEDICAL DEVICES USED IN CLINICAL TRIALS OF MEDICINAL PRODUCTS (DRUG TRIALS ) ............................................................. ............................................................... ........................ 4  \n3 DEFINITIONS ................................................... ............................................................... ............................................................... ............................................................ 5  \n3.1 INVESTIGATIONAL DEVICE  .............................................................. ............................................................... ............................................................... ...................................... 5  \n3.2 ADVERSE EVENT (AE) .......................................................... ............................................................... ............................................................... ............................................... 5  \n3.3 SERIOUS ADVERSE EVENT (SAE).......................................................... ............................................................... ............................................................... ................................. 5  \n3.4 DEVICE DEFICIENCY  .............................................................. ............................................................... ............................................................... .............................................. 5  \n4 REPORTING METHOD .............................................. ............................................................... ............................................................... ................................................... 6  \n4.1 TRANSITION TO REPORTING VIA EUDAMED  .............................................................. ............................................................... ............................................................... ............... 6  \n4.2 OVERVIEW OF FORMATS TO BE USED BY SPONSORS WHEN REPORTING TO NCA S .............................................................. ............................................................... ............................. 6  \n4.3 COLLECTING REPORTS FROM INVESTIGATORS  .............................................................. ............................................................... ............................................................... ............. 6  \n5 REPORTABLE EVENTS ............................................. ............................................................... ............................................................... .................................................... 7  \n5.1 EXCEPTIONS FOR PMCF  INVESTIGATIONS ACCORDING TO MDR  ARTICLE 74.1 .......................................................... ............................................................... ................................... 7  \n5.2 REPORTABLE EVENTS OCCURRING IN THIRD COUNTRIES  .............................................................. ............................................................... .............................................................. 7 \n5.3 TRANSITION PERIOD FOR REPORTABLE EVENTS IN PRE -MARKET CLINICAL INVESTIGATIONS INITIATED UNDER DIRECTIVES LEGIS LATION  .............................................................. ........................ 7  \n5.4 TRANSITION FOR REPORTABLE EVENTS IN PMCF  CLINICAL INVESTIGATIONS INITIATED UNDER DIRECTIVES LEGISLATION  .............................................................. .......................................... 8  \n6 REPORT BY WHOM ................................................ ............................................................... ............................................................... ..................................................... 8  \n7 REPORT TO WHOM ................................................ ............................................................... ............................................................... ..................................................... 8  \n8 REPORTING TIMELINES ........................................... ............................................................... ............................................................... .................................................... 8  \n8.1 REPORT BY SPONSOR TO NCA S............................................................... ............................................................... ............................................................... .............................. 8  \n8.2 REPORT BY THE INVESTIGATOR TO THE SPONSOR  .............................................................. ............................................................... ............................................................... ........ 9  \n9 CAUSALITY ASSESSMENT .......................................... ............................................................... ............................................................... .................................................. 9  \n10 REPORTING FORM ................................................ ............................................................... ............................................................... .................................................... 11  \n10.1 COMPLETION GUIDELINES : FORM HEADER  .............................................................. ............................................................... ............................................................... .............. 11  \n10.2 COMPLETION GUIDELINES : EVENT DETAILS  .............................................................. ............................................................... ............................................................... .............. 13  \n11 REFERENCES .................................................... ............................................................... ............................................................... ......................................................... 16  \n12 APPENDIX \u2013 CLINICAL INVESTIGATION SUMMARY SAFETY REPORTING FORM  .............................................................. ............................................................... .......... 16  \n   \nPage 3 of 16 1 Introduction \n \nSafety reporting in clinical investigations of medical devices shall be performed in line with the requirements of the Regulat ion (EU) 2017/745 \u2013 \nMedical Device Regulation (MDR) Article 80(2):   \nThe sponsor shall report, without delay to all Member States in  which the clinical investigation is being conducted, all of th e following by means of \nthe electronic system referred to in MDR Article 73:  \na) any serious adverse event that has a causal relationship with t he investigational device, the comparator or the investigation procedure or \nwhere such causal relationshi p is reasonably possible;  \nb) any device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention ha d not occurred, \nor circumstances had been less fortunate;  \nc) any new findings in relation to any event referred to in points  a) and b).  \nThe period for reporting shall take account of the severity of the event. Where necessary to ensure timely reporting, the spon sor may submit an \ninitial report t hat is incomplete followed up by a complete rep ort.  \nUpon request by any Member State in which the clinical investig ation is being conducted, the sponsor shall provide all informa tion referred to in \nparagraph 1. \nFor post-market clinical follow up (PMCF) investigations of CE- marked devices1 used within the intended use covered by the CE-marking, report ing \nrequirements of MDR Article 80(5) and (6) apply. This means tha t the vigilance provisions laid down in Articles 87 to 90 and i n the acts adopted \npursuant to Article 91 shall apply for PMCF clinical investigat ions. However, this guidance document is still relevant for PMC F clinical investigations \nas the reporting of serious adverse events where a causal relat ionship to the preceding investigational procedure has been est ablished shall follow \nthe reporting procedures of clin ical investigations as outlined  in Article 80. \n1.1 Safety reporting in the absence of Eudamed \nSince the electronic system referred to in Article 73 (Eudamed)  will not be available and fully functional at the Date of appl ication of the MDR this \nguidance outlines the procedures for safety reporting in clinic al investigations in the absence of Eudamed.  \nThis document defines Serious Ad verse Event (SAE) reporting mod alities and includes a summary tabulation reporting format. \n  \n                                                           \n1 The PMCF investigations referred to in MDR Article 74(1).  \nPage 4 of 16 2 Scope \n2.1 Clinical investigation s of medical devices \nThe reporting modalities and format set out in this guidance ap ply to:   \n\u0081 Pre-market clinical investigations  covered by Articles 62 and 74(2) of the MDR conducted with: \na) Non-CE marked devices, \nb) CE marked devices used outside the intended use(s) covered by t he CE-marking. \nc) The term pre-market clinical inv estigation may also include som e studies covered by MDR Article 82.  \n \nAs MDR Article 82 allows member states to define national requi rements for such clinical investigations, sponsors are encourag ed to check \nwith the applicable NCA2 whether this guidance or other reporting procedures should be applied. \nIn situations where a clinical investigation has started using a non-CE marked device, and the right to bear the CE marking ha s been obtained \nbefore the end of the clinical investigation, the SAE reporting  continues  until  completion of the investigation, according  to the clinical \ninvestigation plan and these guidelines apply throughout the SA E reporting period. \n \nFor pre-market clinical investigations involving CE marked comp arator devices used within their intended purpose, SAEs occurri ng in or to \nsubjects that are in the comparator arm of an investigation sha ll also be reported in accordance with these guidelines.  \n \nNote: SAEs concerning CE marked devices which meet the vigilanc e reporting criteria also need to be handled under the post-mar ket \nsurveillance/vigilance system.  \n \n\u0081 Those Post-Market Clinical Follow Up (PMCF) investigations  that involve procedures additional to those performed under th e normal \nconditions of use of the device, and where those additional pro cedures imposed by the clinical investigation plan are invasive  o r  \nburdensome, covered by MDR Article 74(1). For these clinical in vestigations the safety reporting for events pertaining to MDR Article 80(6) \nfollow the Serious Adverse Event reporting process only, and ar e outlined in this guidance. Events pertaining to MDR Article 8 0(5) are \nreported following the vigilance process only and are outside t he scope of this guidance. \n \n\u0081 Note that other post-market clinical investigations may be subj ect to safety reporting requirements in line with this guidance  due to \nnational requirements following MDR Article 82, but there is no  such general requirement. Sponsors are encouraged to check wit h the \napplicable NCA whether this guidance or other reporting procedu res should be applied. \n \n\u0081 Due to the transitional provisions in MDR Article 120(11) this guidance also covers clinical investigations which have started  to be conducted \nin accordance with Article 10 of Directive 90/385/EEC (AIMDD) o r Article 15 of Directive 93/42/EEC (MDD) prior to 26 May 2021.  These \ninvestigations may continue to be conducted after date of appli cation of the MDR, but the reporting of serious adverse events and device \ndeficiencies shall be carried out in accordance with the MDR re quirements from 26 May 2021 and onwards.  \n2.2 Medical devices used in clinical  trials of medicinal products ( drug trials)  \n\u0081 A CE-marked device which is used outside its intended purpose, or a non-CE marked device in a clinical drug trial would implic itly have to \nbe assessed for safety and performance and the study shall foll ow both MDR (Chapter VI) and the applicable legislation for cli nical drug \ntrials. This guidance document is then relevant for compliance with the MDR regarding safety reporting.  \n \n                                                           \n2 For the purpose of this guidance,\" NCAs\" encompasses the Natio nal Competent Authorities of the EEA, Switzerland and Turkey.   \nPage 5 of 16 \u0081 If a drug-device study (or a drug trial) is not undertaken to a ssess the safety or performance of a device used in the study, the reporting \nrequirements of MDR Article 80 do not apply, as long as the dev ice is CE marked and used within its intended purpose. This gui dance is not \napplicable, but the vigilance re porting provisions of MDR apply  in those situations, as for any commercially available device.  Sponsors \nshould make sure that the device manufacturer is notified about  any incidents related to the device and the legal manufacturer  of the \ndevice is responsible for the subsequent vigilance reporting.  \n \n3 Definitions  \n3.1 Investigational device  \nA device that is assessed in a  clinical investigation  \n(MDR Article 2(46)) \n \nNote: An investigational device can be a non-CE marked device o r a CE marked device. The definition in MDR Article 2(46) does not differentiate \nbetween different regulatory statuses of devices. However, the reporting requirements are different depending on whether the c linical \ninvestigation is done for purposes described in Article 62, 74 or 82. The definition is understood to cover also the devices i nvestigated in PMCF \ninvestigations, even if they are not subject to notification pe r Art 74.1. \n3.2 Adverse Event (AE)  \nAny untoward medical occurrence, unintended disease or injury o r any untoward clinical signs, including an abnormal laboratory  finding, \nin subjects, users or other persons, in the context of a clinic al investigation, whether or not related to the investigational  device.  \n(MDR Article 2(57)) \nNote:  \na. This definition includes events that are anticipated as well as  unanticipated events \nb. This definition includes events occurring in the context of a c linical investigation related to the investigational device, th e comparator or \nthe procedures3 involved. \n3.3 Serious Adverse Event (SAE)  \nAny adverse event that led to any of the following:  \na) death,  \nb) serious deterioration in the health of the subject, that result ed in any of the following:  \ni. life-threatening illness or injury,  \nii. permanent impairment of a body structure or a body function,  \niii. hospitalisation or prolongation of patient hospitalisation,  \niv. medical or surgical intervention to prevent life-threatening il lness or injury or permanent impairment to a body structure or a body \nfunction,  \nv. chronic disease,  \nc) foetal distress, foetal death or a congenital physical or menta l impairment or birth defect \n(MDR Article 2(58)) \n3.4 Device deficiency  \nAny inadequacy in the identity, quality, durability, reliabilit y, safety or performance of an i nvestigational device, includin g malfunction, use errors \nor inadequacy in information supplied by the manufacturer.  \n                                                           \n3 For the purpose of safety reporting all activities related to the use of a medical device may be considered procedures  \nPage 6 of 16 (MDR Article 2(59)) \n \n4 Reporting method \nA new template for the Summary Reporting Form should be used fo r all studies from 26 May 2021. The tabular format featured in the Appendix \nneeds to be filled in/updated for each reportable event or for new findings/updates to already reported events. It shall be tr ansmitted to all NCAs \nwhere the clinical investigation is being performed. \nFor more details on how to complete the form refer to section 10. Reporting form .  \n4.1 Transition to reporting via Eudamed \nOnce Eudamed is available and fully functional the obligations and requirements that relate to performing safety reporting via  Eudamed shall apply \nfrom the date corresponding to six months after the date of pub lication of the notice referred t o in Article 34(3) of the MDR.  \n4.1.1 Ongoing events at time of transition to Eudamed \nIt is acknowledged that at the time of transition to reporting via Eudamed, there will be ongoing events for which initial rep orts have been made \naccording to the procedures described in this document. For the se reportable events follow-up and final reports will be submit ted to the NCAs by \nthe same procedure, but all new reportable events shall be ente red in Eudamed.  \nWhether retrospective uploading of previous event reports to Eu damed will be possible is not clear at the time this guidance i s issued.  \n4.2 Overview of formats to be used b y sponsors when reporting to NC As \n \nUnder directives legislation \nUntil May 25th, 2021: The tabular format from MEDDEV 2.7/3 Appe ndix I should be used  \nTransition period \nFrom May 26th, 2021 \nand until Eudamed is \navailable The Tabular format of this guidance (Appendix- Summary Reporting  \nForm) should be used.  \nWhen Eudamed is \navailable but not yet mandatory and until the timepoint when Eudamed becomes mandatory Either the Tabular format of this guidance (Appendix- Summary \nReporting Form) or the Eudamed web form can be used.  Note: Once the shift to Eudamed reporting has been made for a s pecific \nclinical investigation, Eudamed should continue to be used for reporting \nall new events and updates to those events throughout the remai nder \nof the clinical investigation. \nFrom the timepoint when Eudamed is mandatory*\n*From the date corresponding to six months after the date of publication of the notice referred to in Article 34(3) of the \nMDR. Web form via Eudamed shall be used for all new events, and upda tes to \nthose events.  \nThe Tabular format of this guidance (Appendix- Summary Reporting  \nForm) can be used only to transmit follow-up reports/final repo rts to \nthe NCAs on events which were in itially reported in this format .  \n \n \n4.3 Collecting reports from investigators \nThe format in which sponsors wish to receive single event repor ts from investigators will be up to the sponsor to design and t hey may be adapted \nto an individual clinical investigation. When sponsors design s uch reporting forms, they should consult this guidance document  to  e ns ure  al l  \nrelevant details are captured in the reports from the investiga tor, so that the sponsors can fu lfil their reporting obligation s.  \nPage 7 of 16  \n5 Reportable events  \nFor the purpose of this guidance and based on the definitions a bove, the following events are considered reportable events in accordance \nwith MDR Art. 80(2):  \na) any serious adverse event that has a causal relationship with t he investigational device, the comparator or the investigation procedure or \nwhere such causal relationship is reasonably possible;  \nb) any device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention ha d not \noccurred, or circumstances had been less fortunate;  \nc) any new findings in relation to any event referred to in points  a) and b).  \nSerious adverse events related to a CE marked device which is p art of the investigation procedure (for example a CE-marked imp lanting tool used \nin combination with a non-CE marked investigational device) are  reportable per MDR Article 80(2) if there is a causal, (or rea sonably possible) \nrelationship to the device, the comparator or the investigation  procedure. The reporting procedures described in this guide sh ould then be \nfollowed in addition to the normal vigilance reporting procedur es for CE marked devices.  \nAll causality assessments should be made using the guidance in section 9. Only causality level 1 (i.e. \u201cnot related\u201d) is exclu ded from reporting. If \neither the sponsor or the investigator has assigned a higher ca usality level than \"not related\", the event should be reported.  \n5.1 Exceptions for PMCF investigatio ns according to MDR Article 74. 1 \nFollowing Article 74.1 the SAE reporting for these PMCF clinica l investigations is governed b y Articles 80(5) and 80(6).  \nThis means that the provisions o f vigilance laid down in Articl es 87-90 and acts adopted pursuant to Article 91 shall apply. H owever, the SAEs \nwhere a causal relationship between the serious adverse event a nd the preceding investigational procedure has been established  shall follow the \nreporting procedures of clinical investigations as outlined in Article 80.  \nFor the purpose of this guidance reportable events in PMCF clin ical investigations are thus those serious adverse events where  a causal relationship \nbetween the serious adverse event and a preceding investigation al procedure has been established.  \n\u201cPreceding investigational procedure\u201d shall be understood as a procedure which is imposed by th e Clinical Investigation Plan a nd which has taken \nplace before (or coincided in time) with the serious adverse ev ent. This includes but is not limited to the burdensome or inva sive procedure(s) \nwhich defines whether the study is subject to notification requ irements following MDR article 74(1).  \n5.2 Reportable events occurring in Third Countries \nReportable events occurring in Third Countries4 in which a clinical investigation is performed under the same clinical investigation plan \nhave to be reported in accordance with this guidance to the NCA (s) of the European countries in which the clinical investigati on is being \nconducted.  \n\u0081 The NCA shall start receiving the reportable events occurring i n Third Countries as soon as the clinical investigation is auth orised to start in \nthat Member State.  \n\u0081 Events occurring in Third Countries after the participating Eur opean sites have closed shall continue to be reported.  \n5.3 Transition period for reportable events in pre-market clinical investigations initiated und er directives legislation \nIt is acknowledged that the MDR implies changes to the reportin g requirements compared to the directives\u2019 requirements where a ll SAEs should \nbe reported regardless of relatedness. Under MDR sponsors are n o longer obliged to report SAEs that are \u201cnot related\u201d to the c linical investigation \n                                                           \n4 Countries other than Switzerland, Turkey and those belonging t o the EEA.  \nPage 8 of 16 procedures or the investigational device. At the date of applic ation for MDR there will be ongoing events for clinical investi gations initiated under \ndirectives legislation. As from the 26th of May 2021 sponsors are no longer expected to submit follow-u p reports to NCAs for events that have been \ndeemed \u201cnot related\u201c (see section 9 of this document for guidan ce on causality assessment). For ongoing events that have a cau sality assessment \nother than \u201cnot related\u201d follow up reports will still have to b e provided.  \nTo facilitate the transition and give time for sponsors to upda te Clinical Investigation Plans and study procedures in clinica l investigations a sponsor \nmay continue to report all SAEs t o NCAs until Eudamed reporting  is mandatory (see section 4.1 Transition to reporting via Euda med). This applies \nonly to studies which have started to be conducted5 in accordance with Article 10 of Directive 90/385/EEC or Artic le 15 of Directive 93/42/EEC \nprior to 26 May 2021.  \n5.4 Transition for reportable events in PMCF clinical investigation s initiated under dire ctives legislation  \nIn case of PMCF studies which required SAE reporting according to the Pre-MDR national legislations, MDR article 80 (5) and 80 (6) shall apply from \nMay 26th, 2021.  \n \n6 Report by whom  \nReportable events have to be reported by the sponsor of the cli nical investigation, which could be the manufacturer, the legal  representative \nor another person6 or entity,. \n \n7 Report to whom  \nReportable events must be reported at the same time to all NCAs  where the clinical investigation has commenced using the summary tabulation \nfeatured in the Appendix.  \nA list of clinical investigation contact points within the NCAs  is published at the Commission's homepage. \nFor the purpose of this guidance, an investigation is considere d to have commenced in an individual Member State: \n\u2022 For investigations under the directives: When the sponsor is au thorized to start the investigation in accordance with the noti fication \nprocedures in that Member State. \n\u2022 For investigations started under the MDR: When the sponsor is a uthorized to start the investigation in that Member State in ac cordance \nwith the provisions laid out in the MDR. \nMember States may also require separate reporting to the Ethics  Committee(s). \n \n8 Reporting timelines  \n8.1 Report by sponsor to NCAs.  \nThe sponsor must report to all NCAs where the clinical investig ation is authorised to start: \n\u2022 For all reportable events as described in section 5 which indic ate an imminent risk of death, serious injury, or serious illne ss and that \nrequires prompt remedial action for other patients/subjects, us ers or other persons or a new finding to it: Immediately, but not later \n                                                           \n5 For the purpose of safety reporting this is defined as \u201cAuthor ised to start in the individual Member State in line with appli cable directives legislati on, regardless of whether \nany subjects have been recruited in the Member State or not.\u201d  \n6 Contact person established by the sponsor in line with Article  62(2) if accepted by Member State.   \nPage 9 of 16 than 2 calendar days after awareness by sponsor of a new report able event or of new information in relation with an already re ported \nevent. \nThis includes events that are of significant and unexpected nat ure such that they become alarming as a potential public health  hazard. It \nalso includes the possibility of multiple deaths occurring at s hort intervals. \nThese concerns may be identified by either the NCA or the manuf acturer. \n \n\u2022 Any other reportable events as described in section 5 or a new finding/update to it: Immediately, but not later than 7 calendar days \nfollowing the date of awareness by the sponsor of the new repor table event or of new information in relation with an already r eported \nevent.  \nIn some cases, a different periodicity or different modalities may be agreed between the participating NCAs and the sponsor ac cording to the \ninvestigation\u2019s design and to the pathology under clinical inve stigation. This would allow implementation of adequate provisio n for clinical \ninvestigations in which SAE frequency is expected to be high du e to the natural progression of the disease (e.g. palliative on cology). \n8.2 Report by the investigator to the sponsor  \nThe sponsor shall implement and maintain a system to ensure tha t the reporting of the reportable events as defined under chapt er 5 will be \nprovided by the investigator to the sponsor immediately, but no t later than 3 calendar days after investigation site study per sonnel\u2019s \nawareness of the event.  \n9 Causality assessment  \nThe relationshi p between the use of the medic al device7 (including the medical - surgical procedure) and the occurrence  of each adverse event \nshall be assessed and categorized.  \nD u r i n g  c a u s a l i t y  a s s e s s m e n t  a c t i v i t y ,  c l i n i c a l  j u d g e m e n t  s h a l l  be used and the relevant documents, such as the Investigator\u2019s Brochure, the \nClinical Investigation Plan or the Risk Analysis Report shall b e consulted, as all the foreseeable serious adverse events and the potential risks are \nlisted and assessed there8. The presence of confounding factors, such as concomitant medi cation/treatment, the natural history of the underlying \ndisease, other concurrent illness or risk factors shall also be  c o n s i d e r e d .  \nThe above considerations apply also to the serious adverse even ts occurring in the comparison group. \nFor the purpose of harmonizing reports, each SAE will be classi fied according to four different levels of causality: \n1. Not related \n2. Possible \n3. Probable \n4. Causal relationship \nThe sponsor and the investigators will use the following defini tions to assess the relationship of the serious adverse event t o the investigational \ndevice, the comparator or the investigation procedure. \n1. Not related: Relationship to the device, comparator or procedur es can be excluded when: \n- the event has no temporal relationship with the use of the inve stigational device, or the procedures related to application of  the \ninvestigational device; \n                                                           \n7 Intended as both investigational device and comparator.  \n8 For a comparator device, the Operator\u2019s Manual could be a rele vant document.  \nPage 10 of 16 - the serious adverse event does not follow a known response patt ern to the medical device (if the response pattern is \npreviously known) and is biologically implausible; \n- the discontinuation of medical device application or the reduct ion of the level of activation/exposure - when clinically feasi ble - \nand reintroduction of its use (or increase of the level of acti vation/exposure), do not impact on the serious adverse event; \n- the event involves a body-site or an organ that cannot be affec ted by the device or procedure; \n- the serious adverse event can be attributed to another cause (e .g. an underlying or concurrent illness/ clinical condition, an  effect \nof another device, drug, treatment or other risk factors); \n- the event does not depend on a false result given by the invest igational device used for diagnosis9, when applicable; \nIn order to establish the non-relatedness, not all the criteria  listed above might be met at the same time, depending on the t ype of \ndevice/procedures and the serious adverse event. \n2. Possible: The relationship with the use of the investigational device or comparator, or the relationship with procedures, is w eak but \ncannot be ruled out completely. Alternative causes are also pos sible (e.g. an underlying or concurrent illness/ clinical condi tion or/and \nan effect of another device, drug or treatment). Cases where re latedness cannot be assessed, or no information has been obtain ed \nshould also be classified as possible. \n3. Probable: The relationship with the use of the investigational device or comparator, or the relationship with procedures, seem s \nrelevant and/or the event cannot be reasonably explained by ano ther cause. \n4. Causal relationship: the serious  adverse event is associated with the investigational device, co mparator or with procedures beyond \nreasonable doubt when: \n- the event is a known side effect of the product category the de vice belongs to or of similar devices and procedures; \n- the event has a temporal relationship with investigational devi ce use/application or procedures; \n- the event involves a body-site or organ that \no the investigational device or procedures are applied to; \no the investigational device or procedures have an effect on; \n- the serious adverse event follows a known response pattern to t he medical device (if the response pattern is previously known) ; \n- the discontinuation of medical device application (or reduction  of the level of activation/exposure) and reintroduction of its  use \n(or increase of the level of activation/exposure), impact on th e serious adverse event (when clinically feasible); \n- other possible causes (e.g. an underlying or concurrent illness / clinical condition or/and an effect of another device, drug o r \ntreatment) have been adequately ruled out; \n- harm to the subject is due to error in use; \n- the event depends on a false result given by the investigationa l device used for diagnosis10, when applicable; \nIn order to establish the relatedness, not all the criteria lis ted above might be met at the same time, depending on the type of \ndevice/procedures and the serious adverse event. \n                                                           \n9 If an investigational device gives an incorrect diagnosis, the  patient might, for example, receive an unnecessary treatment a nd incur all the risks that accompany that \ntreatment, or might be incorrectly diagnosed with a serious dis ease. In other cases, the patient might not receive an effectiv e treatment (thereby missing out on the benefits \nthat treatment would confer) or might not be diagnosed with the  correct disease or condition. \n10 If an investigational device gives an incorrect diagnosis, the  patient might, for example, receive an unnecessary treatment a nd incur all the risks that accompany that \ntreatment, or might be incorrectly diagnosed with a serious dis ease. In other cases, the patient might not receive an effectiv e treatment (thereby missing out on the benefits \nthat treatment would confer), or might not be diagnosed with th e correct disease or condition.  \nPage 11 of 16 The sponsor and the investigators will distinguish between the serious adverse events related to the investigational device an d those related to \nthe procedures (any procedure specific to the clinical investig ation). An adverse event can be related both to procedures and the investigational \ndevice. Complications caused by concomitant treatments not impo sed by the clinical investigation plan are considered not relat ed. Similarly, \nseveral routine diagnostic or patient management procedures are  applied to patients regardless of the clinical investigation p lan. If routine \nprocedures are not imposed by the clinical investigation plan, complications caused by them are also considered not related.  \nIn some particular cases the event may not be adequately assess ed because information is insufficient or contradictory and/or the data cannot \nbe verified or supplemented. The sponsor and the Investigators will make the maximum effort to define and categorize the event  a n d  a v o i d  \nthese situations. Where an investigator assessment is not avail able and/or the sponsor remains uncertain about classifying the  serious adverse \nevent, the sponsor should not exclude the relatedness; the even t should be classified as \u201cpossible\u201d and the reporting not be d elayed.  \nParticular attention shall be given to the causality evaluation  of unanticipated serious adverse events. The occurrence of una nticipated events \nrelated could suggest that the clinical investigation places su bjects at increased risk of harm than was to be expected before hand. \n \n10 Reporting form  \nThe reporting form template for the summary SAE tabulation is g iven in the Appendix of this document.  \nThe reporting form is study specific and covers only a given cl inical investigation, defined by a distinct clinical investigat ion plan. English is the \nrecommended language for the reporting form. The report form ca n be modified in any applicable software (not only Microsoft Ex cel) but \nthe file needs to be compatible with Microsoft Excel when sent to the participating NCAs.  \nThe template form contains inserted filters and functionality t o facilitate use of preferred terminology in the reporting. The se are important for the \nanalysis and should be maintained. \nSponsors who generate the excel report file by automated proces ses may implement other technical features in their systems for  e x c e l  f i l e  \ngeneration to ensure the preferred terms listed in metadata are  used.  \nThe table gives a cumulative overview of the reportable events per clinical investigation and will be updated and transmitted to participating \nNCAs each time a new reportable event or a new finding to an al ready reported event is to be reported. More detailed informati on has to be \nprovided on request of an NCA, if so requested by using the ind ividual study specific reporting form (see further section 4.3 Collecting reports \nfrom investigators ).  \n10.1 Completion guidelines: Form header \n10.1.1  EUDAMED/CIV-ID \nThe union-wide Single Identification Number mentioned in MDR Ar ticle 70(1) will not be possible to generate until Eudamed for MDR is fully \nfunctional. For the transition period, clinical investigations will get tracking numbers (CIV-ID) upon registration in the Eud amed2 database which \nis performed by the NCA upon receipt of an application. This CI V ID is provided to the sponsor during the NCA\u2019s handling of th e initial application \nfor the clinical investigation and should be entered on the saf ety reporting form.  \nThe CIV ID should already be available for a clinical investiga tion started under the directives\u2019 legislation, where it should  be indicated on the \nMEDDEV 2.7/3 reporting form etc. Sponsors who are not aware of the CIV ID of their clinical inv estigations are invited to cont act the concerned \nNCA to get this information.  \nPage 12 of 16 10.1.2  Title of Clinical Investigation  \nThe identifying title of the Clinical Investigation. The title indicated here should be consistent with other title entries (s uch as in clinical investigation \napplication form, clinical inves tigation plan cover page etc).  \n10.1.3  CIP number/code \nThe unique identification code or short name assigned to the sp ecific clinical investigation pl an by the Sponsor (numeric, alp hanumeric or acronym) \nshould be indicated.  \n10.1.4  Contact person \nName, address, e-mail and telephone number should be provided f or the person who is sponsor\u2019s point of contact in case NCA hav e follow up \nquestions regarding submitted safety report forms.  \n10.1.5  MS+NCA Reference numbers \nFor each participating Member State indicate the country code11 and the NCA\u2019s national reference number for the clinical inves tigation.  \nExample:  \nSE 5.1-20YY-XXXXXX DK 20YYXXXXXX \n10.1.6  No. of subjects enrolled to date total \nIndicate the total number of subjects who have been enrolled (p er date of report) in the clinical investigation globally.  \n10.1.7  No. of subjects enrolled to date per country \nList all countries where the clinical investigation has been au thorised by date of report and indicate the number of subjects who have been enrolled \nin the clinical investigation (per date of report) in each coun try.  \n10.1.8  Device type \nIndicate the type of device(s) assessed in the clinical investi gation (e.g. pacemaker, coronary stent, hip implant).  \n10.1.9  Reference Member State \nIndicate the name of the Member State which drew the unique EUD AMED/CIV ID (normally the first Member State receiving an appli cation for \nthe clinical investigation). Once the coordinated assessment pr ocedure (per MDR Article 78) is up and running, the coordinatin g Member State \nshould be indicated here.  \n10.1.10  No. of investigational devices used to date total \nIndicate the total number of investigational devices which have  been used (per date of report) in the clinical investigation g lobally.  \n10.1.11  No. of investigational devic es used to date per country \nList all countries where the clinical investigation has been au thorised by date of report and indicate the number of investiga tional devices which \nhave been used in the clinical investigation (per date of repor t) in each country. \n10.1.12  Date of report \nIndicate the date when the report is compiled for transmission to NCAs. Format DD/MM/YYYY.  \n                                                           \n11 Use ISO-3166-1 alpha-2 codes, i.e.two-letter country codes as defined in ISO 3166-1  \nPage 13 of 16 10.2 Completion guidelines: Event details \nEach unique reportable event is presented in a separate line. U pdates to a previously reported event should be made by changin g the information \nin the same line, and clearly identified according to the princ iples described below.  \nAny new information added in the form should be highlighted in bold and/or colour. This includes any new lines added and any c hanges made \nto the information in an already existing line.  \nIn the initial report, in any given line, no fields shall be le ft intentionally blank. To meet this requirement, preliminary i nformation should be filled \nin, despite the need of further updating.  \n10.2.1  Status  \nThe sponsor shall identify the new/updated information in the s tatus column as: \nA = added = new reportable event; M = modified = new finding/update to an already reported event;   \nU = unchanged. \n10.2.2  Date Sponsor received report of SAE/DD \nIndicate the date when the sponsor was first notified by the in vestigation site about the event. This date is checked for comp liance with reporting \ntimelines as outlined in section  8 Reporting timelines .  \nFormat DD/MM/YYYY. \n10.2.3  Country code \nIndicate the country code\n11 for the country in which the subject associated with the event  has been enrolled. \n10.2.4  Investigation site \nName identifying institution or site where the clinical investi gation is carried out.  \n10.2.5  Subject ID code \nThe study specific subject ID code, i.e. the link between study  data and the actual subject identity (which is not to be provi ded in this form).  \n10.2.6  SAE ID code \nThe investigator, sponsor or manufacturer should assign a uniqu e ID to each SAE that has occurred, This number shall remain un changed \nthroughout all other alterations of the particular SAE-reportin g due to ongoing assessment. \n10.2.7  Date of procedure/First use \nIndicate the date of the relevant procedure or the date when th e subject was exposed to the dev ice for first use. Format DD/MM /YYYY. \n10.2.8  Date of event onset \nThe date when the first signs of an event were noticed may be d ifferent (earlier) than the date when the event fulfilled the s eriousness criteria \n(see further the definition in section 3.3 Serious Adverse Even t (SAE)). The date when the event became an SAE should be repor ted as Date of \nevent onset. In case of Device Deficiencies which did not lead to an SAE, the date the DD was discovered should be indicated.  \nFormat DD/MM/YYYY. \n10.2.9  SAE or DD \nChoose one option from SAE(Seriou s Adverse Event) or DD (Device  Deficiency).  \nDo not add other options.  \nPage 14 of 16 10.2.10  Age \nThe subject\u2019s age at date of event onset should be indicated.  \nIn cases where exact date of birth is not available as a basis for age calculation, it is acknowledged that an approximate age  at date of event onset \ncould be calculated based on the age at enrollment.  \nNormally the Age should be indicated in Years, although for pae diatric/neonatal populations it may be more relevant to indicat ed age in months, \nweeks or days. When a different unit than years is used, the un it should be indicated as appropriate. \n10.2.11  Patient gender \nChoose one option from the following list (do not add other opt ions):  \n\u0081 Female \n\u0081 Male \n\u0081 Other \n\u0081 Unknown \n10.2.12  Location of device \nFor this field, it is the location of the device at the time th e report is submitted to NCA is of interest (i.e not at the tim e of investigator or sponsor \nawareness of the event). Changed location of the device is in i tself not a reason to provide an updated report. However, whene ver an update/final \nreport is provided for other reasons, it is relevant to update this field if the device for example has reached the sponsor by  then. \nChoose one option from the following list (do not add other opt ions): \n\u0081 Investigational/study site \n\u0081 Sponsor \n\u0081 Subject \n\u0081 Manufacturer \n\u0081 Remains implanted \n\u0081 Discarded \n\u0081 Unknown \n\u0081 Other \n10.2.13  Classification of event \nChoose one option from the following list of consequence charac teristics (do not add other options):  \n\u0081 Death \n\u0081 Life-threatening illness or injury \n\u0081 Permanent impairment/ Chronic disease \n\u0081 Hospitalization \n\u0081 Medical or surgical intervention \n\u0081 Foetal distress, f\u0153tal death or congenital physical or mental o r birth defect \n\u0081 Not applicable (Note that this option is only to be selected in  case of reportable Device deficiencies that did not lead to an  SAE)  \nPage 15 of 16 It is acknowledged that for a specific event two or more option s may be equally applicable, e.g. \u201d Hospitalization\u201d and \u201cmedica l intervention\u201d. The \nhighest-ranking classification should be indicated, using the f ollowing ranking order: 1) Death , 2) life threatening, 3) foeta l distress, 4) permanent \nimpairment, 5) Medical or surgic al intervention 6) hospitalizat ion. \n10.2.14  Description of event \nProvide a description of the event in free text. Below is a non -exhaustive list of items that  could be relevant to cover:  \n\u0081 Nature of the observed symptoms \n\u0081 Duration and severity of the symptoms \n\u0081 Date of onset of first signs of the event (before it became a S AE) \n\u0081 Medical background of the patient \n\u0081 Medical care of the patient \n\u0081 Comments on the event in relation to already known safety data \nUse of standardised terminology corresponding to relevant IMDRF  codes is encouraged. \n10.2.15  Action/treatment /outcome \nProvide information in free text on actions taken, treatment(s)  administered and the outcome.   \n10.2.16  Relationship to procedure \nChoose one option from the foll owing list of causality levels ( for explanatory texts see sect ion 9 Causality assessment): \n\u0081 Not related \n\u0081 Possible \n\u0081 Probable \n\u0081 Causal \nPlease report the assessments by sponsor and investigator in th e respective columns.   \n10.2.17  Relationship to device \nChoose one option from the foll owing list of causality levels ( for explanatory texts see sect ion 9 Causality assessment) \n\u0081 Not related \n\u0081 Possible \n\u0081 Probable \n\u0081 Causal \nPlease report the assessments by sponsor and investigator in th e respective columns.  \n10.2.18  Unanticipated SADE \nChoose option Yes or No \nAn Unanticipated Serious Adverse Device Effect12 is an effect which by its nature, incidence, severity or outco me has not been identified in the \ncurrent risk assessment. Procedure s associated with the use of a device should be addressed in the risk assessment, which make s it possible to \n                                                           \n12 An adverse device effect is an adverse event related to the us e of an investigational device. A serious adverse device effect  is an adverse device effect that has resulted in \nany of the consequence characteristics of a serious adverse eve nt.   \nPage 16 of 16 determine whether the procedure related SAEs are Unanticipated Serious Adverse Device Effect or not. SAEs related to procedure s imposed by \nthe clinical investigation plan but not with the use of the dev ice should not be considered Serious Adverse Device Effects.  \n10.2.19  Investigation arm \nChoose one option from the following list: \n\u0081 Test group \n\u0081 Comparison group \n\u0081 Blinded \n\u0081 Not applicable \nNote: For some study designs it might be more relevant to add n ame of device; i.e. in a clinical  investigation with several te st groups it might be \nuseful to differentiate which investigational device that the s ubject has been exposed to.  \n10.2.20  Event status \nChoose one option from the following list (do not add other opt ions): \n\u0081 Resolved \n\u0081 Resolved with Sequelae \n\u0081 Ongoing \n\u0081 Death \n10.2.21  Date of event resolution \nAdd date in format DD/MM/YYYY. If event status is \u201cOngoing\u201d ent er Not Applicable.  \n \n11 References \n1. R e g u l a t i o n  ( E U )  2 0 1 7 / 7 4 5  o f  t h e  E u r o p e a n  P a r l i a m e n t  a n d  o f  t h e  council of 5 April 2017 on medical devices, amending Directive \n2001/83/EC, Regulation (EC No 178/2002 and Regulation (EC) No 1 223/2009 and repealing Council Directives 90/385/EEC and 93/42/ EEC.  \n2. Council Directive 90/385/EEC of 20 June 1990 on the approximati on of the laws of the  Member States relating to active implantable medical \ndevices, last amended by Directive  2007/47/EC. \n3. Council Directive 93/42/EEC of 14 June 1993 concerning medical devices, last amended  by Directive 2007/47/EC. \n4. Codes for the representation of names of countries and their su bdivisions \u2013 Part 1: Country codes (ISO 3166-1) published by In ternational \nOrganisation for Standardization (ISO). \n \n12 Appendix \u2013 Clinical Investigation Sum mary Safety Reporting Form"}, {"title": "08 MDCG 2020-8 Guidance on PMCF Evaluation Report Template.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n1 \n  \n \n \nMDCG 2020-8 \n  \n Post-market clinical follow-up (PMCF) Evaluation Report Template \nA guide for manufacturers and notified bodies                \n \n April 2020 \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) established by Article 103 of Regulation (EU) \n2017/745. The MDCG is composed of representatives of all Member States and it is chaired by a representative of the European \nCommission.The document is not a European Commission document and it cannot be regarded as reflecting the official position of the \nEuropean Commission. Any views expressed in this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law. Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n2 \n  \n \n \n \n \n \n \nPost-market clinical follow-up (PMCF) Evaluation Report Template  \nA guide for manufacturers and notified bodies \n \n  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n3 \n  \nContents \nIntroduction  ........................................................................................................................................................................................................................................... 4 \nPost-market clinical follow-up evaluation report Template  ............................................................................................................................................................ 4 \nSection A. Manufacturer contact details ....................................................................................................................................................................................... 5 \nSection B. Medical Device description and specification  .......................................................................................................................................................... 5 \nSection C.   Activities undertaken related to PMCF: results  ..................................................................................................................................................... 7 \nSection D.  Evaluation of clinical data relating to equivalent or similar devices  .................................................................................................................... 7 \nSection E. Impact of the results on the technical documentation  ............................................................................................................................................ 7 \nSection F.  Reference to any common specification(s), harmonized standard(s) or guidance document(s) applied  ...................................................... 9 \nSection G. Conclusions  .................................................................................................................................................................................................................. 9 \n \n  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n4 \n Introduction \n \nThe Medical Device Regulation (EU) 2017/745 (MDR) considers the post-market clinical follow-up (PMCF) as a continuous process that \nupdates the clinical evaluation and that shall be addressed in the manufacturer\u2019s post-market surveillance plan. The MDR reinforces the \nPMCF process by the manufacturer, devoting part B of Annex XIV to it and providing a set of requirements for developing a PMCF plan \nand its evaluation report, necessary to its implementation.  \n \nThe manufacturer shall analyse the findings coming from the activities foreseen in the PMCF plan and document the results in this PMCF \nevaluation report that shall be part of the clinical evaluation report and the technical documentation. \n  \nThe conclusions of the PMCF evaluation report shall be taken into account to update eventually the clinical evaluation, the risk \nmanagement documentation, the post market surveillance plan and the SSCP, if applicable. \n \nThe purpose of the present templates is to guide manufacturers in complying with the requirements of the MDR with respect to the \ncompilation of  the PMCF evaluation report. This would assist manufacturers in a harmonised and complete presentation of post market \nclinical data and facilitate the activity of notified bodies and competent authorities in finding the information in an organized format. \n \nPost-market clinical follow-up evaluation report Template  \nPost-market clinical follow- up (PMCF) plan corresponding to the present evaluation report \nPMCF plan number and version: \n \nPost-market clinical follow- up (PMCF) Evaluation Report \nPMCF report number: \nPMCF report date: \nPMCF report version:  \nRevision history  \nRev Revision date Description of change Revised by \n    Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n5 \n     \n \n \n Section A. Manufacturer  contact details \nLegal manufacturer name: \nAddress: \nSRN: \nPerson responsible for regulatory compliance: \nE-mail: \nPhone: \nFax: \nAuthorised representative (if applicable): \nAddress: \nContact person:  \nE-mail: \nPhone: \nFax: \n \nSection B. Medical Device description and specification \nRefer to section B from PMCF plan, if there are no changes.  \nIf there are changes from PMCF plan, please fill in the different requested fields highlighting those changes.  \nProduct or trade name: \nModel and type: \nGeneral description of the device: Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n6 \n Intended purpose1 \nIntended users \nBasic UDI-DI: \nIntended patient population: \nMedical condition(s)2: \nIndications: \nContraindications: \nWarnings:  \nList and description of any variants and/or configurations covered by this plan: \nList of any accessories covered by this plan: \nCertificate number (if available): \nCND code(s)3:  \nClass: \nClassification rule: \nExpected lifetime4  \nNovel product                                \u2610  yes    \u2610  no \nNovel related clinical procedure:   \u2610  yes    \u2610  no \nExplanation of any novel features: \n \n \n                                                             \n1 Intended purpose means the use for which a device is intended according to the data supplied by the manufacturer on the label in the instructions for use or in promotional or sales \nmaterials or statements and as specified by the manufacturer in the clinical evaluation (MDR, Article 2(12)).  \n2 It refers to the clinical condition that is to be diagnosed, prevented, monitored, treated, alleviated, compensated for, replaced, modified or controlled by the medical device. \n \n4 The expected lifetime is to be defined during the design input phase by considering the current state of the art for a specific intended use and indication of a device.  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n7 \n Section C.   Activities undertaken related to PMCF: results  \nIn this section the manufacturer shall report all the activities described in section C of the PMCF plan which have been performed, all the collected \nclinical data obtained from those completed activities, as well as any justification of deviations from the plan.  \n \nThe discussion shall include the analysis of the findings, whether positive or negative and also the potential impact on the different documents (clinical \nevaluation report, risk management file, SSCP, etc\u2026) initially reviewed during the conformity assessment.  \n \nIt is expected for each activity performed, a description in different subsections, related to the type of activities (device registry, PMCF studies, real \nworld evidence, surveys about the use of device, etc\u2026), and for each subsection, a description about the quality of data collected.5 \n \nSection D.  Evaluation of clinical data relating to equivalent or similar devices  \n \nIn this section the manufacturer shall report all the clinical data collected relating to an equivalent device or selected similar device(s), provide an \nanalysis and conclusions, and whether changes of the state of the art, or newly identified hazards would have an impact on the devices benefit-risk \ndetermination, the clinical evaluation and/or the PMCF plan.  \n \n \n \nProduct name of \nequivalent / similar \ndevice Results discussed References used to get the \nresults (publications, part of \ntechnical documentation from \nthis equivalent / similar device) \n \n \n \n Section E. Impact of the results on the technical documentation  \n \n                                                             \n5 For the analysis and assessment of the clinical data collected, some parts of section 9.3.1 from Meddev 2.7/1 rev.4 could be used to assess the quality of data. \n Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n8 \n In this section, the manufacturer shall discuss the aggregate results coming from each PMCF activity planned and performed, described in section C, \nbut also results coming from equivalent and/or similar device, described in section D, which are considered to impact the technical documentation and \nat least the following documents shall be considered: \n \n1. Clinical evaluation report - CER (date and version)  \n \n\u2610   No relevant information from the clinical evaluation report have been considered. \n \nIf applicable, it is expected from manufacturer to describe why some information that might have an impact on the CER have not been considered. \n \nRelevant information analyzed and monitored: \n- \n- \n \nAnalysis of the outcome is to be reported in the updated clinical evaluation report. \n \n \n2. Risk management file (date and version) \n \n\u2610   No relevant information from the risk management file have been considered \n \nIf applicable, it is expected from manufacturer to describe why some information that might have an impact on the risk management file have not been \nconsidered. \n \n \n \nRelevant information analyzed and monitored: \n \n- \n- \n- \n \n Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n9 \n Analysis outcome to be reported in the risk management file updated: \n- \n- \n \n \n \n \n \nSection F.  Reference to any common specification(s), harmonized standard(s) or guidance document(s) applied  \n \nIn this section the manufacturer should point out whether the collected clinical data related the device in question still confirm adherence to applied \ncommon specifications and/or applied harmonized standards, and/or guidances listed in the PMCF plan. \n \nCommon Specification(s) applied \n(Title, date and version) \n \nHarmonised standard(s) applied \n(Title, date and version) \n \nGuidance(s) followed \n(Title, date and version ) \n \n \nSection G. Conclusions  \n \n \nIn this section, it is expected that the manufacturer shall provide an overall conclusion of the findings and relate them to the aims of the PMCF \nplan. The conclusions shall be taken into account in the following clinical evaluation and in the risk management. Finally, this conclusion shall \nhighlight if any need for preventive and/or corrective measures has been identified. The conclusion may also give input to the next PMCF plan. Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-8  \n \n \n10"}, {"title": "07 MDCG 2020-7 Guidance on PMCF Plan Template.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n1 \n  \n \n \n \nMDCG 2020-7 \n  \n Post-market clinical follow-up (PMCF) Plan Template \nA guide for manufacturers and notified bodies                \n \n April 2020 \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) established by Article 103 of Regulation (EU) \n2017/745. The MDCG is composed of representatives of all Member States and it is chaired by a representative of the European \nCommission.The document is not a European Commission document and it cannot be regarded as reflecting the official position of the \nEuropean Commission. Any views expressed in this document are not legally binding and only the Court of Justice of the European \nUnion can give binding interpretations of Union law. \n  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n2 \n  \n \n \n \n \n \nPost-market clinical follow-up (PMCF) Plan Template  \nA guide for manufacturers and notified bodies \n  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n3 \n  \nContents \nIntroduction  ........................................................................................................................................................................................................................................... 4 \nPost-market clinical follow-up plan Template  .................................................................................................................................................................................. 5 \nSection A. Manufacturer contact details ....................................................................................................................................................................................... 5 \nSection B. Medical Device description and specification  .......................................................................................................................................................... 6 \nSection C. Activities related to PMCF: general and specific methods and procedures  ........................................................................................................ 7 \nSection D. Reference to the relevant parts of the technical documentation  .......................................................................................................................... 9 \nSection E. Evaluation of clinical data relating to equivalent or similar devices  .................................................................................................................... 10 \nSection F. Reference to any applicable common specification(s), harmonized standard(s) or applicable guidance document(s)  ............................. 11 \nSection G. \u2013 Estimated date of the PMCF evaluation report  .................................................................................................................................................. 12 \n \n  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n4 \n Introduction \n \nThe Medical Device Regulation (EU) 2017/745 (MDR) considers the post-market clinical follow-up (PMCF) as a continuous process that \nupdates the clinical evaluation and that shall be addressed in the manufacturer\u2019s post-market surveillance (PMS) plan. The MDR \nreinforces the PMCF process by the manufacturer, devoting part B of Annex XIV to it and providing a set of requirements for developing \na plan, necessary to implement PMCF.  \n \nA PMCF plan shall specify the methods and procedures set up by the manufacturer, to proactively collect and evaluate clinical data from \nthe use in or on humans of a CE marked medical device, placed on the market or put into service within its intended purpose, as referred \nto in the relevant conformity assessment procedure. \n  \nThe aim of the PMCF plan is: \n\uf0b7 confirming the safety1 and performance, including the clinical benefit if applicable, of the device throughout its expected lifetime; \n\uf0b7 identifying previously unknown side-effects and monitor the identified side-effects and contraindications; \n\uf0b7 identifying and analysing emergent risks on the basis of factual evidence; \n\uf0b7 ensuring the continued acceptability of the benefit-risk ratio, referred to in Section 1 and 9 of Annex I in the MDR;  \n\uf0b7 identifying possible systematic misuse or off-label use of the device, with a view to verifying that the intended purpose is correct. \n \nThe PMCF plan shall be part of the post-market surveillance plan.  \n \nThe findings of the PMCF shall be analysed by the manufacturer who shall document the results in a PMCF evaluation report. The \nPMCF evaluation report shall be part of the clinical evaluation report and the technical documentation. The adequateness of the PMCF \nplan and its application is subject to assessment by the notified body. The notified body\u2019s assessment of the clinical evaluation shall also \ncover the manufacturer\u2019s procedures and documentation of the PMCF,  as well as the justification in relation to non-performance of \nPMCF. \n  \nThe purpose of the present template is to guide manufacturers in complying with the requirements of the MDR with respect to the \ncompilation of the PMCF plan. This would assist manufacturers in a harmonised and complete presentation of post market clinical data \nand facilitate the activity of notified bodies and competent authorities in finding the information in an organised format. \n                                                             \n1 The confirmation of the safety includes the acceptability of identified risks and particularly residual risks.  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n5 \n  \nPost-market clinical follow-up plan Template \n \nPMCF plan number: \nPMCF plan date: \nPMCF plan version:  \nRevision history  \nRev Revision date Description of change  Revised by  \n    \n    \n \nSection A. Manufacturer  contact details \nLegal manufacturer name: \nAddress: \nSRN: \nPerson responsible for regulatory compliance: \nE-mail: \nPhone: \nFax: \nAuthorised representative (if applicable): \nAddress: \nContact person:  \nE-mail: \nPhone: \nFax: \n Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n6 \n Section B2. Medical Device description and specification \nProduct or trade name: \nModel and type: \nGeneral description of the device:  \nIntended purpose3: \nIntended users \n Basic UDI-DI: \nIntended patient population: \nMedical condition(s)4: \nIndications: \nContraindications: \nWarnings: \n \n \nList and description of any variants and/or configurations covered by this plan: \n \nList of any accessories covered by this plan: \nCertificate number (if available): \nCND code(s)5:  \nClass: \nClassification rule: \n                                                             \n2 MDR, Annex II, 1,1. \n3 Intended purpose means the use for which a device is intended according to the data supplied by the manufacturer on the label in the instructions for use or in promotional or \nsales materials or statements and as specified by the manufacturer in the clinical evaluation (MDR, Article 2(12)).  \n4 It refers to the clinical condition that is to be diagnosed, prevented, monitored, treated, alleviated, compensated for, replaced, modified or controlled by the medical device \n5 Per article 26 of MDR.  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n7 \n Expected lifetime:6  \nNovel product:                              \u2610 yes   \u2610  no \nNovel related clinical procedure:  \u2610 yes   \u2610 no \nExplanation of any novel features: \n \nSection C. Activities related to PMCF: general and specific methods and procedures  \n \nIn this section it is expected to describe the different activities that will be conducted in post-market, including general and specific methods / procedures \nto conduct  in relation to the product covered by the scope of PMCF, also the aim of each activity described and the rational for the appropriateness of \nthe chosen general and specific methods to achieve those objectives as well as the known limitations of the planned activities such as for example \nincomplete follow up, missing data and so on. The timelines of those activities shall be also defined quarterly or at least yearly.  \nHere are some examples of different activities related to PMCF: \n\uf0b7 A manufacturer device registry  (specific for the type of device or the group of the medical devices the product belongs to) can be indicated \ntogether with a description and a summary of the plan. A pre-specification of what quality and quantity data \u2013 based on the risk of the device(s) \nand the associated accessories \u2013 to be collected and analysed shall be included. Any possible evaluation of suitable national public registries  \nwith clinical data on the manufacturer\u2019s own device and/or on  similar devices could be specified in this section, identifying the expected quantity \nand quality of data to be gathered and the search protocols to be adopted.  \n\uf0b7 PMCF studies  planned could be indicated in this section, together with a summary of the plan including the design, sample size, the endpoints, \nthe inclusion/exclusion criteria (e.g. extended follow up of patients included in the pre-market clinical investigations, new clinical investigations \nwithin the intended use, retrospective studies). In case of implantable devices and class III devices where clinical investigations have not been \nperformed pursuant to Article 61 (4), the PMCF plan shall include post market studies to confirm the safety and performance of the device. \n\uf0b7 Planned Real-world evidence  (RWE) analyses could be indicated in this section, together with a summary of the plan including the design, \nsample size, the endpoints, and analysis population. The real-world data (RWD) from which these analyses are based on should be of sufficient \nquality and come from reliable data sources. \n\uf0b7 Surveys  planned to collect information about the use of the concerned medical device could be described.  \nEach activity will be developed in a different subsection (e.g.  C.1,  C.2, \u2026), and for which the manufacturer will: \n                                                             \n6 The expected lifetime is to be defined during the design input phase by considering the current state of the art for a specific intended use and indication of a device.  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n8 \n \uf0b7 Define where the need of conducting the PMCF activity is coming from (requested by notified body, clinical evaluation report, PMS, risk \nmanagement report, previous PMCF report, etc\u2026) \n\uf0b7 Provide the description of activity, and if it is a general or specific procedure / method. \n\uf0b7 Define the aim of this activity:  \no confirming the safety of the medical device \no confirming the performance of the medical device \no identifying previously unknown side-effects (related to the procedures or to the medical devices). \no monitoring the identified side-effects and contraindications \no identifying and analysing emergent risks \no ensuring the continued acceptability of the benefit-risk ratio \no identifying possible systematic misuse or off-label use of the device \n \n\uf0b7 Describe the different procedures which will be used as part of PMCF: \no screening of scientific literature and other sources of clinical data  \no post-market studies  \no collecting data in registries \no survey from health care professional \no survey from patients/users \no review of case reports which may reveal misuse or off-label use \n \n\uf0b7 Describe the rationale for the appropriateness of the chosen methods/procedures, including:  \no the justification for sample size, timescales and endpoints \no justification for comparator, on the basis of intended purpose and state of the art \no justification of the study design on the basis of all of the above, and why it is sufficient to ensure representative patient populations and \nprovide for adequate controls on sources of bias (an evaluation of the potential sources of bias should form part of this) \no a statistical justification for the expected quality of outcomes, and justification for why this is satisfactory in light of the residual risks. This \nis an important consideration. For example, retrospective surveys with no justification other than \u201cthis should demonstrate the expected \nquality of evidence that we require,\u201d but without showing a statistical rationale, are not acceptable.  \n \n\uf0b7 Provide the timelines of the activity. A detailed and adequately justified time schedule for PMCF activities, such as the analysis of PMCF data and \nreporting, shall be described.  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n9 \n A summary table of the different PMCF activities foreseen by the manufacturer is provided below: \nNumber \nof \nactivity Description of activity Aim of the activity  \nRationale and known \nlimitations of the activity Timelines of the activity \n   \n   \n \n \n \nSection D. Reference to the relevant parts of the technical documentation  \n \nIn this section the manufacturer is required to include references to the relevant information from the clinical evaluation report and  from the risk \nmanagement file, which need to be analysed, followed up, and evaluated in this plan. As an alternative, the manufacturer is required to state that there is \nno relevant information from the clinical evaluation report and/or from the risk management file to be considered in this plan.  \n \nClinical Evaluation Report (date and version) \nRelevant information to be further analysed and monitored: \n- \n- \n- \n \nRisk Management File (date and version) \nRelevant information to be further analysed and monitored: Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n10 \n - \n- \n- \n \n\u2610 No relevant information from the clinical evaluation report to be considered in this plan \n \n \n\u2610  No relevant information from the risk management file to be considered in this plan \n \nSection E. Evaluation of clinical data relating to equivalent or similar7 devices \n \nThe manufacturer shall gather in this section information regarding equivalent / similar devices for which clinical data will be further evaluated and \npresented in the PMCF report. \nPlease note that PMCF data intended to demonstrate continuing safety and performance should be sourced from the device under evaluation.  \nData from equivalent or similar devices may be used, for example to update the information relating to the state of the art, to identify and further assess \nrelevant safety outcomes etc. \nThe selected devices shall be consistent throughout the technical documentation. Indicate whether the selected device is demonstrated to be equivalent \nor is a similar device. For each device listed, a clear reference to the pertinent parts of the CER can be made. \nThe following items of each equivalent and/or similar devices would be at least provided, in a table format: \n                                                             \n7 Section 5, MDCG 2020-5 Clinical Evaluation \u2013 Equivalence, A guide for manufacturers and notified bodies.  Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n11 \n Product name of \nequivalent / similar \ndevice Intended purpose Intended users Intended patient population Medical condition Indication Reference to clinical \ndata evaluation in \nthe CER ( date, \nversion and location in \nthe text) \n \n  \n \n \nSection F. Reference to any applicable common specification(s), harmonized standard(s) or applicable guidance \ndocument(s)  \n \n \nCommon specification(s) to comply with, if applicable: \n(Title, date and version) \n \n \n \nHarmonised standards to apply, if applicable \n(Title, date and version) \n \n \nGuidance on PMCF, if applicable Medical Device       \nMedical Device Coordination Group Document            MDCG  2020-7  \n \n12 \n (Title, date and version) \n \n \n \n \nSection G. \u2013 Estimated date of the PMCF evaluation report  \n \nWhen the manufacturer plans to have the first report. The timelines shall be defined quarterly or at least yearly."}, {"title": "06 MDCG 2020-6 Guidance on Sufficient Clinical Evidence for Legacy Devices.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document   MDCG  2020-6  \n  \n \n \n \n \n \n \n \n \nMDCG 2020-6 \n  \n         Regulation (EU) 2017/745: Clinical evidence needed for  \n        medical devices previously CE marked under \n        Directives 93/42/EEC or 90/385/EEC   \n \nA guide for manufacturers and notified bodies  \n             \n \n April 2020 \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) \nestablished by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of \nrepresentatives of all Member States and it is chaired by a representative of the European \nCommission.The document is not a European Commission document and it cannot be \nregarded as reflecting the official position of the European Commission. Any views \nexpressed in this document are not legally binding and only the Court of Justice of the \nEuropean Union can give binding interpretations of Union law. \n   \n \nPage 2 of 22  \n \n  \n \n \n \n \n \n \n \nRegulation (EU) 2017/745: Clinical evidence needed for medical devices \npreviously CE marked under Directives 93/42/EEC or 90/385/EEC  \n \nA guide for manufacturers and notified bodies  \n   \n \nPage 3 of 22  \n \n  \nTable of contents  \n1. Definitions ...................................................................................................................................................... 4  \n1.1. Terms defined in MDR Article 2 .................................................................................. 4  \n1.2. Additional terms not defined in MDR Article 2 ............................................................ 4  \n2. Reference documents ............................................................................................................................... 6  \n3. Scope ................................................................................................................................................................ 6  \n4. Introduction and context ......................................................................................................................... 7  \n5. General aspects ............................................................................................................................................ 8  \n6. Guidance on specific aspects of clinical evaluation for legacy devices ........................... 10  \n6.1. Annex XIV Part A Section 1a: Establish or update a clinical evaluation plan .............. 10  \n6.2. Annex XIV Part A Section 1b: Identify available clinical data .................................... 11  \n6.2.1. Pre-market sources of clinical data ...................................................................... 12  \n6.2.2. Post-market sources of clinical data ..................................................................... 12  \n6.3. Annex XIV Part A Section 1c: Appraisal of the clinical data ...................................... 12  \n6.4. Annex XIV Part A Section 1d: Generation of new clinical data .................................. 13  \n6.5. Annex XIV Part A Section 1e: Analysis of the clinical data ........................................ 14  \nAppendix I - Sections of MEDDEV 2.7/1 rev. 4 which are still relevant under the MDR for \nthe application of this guidance ................................................................................................................. 18  \nAppendix II \u2013 Clinical Evaluation Plan for Legacy Devices .............................................................. 19  \nAppendix III \u2013 Suggested hierarchy of clinical evidence for confirmation of conformity \nwith relevant GSPRs under the MDR ........................................................................................................ 20  \n \n \n   \n \nPage 4 of 22  \n \n This guidance document is not legally binding. It has been put together following \ncontribution from national competent authorities, industry and relevant stakeholders and \nit should therefore be recognised as best practice. It also intends to support a harmonised \napproach with respect to clinical data providing sufficient clinical evidence necessary to \ndemonstrate conformity with the relevant General Safety and Performance Requirements \n(GSPR) across European Union Member States. \n \n1. Definitions \n \n1.1. Terms defined in MDR Article 2 \nThe following terms are used as defined in the Medical Device Regulation (EU) 2017/745 \n(MDR): \n\uf0b7 \u2018performance\u2019;1  \n\uf0b7 \u2018risk\u2019;2  \n\uf0b7 \u2018intended purpose\u20193 \n\uf0b7 \u2018benefit-risk determination\u2019;4 \n\uf0b7 \u2018clinical evaluation\u2019;5 \n\uf0b7 \u2018clinical investigation\u2019;6 \n\uf0b7 \u2018clinical data\u2019;7 \n\uf0b7 \u2018clinical evidence\u2019;8  \n\uf0b7 \u2018clinical performance\u2019;9  \nIt should be noted that clinical performance may arise from either \u2018direct or indirect \nmedical effects\u2019 \u2018leading to a clinical benefit for patients\u2019; see comments for \nrelevance to clinical benefit below \n\uf0b7 \u2018clinical benefit\u2019.10  \nIt should be noted that clinical benefits may be either direct or indirect; for example \ndevices such as guidewires may assist other medical devices in achieving their \nintended purpose, without having a direct therapeutic or diagnostic function \nthemselves. \n\uf0b7 \u2018generic device group\u2019.11 \n \n1.2. Additional terms not defined in MDR Article 2 \nAdditional terms which are not explicitly defined in Article 2 of the MDR, but which are \nessential to evaluation of benefit-risk and clinical evaluation conclusions: \n                                                \n \n1 MDR, Article 2(22). \n2 MDR, Article 2(23). \n3 MDR, Article 2(12). \n4 MDR, Article 2(24). \n5 MDR, Article 2(44). \n6 MDR, Article 2(45). \n7 MDR, Article 2(48). \n8 MDR, Article 2(51). \n9 MDR, Article 2(52). \n10 MDR, Article 2(53).  \n11 MDR, Article 2(7).  \n \nPage 5 of 22  \n \n \uf0b7 \u2018legacy devices\u2019: this is considered to include all devices previously CE marked \nunder the European Medical Devices Directive 93/42/EEC (MDD) or Active \nImplantable Medical Devices Directive 90/385/EEC (AIMDD) \n\uf0b7 \u2018well-established technology\u2019: this terminology is used in Article 52(5) and Article \n61(8) of the MDR, but is not defined in these articles. The term is not restricted to \nthe devices listed in Article 61(6b); Article 61(8) explicitly states that this includes \ndevices similar to  the exempted devices listed in Article 61(6b), which might be \nadded to that list in future. The common features of the devices which are well-\nestablished technologies are that they all have: \no relatively simple, common and stable designs with little evolution; \no their generic device group has well-known safety and has not been \nassociated with safety issues in the past;  \no well-known clinical performance characteristics and their generic device \ngroup are standard of care devices where there is little evolution in \nindications and the state of the art; \no a long history on the market. \nTherefore, any devices that meet all these criteria may be considered \u201cwell-\nestablished technologies\u201d. \n\uf0b7 \u2018scientific validity\u2019, \u2018scientifically valid\u2019: this terminology is used in the MDR in \nreference to clinical data planning, evaluation and conclusions12. Clinical \nevaluations must follow a \u201cdefined and methodologically sound procedure\u201d13, for \nwhich expectations of scientific validity are implicit. Embedded in the term \n\u2018scientific validity\u2019 are concepts including adequacy of study design and controls \nfor bias, appropriateness and relevance of research questions, adequacy of \nsample sizes and statistical analyses, completeness of data, adequacy of follow \nup period, and appropriateness of conclusions on the basis of objective evidence. \nSection 9.3.1 of MEDDEV 2.7/1 rev. 4 provides guidance for the evaluation of \nmethodological quality and scientific validity under the MDD/AIMDD which are \nequally valid under the MDR which can be considered to apply when referencing \n\u2018scientific validity\u2019 in this guidance. \n\uf0b7 \u2018level of clinical evidence\u2019:  this terminology is used in the MDR with respect to \nrequirements for demonstration of conformity with the relevant GSPR and overall \nbenefit-risk14. It is understood to encompass the amount and quality of evidence \n(i.e. its characterisation by quality, quantity, completeness and statistical validity, \netc.) required to demonstrate safety, performance and the benefit-risk conclusion \nof a medical device. It should not be confused with the term \u2018levels of evidence\u2019 \n(as used in evidence-based medicine) which is used to rank study designs, and is \nonly a part of the concept \u2018level of clinical evidence\u2019. Regarding the assessment of \nthe level of clinical evidence for the device in question, see sections 6.3 and 6.5d \nof this document. \n\uf0b7 \u2018state of the art\u2019: IMDRF/GRRP WG/N47 provides the following definition: \nDeveloped stage of current technical capability and/or accepted clinical practice in \nregard to products, processes and patient management, based on the relevant \nconsolidated findings of science, technology and experience.  \n                                                \n \n12 MDR Annex XV, Chapter I, Article 2(2.1) and (2.6). \n13 MDR Article 61(3). \n14 MDR Article 61(1), Annex IX section 5.1.   \n \nPage 6 of 22  \n \n Note: The state-of-the-art embodies what is currently and generally accepted as \ngood practice in technology and medicine. The state-of-the-art does not \nnecessarily imply the most technologically advanced solution. The state-of-the-art \ndescribed here is sometimes referred to as the \u201cgenerally acknowledged state-of-\nthe-art \n\uf0b7 \u2018intended use\u2019: The MDR defines \u2018intended purpose\u2019, but not \u2018intended use\u2019. \n\u2018intended use\u2019 should be considered to have the same meaning as \u2018intended \npurpose\u2019.  \n\uf0b7 \u2018indication\u2019, \u2018indication for use\u2019: refers to the clinical condition that is to be \ndiagnosed, prevented, monitored, treated, alleviated, compensated for, replaced, \nmodified or controlled by the medical device. It should be distinguished from \n\u2018intended purpose/intended use\u2019, which describes the effect of a device. All devices \nhave an intended purpose/intended use, but not all devices have an indication (e.g. \nmedical devices with an intended purpose of disinfection or sterilisation of \ndevices). \n\uf0b7 \u2018similar device\u2019: devices belonging to the same generic device group. The MDR \ndefines this as a set of devices having the same or similar intended purposes or a \ncommonality of technology allowing them to be classified in a generic manner not \nreflecting specific characteristics15.  \n    \n2. Reference documents \nThis document provides facilitative guidance to the requirements of MDR Chapter VI and \nAnnex XIV, and references the following MDD/AIMDD guidance documents: \n\uf0b7 MEDDEV 2.7/1 rev. 4: Clinical Evaluation: A Guide for Manufacturers and Notified \nBodies under Directives 93/42/EEC and 90/385/EEC \n\uf0b7 MEDDEV 2.12/2 rev 2: Post Market Clinical Follow-Up Studies: A Guide for \nManufacturers and Notified Bodies \n \n3. Scope \nThis document seeks to provide guidance for clinical data providing sufficient clinical \nevidence necessary to demonstrate conformity with the relevant GSPR, as per Article \n61(1) MDR, for legacy devices CE marked with respect to Directives 93/42/EEC (MDD) \nor 90/385/EEC (AIMDD). \nThis document aims to provide guidance for manufacturers and notified bodies to prepare \nfor the conformity assessment procedure according to the MDR.  \nThis document does not provide comprehensive guidance with respect to the process or \nmethodology relating to clinical evaluation. It is general and not restricted to any particular \ndevice technology or risk class. Following on from the principles described in Section 3 \nhowever, special attention is given to those described in Article 61(6). \n \n                                                \n \n15 MDR, Article 2(7).   \n \nPage 7 of 22  \n \n 4. Introduction and context  \nThis section is intended to provide an introduction and context, and not to modify the \ninterpretation of the MDR. \nMDR Article 61(1) states: \nConfirmation of conformity with relevant general safety and performance \nrequirements set out in Annex I under the normal conditions of the intended use of \nthe device, and the evaluation of the undesirable side-effects and of the \nacceptability of the benefit-risk ratio referred to in Sections 1 and 8 of Annex I, shall \nbe based on clinical data providing sufficient clinical evidence, including where \napplicable relevant data as referred to in Annex III.  \nThe manufacturer shall specify and justify the level of clinical evidence necessary \nto demonstrate conformity with the relevant general safety and performance \nrequirements. That level of clinical evidence shall be appropriate in view of the \ncharacteristics of the device and its intended purpose.  \nTo that end, manufacturers shall plan, conduct and document a clinical evaluation \nin accordance with this Article and Part A of Annex XIV. \n \nMDR Article 61(4) states that clinical investigations shall be performed for Class III and \nimplantable devices, but distinct exemptions from this requirement are identified both in \nthis article and in Articles 61(5) and 61(6). The common theme of these exempted devices \nis that they have been previously marketed (Article 61(6)) or have been demonstrated to \nbe equivalent to devices previously marketed (Article 61(5)).  \nArticle 61(6a and b) further distinguishes between legacy devices (Article 61(6a)) which \nhave been previously marketed under 93/42/EEC or 90/385/EEC and a specific subset \nof well-established technologies (WET) (Article 61(6b)). \nThe following should be noted: \n\uf0b7 all such exemptions from clinical investigations require that the clinical evaluation \nis based on \u201csufficient clinical data\u201d; \n\uf0b7 the basic clinical evaluation requirements for the legacy devices described in \nArticle 61(6a) and the devices of Article 61(6b) are the same: \u201csufficient clinical \ndata\u201d and compliance to common specifications where these exist. The distinction \nbetween the two is that the devices listed in Article 61(6b) are not explicitly required \nto have had prior certification under the Directives to be exempted from the \nrequirement for clinical investigations that otherwise apply to Class III and \nimplantable devices; \n\uf0b7 both the Directives and the MDR require the quantity and quality of clinical data to \nbe sufficient to demonstrate safety, performance and the acceptability of the \nbenefit-risk ratio: both the Directives and the MDR require clinical evidence to be \nsound and the conclusions derived from this evidence to be scientifically valid.  \nArticle 61(10)16 allows for the use of non-clinical data for demonstration of conformity with \nGSPRs: \nWithout prejudice to paragraph 4,where the demonstration of conformity with \ngeneral safety and performance requirements based on clinical data is not deemed \n                                                \n \n16 See MDCG guidance on the CEAR template for notes related to use of Article 61(10).  \n \nPage 8 of 22  \n \n appropriate, adequate justification for any such exception shall be given based on \nthe results of the manufacturer's risk management and on consideration of the \nspecifics of the interaction between the device and the human body, the clinical \nperformance intended and the claims of the manufacturer. \nArticle 61(10) cannot be applied to Class III or implantable devices. In exceptional cases \nArticle 61(10) may be applied for all other device classifications. \n5. General aspects \n\u201cSufficient clinical evidence\u201d is not defined in the MDR. The definition of \u201cclinical evidence\u201d \nitself contains the word \u201dsufficient\u201d but it is related to the amount and quality of the clinical \ndata and the clinical evaluation results which \u201callow a qualified assessment of whether \nthe device is safe and achieves the intended clinical benefits when used as intended by \nthe manufacturer\u201d.17 Sufficient clinical evidence is also mentioned in the MDR Article 61 \nwhere  it is provided that the confirmation of conformity with the relevant GSPR shall be \nbased on sufficient clinical evidence. Therefore, \u201csufficient clinical evidence\u201d is \nunderstood as \u201cthe present result of the qualified assessment which has reached the \nconclusion that the device is safe and achieves the intended benefits\u201d. It is important to \nnote that clinical evaluation is a process where this qualified assessment has to be done \non a continuous basis.  \nCompared to Directives 93/42/EEC and 90/385/EEC, MDR provides greater detail and \nadditional requirements with respect to the process of clinical evaluation, for the purpose \nof confirmation of conformity with relevant GSPR. The generation of clinical data and their \nevaluation providing sufficient clinical evidence is part of a lifecycle approach to medical \ndevices.  \nThe MDR reinforces a number of important factors which are relevant to clinical \nevaluation. This includes: \n\uf0b7 Consideration of available alternative treatment options  is required for the \nconfirmation of the acceptability of the benefit-risk ratio.18 \n\uf0b7 The acceptability of the benefit-risk ratio must be based upon clinical data \nproviding sufficient clinical evidence including where applicable relevant data from \npost-market surveillance.19 \n\uf0b7 The term \u201cclinical evidence\u201d is introduced and the level of clinical evidence  \nmust be specified and justified by the manufacturer, taking the characteristics of \nthe device and the intended purpose into account.20 \n\uf0b7 The incorporation of post market surveillance (PMS) data in particular the \npost-market clinical follow-up (PMCF) data into the process of clinical evaluation.21 \nManufacturers are required to establish a post-market surveillance plan in \naccordance with Annex III of the MDR and the clinical data arising from this PMS \nshall be incorporated into the clinical evaluation. \n\uf0b7 The definition of equivalence is now included in the text of the MDR,22 and the \nprocess to demonstrate equivalence is defined23. \n                                                \n \n17 MDR, Article 2(51).  \n18 MDR, Article 61(3)(c). \n19 MDR, Article 61(1) and Annex III. \n20 MDR, Article 61(1). \n21 MDR, Article 61(1) and (11). \n22 MDR, Annex XIV, Part A, section 3. \n23 MDCG 2020-5 Clinical Evaluation \u2013 Equivalence, A guide for manufacturers and notified bodies.  \n \nPage 9 of 22  \n \n \uf0b7 A definition of \u201cclinical data\u201d  is provided.24 \nWhen it comes to the first MDR conformity assessment of a legacy device the pre-market \nand post-market clinical data generated for the purpose of MDD/AIMDD can be taken into \naccount. As requirements and guidance developed over time, it is not necessarily the \ncase that the clinical data used for conformity assessment under the Directives is clinical \ndata providing sufficient clinical evidence for the purpose of MDR requirements. Legacy \ndevices which have been placed on the market have been subjected to conformity \nassessment and therefore are presumed to have been supported by clinical data25. Post-\nmarket clinical data together with the clinical data generated for the conformity \nassessment under the MDD/AIMDD will be the basis of the clinical evaluation process for \nlegacy devices under the MDR. \nDuring the period of validity of the MDD/AIMDD certificates, the MDR requirements for \nthe PMS apply from the MDR date of application. Legacy devices are therefore not \nexempted from the additional requirements in MDR concerning PMS, including PMCF. \nPMS data and clinical evaluation plans and reports need to be produced and updated. \nThe MDR compliant clinical evaluation for a legacy device must contain the identification \nof available clinical data as well as their appraisal / analysis / evaluation and shall lead to \na demonstration of conformity to the MDR GSPR based on clinical data providing \nsufficient clinical evidence as part of a lifecycle approach. \nThe European Commission guidance MEDDEV 2.12/2 regarding PMCF studies notes \ndifferent instances where a PMCF study may have been justified:26  \n\uf0b7 Route chosen for clinical evaluation : where CE marking for legacy devices was \nbased upon equivalence, PMCF studies may have been necessary. The European \nCommission guidance MEDDEV 2.12/2 regarding PMCF also notes that in the \ncase that clinical evaluation was based exclusively on clinical data from equivalent \ndevices for initial conformity assessment, the certifying notified body shall verify \nthat PMCF studies have been conducted,27 in accordance with the relevant \nprovisions of the Directives.28  \n\uf0b7 Device related factors : There are a number of device-related factors where \nPMCF studies may have been necessary.29 \nWhen assessing the conformity of legacy devices under the MDR, it is important to verify \nwhether PMCF studies considered necessary under the MDD/AIMDD (and where \napplicable, during the transition period, under the MDR), have been appropriately \nconducted, and results are taken fully into account for in the clinical evaluation for the \nconformity assessment under MDR. \nGuidance on the general process of conducting clinical evaluation is also available in the \nMEDDEV 2.7/1 rev. 4. This guidance was written with respect to the MDD and AIMDD to \nprovide practical guidance on several scientific and clinical aspects that are relevant for \nconducting clinical evaluation. However only the text of the MDR is authentic in law, \nsections relevant to the MDR are listed in Appendix I to this document. \n                                                \n \n24 MDR, Article 2(48). \n25 Except where non-clinical testing were demonstrated to be adequate (MDD, Annex X, 1.1(d); AIMD, Annex 7, 1.5). \n26 MEDDEV 2.12/2, section 5 https://ec.europa.eu/growth/sectors/medical-devices/current-directives/guidance_en   \n27 MEDDEV 2.12/2, section 8. \n28 Annex II.4, Annex II.7, Annex III, Annex V.6 and Annex VI.6 of Directive 93/42/EEC and Annex II.4, Annex II.7, Annex III and Annex \nV.6 of Directive 90/385/EEC. \n29 MEDDEV 2.12/2, section 5.  \n \nPage 10 of 22  \n \n 6. Guidance on specific aspects of clinical evaluation for legacy devices \nSections 6.1 \u2013 6.5 below provide guidance on each stage of the clinical evaluation \nprocess of MDR Annex XIV Part A Section 1. \n6.1. Annex XIV Part A Section 1a: Establish or update a clinical evaluation plan30 \nManufacturers are required to document a clinical evaluation plan to meet the \nrequirements of MDR Annex XIV Section 1a.  \nPremarket elements of the plan as described in the final indent of MDR Annex XIV Section \n1a (first-in-man studies, feasibility and pilot studies) are not generally relevant to legacy \ndevices which are unchanged in design or indications. However, the context for the plan \nas described in indents 1-7 and the basis for the PMCF as described in indent 8 of MDR \nAnnex XIV Section 1a are considered relevant and necessary for demonstration of \ncompliance to the MDR.  Appendix II of this guidance document suggests a minimum \ncontent for clinical evaluation plans for legacy devices. Further advice regarding specific \nsub-indents of MDR Annex XIV Section 1a are provided below. \na. Identification of the relevant GSPRs (indent 1 of MDR Annex XIV Section 1a): \nclinical evaluation planning under the Directives required an identification of the \nrelevant Essential Requirements (ER) for which demonstration of conformity \nrequired clinical data. The manufacturer should conduct an analysis with respect \nto the GSPRs of the MDR, to determine if additional data to support the clinical \nevidence are required to meet additional MDR requirements. This could be \nachieved either through a gap analysis with respect to new MDR requirements, or \nby creation of an entirely new analysis for the MDR. As noted in Section 3, Article \n61(10) cannot be applied to Class III or implantable devices, but may be applied \nto some or all requirements for confirmation of conformity with relevant GSPRs for \nall other device classifications if adequately justified. \nb. Specification of the intended purpose, target groups, indications, contraindications \n(indents 2-3 of MDR Annex XIV Section 1a):  Appendix A3 of MEDDEV 2.7/1 rev. \n4 lists additional information to Annex II of the MDR about device description that \ncan be relevant for planning clinical evaluations. The manufacturer needs to \nensure that inputs for the clinical evaluation plan are in line with the device\u2019s \u201clabel, \ninstructions for use, promotional or sales materials or statements\u201d31 and with the \ndevice\u2019s updated risk management documents.  \nc. Detailed description of intended clinical benefits with relevant and specified clinical \noutcome parameters (indent 4 of MDR Annex XIV Section 1a): MEDDEV 2.7/1 rev. \n4 Appendix A7.2 Section b provides relevant additional information with respect to \nthe definition of clinical benefits. MEDDEV 2.7/1 rev. 4 Appendix A7.2 Section c \nprovides relevant information with respect to the quantification of benefits and \ndetermination of relevant outcome parameters, which may be useful for clinical \nevaluation planning.   \nd. Specification of qualitative and quantitative aspects of clinical safety and \nperformance (indents 5-7 of MDR Annex XIV Section 1a): The level of clinical \nevidence required for the device under evaluation needs to be determined by the \nmanufacturer and verified by the notified body. The level of clinical evidence shall \n                                                \n \n30 MDR, Annex XIV, Part A, section 1.  \n31 MDR, Article 2 (12).  \n \nPage 11 of 22  \n \n be appropriate in view of the characteristics of the device and its intended \npurpose.32  \nThe proposed level of clinical evidence should take into account the specification \nof methods to be used for examination of qualitative and quantitative aspects of \nclinical performance and clinical safety with clear reference to the determination of \nresidual risks and side-effects. MEDDEV 2.7/1 rev. 4 appendix A6 describes \nexamples of studies that lack scientific validity for the demonstration of adequate \nclinical performance and/or clinical safety. MEDDEV 2.7/1 rev. 4 section 9.3.2 also \nprovides relevant guidance. It also has to take into account the intended clinical \nbenefits to patients with relevant and specified clinical outcome parameters as well \nas  an indicative list and specification of parameters to be used to determine, based \non the state of the art in medicine, the acceptability of the benefit-risk ratio for the \nvarious indications and for the intended purpose or purposes of the device.33 \nFor medical devices which have been subject to conformity assessment according \nto Directives, it should be possible to provide a clear justification for the level of \nclinical evidence required to reach a demonstration of conformity based on clinical \ndata providing sufficient clinical evidence at the end of the data analysis stage. \nManufacturers should identify benefits and risks of the device under evaluation, \ntake into account available alternative treatment options and a clinical assessment \nof residual risks associated with the device before justifying the level of clinical \nevidence. As an outcome of this step, it should be possible to conclude if the device \nis one which has a clearly positive benefit\u2013risk determination, when alternatives \nare considered, or a marginal one. Special attention is required, with respect to \ndevices with a marginal benefit-risk, at both the stage of initial conformity \nassessment and when designing the post-market surveillance or clinical follow-up \nof the device. \nAccording to the MDR, parameters to be used to \u201c determine\u2026. the acceptability of \nthe benefit-risk ratio for the various indications and for the intended purpose or \npurposes of the device\u201d  need to be based on the state of the art in medicine.34 \nSection 8.2. of MEDDEV 2.7/1 rev. 4 indicates how data on the current state of the \nart in medicine can be identified. \n6.2. Annex XIV Part A Section 1b: Identify available clinical data35  \nIt is important to identify all available sources of clinical data from both the pre-market \nand post-market phases. This will include all of the clinical data which is generated and \nheld by the manufacturer as well as clinical data for equivalent or similar devices36. \nClinical data is defined in the MDR and the sources of data are specified in Article 2(48). \nSections 6.2.1 and 6.2.3 below provide additional guidance with respect to the use of \nthese data sources for legacy devices. \nIt should be noted that, apart from devices for which Article 61(10) may be applied, the \nMDR requires confirmation of conformity with the relevant GSPRs to be based on clinical \ndata as defined in Article 2(48). However, other types of data may provide supportive or \nclarifying information: this may include data derived through evaluation of state of the art, \n                                                \n \n32 MDR, Article 61(1). \n33 MDR, Annex XIV, Part A, section 1 (a) 5th indent. \n34 MDR, Annex XIV, Part A, section 1.  \n35 Guidance with respect to identification of clinical data is provided in section 8 and Appendix A4 and A5 of MEDDEV 2.7/1 rev. 4. \n36 Section 5, MDCG 2020-05 Clinical Evaluation \u2013 Equivalence, A guide for manufacturers and notified bodies.  \n \nPage 12 of 22  \n \n evaluation of clinical data for similar devices (as described in Section 1.2 of this \ndocument), usability or simulated use testing, etc. A summary of considerations related \nto use of clinical and non-clinical data sources is provided in Appendix III of this document. \n6.2.1. Pre-market sources of clinical data \nFor the purpose of legacy devices, pre-market sources of clinical data may include: \n\uf0b7 Clinical investigation reports of the device concerned; \n\uf0b7 Clinical investigation reports or other studies reported in scientific literature, of a \ndevice for which equivalence to the device in question can be demonstrated in \naccordance with the MDR; \n\uf0b7 Reports published in peer reviewed scientific literature on other clinical experience of \neither the device in question or a device for which equivalence to the device in \nquestion can be demonstrated; \n\uf0b7 Other pre-market data, e.g. case reports on experience with the use of the device in \nquestion, such as compassionate or humanitarian exceptional use reports. Note that \nthis kind of pre-market data may be more prone to bias, compared to those listed \nabove. \nIt should be noted that MDR Article 2(48) provides a narrower definition of what \nconstitutes clinical data sources as compared to the Directives which allow unpublished \nreports on other clinical experience to contribute to the clinical evaluation. Such data \nsources may provide informative context for the clinical evaluation of legacy devices. \n6.2.2. Post-market sources of clinical data \nPost-market sources of clinical data refer to data collected following the initial CE marking \nunder the Directives (or prior to introduction of a new indication or design variant). This \nmay include: \n\uf0b7 PMS clinical data, complaint and incident reports; \n\uf0b7 PMCF studies, including post-market clinical investigations; \n\uf0b7 Independent clinical studies conducted using the device37; \n\uf0b7 Device registries;  \n\uf0b7 Data retrieved from the literature. \nFor well-established technologies the clinical evaluation can be based on data coming \nfrom similar devices, under the conditions detailed in paragraph 6.5 (e). With respect to \nlegacy devices, when clinical data from equivalent devices is used, equivalence must be \ndemonstrated according to the requirements of the MDR.38,39 \n6.3. Annex XIV Part A Section 1c: Appraisal of the clinical data \nThe clinical data sets should be subject to an appraisal with respect to their relative \ncontribution to the overall clinical evaluation. It is important to perform analysis of the \nmethodological quality of data obtained from different sources to identify and assess the \nlevel of evidence, bias, other inherent weakness or other possible shortcomings. \nClinical investigations, other sources of clinical data and post-market sources of clinical \ndata can be of variable methodological quality and therefore an appraisal of the design of \n                                                \n \n37 Including for example devices used during clinical trials of pharmaceutical substances, or accessories to other medical devices, \nwhere the device is clearly identified. \n38 MDR, Annex XIV and Article 2(48). \n39 MDCG 2020-5 Clinical Evaluation \u2013 Equivalence, A guide for manufacturers and notified bodies.   \n \nPage 13 of 22  \n \n these studies is important. Examples of studies that lack scientific validity for \ndemonstration of adequate clinical performance and / or clinical safety can be found in \nAppendix A6 General principles of clinical evaluation of MEDDEV 2.7/1 rev. 4. The use \nof vigilance data, in general is appropriate for identification of any new risks, events in \nsubpopulations, examining trends in PMS reports etc. With respect to the utilisation of \npost-market surveillance data for the purpose of conformity assessment, it is important to \nrecognise that uncontrolled sources of clinical data \u2013 for example complaint or incident \nreport data \u2013 cannot always provide reliable data with respect to the incidence of risks \nand cannot provide an estimate of uncertainty i.e. a confidence interval. Due to limitations \nof complaints reporting, the use of estimates such as [number of incidents or complaints] \n/ [number of device sales] cannot generally be considered sufficient to provide proof of \nsafety; their use should be limited to cases where data from pre-market or post-market \nclinical investigations or PMCF studies are not deemed appropriate. \nAdditional information on the use of information derived from vigilance data, device \nregistry data, case series, patient dossiers and other use data can be found in section \n9.3.1 (c) of MEDDEV 2.7/1 rev. 4. \nClinical data appraisal should be conducted using verified/validated assessment tools. \nExamples include methodological quality assessment tools developed by medical \nresearchers and scientists to assess published clinical data such as Appendix F of IMDRF \nMDCE WG/N56 on Clinical Evaluation, Cochrane Collaboration\u2019s tool for Randomized \nControlled Trials (RTC), MINORS (Methodological index for non-randomized studies), \nReisch tool (for non-randomized interventional studies), Newcastle-Ottawa Scale (NOS) \nfor assessing the quality of nonrandomised studies in meta-analyses. Their detailed \ndescription, the inclusive list of major components of each tool is included in the paper by \nZeng X, Zhang Y, Kwong JS et al. \u201cThe methodological quality assessment tools for \npreclinical and clinical studies, systematic review and meta-analysis, and clinical practice \nguideline: a systematic review\u201d40. This list is not exhaustive. Additional validated tools \nmay become available in the future. \n6.4. Annex XIV Part A Section 1d: Generation of new clinical data \nLegacy devices following the MEDDEV 2.12/2 guidance for PMCF should normally have \ncollected data on the devices themselves in the post-market phase. In the event that the \npostmarket data on the device itself (including PMCF) is not adequately comprehensive \nto provide sufficient clinical evidence, and the demonstration of equivalence is no longer \npossible under the definition of equivalence in the MDR, new data may need to be \ngenerated prior to CE-marking under the MDR.  \nIn general, there shall be sufficient clinical evidence to confirm safety, performance and \nthe acceptability of the benefit-risk determination in relation to the state of the art for the \nlegacy devices prior to CE-marking under the MDR, and such demonstration should not \nrely on new PMCF studies started under the MDR to bridge gaps (e.g. indications not \nsupported by clinical evidence). Where other evidence, for example results of pre-clinical \ntesting etc. as described in MDR Article 61(10), is used for confirmation of safety and \nperformance, PMCF studies may be undertaken to confirm these conclusions. \n                                                \n \n40 J Evid Based Med. 2015 Feb;8(1):2-10. doi: 10.1111/jebm.12141. Review. https://www.ncbi.nlm.nih.gov/pubmed/25594108   \n \nPage 14 of 22  \n \n 6.5. Annex XIV Part A Section 1e: Analysis of the clinical data \nThe aim of this stage is the determination if all clinical data collected and appraised, as \ndescribed in previous stages, demonstrate together conformity with relevant GSPR. In \norder to determine the benefit-risk ratio, it is necessary to identify the benefits and risks \nassociated with the device and the alternatives (if any). Practical guidance is available in \nsection 10 of MEDDEV 2.7/1 rev. 4.41  \nDemonstration of compliance with the GSPR, relevant for the device in question have to \nbe based on: \n\uf0b7 The usage of reliable, justified and sound analytical methods (where applicable \nqualitative, quantitative, or both);  \n\uf0b7 Results of performed comprehensive analysis; \n\uf0b7 Identification of any missing data and/or gaps; \n\uf0b7 Determination of PMCF needs.    \n \na. Clinical benefits \nClinical benefit means \u201cthe positive impact of a device on the health of an individual, \nexpressed in terms of a meaningful, measurable, patient-relevant clinical outcome(s), \nincluding outcome(s) related to diagnosis, or a positive impact on patient management or \npublic health\u201d.42 The type of clinical benefit associated with a device depends upon the \ndevice under evaluation and its intended purpose. Examples of clinical benefits and their \nquantification can be found in Appendix A7.2 letters (b) and (c) of MEDDEV 2.7/1 rev. 4. \nIt should be noted that while direct clinical benefits should be supported by clinical data, \nindirect clinical benefits may be demonstrable by other evidence such as: \n\uf0b7 pre-clinical and bench test data (eg compliance to product standards or common \nspecifications); \n\uf0b7 real world data such as registries, information deriving from insurance database \nrecords, etc; \n\uf0b7 data from another device that is used with the subject device which does have \ndirect clinical data (eg, data from a stent used to justify safety and performance of \na guidewire).  \nA determination of the level of clinical evidence required to demonstrate an indirect clinical \nbenefit should be made on the basis of a thorough risk assessment and evaluation of \nshort, medium and long term clinical risks (for example, a guidewire, although used \ntransiently, may have long term clinical risks if it leads to vessel dissection). \n \nb. Risks \nRisk means the combination of the probability of occurrence of harm and the severity of \nthat harm.43 The MDR requires manufacturers to establish, document, implement and \nmaintain a system for risk management.44 The standard ISO 1497145 provides such a \nprocess for managing risks associated with medical devices, as part of an ongoing, \n                                                \n \n41 This chapter includes references to the MDD, MDR requirements should be used instead, ie. reference to \u2018Essential requirements\u2019 \nshould be replaced by GSPR and reference to PMCF should be replaced by the relevant MDR requirements, i.e. in Annex XIV, part B.  \n42 MDR, Article 2(53). \n43 MDR, Article 2(23). \n44 MDR, Article 10(2). \n45 Medical devices \u2014 Application of risk management to medical devices.  \n \nPage 15 of 22  \n \n lifecycle approach. The Annex I of the MDR require that manufacturers reduce risks as \nfar as possible, and to do this, manufacturers must estimate and evaluate the risks \nassociated with, and occurring during, the intended use and during reasonably \nforeseeable misuse.46 \nThe determination as to which risks require the generation of clinical data to support either \nthe probability and severity of a particular harm, or the effectiveness of a risk control \nmeasure, is one which must be reached upon a case by case basis,47 and the decision \nas to when it is necessary to generate further clinical data is not addressed by ISO 14971 \nand should be an output of the process of clinical evaluation. \nConsiderations on aspects of risk evaluation, and considerations on the number of \npatients needed to obtain sufficient data can be found in Appendix A7 of MEDDEV 2.7/1 \nrev. 4. \n \nc. Benefit-risk determination, state of the art, alternative treatment options \nThe MDR requires that any risks which may be associated with the use of the device are \n\u201ccompatible with a high level of protection of health and safety, taking into account the \ngenerally acknowledged state of the art\u201d48 and that the determination of the acceptability \nof the benefit-risk ratio is \u201c based on the state of the art in medicine \u201d.49  \nIt is important to remember that a medical device may be used for an indication for which \nthere are many alternative medical options. This may include the use of medicinal \nproducts, other medical devices, other medical or allied health professional interventions, \na combination of any of these or no intervention. As such, in order to determine a benefit-\nrisk ratio, up-to-date alternatives must be considered for legacy devices. The \nappropriateness and relevance of an alternative treatment option depends upon a wide \nrange of factors, including the nature of the healthcare system and patient preferences. \nTo help to describe alternatives, it is necessary to describe the \u2018state of the art\u2019 for the \ntreatment of the indicated clinical condition taking alternative treatments into account. The \nstate of the art in this context can be taken to mean the generally accepted most effective \ntreatment option, for the intended purpose relevant to the device under consideration. \nOccasionally, this may be subject to differences of opinion between clinical evaluators as \nto what is the state of the art, and where such differences exist, these should be described \nand taken into account insofar as is possible. In such cases, a thorough evaluation of the \nresults from published clinical studies of high methodological quality shall be taken into \naccount. Moreover, where applicable, particular attention shall be paid to therapy \nguidelines grounded on principles of evidence based medicine. Novel and innovative \ndevice technology may be subject to a rapidly evolving state of the art for a particular \nindication, and where this exists, it should also be noted. \nAspects that influence the acceptability of benefits and risks can be found in Appendix \nA7.2 letter (e) and in Appendix A7.4 of MEDDEV 2.7/1 rev. 4. \n \n                                                \n \n46 MDR, Annex I, Chapter 1, section 3(c). \n47 ISO14971:2007, page v, notes that an individual\u2019s perception of risk can depend upon a range of factors including their cultural \nbackground, the socio-economic and educational background of the society concerned, the actual and perceived state of health of \nthe patient, and many other factors. \n48 MDR, Annex I, Chapter 1, Section 1. \n49 MDR, Annex XIV, Part A, Section 1(a).   \n \nPage 16 of 22  \n \n d. The level of clinical evidence available to demonstrate conformity based on clinical \ndata providing sufficient clinical evidence \nThe MDR requires that the level of clinical evidence is justified and specified by the \nmanufacturer. The required level of clinical evidence has to be identified, specified and \njustified by the manufacturer during the clinical evaluation process. This level has to be \nappropriate to demonstrate conformity with the relevant GSPR.  \nTo reach a determination of sufficiency, when considering the available level of clinical \nevidence, the manufacturer may use widely available and validated tools when examining \nclinical data. These tools are methodological quality assessment tools developed by \nmedical researchers and scientists to assess published clinical data.50 Examples of these \ntools include the Cochrane Collaboration\u00b4s tool for RCT or NOS checklist for analytical \nstudies (see Footnote 40). See MEDDEV 2.7.1 rev 4, Section 9.3.2 \u2018How to determine \nthe relevance of a data set for the clinical evaluation\u2019, for further information. \n \ne. Lack of clinical data providing sufficient clinical evidence  \nManufacturers should conduct a gap analysis with respect to the MDR requirements. If \ndata gaps have been identified, there are different possibilities to bridge those gaps.    \nWhile controlled clinical investigations might be the preferred method for collecting clinical \ndata as part of the PMCF studies for some products, there are other possibilities to gather \nrelevant clinical data in the field in order to close the clinical data gap. Other alternatives \ninclude, but are not limited to systematic reviews of clinical data published in the literature, \nevaluation of results from PMCF studies such as clinically relevant scientifically sound \nquestionnaires51 or registries. Scientifically sound studies will normally include (note, this \nis not a complete list): \n\uf0b7 Clearly stated research question(s), objective(s) and related endpoints; \n\uf0b7 An evaluation of potential sources of bias or study distortion, and the impact of \nthese factors on the potential validity of results; \n\uf0b7 Design with an appropriate rationale and statistical analysis plan; \n\uf0b7 A plan for an analysis of the data and for drawing appropriate conclusion(s). \nIf there is not sufficient supportive clinical evidence with regard to the declared intended \npurpose52 including the indications and claims as appropriate, manufacturers shall narrow \nthe intended purpose of the device under evaluation until it is supported by the available \nclinical evidence. \nAs noted in Section 4, some legacy devices may have limited clinical data, particularly if \nthey were marketed prior to the publication of the Directives. In some cases, it may be \nnecessary for the manufacturer to undertake PMCF to generate new data for these legacy \ndevices prior to CE marking under the MDR, whereas in other cases, particularly for low \nrisk standard of care devices where there is little evolution in the state of the art, it may \nbe possible to demonstrate conformity with the relevant GSPRs with a more limited \nclinical data set. \nDevices previously certified under the Directives might not be considered to have \nsufficient clinical data for certification under the MDR. Reasons may include: \n                                                \n \n50 The suggested tools may also be relevant for unpublished data. \n51 Clinically relevant and where possible validated.  \n52 MDR, Article 2(12).  \n \nPage 17 of 22  \n \n \uf0b7 changes in the state of the art  \n\uf0b7 data arising from PMS may identify new risks or provide additional clarity with \nrespect to indications and contraindications  \n\uf0b7 devices previously certified under Quality System annexes of the Directive may \nnot have been sampled prior to an application for MDR certification, and the \nclinical evidence therefore not subject to Notified Body scrutiny \n\uf0b7 the MDR introduces new requirements on the use of equivalence, which may \nreduce the overall volume of data available for demonstration of conformity with \nthe relevant GSPRs \n\uf0b7 the MDR has a more explicit definition of what constitutes clinical data, which may \nremove some data sources previously used \nAlthough the Directives indicate that data shall be collected in the post-market phase for \nall devices53, in practise the data collected may not meet MDR criteria, if the devices were \nconsidered standard of care and were not associated with safety concerns. Stable, well-\nestablished technologies that perform as intended and are not associated with safety \nconcerns, and where there has been no innovation, are less likely to be the subject of \nresearch, and therefore literature data may be limited or non-existent. In some cases, it \nmay be necessary for the manufacturer to undertake PMCF to generate new clinical data \nfor these devices prior to certification under the MDR, even if they are well-established \nand have been on the market for several decades, to enable an evaluation of their safety \nand clinical performance in relation to an evolving state of the art.  \nIn exceptional cases, particularly for low risk standard of care devices where there is little \nevolution in the state of the art, and the device is identified as belonging to the group of \n\u2018well-established technologies\u2019 (see section 1.2 and Appendix III in this document) a lower \nlevel of clinical evidence may be justified to be sufficient for the confirmation of conformity \nwith relevant GSPRs. This may be supported by clinical data from the PMS provided that \nthere has been a quality management system in place to systematically collect and \nanalyse any complaints and incident reports, and that the collected data support the \nsafety and performance of the device. \n \n                                                \n \n53 MDD, Annex II(3.1) indent 7, Annex IV(3), Annex V(3.1) indent 8, Annex VI(3.1) indent 8, Annex VII(4).  \n \nPage 18 of 22  \n \n Appendix I - Sections of MEDDEV 2.7/1 rev. 4 which are still relevant under the MDR \nfor the application of this guidance \n \nThe identified sections of MEDDEV 2.7/1 rev. 4 are considered relevant to MDR as they \ncontain helpful information regarding how to perform activities associated with clinical \nevaluation: \n\uf0b7 6.4. Who should perform the clinical evaluation? \n\uf0b7 8. Identification of pertinent data (Stage 1) \n\uf0b7 9. Appraisal of pertinent data (Stage 2) \n\uf0b7 10. Analysis of the clinical data (Stage 3). This chapter includes references to the \nMDD, MDR requirements should be used instead \n\uf0b7 A3. Device description - typical contents \n\uf0b7 A4. Sources of literature \n\uf0b7 A5. Literature search and literature review protocol, key elements \n\uf0b7 A6. Appraisal of clinical data - examples of studies that lack scientific validity for \ndemonstration of adequate clinical performance and/or clinical safety \n\uf0b7 A7.2. Conformity assessment with requirement on acceptable benefit/risk profile \n\uf0b7 A7.3. Conformity assessment with requirement on performance \n\uf0b7 A7.4. Conformity assessment with requirements on acceptability of undesirable \nside-effects \n\uf0b7 A10. Proposed checklist for the release of the clinical evaluation report. \n   \n \nPage 19 of 22  \n \n Appendix II \u2013 Clinical Evaluation Plan for Legacy Devices54 \nA modified Clinical Evaluation Plan for legacy devices should include at least:55 \n\uf0b7 An identification of the GSPR that require support from relevant clinical data.   \n\uf0b7 A specification of the intended purpose of the device.56 \n\uf0b7 A clear specification of intended target groups with clear indications and contra-\nindications.   \n\uf0b7 A detailed description of intended clinical benefits to patients with relevant and \nspecified clinical outcome parameters. \n\uf0b7 A strategy to identify, analyse and assess alternative treatments57.  \n\uf0b7 A specification of methods to be used for examination of qualitative and \nquantitative aspects of clinical safety with clear reference to the determination of \nresidual risks and side-effects; \n\uf0b7 An indicative list and specification of parameters to be used to determine, based \non the state of the art in medicine, the acceptability of the benefit-risk ratio for the \nvarious indications and for the intended purpose or purposes of the device.  \n\uf0b7 An indication how benefit-risk issues relating to specific components such as use \nof pharmaceutical, non- viable animal or human tissues, are to be addressed.  \n\uf0b7 A strategy and methodology to identify, analyse and appraise all relevant available \nclinical data in light of the changed definition for clinical data. \n\uf0b7 Evidence for equivalence, if clinical data from an equivalent device is included in \nthe clinical evaluation. \n\uf0b7 A definition of the required level of clinical evidence, which shall be appropriate in \nview of the characteristics of the device and its intended purpose.58 59 60 \n\uf0b7 A strategy and methodology to systematically collect, summarise and assess post \nmarket surveillance data to demonstrate continuing safety and performance, and \nto what extent complaints with regards to safety and performance have been \nobserved with the legacy devices.61  \n                                                \n \n54 MDR, Annex VII, 4.11. \n55 Appendix A3 of MEDDEV 2.7/1 rev. 4 lists information that can be relevant for planning clinical evaluations. The manufacturer needs \nto make sure that input for the clinical evaluation plan are in line with the device\u2019s \u201clabel, instructions for use, promotional or sales \nmaterials or statements\u201d and with the device\u2019s updated risk management documents. \n56 In order to fully identify the intended purpose(s) of a legacy device, the manufacturer needs to consider the data that is foreseen on \nthe label, in the instructions for use or in promotional or sales materials or statements that are foreseen for the device. Typical elements \nof the intended purpose can be found in Appendix A3 of MEDDEV 2.7/1 rev. 4. \n57 MDR, Article 61(3)(c). \n58 MDR, Article 61(1). \n59 The proposed level of clinical evidence should take into account the specification of methods to be used for examination of qualitative \nand quantitative aspects of clinical safety with clear reference to the determination of residual risks and side-effects. \n60 To determine the level of clinical evidence it is necessary to identify benefits and risks of the device under evaluation and to take \ninto account available alternative treatment options, and a clinical assessment of failure modes associated with the device. \n61 MDR Article 83 and MDR Annex III.   \n \nPage 20 of 22  \n \n Appendix III \u2013 Suggested hierarchy of clinical evidence for confirmation of \nconformity with relevant GSPRs under the MDR \nSources of pre- and post- market clinical data are described in Sections 6.2.1 and 6.2.2 \nof this document. Reference is also made to clinical evidence which may provide \ncontextual, supportive or clarifying information for demonstration of conformity with the \nrelevant GSPRs. A suggested hierarchy of evidence and considerations to apply is \nprovided in the table below, ranked roughly in order from strongest to weakest (some \nvariations may apply dependent on the device, GSPR for which evidence is required, and \nquality of individual data sources): \nRank Types of clinical data and \nevidence Considerations / comments \n1 Results of high quality62 \nclinical investigations \ncovering all device variants, \nindications, patient \npopulations, duration of \ntreatment effect, etc This may not feasible or necessary for certain \nwell-established devices with broad indications \n(eg Class IIb legacy sutures, which could be \nused in every conceivable patient population) \n2 Results of high quality \nclinical investigations with \nsome gaps  Gaps must be justified / addressed with other \nevidence in line with an appropriate risk \nassessment, and clinical safety, performance, \nbenefit and device claims. \nAssuming the gaps can be justified, there should \nbe an appropriate PMCF plan to address \nresidual risks.  \nOtherwise, manufacturers shall narrow the \nintended purpose of the device until sufficient \nclinical data has also been generated. \n3 Outcomes from high quality \nclinical data collection \nsystems such as registries63 Is there sufficient evidence of the quality of the \ndata collected by the registry64, 65? \nAre the devices adequately represented? \nAre the data appropriately stratified? \nAre the endpoints appropriate to the safety, \nperformances and endpoints identified in the \nclinical evaluation plan? \n4 Outcomes from studies with \npotential methodological \nflaws but where data can still \nbe quantified and \nacceptability justified66 Many literature sources fall into this category, \ndue to limitations such as missing information, \npublication bias, time lag bias, etc. This applies \nequally to publications in the peer-reviewed \nscientific literature. However, for legacy devices \n                                                \n \n62 Refer to data appraisal considerations described in Section 6.3 of this guidance. \n63 Please note that the Considerations / Comments listed in point 2 also apply to these studies.  \n64 http://www.imdrf.org/docs/imdrf/final/technical/imdrf-tech-170316-methodological-principles.pdf   \n65 http://www.imdrf.org/docs/imdrf/final/technical/imdrf-tech-160930-principles-system-registries.pdf   \n66 Please note that the Considerations / Comments listed in point 2 also apply to these studies.  \n \nPage 21 of 22  \n \n where no safety or performance concerns have \nbeen identified, these sources can be sufficient \nfor confirmation of conformity to the relevant \nGSPRs if appropriately appraised and the gaps \nare identified and handled.  \nHigh quality surveys may also fall into this \ncategory. \nClass III legacy devices and implantable legacy devices which are not well-established \ntechnologies should have sufficient clinical data as a minimum at level 4. Those devices \nwhich are well-established technologies may be able to confirm conformity with the \nrelevant GSPRs via an evaluation of cumulative evidence from additional sources as \nlisted below. Reliance solely on complaints and vigilance is not sufficient. \n5 Equivalence data (reliable / \nquantifiable) Equivalence must meet MDR criteria.  \nIt is normally expected that manufacturers \nshould gather data on their own devices in the \npost-market phase, therefore reliance on \nequivalence should be duly justified, and linked \nto appropriate PMCF or proactive PMS. \n6 Evaluation of state of the art, \nincluding evaluation of \nclinical data from similar \ndevices as defined in \nSection 1.2 of this document  This is not considered clinical data under the \nMDR, but for well-established technologies only \ncan be considered supportive of confirmation of \nconformity to the relevant GSPRs. \nData from similar devices may be also important \nto establish whether the device under evaluation \nand similar devices belong to the group of \ndevices considered as \u201cwell established \ntechnologies\u201d (WET). See section 1.2 in this \ndocument for the criteria for WET. Data from \nsimilar devices may be used, for example, to \ndemonstrate ubiquity of design, lack of novelty, \nknown safety and performance profile of a \ngeneric group of devices, etc. \n7 Complaints and vigilance \ndata; curated data This falls within the definition of clinical data \nunder MDR Article 2(48), but is not generally \nconsidered a high quality source of data due to \nlimitations in reporting. It may be useful for \nidentifying safety trends or performance issues. \nHigh volume data collected within a robust \nquality system may provide supportive evidence \nof device safety. \n8 Proactive PMS data, such \nas that derived from surveys  This falls within the definition of clinical data \nunder MDR Article 2(48), but is not generally \nconsidered a high quality source of data due \nlimitations associated with sources of bias and \nquality of data collection. It may be useful for  \n \nPage 22 of 22  \n \n identifying safety concerns or performance \nissues. \n9 Individual case reports on \nthe subject device This falls within the definition of clinical data \nunder MDR Article 2(48), but is not considered a \nhigh quality source of data due to limitations in \ngeneralising findings to a wider patient \npopulation, reporting bias, etc. It may provide \nsupportive or illustrative information with respect \nto specific claims. \n10 Compliance to non-clinical \nelements of common \nspecifications considered \nrelevant to device safety and \nperformance  Common specifications which address clinical \ninvestigation or data requirements directly would \nrank higher in this hierarchy. Common \nspecifications may address clinically relevant \nendpoints through non-clinical evidence such as \nmechanical testing for strength and endurance, \nbiological safety, usability, etc. \n11 Simulated use / animal / \ncadaveric testing involving \nhealthcare professionals or \nother end users67 This is not clinical data, but may be considered \nevidence of confirmation of conformity to \nrelevant GSPRs, particularly in terms of \nusability, such as for accessories or instruments.  \n12 Pre-clinical and bench \ntesting / compliance to \nstandards62 Pre-clinical and bench testing may address \nclinically relevant endpoints through non-clinical \nevidence such as mechanical testing for \nstrength and endurance, biological safety, \nusability, etc. \n \n                                                \n \n67 This may be of interest in the case of application of Article 61(10)."}, {"title": "mdcg_clinical_evaluationtemplate_en.pdf.txt", "text": "Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n0 \n   \n \n \n \n \n \n \nMDCG 2020-13 \n  \nClinical evaluation assessment report template   \n \nJuly 2020 \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) established \nby Article 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member States and a representative of the European Commission chairs it. The document is not a European Commission document and it cannot be regarded as reflecting the official position of the European Commission. Any views expressed in this document are not legally binding and only the Court of Justice of the European Union can give binding interpretations of Union law. \n  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n1 \n  \nContents \n \nIntroduction ............................................................................................................................... ....... 3  \nScope ......................................................................................................................... ..................... 3  \nApproach to Template .......................................................................................................... ........... 4  \nTemplate CEAR ................................................................................................................. ............. 6  \nSection A: Administrative particulars (notified body, manufacturer, product and clinical \nevaluation report reference) .................................................................................................. ....... 6  \nSection B: Reviewers involved in the notified body assessment of the clinical evaluation ........... 7  \nSection C: Device description, classification, clinical evaluation plan, information materials \nsupplied by the manufacturer, common specifications and harmonised standards applied, equivalence and state of the art .............................................................................................. ..... 8\n \nSection D: Clinical literature review.......................................................................................... .. 15  \nSection E: Clinical investigations and related documentation .................................................... 18  \nSection F: PMS, PMCF and the plan for updates ...................................................................... 20  \nSection G: IFU, SSCP, labelling and other information supplied with the device ....................... 21  \nOverall Conc lusions: .......................................................................................................... ........ 24  \nSpecific Considerations ....................................................................................................... .......... 25  \nSection I: Clinical evaluation c onsultation procedure for certain class III and class IIb devices \n(Article 54) .................................................................................................................. ............... 25  \nSection J: Where demonstration of conformity based on clinical data is not deemed appropriate \n(Article 61(10)) .............................................................................................................. ............. 28  \nSection K: The voluntary clinical consultation on the clinical development strategy (Article 61(2))\n .............................................................................................................................. ..................... 30  \n \n \n  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n2 \n  \nList of acronyms \nCEAR   Clinical Evaluation Assessment Report \nCECP   Clinical Evaluation Consultation Procedure CER   Clinical Evaluation Report CIP   Clinical Investigation Plan EUDAMED  European Databank on Medical Devices IFU   Instructions for Use MDR   Medical Device Regulation (Regulation (EU) 2017/745 on me dical devices) \nPMCF   Post-Market Clinical Follow-up PMS   Post-Market Surveillance PSUR   Post-Market Surveillance Update Report \nSRN   Single Registration Number \nSSCP   Summary of Safety and Clinical Performance  TDAR   Technical Documentation Assessment Report  UDI-DI   Unique Device Identification Device Identifier \n  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n3 \n Introduction  \nA  c l i n i c a l  e v a l u a t i o n  a s s e s s m e n t  r e p o r t  ( C E A R )  i s  a  r e p o r t  u s e d  b y  t h e  n o t i f i e d  b o d y  t o  c l e a r l y  d o c u m e n t  t h e  \nconclusions of its assessment of the clinical evidence presente d by the manufacturer in the clinical evaluation report \n(CER) and the related clinical evaluation that was conducted \u2013 a core requirement of the Medical Device Regulation \n(EU) 2017/745 (MDR).   The clinical evaluation must be a part of the manufacturer's qu ality management. It should also be aligned with and \nreflected in other aspects of the technical documentation, such  as: \n\u2022 The interface of the clinical eva luation with the risk manageme nt process and its appraisal and analysis of the pre-\nclinical and clinical evaluation and their relevance for the de m o n s t r a t i o n  o f  c o n f o r m i t y  w i t h  t h e  r e l e v a n t  \nrequirements in Annex I.\n1 \n\u2022 Post-market surveillance including  any corrective and preventiv e actions involving the device. \n\u2022 Post-market clinical follow-up pl an and where appropriate the p ost-market clinical follow-up report. \n\u2022 Instructions for use, which provide adequate information on int ended purpose, proper use and warnings about \nrisks to patients and healthcare practitioners. \n As part of its conformity assessment activities the notified bo dy shall examine, validate and verify that manufacturers' \nprocedures and documentation adequately address the requirement s relating to the technical documentation\n2 and \nclearly document its assessment3.  \n \nThe notified body shall review the clinical evidence presented by the manufacturer in the clinical evaluation report \nand the related clinical evaluation that was conducted, which i ncludes4:  \n \n\u0081 Assessing the suitability of using data from claimed equivalent  devices, taking into account factors such as new \nindications and innovation. The notified body shall clearly doc ument its conclusions on the claimed equivalence, \nand on the relevance and adequacy of the data for demonstrating  conformity. For any characteristic of the device \nclaimed as innovative by the manufacturer or for new indication s, the notified body shall assess to what extent \nspecific claims are supported by specific pre-clinical and clin ical data and risk analysis. \n\u0081 Verifying that the clinical evidence and the clinical evaluatio n are adequate and shall verify the conclusions drawn \nby the manufacturer on the conformity with the relevant general  safety and performance requirements. That \nverification shall include consideration of the adequacy of the  benefit-risk determination, the risk management, \nthe instructions for use, the user training and the manufacture r's post-market surveillance plan, and include a \nreview of the need for, and the adequacy of, the PMCF plan prop osed, where applicable. \n\u0081 Considering the clinical evaluation and the benefit-risk determ ination, and whether specific milestones need to be \ndefined to allow the notified body to review updates to the cli nical evidence that result from post-market \nsurveillance and PMCF data.   \n The outcome of this assessment must be clearly documented in th e CEAR.\n5 A harmonised CEAR template provides a \nstandardised method for documenting the notified body\u2019s assessm ent of the manufacturer\u2019s clinical evaluation and \nrelated documents. CEARs in this format will also support specific additional requirements  such as the clinical \nevaluation consultation procedure6 and reviews by designating authorities.7  \nScope \nThis template applies to MDR Annexes IX section 4 and Annex X s ection 3. It also applies to assessments of technical \ndocumentations on a sampling basis for class IIa/IIb devices in  accordance with Annex IX sections 2.3 and 3.5 and \n                                            \n1 MDR, Annex VII Section 4.5.1 and 4.5.5 \n2 MDR, Annexes II and III \n3 MDR Annex VII Section 4.5.5 and 4.6  \n4 MDR, Annex IX Sections 4.4 to 4.7  \n5 MDR, Annex IX 4.8   \n6 MDR, Article 54 \n7 MDR, Article 45 Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n4 \n Section 10 of Annex XI(A).8 Aspects related to the clinical evaluation assessment are also  laid down in Section 4.5.5 \nan d  oth er r ele van t s ecti on s of A n n e x V II.   It als o ap p lies to  m ed ical d e vice s fo r wh ich  clin ical d at a is n o t  d ee med  \nappropriate,9 to demonstrate conformity with Annex I, and the demonstration of an adequate justification for this.10 \nApproach to Template \nPlease note that the explanatory text under each heading provid es brief descriptions of the type of information which \nwill be included by the  notified body, however it is not an all -inclusive list and further detail may be required depending \nupon the device or the intended purpose for which it will be us ed. This template represents the minimum  content  for \na CEAR and needs to be incorporated into the process and proced ures of the notified body.11 The CEAR shall also make \na recommendation to support a final review and a final decision  to be taken by the notified body.  \n \nAny non-compliances identified during the assessment of the asp ects described in the relevant sections of the \ntemplate, as well as the appropriate follow up actions taken by  the manufacturer to close them need to be \ndocumented. This template may be used by the notified body to d ocument the non-compliance/deficiencies and \nqueries raised during the assessment and the assessment of resp onses received. It is important to note that the \ncompleted CEAR may not necessarily contain comprehensive inform ation regarding the non-compliance/deficiencies, \nwhich were raised by the notifie d body during the course of the  assessment. The CEAR shall document the outcome12 \nand the conclusions13 of the assessment.  \n Designating authorities shall assess whether the clinical evalu ation assessment was conducted appropriately, \nconsidering the assessment, procedures, associated documentatio n and the conclusions;\n14 Designating authorities will \nhave access to the complete \u2018audit trail\u2019 of the notified body.   \n \nExpert panels who are conducting a clinical evaluation consulta tion procedure shall assess the CEAR, however they \nmay not have access to the complete conformity assessment for t he device and associated procedures and \ndocumentation. To enable the expert panel work, the CEAR shall provide sufficient information with respect to the \nclinical evidence provided by the manufacturer, in particular c oncerning the benefit-risk determination, the \nconsistency of that evidence with the intended purpose, includi ng the medical indication or indications and the PMCF \nplan.15 Expert panels may also request the notified body to present it s conclusions regarding the clinical evaluation \nassessment report.16  \n \nIt is only once all the non-compliances have been closed out th at the relevant tick-box should be completed to signal \nt h a t  t h e  a s s e s s m e n t  i s  p o s i t i v e .  I n  t h e  r a r e  e v e n t  t h a t  t h e r e  i s one or more open minor non-compliances at the \nconclusion of the assessment stage, this must be clearly descri bed in the template, together with appropriate follow-\nu p  a c t i o n s  t o  c l o s e  t h e m ,  a n d  e x p e c t e d  c o m p l e t i o n  t i m e l i n e s  t o  be followed by the manufacturer under the \nsupervision of the notified body.  \n \nThe sections covered in Annex I of this template are generally applicable depending on the type of assessment. The \nsections covered in Annex II may be applicable, depending upon the device under evaluation. All applicable sections \nshould be completed, relevant conclusions reached and correspon ding boxes ticked for the report to be complete . \nThe CEAR should be signed-off by the relevant personnel in acco rdance with the quality management system of the \nnotified body. When making available the CEAR to third parties,  the notified body should treat the personal data within \n                                            \n8 MDCG 2019-13  \n9 Article 61(10) \n10 Based on the results of the manufacturer's risk management and  on consideration of the specifics of the interaction between \nthe device and the human body, the clinical performance intende d and the claims of the manufacturer. \n11 MDR, Annex VII Section 4.6  \n12 MDR, Annex IX Section 4.8 \n13 MDR, Annex VII Section 4.6 \n14 MDR, Article 45(3) \n15 MDR, Annex IX Section 5.1(c) \n16 MDR, Annex IX Section 5.1(b)  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n5 \n it as per its procedures for the management of personal data, i n compliance with Regulation (EU) 2016/679 General \nData Protection Regulation.  \n \n Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n6 \n Template CEAR \n \nSection A: Administrative particulars (notified body, manufactu rer, product and clinical evaluation report reference)  \nMedical device name model and type:  \n\u2610 Basic UDI-DI(s) (if available): \n \n\u2610 Certificate number (if applicable): \n Project number:  Risk Class:  \n \nApplicable code(s) per Commission Implementing \nRegulation (EU) 2017/2185: \n Manufacturer(s) name and SRN:\n  \n Authorised representative (if applicable) \nname and SRN: \n \n  Notified body:  \n Notified body number:  \n \nE-mail contact of NB: \n Telephone contact of NB:   \n Parts of this template which have been \napplied \n \nGeneral considerations\n17 \n\u2610 Section A: Administrative particulars  \n\u2610 Section B: Reviewers involved  \n\u2610 Section C: Device description, \nclassification, clinical evaluation plan, \ninformation materials supplied by the \nmanufacturer, common specifications and harmonised standards applied, equivalence and state of the art \n\u2610 Section D: Clinical literature review \n\u2610 Section E: Clinical investigations and \nrelated documentation \n\u2610 Section F: PMS and PMCF \n\u2610 Section G: IFU, SSCP, labelling and other \ninformation supplied with the device \n\u2610 Section H: Summary of all available data \nand conclusions \n\u2610 Overall Conclusions \n \nSpecific Considerations Type of assessment:  \n\u2610 Initial conformity assessment  \n\u2610 Assessment of changes18 and update of the clinical \nevaluation19 \n\u2610 Re-certification assessment \n\u2610 Assessment of technical documentation for class IIa \n/ IIb devices on a sampling basis \n Intended purpose: \n Check of clinical evaluation report authors \n\u2610 CER dated and signed \n\u2610 CVs provided for CER author(s) \n \nComments: \nConfirm CVs are up to date \nConfirm CER authors have full range of \nrequired expertise represented (e.g. research methods, information \n                                            \n17 These must be completed in all cases \n18 MDR, Annex IX Section 4.10 \n19 For example in accordance with Annex VII, Section 4(10) Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n7 \n According to Annex / section:   \nInsert the Annex and section  management, regulatory requirements, \ndevice technology, diagnosis and \nmanagement of conditions to be treated) \nCVs are considered acceptable: \u2610 \n \u2610 Section I: Clinical evaluation \nconsultation procedure for certain class III and class IIb devices (Article 54) \n\u2610 Section J: Where demonstration of \nconformity based on clinical data is not deemed appropriate (Article 61(10)) \n\u2610 Section K: The voluntary clinical \nconsultation on the clinical development strategy (Article 61(2)) \nTechnical file identification number and technical documentatio n assessment report (TDAR) reference if available or any other references that allow the correlation between TDAR and \nCEAR: \n \nDocuments assessed: \nFor example, clinical evaluation report, clinical investigation  plan, clinical investigation re port, ethics committee approval , Competent Authority approval, post market surveillance data, \npublications. \nInclude the title, version number/reference and date of the doc uments.  \nWhen the CER has been updated verify that this update correspon ds to the most recently updated PMS/PMCF reports and any condit ions set on the first certification, if applicable. \nNote that references to the technical documentation should be m ade in order to ensure document control. \n \n \n \nSection B: Reviewers involved in the notified body assessment o f the clinical evaluation  \nProvide the name or the employee code of the personnel with rel evant clinical expertise (as  per 3.2.4 of annex VII): \n \nRelevant clinical expertise:  \n \nHave additional reviewers been involved? Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n8 \n \u2610Yes \n\u2610No  \nProvide a justification: \n \nAdditional reviewers assigned to review the clinical evaluation  \nNumber of additional reviewers \nNames of additional reviewers: \nSeparate the internal and external clinical \nreviewers. \nYou may use employee codes \n Specific aspects assessed (by each additional reviewer): For example, rationale \nfor the design and chosen statistical methodology of clinical i nvestigation etc.  Competence area / codes: List of relevant MDR codes \nor area this person is authorised to, according to the \nAuthorisation Matrix, as of Annex VII, 3.3.2)  \nRelevant expertise:  \n \n \n \nSection C: Device description, classification, clinical evaluat ion plan, information materials supplied by the manufacturer, c ommon specifications and harmonised standards applied, \nequivalence and state of the art \nDevice description  \nDescribe the device and comment on the intended purpose, includ ing:  \n\u0081 The intended patient population and medical conditions to be di agnosed, treated and/or monitored.  \n\u0081 A general description of the key functional elements: its parts /components (including software if appropriate), its formulatio n, its composition, its functionality and, where relevant, \nits qualitative and quantitative composition.  \n\u0081 The principles of operation of the device and its mode of actio n; explanation of any novel features. \n \nClassification \nList the applicable classifica tion rule(s) and indents. \n Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n9 \n Device configurations/variants included in this application: \nInclude the manufacturers description of the sizes, differences  in design features, different configurations etc.  \nInclude an image of the device where possible.  \nIf applicable, include the manufacturers description of the dev ice history and/or changes in the device since its last assessm ent. \nWhere relevant, include the manufacturers description of the re ason for differences in design variants with illu strative image s where possible. \n \nAccessories or compatible devices: Describe any accessories or compatible devices if any or state,  \u201cnone\u201d). \nInclude component devices in case of system/procedure pack. If the use of accessories or compatible devices has an impact o n clinical safety or performance or the scope or validity of th e clinical evaluation,  identify this here.  \nIf it is necessary to understand the usage of the device, inclu de images or other relevant inf ormation such as diagrams. \n \nPrevious generations of the device and similar devices (if appl icable):  \nVerify that the manufacturer has provided:  \n\u0081 an overview of the previous generation or generations of the de vice produced by the manufacturer, where such devices exist. \n\u0081 an overview of identified similar  devices available on the Unio n or international markets, where such devices exist, including  length of time on the market, sales volume etc. \nNon-compliances identified and resolved for this section may be  briefly described in this box \nDevice details, intended purpose and classification are:  \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 \n \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \nClinical evaluation plan Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n10 \n Briefly summarise the manufacture r\u2019s clinical evaluation plan a nd confirm that it meets the requirements of Annex XIV Part A S ection 1a, highlighting the areas which require particular \nattention for this assessment: \n\u0081 an identification of the general safety and performance require ments that require support from relevant clinical data; \n\u0081 a specification of the intended purpose of the device;  \n\u0081 a clear specification of intended target groups with clear indi cations and contra-indications;  \n\u0081 a detailed description of intended clinical benefits to patient s with relevant and specified clinical outcome parameters;  \n\u0081 a specification of methods to be used for examination of qualit ative and quantitative aspects of  clinical safety with clear re ference to the determination of residual risks and side-\neffects;  \n\u0081 an indicative list and specification of parameters to be used t o determine, based on the state of the art in medicine, the acc eptability of the benefit-risk ratio for the various indication s \nand for the intended purpose or purposes of the device;  \n\u0081 an indication  how benefit-risk issues relating to specific components such a s use of pharmaceutical, non-viable animal or human tissues, ar e to be addressed; and  \n\u0081 a clinical development plan indi cating progression from explora tory investigations, such as first-in-man studies, feasibility and pilot studies, to confirmat ory investigations, such as \npivotal clinical investigations, and a PMCF as referred to in P art B of Annex XIV of MDR, with an indication of milestones and  a description of potential acceptance criteria. \nA detailed description of the clinical development plan is not required for the purpose of this template unless there are spec ific concerns.  \nAdd the manufacturer\u2019s reference and version and date of the cl inical evaluation plan. \nClinical performance \nSummarise the clinical data to d emonstrate the ability of the d evice, resulting from any direc t or indirect medical effects wh ich stem from its technical or functional characteristics, incl uding \ndiagnostic characteristics, to achieve its intended purpose as claimed by the manufacturer, thereby leading to a clinical bene fit for patients, when used as intended by the manufacturer. \nDescribe the clinical benefits. \nSafety \nDoes the clinical evaluation adequately addresses the qualitati ve and quantitative aspects of clinical safety with clear refer ence to the determination of residual risks and undesirable sid e-\neffects and the confirmation of the relevant safety and perform ance requirements provided for in Annex I? \nSummarise the clinical data regarding safety, and also describe  residual risks and any undesirable side- effects. \nDoes the clinical evaluation spec ify the methods to be used for  examination of qualitative and quantitative aspects of clinica l safety with clear reference to the determination of residual risks \nand undesirable side-effects? \nIf relevant, briefly summarise any  significant complaint, trend s or vigilance issues associated w ith earlier device iterations , which may be equivalent or similar devices, and explain wheth er \nor not they have any impact on the clinical evaluation assessme nt. \nNon-compliances identified and resolved for this section may be  briefly described in this box Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n11 \n The clinical evaluation plan is: \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 \n \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \nCommon specifications, harmonised standards or other solutions applied \nAre there common specifications relevant to the device under ev aluation? \nHave they been complied with? If not:\n20  \n\u0081 Explain any deviations and how t hese might affect the validity of the clinical evaluation and its conclusions, and any equival ence claims. \n\u0081 Confirm that the manufacturer has adopted solutions that ensure  a level of safety and performanc e that is at least equivalent thereto in accordance with Article 9(3). \n \nAre there harmonised standards relevant to the clinical evaluat ion of the device under evaluation? \nHave they been applied? If partially applied add the manufacturers justification and co nfirm that the manufacturer has adopted solutions that ensure a  level of safety and performanc e required by the Regulation \n(EU) 2017/745. \nIf there are deviations explai n any deviations and how these mi ght affect the validity of the clinical evaluation and its conc lusions, and any equivalence claims. \nIs the most up-to-date revision being used by the manufacturer?  (state which revision was used) \n \nAre there other solutions that have been applied? \nDescribe any standards, guidance or other solutions that have b een applied, and the manufacturers justification  \nNon-compliances identified and resolved for this section may be  briefly described in this box \n                                            \n20 Excluding devices listed in Annex  XVI which must comply with th e relevant common specifications  in accordance with Article 9(4 ). Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n12 \n The application of CS, harmonised standards or other solutions is:  \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 \n \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \nThe demonstration of equivalence \nIs the clinical evaluation based upon clinical investigation(s)  or other studies reported in scientific literature, of a devic e for which equivalence to the device in question can be \ndemonstrated? \nState Yes / No Device(s) to which equivalence has been claimed: \n \nIs the clinical evaluation based upon reports published in peer  reviewed scientific literature on a device for which equivalen ce to the device in question can be demonstrated?  \nState Yes / No \nIf yes, specify the source(s) of the data, if it is the device in question, or an equivalent device, or both. \n \nDevice(s) to which equivalence has been claimed:  \n \nDevice which is most relevant: \n \nAssessment of equivalence \n1. Equivalence rationales: \nIndicate which devices are/are not equivalent, and confirm that  data relating to devices which are not equivalent have been ex cluded from the analysis of clinical data for the purposes for \ndemonstrating safety and performance. \n \nIf equivalence has been claimed to more than one device, each d emonstration of equivalence can only be based on a single devic e. Each equivalent device must meet all three equivalence \ncriteria (clinical, technical, biological). \n \n2. Are the devices equivalent in accordance with Section 3 of Anne x XIV including technical, biologi cal and clinical characterist ics? \nState Yes / No \nIdentify any differences in these parameters, and verify why th ese are not expected to adversely affect the safety and perform ance of the medical device under evaluation. Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n13 \n Non-compliances identified and resolved for this section may be  briefly described in this box \nThe demonstration of equivalence is:  \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 \n \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \nAccess to data  \nComment on the manufacturer\u2019s access to data, relating to devic es with which they are claiming equivalence in order to justify  their claims of equivalence. \nFor implantable and Class III device s, if equivalence is claime d with a device marketed by another manufacturer, confirm that there is a current valid contract between the two \nmanufacturers allowing ongoing access to the technical document ation in accordance with Article 61 (5) of the MDR. \nHas the original clinical evaluat ion been performed in complian ce with the requirements of Regulation 2017/745, and has the ma nufacturer of the second device provided clear evidence \nthereof? \n State Yes / No  \nConfirm that access to data is sufficient to provide the manufa cturer with enough information about the equivalent devices to support equivalence claims, in cluding any testing which may \nhave been undertaken to confirm equivalence of specifications/p erformance/etc.  \n \nAny other limitations with re spect to equivalent devices: \nComment on any other limitations with respect to the equivalent  devices or manufacturer\u2019s equivalence claims, and the extent t o which these limitations impact the manufacturer\u2019s clinical \nevaluation and conclusions. \n \nNon-compliances identified and resolved for this section may be  briefly described in this box \nManufacturer demonstration of equivalence and access to data is : \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n14 \n  \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \nState of the art \nBenchmark devices, state of the art and other available treatme nt options: \nDescribe the alternative availabl e treatment options identified  by the manufacturer which could offer comparable safety and pe rformance for the same treatment indications / patient \npopulations, etc. \n \nBriefly describe how benchmarks for safety and performance have  been identified by the manufacturer in terms of the state of t he art. Benchmarks will norma lly be based on aggregate data \nfrom several devices considered to have acceptable performance (e.g. systematic reviews or registry analysis); if individual d evices are selected as benchmarks for safety and performance, a  \nsuitable rationale should be provided. \n Confirm that the manufacturer's description of the state of the  art is based upon an appropriate literature search (see sectio n D)?  \n \nFor devices previously marketed, is the description of the stat e of the art still accurate? Can the device still be considered  to be state of the art? \n Safety, performance and benefit-risk claims - requirements in t erms of the state of the art: \nWhat performance and safety endpoints has the manufacturer iden tified? \nIn light of the outcomes achievable with benchmark products and  other treatment options, are these endpoints appropriate and c linically relevant? Have surrogate endpoints been \nadequately justified? \n \nHas the manufacturer adequately described an indicative list an d specification of parameters used to determine, based on the s tate of the art in medicine, the  acceptability of the benefit-\nrisk ratio for the various indications and for the intended pur pose or purposes of the device? \n \nNon-compliances identified and resolved for this section may be  briefly described in this box \nManufacturer demonstration of state of the art is: \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n15 \n  \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \nNovelty \nInclude the manufacturer\u2019s explanation of any novel features of  the device and/or the related  clinical procedures and their pu rpose.  \nWhat is the possible clinical or health impact in terms of bene fit/risk? \nIs novelty adequately addressed? \u2610 \n \n \nSection D: Clinical literature review  \nWith respect to the search criteria  of the literature review, does it: \n\u2610 Address all device sizes, variants, model and accessories? \n\u2610 Address the same clinical condition? \nFurther information regarding literature search methods is avai lable in MEDDEV 2.7/1 revision 4, section A5. \nSearches for the device in question, equivalent devices and oth er devices (for example to support a description of the state o f the art) should be described separately. \n With respect to the selection criteria  of the literature review, does it relate to both below: \n\u2610 The device under evaluation or to a device demonstrated to be equivalent? \n\u2610 The state of the art or alternative available treatment option ? \nThe clinical evaluation should c learly describe the selection c riteria with respect to the regulatory purpose to which it will  apply. The CER should clearly differentiate between the two ty pes \nof data referenced above. If the data does not relate to either  of the above, provide a rationale with respect to its inclusio n.  \n \nLiterature search protocol21 \nProvide a brief summary of the literature search strategy appli ed, commenting on: \n                                            \n21 For general guidance on a literat ure search, see MEDDEV 2.7/1 r evision 4, A5. Literature search and literature review protocol , key elements.  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n16 \n \u2022 The adequacy of search terms: for example, it should be suffici ently broad to establish benchmarks, determine the general stat e of the art, determine potential risk, adverse \nevents, undesirable side-effects, etc.  \nNote that a search which is restricted to the manufacturer\u2019s ow n product or the name of their chosen equivalent could miss imp ortant information and therefore is not \nacceptable. \n\u2022 Databases used (to minimize bias multiple databases should be u sed). \n\u2022 Acceptability of inclusion and exclusion criteria.  \n\u2022 Both favourable and unfavourable data included. \n\u2022 Strategies for avoiding duplication of data (for example, acros s different publications or between manufacturer and published data). \n\u2022 Literature search and review protocol (i.e. how did the manufac turer test this protocol to ensure comprehensive identification  of relevant data / demonstrate that all relevant \ndata has been retrieved?). \n\u2022 Any deviations from the manufacturer\u2019s literature search protoc ol. \n\u2022 Overall conclusions regarding the adequacy of search methods, l ikelihood of having retrieved all relevant data, and methods us ed to avoid bias. \nComment if systematic search and review methods such as the fol lowing have been used: \n\u2022 PICO (patient characteristics, type of intervention, control, a nd outcome queries). \n\u2022 Cochrane Handbook for Systematic Reviews of Interventions. \n\u2022 PRISMA (The Preferred Reporting Items for Systematic Reviews an d Meta-Analyses) Statement. \n\u2022 MOOSE Proposal (Meta-analysis Of Observational Studies in Epide miology). \n\u2022 Other (specify or describe). \nLiterature searc h documentation: \n\u2610 Literature search protocol provided \n\u2610 Literature search reports provided \n\u2610 Full list of retrieved articles provided \n\u2610 Full list of excluded articles provided, with reasons for excl usion \n\u2610 Full text copies of relevant documents available \n Comments: \nProvide rationale if any of the above has not been provided. Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n17 \n Nota bene: \n\u2022 A literature search and other retrieval of data should be carri ed out based on a search protocol. The search protocol should d ocument the planning of the search before execution.  \n\u2022 Once the searches have been executed, the adequacy of the searc hes should be verified and a literature search report should be  compiled to present details of the execution, any \ndeviations from the literature search protocol, and the results  of the search. \n\u2022 It is important that the literature search is documented to suc h degree that the methods can be appraised critically, the resu lts can be verified, and the search reproduced if \nnecessary. \n\u2022 Abstracts lack sufficient detail to allow issues to be evaluate d thoroughly and independently, but may be sufficient to allow a first evaluation of the relevance of a paper. Copies of \nthe full text papers and documents should be obtained for the a ppraisal stage. \n\u2022 The literature search protocol(s), the literature search report (s), and full text copies of relevant documents using URL links , become part of the clinical evidence and, in turn, the \ntechnical documentation for the medical device. \nNon-compliances identified and resolved for this section may be  briefly described in this box  \nLiterature search protocol and outputs are: \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 \n \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \nData appraisal: \nProvide a brief summary of the manufacturer\u2019s data appraisal me thods (i.e. how they determine whether the data from a given st udy or other source of data is of sufficient quality and \nrelevance to be included in the clinical evaluation. This inclu des evaluation of criteria incl uding study design, sources of b ias, peer review, relevance to subject device, etc. Retrieved s tudies \nand data sets should be weighted on the basis of scientific qua lity and relevance to the scope and objectives of the clinical evaluation for the subject devices). \nJustify the acceptability of the appraisal in terms of: \n\u2022 Methodological quality and scient ific validity of articles retr ieved and evaluated appropriately. \n\u2022 Relevance of the information to the clinical evaluation determi ned and documented. \n\u2022 Contribution of each data set to the clinical evaluation weight ed according to systematic criteria. Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n18 \n   \nNon-compliances identified and resolved for this section may be  briefly described in this box  \nData appraisal is:  \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 \n \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer.  \n \n \nSection E: Clinical investigations and related documentation  \nHas the manufacturer conducted clinical investigation(s)?  \nState Yes / No \n Has the manufacturer conducted pre-market or post-market clinic al investigations? \nProvide detail \n If the manufacturer has not conducted clinical investigation: What is the rationale?  \nWhy is this acceptable / unacceptable? \n Has the manufacturer provided a c opy of all clinical investigat ion reports? \nState Yes / No \n \nWere all clinical investiga tions publicly registered? \nState Yes / No \n \nHave been verified that clinical investigations conducted with respect to Regulation (EU) 745/ 2017 publicly registered on EUDA MED? \nState Yes / No Provide the EUDAMED single regist ration number where available.  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n19 \n  \nDid the clinical investigations result in a publication in a sc ientific journal? \nState Yes / No If yes, does the clinical investigation report reflect the resu lts of clinical investigation(s) or other studies reported in s cientific literature, or reports published in peer reviewed sci entific \nliterature on other clinical experience? If there are any diffe rences describe these and summarise the rationale provided by t he manufacturer. \n \nHas the manufacturer provided all Competent/Regulatory Authorit y correspondence (from all countries, including outside of EU) \nState Yes / No \n \nAre the conclusions drawn by the manufacturer, based upon the r esults of the clinical investiga tion, valid in the light of the  approved clinical investigation plan? \nProvide detail  \nIf clinical investigations not performed under Regulation (EU) 745/2017 were not publicly registered or published: \n\u0081 Confirm that a rationale was provided. \n\u0081 Confirm that the SSCP and where relevant the IFU (for example w ith respect to the description of clinical benefits) adequately  provide information for the intended user and if \nrelevant, the patient. \nClinical Investigation  Plan (CIP) reference \n CIP complies with MDR, Annex XV, and EN ISO 14155 Annex A  \nState Yes / No \n CIP scope and study design  \nAdequacy of CIP scope and study design for demonstration of saf ety, performance and benefit risk of subject devices: \n\u0081 Study design. \n\u0081 Devices identified.  \n\u0081 Patient population. \n\u0081 Patient numbers. \n\u0081 Objectives and endpoints. \n\u0081 Length of follow up and intervals. \n\u0081 Study locations. \n\u0081 Overall conclusions. \nNon-compliances identified and resolved for this section may be  briefly described in this box Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n20 \n Manufacturer clinical investigati ons and related documentation are: \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 \n \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \n \nSection F: PMS, PMCF and the plan for updates \nDocuments reviewed, where relevant: \n\u2610 PMS Plan  \n\u2610 PMS Report (where relevant)  \n\u2610 PMCF Plan  \n\u2610 PMCF Report (where relevant)  \n\u2610 PSUR (if available) \nInclude references to the above documents. The demonstration of equivalence and the link to post-market cl inical follow-up \nDescribe how the manufacturer will verify the presumption that there would be no clinically significant difference in the safe ty and clinical performance of the device under evaluation \ncompared with the equivalent device by post market surveillance  or post market clinical follow-up? \n Is there a post-market clinical follow-up planned? \nState Yes / No \n Is this an implantable or class III device for which clinical i nvestigations have not been perfo rmed in accordance with Articl e 61(4)? \nState Yes / No \nFor these devices the PMCF plan should include post market clin ical studies to demonstrate the safety and performance of the d evice. \n Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n21 \n Clinical evaluation updates: \nIdentify when updates to the clinical evaluation report shall b e assessed during the surveillance and post certification monit oring activities and which frequency should be considered.  \nProvide further detail taking into account the manufacturer's P MCF plan and the post-market surveillance plan.  \nNon-compliances identified and resolved for this section may be  briefly described in this box \nThe PMS, PMCF and the plan for updates are: \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 \n \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \n \n \nSection G: IFU, SSCP, labelling and other information supplied with the device \n \nInformation materials supplied by the manufacturer and the inst ructions for use: \nDescribe what has been reviewed \u2013 IFU, promotional materials (i f available), SSCP, labelling etc.  In case several documents ha ve been assessed, identify answers to the questions below for \neach of the documents.22  \n \n                                            \n22 Note that the SSCP requires a separate validation report. Comments on appropriateness of PMS/PMCF Plan: \n \nIf no PMCF is planned, has the manufacturer provided an accepta ble justification for not conducting a PMCF? \nState Yes / No  \n Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n22 \n Intended purpose: \nDoes the clinical evidence support this? \nIntended patient population: Who is the intended patient population?  Does the clinical evidence support this? \nAre all the appropriate/relevant restrictions, warnings or cont raindications in place?  \n \nIntended users: \nIs the device to be used by healthcare professionals or lay use rs? Does the IFU provide all the appropriate/relevant informati on for the intended user?  \nHas the manufacturer taken into account the technical knowledge , experience, education, training and use environment, where ap plicable, and the medical and physical conditions of \nintended users (design for lay, professional, disabled or other  users). \nIs any training for users required as a risk control measure? I f not, is this justified with respect to the risk management fi le and the clinical evaluation? \n \nLimitations: \nHas the manufacturer adequately/clearly described any limitatio ns for the device use? \nDoes the device require any specific limitations? \n \nContraindications: Have contraindications been adequately/clearly described? \nAre any further contraindications necessary?  \n \nWarnings and precautions:  \nHave warnings, precautions and/or measures to be taken in the e vent of malfunction of the device or changes in its performance  that may affect safety been adequately descried? \n \nDoes the information supplied by the manufacturer adequately/cl early provide the safety and performance information relevant t o the user, or any other person, as appropriate/relevant? \nIs the estimation of associated risks and residual risk adequat e? Is this estimation quantitative (i.e. a percentage rate or r ate with a confidence interval) or qualitative? Is the descript ion \nappropriate for patients and users? Is the information provided to the end user written in a clear and understandable way (instruction s of use, indications, and w arnings)? \n \nIs the IFU and other information materials supplied by the manu facturer aligned with the other parts of the technical document ation? \nConsider: \n\u2022 the clinical evaluation (the dev ice description used for the cl inical evaluation, other content s of the clinical evaluation re port).  \n\u2022 the available clinical data (such as the public registration an d results of clinical investigations, publications, PMCF studie s, etc.). Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n23 \n \u2022 PMS report or PSUR. \n\u2022 the risk management file. \n \nNon-compliances identified and resolved for this section may be  briefly described in this box \nIFU, promotional materials, labelling are:  \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 \n \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \n \n \nSection H: Summary of all available data and conclusions  \nHas the manufacturer conducted clinical investigation(s) for th e device under evaluation? \nState Yes / No  \nHas the manufacturer demonstrated equivalence with respect to s ection 3 of Annex XIV of the MDR?  \nState Yes / No \n \nIf the manufacturer conducted CIs, does clinical data from clin ical investigations of the device under evaluation adequately d emonstrate compliance with the relevant general safety and \nperformance requirements? \nState Yes / No  \nHas the reliability of the sourc e of clinical investigation dat a been assured through monitoring activities and verification o f the application of appropriate clinical research standards? \nState Yes / No  \nIf the manufacturer demonstrated equivalence with respect to se ction 3 of Annex XIV of the MDR does the data from an equivalen t device demonstrate compliance with Annex I? State Yes / \nNo Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n24 \n Provide a summary of safety data (with reference to the relevan t section of the CER). \n \nProvide a summary of performance data (with reference to the re levant section of the CER) \n \nDoes the clinical data provide su fficient clinical evidence to:23 \n\u2022 Demonstrate compliance with the relevant general safety and per formance requirements? State Yes  / No, and provide additional i nformation if relevant  \n\u2022 Support the intended purpose, the claims and the information in  the IFU and SSCP?  State Yes / No, and provide addi tional information if relevant  \n \nWhat are the remaining unanswered questions regarding the devic e under evaluation? \nDescribe these with respect to the plan for PMS / PMCF  \n \n \n \nOverall Conclusions:  \nBenefit-risk conclusions: \nSummarise the clinical benefits. D escribe them briefly in relat ion to the meaningful and measu rable patient relevant clinical outcomes, including outcome(s) related to diagnosis. Describe \ntheir positive impact on patient management or public health.  \nSummarise the risks with clinical relevance (e.g uncertainties or limitations of clinical data, undesirable side-effects, pote ntial for misuse, etc) and provide a short description (e.g. in cidence, \nseverity, duration, vulnerable patient subgroups, dose-response  relationship where relevant, etc). \nDiscuss the impact of risks (as described above) in relation to  the clinical benefits taking into account the factors describe d and in particular the uncertain ties in relation to available clinical \ndata. \n \nHave all the risks that could have a significant impact on the benefit-risk analysis' been identified in the clinical evaluati on?  \nIs there alignment between the risk management and clinical eva luation? \n \n                                            \n23 For legacy products, see MDCG 2020-6  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n25 \n State Yes / No \nDescribe how the clinical benefits outweigh the risks also cons idering the current state of the art.  \n \nHave all deficiencies/non-compliances been raised and satisfact orily addressed in the course of this clinical evaluation asses sment?  \n \nState Yes / No \n \nIs it possible to follow the changes that have been made to add ress them?  \nOverall conclusion on the assessment of the manufacturer's clin ical evaluation including a clinical judgement of the opinion p rovided by any external expert. \nMake a clear recommendation to the  notified body's decision mak er in regards to the conclusions of this assessment for the pur pose of granting certification, stating in addition: \n\u2022 whether the post-market surve illance plan, including the PMCF p lan, is adequate.  \n\u2022 specific milestones to be set for further review of the up to d ate clinical evaluation by the notified body.  \n\u2022 considerations to define the period of certification. \n\u2022 additional conditions on the cer tification to be considered.  \n \nSufficient information are prov ided to demonstrate acceptabilit y of benefit-risk conclusions and confirm that the relevant MDR  requirements are met : \u2610 \n \nSpecific Considerations \n \nSection I: Clinical evaluation consultation procedure for certa in class III and class IIb  devices (Article 54) \n \nIs the procedure required by Article 54(1) to be applied? State Yes / No Provide further information where necessary with respect to thi s justification \n \nIf this procedure is not to be applied, with respect to Article  54(2) what is the reason?\n24 \n                                            \n24 See MDCG 2019-3, Interpretation of Article 54(2)b  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n26 \n (a) renewal of a certificate issued under the MDR; \u2610 \n(b) the device has been designed by modifying a device already marketed by the same manufacturer for the same intended purpose , and the manufacturer has demonstrated to the \nsatisfaction of the notified body that the modifications do not  adversely affect the benefit-risk ratio of the device; \u2610 \n Provide a summary of the modification(s) that have been made to  the device? \nProvide a summary of the manufacturer\u2019s rationale demonstrating  that the benefit-risk ratio of the device is not adversely aff ected. \nHas the clinical data been provided to support the conclusions of the manufacturer regarding the benefit-risk of the modified device with respect to the previous version? \n For legacy devices, verify:  \n\u0081 that the modifications do not adversely affect the benefit-risk  ratio. \n\u0081 that the device in question had a valid certificate under the D irectives. \n\u0081 in case the certificate has been withdrawn, suspended\n25 or expired, if there is an impact on compliance with the gener al safety and performance requirements, and \n\u0081 that there is no pending assessment of changes for the device o r outstanding non-compliance. \n\u0081 the description of modifications provided and assess if these m odifications are limited only to those needed in order to compl y with the new legal requirements introduced by the MDR. \n \nNote: limitations of the intended purpose of the device should not trigger the consultation procedure in accordance to Art. 54 . \n \n(c) the principles of the clinical  evaluation of the device typ e or category have been addressed in a CS referred to in Articl e 9 and the notified body confir ms that the clinical evaluation  of \nthe manufacturer for this device is in compliance with the rele vant CS for clinical evaluation of that kind of device. \u2610 \nRelevant scientific panel and associated competence area(s)  \nIndicate your opinion on the r elevant scientific and associated  competence area(s)  for the device under assessment: \n \n  Medical area(s)  Associated competence-related areas  \n Orthopaedics, traumatology, rehabilitation, \nrheumatology   Joint replacements (hip, knee, shoulder) \n Spinal devices \n Non-articulating devices, rehabilitation \n Other \n                                            \n25 The devices for which the certificates were withdrawn or suspe nded due to lack of compliance wi th essential requirements will  require a clinical evaluation consultation procedure as this \nadversely affects the benefit-risk ratio of the device.  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n27 \n  Circulatory system: cardiovascular / lymphatic \nsystem   Prosthetic heart valves and devices for heart valve repair \n Cardiovascular stents (metallic and bioresorbable) and vascular  prostheses \n Active implantable cardiac devic es and electrophysiological dev ices \n Structural interventions and new devices (e.g. LAA/PFO occluder s, heart failure devices) \n Cardiac surgery including extracorporeal membrane oxygenation, cardiopulmonary bypass devices, artificial hearts (and \nleft ventricular assist devices) \n Other \n Respiratory, anaesthesiology, intensive care   Respiratory and anaesthetic devices \n Neurology   Central and peripheral nervous system devices \n Implants for hearing and vision (sensory recovery) \n Neurosurgical devices \n Other \n Endocrinology and diabetes   Endocrinology and diabetes (e.g. insulin delivery systems and c losed-loop systems, continuous glucose monitoring)  \nImplantable systems \n General and plastic surgery, dentistry   Surgical implants and general surgery \n Plastic surgery and wound care \n Maxillofacial surgery \n Dentistry (devices for dentistry  (oral surgery, implantology, d ental materials incl.)) \n Other \n Obstetrics & gynaecology including reproductive \nmedicine   Devices for obstetrics and gynaecology \n Gastroenterology & hepatology   Devices for gastroente rology and hepatology \n \n Nephrology & urology  Devices for nephrology and urology \n Ophthalmology  Devices for ophthalmology Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n28 \n  \nProvide further information necessary with respect to this just ification \n \n \nConclusion for certain class III and IIb devices to be consider ed by the expert panel \nNovel aspects \nSee section C, subsection \u2018Novelty\u2019 \n  \n \nBenefit-risk determination  See section H and the Overall Conclusion sections \n \nConsistency of clinical evidence with intended purpose and PMCF  \nProvide an assessment of the consistency of the clinical eviden ce with:  \n(a) the intended purpose, including medical indication(s),  \n(b) the post-market clinical follow-up (PMCF) plan. \n \n \n \nSection J: Where demonstration o f conformity based on clinical data is not deemed appropriate (Article 61(10)) \n \nHas the manufacturer claimed that the demonstration of conformi ty with general safety and performance requirements based on cl inical data is not deemed appropriate in accordance \nwith Article 61(10)? \nState Yes / No \nNota bene : A clinical evaluation is still required and the above informa tion and evidence-based justifica tion shall be presented in the  clinical evaluation report. \n Has the manufacturer provided a justification for reliance upon  Article 61(10)? \nState Yes / No \n If yes, describe the evidence which the manufacturer is relying on, w ith respect to: \n\u0081 Performance evaluation \n\u0081 Bench testing  Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n29 \n \u0081 Pre-clinical evaluation \n \nConsider: \n\u0081 Has any available clinical data for the device or an equivalent  device been searched for and/or identified by the manufacturer ?  \nIf yes \u2013was the identified clinic al data integrated in the clin ical evaluation. \nThis should include an evaluation of clinical data identified f rom the literature, and an appraisal of their relevance to the device under evaluation. \n \n\u0081 Is clinical data available for si milar devices, does this provi de information with relevant to the safety and performance of t he device under evaluation? \nHas the manufacturer conducted an appropriate search of scienti fic literature?  \nIf clinical data for similar devi ces is available \u2013 this should  be included in the CER and evaluated and may be of particular relevance to post-market surveillance / PMCF planning. \n \n\u0081 The results of the manufacturer's risk management \nAre the results of the manufacturer's risk management supportiv e of the use of non-clinical testing methods? \n \n\u0081 Consideration of the specifics of the interaction between the d evice and the human body \nIs the device under assessment part of a system or stand-alone?  \nIs there sufficient information regarding this interaction avai lable from sources other than clinical data?  \n \n\u0081 The clinical performance intended \nWhat is the intended performance? Is it reasonable to rely upon  non-clinical data for the proposed intended performance? \n \n\u0081 The claims of the manufacturer  \nThe manufacturer should not make any claims which are not suppo rted by clinical data. \n \n Overall conclusion  \n \nNon-compliances identified and resolved for this section may be  briefly described in this box \nThe justification of the manufacturer for reliance upon Article  61(10) is:  \nCompliant with the applicable requirements of the MDR: \u2610 \nInclude any relevant comments \nCompliant with the applicable requirements of the MDR with the exception of the minor non-compliance below: \u2610 Medical Devices \nMedical Devices Coordination Group Document                                            MDCG  2020-13         \n30 \n  \nAdd a clear description of any remaining minor non-compliance t ogether with required follow-up actions to close them and timel ines for their completion to be followed by the \nmanufacturer. \n \n \nSection K: The voluntary clinical consultation on the clinical development strategy (Article 61(2))  \nExpert Panel consultation reference: \n Expert Panel recommendations: \nHave the views of the expert panel been given due consideration  by the manufacturer? \nHas this been included in the  clinical evaluation report? \nIs there any divergence between the manufacturers clinical deve lopment strategy and the views of the expert panel? If yes \u2013 wh at is the justification for this? Is this acceptable? Explain \nwhy."}, {"title": "MDCG 2020-1.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document         MDCG  2020-1  \n  \n \n \n \n \n \nMDCG  2020-1  \n       Guidance on Clinical Evaluation (MDR) \n      / Performance Evaluation (IVDR) of  \n      Medical Device Software              \n \n             March 2020 \n \n \n  \n \nThis document has been endorsed by the Medical Device Coordination Group (MDCG) \nestablished by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of \nrepresentatives of all Member States and it is chaired by a representative of the European \nCommission. \nThe document is not a European Commission document and it cannot be regarded as reflecting \nthe official position of the European Commission. Any views expressed in this document are not \nlegally binding and only the Court of Justice of the European Union can give binding \ninterpretations of Union law.  \n \n  \nPage 1 of 21 \n  \n  Guidance on \nClinical Evaluation/  \nPerformance \nEvaluation of \nMedical Device \nSoftware \nMarch 2020  \n \nGuidance on Clinical Evaluation \n(MDR) / Performance Evaluation \n(IVDR) of Medical Device Software  \n  \nPage 2 of 21 \n Table of Contents \n \n1. Purpose ............................................................................................................................................ 3 \n2. Scope ............................................................................................................................................... 3 \n3. Background ..................................................................................................................................... 4 \n3.1. Abbreviations ........................................................................................................................... 5 \n3.2. Formats used within this document........................................................................................... 5 \n3.3. Definitions ............................................................................................................................... 5 \n4. General principles of the MDSW CLINICAL EVALUATION  (MDR) / PERFORMANCE EVALUATION  \n(IVDR) process ....................................................................................................................................... 9 \n4.1. Introduction ............................................................................................................................. 9 \n4.2. Determination of the valid clinical association / scientific validity .......................................... 12 \n4.3. Technical Performance /Analytical Performance .................................................................... 12 \n4.4. Clinical Performance .............................................................................................................. 13 \n4.4.1. Clinical investigations and clinical performance studies .................................................. 14 \n4.4.2. Where demonstration of conformity based on clinical data is not deemed appropriate ..... 15 \n4.5. Final analysis and conclusion of the clinical evaluation (MDR) / performance evaluation \n(IVDR) .............................................................................................................................................. 15 \n4.6. Continuous update of the clinical evaluation (MDR) / performance evaluation (IVDR)........... 15 \nAnnex I \u2013 Methodological principle for generation of CLINICAL EVIDENCE  ........................................ 17 \nAnnex II \u2013 Examples of CLINICAL EVALUATION (MDR) /  PERFORMANCE EVALUATION  (IVDR) \nstrategies ........................................................................................................................................... 18 \na) MDSW intended to analyse sleep quality data .................................................................... 18 \nb) MDSW intended for image segmentation ............................................................................ 19 \nc) MDSW intended to detect inflammatory bowel diseases (IBD) .......................................... 20 \nd) Active devices containing MDSW to enable their intended purpose .................................. 21 \ne) MDSW which provides an additional user-interface to control an insulin pump ............... 21 \nf) MDSW intended to analyse exhaled CO2 in a life-sustaining device in order to control \nventilator settings ......................................................................................................................... 21 \n \n   \nPage 3 of 21 \n 1. Purpose \nThe purpose of this guidance is to provide a framework for the determination of the appropriate level of \nCLINICAL EVIDENCE  required for MEDICAL DEVICE SOFTWARE  (MDSW) to fulfil the requirements set out \nin Regulation (EU) 2017/745 \u2013 Medical Devices Regulation (MDR) and Regulation (EU) 2017/746 \u2013 In \nVitro Diagnostic Medical Devices Regulation (IVDR).1  \nIn order to promote global convergence, this document takes into account certain concepts outlined in \nInternational Medical Device Regulators Forum (IMDRF) guidance documents (such as N41).2 \n2. Scope \nThis guidance should be applied to MDSW. For the purpose of this guidance, MDSW is software that is \nintended to be used, alone or in combination, for a purpose as specified in the definition of a \u201cmedical \ndevice\u201d in the medical devices regulation or in vitro diagnostic medical devices regulation.  \nIt should be noted that software can be associated3 with another medical device, by driving or influencing \nits use. The guideline MDCG 2019-11 clarifies that software which is driving or influencing is covered by \nthe medical devices regulations4 either as a part/component of a device or as an accessory for a medical \ndevice.  \nSoftware developers should refer to MDCG 2019-11 for guidance on the appropriate qualification and \nclassification of software prior to such software being introduced into the market. The same principles of \nCLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) apply to all MDSW. Conceptually, \nthe following models of software can be understood (whereas combinations may be possible, refer to Table \n1):  \na) Software for which the manufacturer claims a specific medical intended purpose. Such software \nhas a CLINICAL BENEFIT  and requires CLINICAL EVIDENCE  within its own conformity assessment. \nb) Software for which the manufacturer does not claim any medical intended purpose. Such software \nis intended to drive or influence a medical device. The CLINICAL EVIDENCE  is provided within the \ncontext of the driven or influenced device and is therefore out of the scope of this document. \nIt should be recognised that the concept of a CLINICAL BENEFIT  for MDSW may deviate from that which \napplies in the case of pharmaceuticals or other medical devices, since the benefit of MDSW may lie in \nproviding accurate medical information on patients, where appropriate, assessed against medical \ninformation obtained through the use of other diagnostic options and technologies, whereas the final clinical \noutcome for the patient is dependent on further diagnostic and/or therapeutic options which could be \navailable. \n                                                \n1 Depending on the device in question, the level of Clinical Evidence may differ and shall be assessed on a case by case basis.  \n2 International Medical Device Regulators Forum \u2013 IMDRF/SaMD WG/N41FINAL:2017 \u2013 Guidance on Software as a Medical \nDevice (SaMD): Clinical Evaluation  \n3 Associated medical device may be software or hardware. \n4  The use of \u201cThe Medical Devices Regulations\u201d from here on out refers to both Regulation (EU) 2017/745 \u2013 MDR and Regulation \n(EU) 2017/746 \u2013 IVDR.   \nPage 4 of 21 \n Model of Software CLINICAL EVALUATION (MDR) / \nPERFORMANCE EVALUATION \n(IVDR)  - scope \nMDSW \n(with independent intended purpose and claimed CLINICAL \nBENEFIT)  MDSW only \nMDSW \n(with intended purpose and claimed CLINICAL BENEFIT  related \nto driving or influencing a medical device for a medical \npurpose) MDSW and the driven or influenced \nmedical device Notes 1,2 \nSoftware driving or influencing the use of a medical device \n(with no independent intended purpose or independent claimed \nCLINICAL BENEFIT ) Driven or influenced medical device \nincluding the software (component or \naccessory) \nTable 1 Different MDSW and CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION  (IVDR) \nrequirements \nNote 1: If a software is driving/ influencing more than one medical device, an independent CLINICAL \nEVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) is required for each foreseen and clinically \nviable software \u2013 device combination. \nNote 2: Out of scope of this guidance (See MDCG 2019-11 for examples). \n3. Background \nArticle 61 (1) of the MDR and Article 56 (1) of the IVDR state the following: \n\u2018The manufacturer shall specify and justify the level of CLINICAL EVIDENCE  necessary to \ndemonstrate conformity with the relevant general safety and performance requirements. That level \nof CLINICAL EVIDENCE  shall be appropriate in view of the characteristics of the device and its \nintended purpose.\u2019 \nArticle 2 (51) of the MDR and Article 2 (36) of the IVDR define \u2018 CLINICAL EVIDENCE \u2019 as:  \n\u2018clinical data and CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) results \npertaining to a device of a sufficient amount and quality to allow a qualified assessment of whether \nthe device is safe and achieves the intended CLINICAL BENEFIT (S), when used as intended by the \nmanufacturer.\u2019 \nIn order to provide guidance relating to the level of CLINICAL EVIDENCE  required for MDSW and as set out \nin recital (5) of the MDR and IVDR, this guidance takes into account internationally converged principles \nadopted by an international group of regulators, IMDRF ( http://www.imdrf.org ). Adoption of these \nprinciples provides European regulators an initial framework when further developing MDR/ IVDR-\nspecific regulatory approaches and expectations for regulatory oversight. \nWhile this document describes a converged approach to CLINICAL EVALUATION (MDR) / PERFORMANCE \nEVALUATION (IVDR) for MDSW , it should be read in conjunction with other documents that aim to provide  \nPage 5 of 21 \n horizontal guidance for the CLINICAL EVALUATION  of medical devices or PERFORMANCE EVALUATION  of \nin vitro diagnostic medical devices.5 \nNote: Please be advised that this document is subject to revision upon the publication of the aforementioned \nhorizontal guidance.  \nClinical expertise and judgments are required at every step of the CLINICAL EVALUATION (MDR) / \nPERFORMANCE EVALUATION (IVDR), including literature search and appraisal. Each indication and \nclaimed CLINICAL BENEFIT  that is part of the intended purpose should be assessed individually and have \nthe supporting CLINICAL EVIDENCE . Systematic and explicit approach for the appraisal of supporting data \nallows achieving confident, scientifically substantiated conclusions and facilitates transparency of these \njudgments. \n3.1. Abbreviations \nGSPR General Safety and Performance Requirements  \nIMDRF International Medical Device Regulators Forum  \nIVDR In Vitro Diagnostic  Medical Devices Regulation; EU 2017/746  \nMDCG Medical Device Coordination Group  \nMDR Medical Devices Regulation; EU 2017/745  \nMDSW Medical Device Software  \nPMCF Post Market Clinical Follow -up \nPMPF Post Market Performance Follow -up \nPMS Post Market Surveillance  \nRWE Real-World Evidence  \nSaMD Software as a Medical Device  \nSOTA State-of-the-Art \nSSCP Summary of Safety and Clinical Performance  \nSSP Summary of Safety and Performance  \n \n3.2. Formats used within this document \nCursive A note to a text \nCAPITALIZED  Terms defined in this document or the Regulations  \nsubscript References  \n \n3.3. Definitions \nThe definitions elaborated within this section and utilised within this document are intended to apply \nsolely to Medical Device Software (MDSW) according to the MDR and IVDR. \n                                                \n5 These guidance documents are under development and will be published on the Commission\u2019s Medical Devices website.   \nPage 6 of 21 \n CLINICAL BENEFIT  Article 2 (53) MDR defines CLINICAL BENEFIT  as the positive impact \nof a device on the health of an individual, expressed in the terms of a \nmeaningful, measurable, patient-relevant clinical outcome(s), \nincluding outcome(s) related to diagnosis, or a positive impact on \npatient management or public health; whereas  \n \nArticle 2 (37) IVDR defines CLINICAL BENEFIT as the positive impact \nof a device related to its function, such as that of screening, \nmonitoring, diagnosis or aid to diagnosis of patients, or a positive \nimpact on patient management or public health.6 \nSource: EU 2017/745 (MDR), Article 2 (53); EU 2017/746 (IVDR), Article 2 (37) and IVDR recital (64)   \nCLINICAL DATA  (MDR) Information concerning safety or performance that is \ngenerated from the use of a device and is sourced from the following: \n- clinical investigation(s) of the device concerned, \n- clinical investigation(s) or other studies reported in scientific \nliterature, of a device for which equivalence to the device in \nquestion can be demonstrated, \n- reports published in peer reviewed scientific literature on \nother clinical experience of either the device in question or a \ndevice for which equivalence to the device in question can \nbe demonstrated, \n- clinically relevant information coming from post-market \nsurveillance, in particular the post-market clinical follow-up;  \nSource: EU 2017/745 (MDR)  \n(IVDR) Clinical Data, in particular:  \n- from relevant peer-reviewed scientific literature and \navailable consensus expert opinions or positions from \nrelevant professional associations relating to the safety, \nperformance, clinical benefits to patients, design \ncharacteristics, scientific validity, clinical performance and \nintended purpose of the device and/or of equivalent or similar \ndevices; or \n- other relevant clinical data available relating to the safety, \nscientific validity, clinical performance, clinical benefits to \npatients, design characteristics and intended purpose of \nsimilar devices, including details of their similarities and \ndifferences with the device in question \n- clinically relevant information coming from post-market \nsurveillance, in particular the post-market performance \nfollow-up; \nSource: Adopted from EU 2017/746 (IVDR) Annex XIV (2.4) and Annex VII (4.10) and (4.1 1) \n                                                \n6 IVDR recital (64) states : It should be recognised that the concept of clinical benefit for in vitro diagnostic medical devices is \nfundamentally different from that which applies in the case of pharmaceuticals or of therapeutic medical devices, since the benefit \nof in vitro diagnostic medical devices lies in providing accurate medical information on patients, where appropriate, assessed \nagainst medical information obtained through the use of other diagnostic options and technologies, whereas the final clinical \noutcome for the patient is dependent on further diagnostic and/or therapeutic options which could be available.   \nPage 7 of 21 \n CLINICAL DEVELOPMENT PLAN \n(MDR) A plan indicating progression from exploratory investigations, such \nas first-in-man studies, feasibility and pilot studies, to confirmatory \ninvestigations, such as pivotal clinical investigations and a PMCF \nwith an indication of milestones and a description of potential \nacceptance criteria. \nSource: EU 2017/745 (MDR), Annex XIV, part A  \nCLINICAL EVALUATION (MDR) A systematic and planned process to continuously generate, collect, \nanalyse and assess the clinical data pertaining to a device in order to \nverify the safety and performance, including CLINICAL BENEFITS , of \nthe device when used as intended by the manufacturer. \nSource: EU 2017/745 (MDR), Article 2 (44) \nCLINICAL EVIDENCE  Clinical data and CLINICAL EVALUATION (MDR) / PERFORMANCE \nEVALUATION (IVDR)  results pertaining to a device of a sufficient \namount and quality to allow a qualified assessment of whether the \ndevice is safe and achieves the intended CLINICAL BENEFIT (S), when \nused as intended by the manufacturer. \nSource: EU 2017/745 (MDR), Article 2 (51)); EU 2017/746 (IVDR), Article 2 (36) \nCLINICAL INVESTIGATION \n(MDR) Any systematic investigation involving one or more human subjects, \nundertaken to assess the safety or performance of a device. \nSource: EU 2017/745 (MDR), Article 2 (45) \nCLINICAL PERFORMANCE  Article 2 (52) MDR defines clinical performance as the ability of a \ndevice, resulting from any direct or indirect medical effects which \nstem from its technical or functional characteristics, including \ndiagnostic characteristics, to achieve its intended purpose as claimed \nby the manufacturer, thereby leading to a CLINICAL BENEFIT  for \npatients, when used as intended by the manufacturer; whereas \n \nArticle 2 (41) IVDR defines clinical performance as the ability of a \ndevice to yield results that are correlated with a particular clinical \ncondition or a physiological or pathological process or state in \naccordance with the target population and intended user.  \nSource: EU 2017/745 (MDR), Article 2 (52); EU 2017/746 (IVDR), Article 2 (41)  \nCURATED DATABASE / CURATED \nREGISTRY  For the purpose of this document, a curated database /curated registry  \nis any kind of structured repository such as a traditional database, an \nontology or an XML file, that is created and updated with a great deal \nof human effort through the consultation, verification, and \naggregation of existing sources, and the interpretation of new (often \nexperimentally obtained) raw data.  \nGENERALISABILITY  Generalisability  refers to the ability of a MDSW to extend the \nintended performance tested on a specified set of data to the broader \nintended population.  \nPage 8 of 21 \n HUMAN FACTORS ENGINEERING  Human factors engineering refers to the a pplication of knowledge \nabout human behaviour, abilities, limitations, and other \ncharacteristics to the design of and interactions with a MDSW to \nachieve adequate USABILITY . \nPERFORMANCE EVALUATION \n(IVDR) An assessment and analysis of data to establish or verify the \nSCIENTIFIC VALIDITY , the ANALYTICAL  and, where applicable, the \nCLINICAL PERFORMANCE  of a device. \nSource: EU 2017/746 (IVDR), Article 2 (44) \nPERFORMANCE STUDY (IVDR) A study undertaken to establish or confirm the analytical or CLINICAL \nPERFORMANCE  of a device. \nSource: EU 2017/746 (IVDR), Article 2 (42) \nREAL-WORLD PERFORMANCE  Information on real -world device use and performance from a wider \npatient population than a controlled study.  \nSource: Definition derived from IMDRF/SaMD WG/N41FINAL:2017  \nSTATE-OF-THE-ART Developed stage of current technical capability and/or accepted \nclinical practice in regard to products, processes and patient \nmanagement, based on the relevant consolidated findings of science, \ntechnology and experience.  \n \nNote: The STATE-OF-THE-ART embodies what is currently and \ngenerally accepted as good practice in technology and medicine. The \nstate-of-the-art does not necessarily imply the most technologically \nadvanced solution. The STATE-OF-THE-ART described here is \nsometimes referred to as the \u201cgenerally acknowledged STATE-OF-\nTHE-ART\u201d \nSource: Modified from IMDRF/GRRP WG/N47 FINAL:2018  \nTECHNICAL PERFORMANCE \n(MDR) /ANALYTICAL (IVDR))  \nPERFORMANCE  Capability of a MDSW to accurately and reliably generate the \nintended technical/analytical output from the input data.  \nSource:  IMDRF/SaMD WG/N41FINAL:2017 \nSource: EU 2017/746 (IVDR) Article 2 (40)  \n \nUSABILITY For the purpose of this document, usability refers to the c haracteristic \nof the user interface that establishes effectiveness, efficiency and ease \nof user learning and user satisfaction.   \nVALID CLINICAL ASSOCIATION \n(MDR) / SCIENTIFIC VALIDITY \n(IVDR) Means the association of an MDSW output with a clinical condition \nor physiological state. \nSource: Derived from IMDRF/SaMD WG/N41FINAL:2017 \nSource: EU 2017/746 (IVDR), Article 2 (38) \n \n  \nPage 9 of 21 \n 4. General principles of the MDSW CLINICAL EVALUATION  (MDR) / \nPERFORMANCE EVALUATION  (IVDR) process \n4.1. Introduction \nCLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) is an ongoing process, conducted \nthroughout the life cycle of a MDSW. It is a structured, transparent, iterative and continuous process which \nis part of the quality management system for a device. Software that qualifies as a MD or an IVD is subject \nto the same general CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) principles, laid \ndown in the applicable guidelines and regulatory documents, as other MDs/ IVDs, such as: \n- Establishing and maintaining a CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION \n(IVDR) plan and criteria applied to generate the necessary CLINICAL EVIDENCE  based on the \ncharacteristics of the device; \n- Identification of the relevant data pertaining to performance and/ or safety of the device and any \nremaining unaddressed issues or gaps in the data; \n- Appraisal of the relevant data in terms of quality and its contribution to the CLINICAL EVALUATION \n(MDR) / PERFORMANCE EVALUATION (IVDR); \n- Analysis of the available data and its relevance with regard to demonstrating conformity with the \nrelevant General Safety and Performance Requirements (GSPRs); \n- Documenting the relevant data, their assessment and the CLINICAL EVIDENCE  derived therefrom, in \nthe CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) report; \n- Updating the CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) and its \ndocumentation throughout the life cycle of the MDSW concerned with data obtained from \nimplementation of the manufacturer's Post Market Clinical Follow-up / Post Market Performance \nFollow-up (PMCF /PMPF) plan. \nThese methodological principles are depicted in Figure 1. \n \nFigure 1 Overview of the stages of the CLINICAL  EVALUATION (MDR) / PERFORMANCE  EVALUATION (IVDR) \n \nPage 10 of 21 \n The requirements for CLINICAL EVALUATION  and PERFORMANCE EVALUATION are outlined in Article 61 of \nthe MDR (including Annex XIV) and Article 56 of the IVDR (including Annex XIII), respectively. \nWhile the definition of CLINICAL EVALUATION  in the MDR and PERFORMANCE EVALUATION  in the IVDR \nare not identical (see section 0), there is a shared expectation for providing sufficient CLINICAL EVIDENCE  \nto demonstrate conformity with relevant GSPRs under the normal conditions of the device\u2019s intended use. \nCLINICAL EVIDENCE  should be sufficient and appropriate in view of the characteristics of the device, clinical \nrisks and its intended purpose. The level of CLINICAL EVIDENCE  necessary should be specified and justified \nby the manufacturer.  \nThree key components should be taken into account when compiling CLINICAL EVIDENCE  for every MDSW \n(Figure 1), and each is described below in further detail.  \nVALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY is understood as  the extent to which, the MDSW\u2019s \noutput (e.g. concept, conclusion, calculations) based on the inputs and algorithms selected, is associated \nwith the targeted physiological state or clinical condition. This association should be well founded or \nclinically accepted (e.g. existence of a scientific framework or sufficient level of evidence as further \nelaborated in section 4.2 of this document). The V ALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY  of \na MDSW should demonstrate that it corresponds to the clinical situation, condition, indication or parameter \ndefined in the intended purpose of the MDSW.  \nNOTE: The VALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY  seeks to establish that there are sound \nscientific principles underpinning the use of the MDSW in question. The information provided for the \nestablishment of the V ALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY  should put forward the case that \nthe MDSW has an association with a clinical condition or physiological state. This association may not \nalways be readily established. Thus, the C LINICAL PERFORMANCE  can serve as an additional input to the \nVALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY  from a clinical perspective for the specific intended \npurpose (see Annex I).    \nExample: MDSW that detects heart arrhythmia by analysing auscultation sound obtained by a digital \nstethoscope requires demonstrating VALID CLINICAL ASSOCIATION of the association between abnormal \ncardiac sounds and heart arrhythmia. \nEvidence supporting VALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY  can be generated e.g. through \nliterature research, professional guidelines, proof of concept studies, or manufacturer\u2019s own clinical \ninvestigations/clinical performance studies. \nValidation of the  TECHNICAL PERFORMANCE / ANALYTICAL PERFORMANCE is the demonstration of the \nMDSW\u2019s ability to accurately, reliably and precisely generate the intended output, from the input data. \nEvidence supporting T ECHNICAL PERFORMANCE  / ANALYTICAL PERFORMANCE can be generated through \nverification and validation activities, e.g. unit-level, integration, and system testing or by generating new \nevidence through use of curated databases, curated registries, reference databases or use of previously \ncollected patient data. \nValidation of the  CLINICAL PERFORMANCE  is the demonstration of a MDSW\u2019s ability to yield clinically \nrelevant output in accordance with the intended purpose. The clinical relevance of a MDSW\u2019s output is a \npositive impact  \nPage 11 of 21 \n - on the health of an individual expressed in terms of measurable, patient-relevant clinical \noutcome(s), including outcome(s) related to diagnosis, prediction of risk, prediction of \ntreatment response(s), or \n- related to its function, such as that of screening, monitoring, diagnosis or aid to diagnosis \nof patients, or \n- on patient management or public health. \nEvidence supporting C LINICAL PERFORMANCE can be generated by testing the MDSW under evaluation, \nor an equivalent device, in the target population and for the intended use. The applied methodology should \nbe appropriate in light of the device characteristics and intended purpose and may include pre-clinical \ntesting, a clinical investigation or a clinical performance study. \nSpecifically, for MDSW not claiming C LINICAL BENEFITS that can be specified through measurable, \npatient-relevant clinical outcome(s), clinically relevant outputs are achieved through demonstrated \npredictable and reliable use and USABILITY  (please refer to section 4.2 of this document).  \nIn addition, CLINICAL EVALUATION  or PERFORMANCE EVALUATION  of MDSW must consider the benefit-\nrisk ratio in light of the STATE-OF-THE-ART related to practice of medicine for diagnosis, treatment or patient \nmanagement. It is further expected that the assessment of MDSW considers all components of the CLINICAL \nEVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) (see Figure 1 and Annex 0). \nThe three components described above do not represent a distinct stepwise approach but rather portray a \nmethodological principle for the generation of CLINICAL EVIDENCE .  \nTo determine and justify the level of CLINICAL EVIDENCE , both amount and quality of supporting data \nshould be evaluated. This assessment may be guided by the following non-exhaustive questions: \nSufficient amount \n- Does the data support the intended use, indications, target groups, clinical claims and \ncontraindications? \n- Have the clinical risks and analytical performance/ clinical performance been investigated? \n- Have relevant MDSW\u2019s characteristics, such as the data input and output, the applied algorithms \nor type of interconnection been considered when generating the data to support the performance of \nthe device? \n- What is the grade of innovation/ history on the market (how big is the body of scientific evidence)? \n- Other, as applicable. \nSufficient quality \n- Were the type and the design of the study/ test appropriate to meet the research objectives? \n- Was the data set appropriate and actual (state of the art)? \n- Was the statistical approach appropriate to reach a valid conclusion? \n- Were all ethical, legal and regulatory considerations/ requirements taken into account? \n- Is there any conflict of interest?  \nPage 12 of 21 \n - Other, as applicable. \n4.2. Determination of the valid clinical association / scientific validity \nIn the first step, the manufacturer should verify the association between the output of the MDSW (based on \nthe inputs and algorithms selected) and the targeted physiological/ clinical condition, clinical situation or \nclinical parameter, as defined in the intended purpose of the MDSW. MDSW may include a multitude of \nclinical features governed by its intended purpose which require individual assessment.  \nThis association should be clinically accepted or well founded, which means accepted by the broad medical \ncommunity and/or described in scientific (peer-reviewed) literature.  \nVALID CLINICAL ASSOCIATION / SCIENTIFIC VALIDITY can be demonstrated through the use of existing \nCLINICAL PERFORMANCE DATA  while taking into account the generally acknowledged STATE-OF-THE-ART. \nVALID CLINICAL ASSOCIATION  / SCIENTIFIC VALIDITY may further be demonstrated by the creation of new \nCLINICAL PERFORMANCE DATA  in the cases where existing data is not sufficient. For example, as a result \nof a gap analysis, the manufacturer could conclude that additional data may be required. \nExamples of existing data (in no particular order) \n- Technical standards \n- Professional medical society guidelines \n- Systematic scientific literature review  \n- CLINICAL INVESTIGATION s/ CLINICAL PERFORMANCE  STUDIES \n- Published CLINICAL DATA  (e.g. Summary of Safety and Clinical Performance (SSCP) / Summary \nof Safety and Performance (SSP), Registries and databases from authorities)  \nExamples of generating new evidence (in no particular order) \n- Secondary data analysis (Analysis of real-world data) \n- Perform CLINICAL INVESTIGATION / CLINICAL PERFORMANCE  STUDY \n4.3. Technical Performance /Analytical Performance \nThe manufacturer should verify that the MDSW reliably, accurately and consistently meets the intended \npurpose in real-world usage.  \nThe relevant performance characteristics, as part of the GSPRs and linked to the analytical and / or clinical \nfeatures, should be supported by evidence generated during verification and validation activities as part of \ngood manufacturing practices for software, or by generating new evidence through the use of curated \ndatabases, curated registries, reference databases or use of previously collected patient data.   \nPage 13 of 21 \n TECHNICAL PERFORMANCE  / ANALYTICAL PERFORMANCE  is confirmed by the examination and provision \nof objective evidence that the MDSW specifications conform to user needs and intended uses, and that the \nrequirements implemented can be consistently fulfilled.7 \nFor example, performance verification and validation in the intended computing8 and use environments9,10 \ncan be characterised by the demonstration of  \n- availability, \n- confidentiality, \n- integrity, \n- reliability, \n- accuracy (resulting from trueness and precision),  \n- analytical sensitivity,  \n- limit of detection,  \n- limit of quantitation,  \n- analytical specificity,  \n- linearity,  \n- cut-off value(s),  \n- measuring interval (range),  \n- GENERALISABILITY , \n- expected data rate or quality,  \n- absence of inacceptable cybersecurity vulnerabilities,  \n- HUMAN FACTORS ENGINEERING .  \nIdentification of gaps during the validation of the T ECHNICAL PERFORMANCE /ANALYTICAL \nPERFORMANCE  could require generation of new evidence, for example, to demonstrate generalisability with \nreal-life datasets or to extend the usability evaluation to omitted user groups.  \n4.4. Clinical Performance \nFor the validation of a MDSW\u2019s  CLINICAL PERFORMANCE , the manufacturer should demonstrate that the \nMDSW has been tested for the intended use(s), target population(s), use condition(s), operating- and use \nenvironment(s) and with all intended user group(s). Section 4.1 of this document further provides context \nthat validation of C LINICAL PERFORMANCE  includes the assessment of clinical safety, effectiveness, \nperformance and can support the demonstration of CLINICAL BENEFIT . Validation of the CLINICAL \nPERFORMANCE should be considered at each change of the software to a new release. If no validation is \nperformed, a justification should be stated in the technical documentation.  \nWith a validation of C LINICAL PERFORMANCE , it is demonstrated that users can achieve clinically relevant \noutputs through predictable and reliable use of the MDSW.  \n                                                \n7 Derived from Source: GHTF/SG3/N18:2010. \n8 Computing environment: e.g., hardware, memory size, processing unit, time zone, network infrastructure) under which the \nsoftware is to perform. \n9 Use environment: actual conditions and setting in which users interact with the medical device.  \n10 Example on operating environments with distinct requirements are cloud or remote networks.   \nPage 14 of 21 \n The manufacturer should consider the intended use(s), indication(s), desired clinical output(s) expressed as \nclaims, leading to expected CLINICAL BENEFIT s as part of the CLINICAL PERFORMANCE  validation.  \nA MDSW may have multiple features with only some features claiming a specific CLINICAL BENEFIT . \nCLINICAL PERFORMANCE  is only applicable to those features. Since MDSW can be modular in nature, \nvalidation of the C LINICAL PERFORMANCE  is also permissible on module level when the functionality of \nthe modules is independent of the other modules. This would allow the confirmation of a continuous benefit \n/ risk acceptability only for the MDSW modules that have changed. In cases where the final combination \nof modules changes product indications and intended purposes, the performance of that final product \nconfiguration should also be evaluated. Validation of the C LINICAL PERFORMANCE  can be characterised by \nthe demonstration of applicable C LINICAL DATA to the MDSW in question, such as (non-exhaustive): \n- clinical/ diagnostic sensitivity, \n- clinical/ diagnostic specificity, \n- positive predictive value, \n- negative predictive value, \n- number needed to treat (average number of patients that need to be diagnosed/ treated in order to \nhave an impact on one person), \n- number needed to harm (number of patients that need to be diagnosed/ treated in order have an \nadverse effect on one patient),  \n- positive likelihood ratio, \n- negative likelihood ratio, \n- odds ratio, \n- USABILITY / user interface, \n- confidence interval(s). \nCLINICAL DATA  can be obtained by one or multiple methods such as those referred to in \nGHTF/SG5/N7:2012 and IMDRF/SaMD WG/N41FINAL:2017. \nIn addition to the considerations above, C LINICAL EVALUATION  of class III and implantable devices \n(MDR), shall include data from a C LINICAL INVESTIGATION  unless the conditions of Article 61(4), (5) or \n(6) of the MDR have been fulfilled. \nFor MDSW falling under the IVDR, the evaluation of clinical performance requires the carrying out of \nclinical performance studies  regardless of the classification of the device, unless due justification is \nprovided for relying on other sources of clinical performance data. \nRelevant common specifications should be taken into account.    \n4.4.1. Clinical investigations and clinical performance studies \nThe practical and achievable benefits of a C LINICAL INVESTIGATION / CLINICAL PERFORMANCE STUDY \nshould be considered as part of determining what data are needed for demonstrating the safety and \nperformance of a new or modified MDSW.  The investigation or study should account for potential risks, \nshould follow appropriate ethical requirements, and should be compliant with all relevant legal and \nregulatory requirements.  \nPage 15 of 21 \n MDSW has specific characteristics that should be considered when setting up a clinical investigation or \nclinical performance study.  If the MDSW is used for the determination of a patient\u2019s future state (e.g. \npredisposition, prognosis, prediction) or if the output of the MDSW impacts clinical outcomes (e.g. \ntreatment efficacy) or patient management decisions, then a prospective study  may be required as part of \nthe device\u2019s CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR). In other situations, \nretrospective analysis may be more appropriate to generate the necessary data to support compliance with \nthe GSPRs, as there is no impact on patient management and the research does not introduce any risks to \nthe patients. Such an approach is only possible under condition that there is an adequate access to data sets \nof sufficient amount and quality and obtained from the target population. \nFormal requirements of MDR Articles 62 (1), 74 and 82 need to be met as far as appropriate for pre-market \nretrospective studies of MDSW falling under the MDR. \n4.4.2. Where demonstration of conformity based on clinical data is not deemed appropriate  \nIn line with the provisions of MDR Article 61 (1) and IVDR Article 56(1), the level of CLINICAL EVIDENCE  \nrequired should be appropriate in view of the device claims and characteristics. For medical devices, where \nthe demonstration of conformity with GSPRs based on clinical data is not deemed appropriate (MDR \nArticle 61 (10)), the manufacturer shall duly substantiate in the technical documentation why it is adequate \nto demonstrate conformity based on the results of non-clinical testing methods alone, including \nPERFORMANCE EVALUATION , bench testing and preclinical evaluation, and USABILITY  assessment. \nThe justification must be based on the output of the risk management process. This should include an \nevaluation of clinical STATE-OF-THE-ART, including alternative diagnostic and treatment options, including \nthose identified from literature, and an appraisal of their relevance to the device under evaluation. The \ndevice / body interaction, the CLINICAL PERFORMANCE s intended, and the claims of the manufacturer should \nbe specifically considered. \nA CLINICAL EVALUATION (MDR) is still required, and the above information and evidence-based \njustification should be presented in the clinical evaluation report. \nSimilarly for IVDs, where due to specific device characteristics, demonstration of conformity with GSPRs \nbased on clinical data is not deemed appropriate, a PERFORMANCE EVALUATION (IVDR) is still required \nand a justification shall be provided and documented in the Performance Evaluation Plan and the \ncorresponding Performance Evaluation Report. \n4.5. Final analysis and conclusion of the clinical evaluation (MDR) / \nperformance evaluation (IVDR) \nThe manufacturer should compile evidence, perform the benefit-risk analysis and document the CLINICAL \nor PERFORMANCE EVALUATION and its output in the CLINICAL EVALUATION (MDR) / PERFORMANCE \nEVALUATION (IVDR)  report.  \n4.6. Continuous update of the clinical evaluation (MDR) / performance \nevaluation (IVDR) \nThe safety, effectiveness and performance of the MDSW should be actively and continuously monitored \nby the manufacturer.   \nPage 16 of 21 \n Such data may include, but is not limited to post-market information such as complaints, PMCF/ PMPF \ndata, REAL-WORLD PERFORMANCE  data, direct end-user feedback or newly published research / guidelines \nand should be subject to the CLINICAL EVALUATION (MDR) / PERFORMANCE EVALUATION (IVDR) \nprinciples depicted in Figure 1. \nThe unique level of connectivity of MDSW facilitates access to REAL-WORLD PERFORMANCE  data, which \ncan be used for multiple purposes, including, but not limited to \n- timely detection and correction of malfunctions; \n- detection of systematic misuse; \n- understanding user interactions; \n- to conduct ongoing monitoring of CLINICAL PERFORMANCE ; \n- to improve effectiveness; \n- develop the claims in the CLINICAL DEVELOPMENT PLAN (MDR) or future releases. \nMDSW can be released for CE marking with initially claimed and validated CLINICAL BENEFITS . \nMonitoring of REAL-WORLD PERFORMANCE  data can help formulate hypotheses about future MDSW \nfunctionalities and intended use(s).   \nPage 17 of 21 \n Annex I \u2013 Methodological principle for generation of CLINICAL EVIDENCE  \n \n \nPage 18 of 21 \n Annex II \u2013 Examples of CLINICAL EVALUATION (MDR) /  PERFORMANCE \nEVALUATION  (IVDR) strategies  \nThe high-level examples provided here are for guidance purposes only and aim to provide general \nindications on how to develop a CLINICAL EVALUATION / PERFORMANCE EVALUATION  strategy. The \nstrategy presented in each example is not a confirmation  of the pathway for a CLINICAL EVALUATION / \nPERFORMANCE EVALUATION  of the device, as other factors need to be considered.  \nMoreover, the proposed pathway reflects the specific intended purpose, or the healthcare context or \nsituation, in which the device is used as described in the example itself. Any change to the intended purpose \nor the healthcare context / situation in which that same device is used might result in a different approach. \nData source Examples \nPeer-reviewed, relevant scientific literature  - Existing data from studies conducted \nwith the subject device or equivalent \ndevice \nCLINICAL INVESTIGATION / CLINICAL \nPERFORMANCE  STUDIES - Prospective or retrospective studies \n- Existing manufacturer data  \n- Data from equivalent devices \n- Data from curated \ndatabases/registries/reference databases \n- Data from outside the EU with \njustification on applicability \n \nPublished experience gained by routine \ndiagnostic testing - REAL-WORLD PERFORMANCE DATA  \n- Data obtained from PMPF/ PMCF \n \n \na) MDSW intended to analyse sleep quality data \nAn independent MDSW intended to take into account accelerometer and microphone data to determine \nquality of sleep and to estimate the expected success rate of CPAP (continuous positive airway pressure) \ntreatment for sleep apnoea.  \nThe Manufacturer claims that the MDSW \n- determines the quality of sleep that impacts the general well-being. \n- monitors quality of sleep in patients with sleep disorders such as sleep apnoea (using phone \nsensors/wearable devices) \n- estimates the expected success rate of CPAP therapy. \nValid Clinical Association  \nTo establish VALID CLINICAL ASSOCIATION , review literature. \n- Objective quality of sleep is measured by sleep duration, efficiency and fragmentation.  It is further \nwell-established that quality of sleep impacts general well-being such as concentration, risk-factors \nfor cardiovascular disease, mood, cognitive abilities, etc.   \nPage 19 of 21 \n - It is not well-established that the success of CPAP therapy can be predicted by monitoring the \nquality of sleep. \n- Address the association of accelerometer and microphone data to established quality of sleep \nparameters (e.g. sleep duration, efficiency and fragmentation). \nThe VALID CLINICAL ASSOCIATION  has been not established without gaps for prediction of success of CPAP \ntherapy, which requires generation of missing clinical data. \nTechnical Performance  \n- Confirm with verification and validation tests that the app can reliably and reproducibly calculate \nsleep quality scoring. \n- Confirm compatibility between the MDSW and the device equipped with the sensors to ensure data \ncan be utilised in the intended way.  \nClinical Performance  \n- In addition to the USABILITY  assessment, the manufacturer would perform a retrospective study on \npreviously obtained data to confirm that success of CPAP therapy can be predicted based on the \nquality of sleep.  \nb) MDSW intended for image segmentation \nAn independent MDSW intended to allow automatic detection of organs and anatomical structures (such \nas the aorta) in CT scans with the accuracy of a radiologist. \nThe Manufacturer claims that the MDSW: \n- detects abdominal aortic aneurisms on abdominal CT scans, \n- detects compression fractures on vertebrae,  \n- detects liver cysts. \nValid Clinical Association  \nTo establish VALID CLINICAL ASSOCIATION , review literature. \n- The normal shape and size of anatomy is well established. \n- Segmentation techniques on cross-sectional images correlates well with the actual size and shape. \nThe VALID CLINICAL ASSOCIATION  has been established without gaps identified.  \nTechnical Performance  \n- Confirm with verification and validation tests the basic technical performance such as display, \nmodification, window levelling of images, measurements including confirmation of accuracy, \nsensitivity and reliability of the MDSW as per the expected performance. \n   \nPage 20 of 21 \n Clinical Performance  \n- USABILITY  assessment including the intended user groups in conjunction with the VALID CLINICAL \nASSOCIATION  and validation of T ECHNICAL PERFORMANCE  results has been determined as \nsufficient to demonstrate conformity with relevant GSPRs. \n- In cases where data is available, a retrospective analysis can be performed. In cases where data \ndoes not represent the variability of input parameters, for the CLINICAL PERFORMANCE  of the \nsegmentation algorithm, the missing data could be generated in a prospective CLINICAL \nINVESTIGATION .  \nc) MDSW intended to detect inflammatory bowel diseases (IBD) \nSelf-testing independent MDSW intended for the semi-quantitative detection of calprotectin from a faecal \nsample. Reagents are added to the sample resulting in a colour change. The sample is then photographed \non a smartphone, and the image is evaluated by an MDSW application (app) running on the phone. The \nMDSW app detects the colour change in the sample and interprets the concentration of calprotectin. The \ntest is intended as an aid in monitoring and staging of patients with inflammatory bowel disease (IBD). \nManufacturer\u2019s claims that the MDSW app \n- aids in monitoring and staging the disease level of patients with inflammatory bowel diseases \n(IBD). \n- aids in differentiation between IBD and functional bowel disorders.  \n- helps patients avoid unnecessary clinical visits.  \nScientific Validity  \nTo establish S CIENTIFIC VALIDITY, review literature.  \n- The SCIENTIFIC VALIDITY could address how the calprotectin level corresponds to the IBD level \nand stages. Furthermore, it should address, whether calprotectin levels are suitable to differentiate \nbetween IBD and functional bowel disorders. \n- It is well-established that calprotectin concentration in faecal matter can be reliably measured in \ntest strips by change of colour.  \n- The colour intensity is directly representative of the concentration of calprotectin.  \nAnalytical Performance  \n- Confirm the MDSW app can detect reliably and accurately the colour of the test strip compared to \nhuman observation, taking into account environmental factors.  \nClinical Performance  \n- The manufacturer should assess the initial performance and feasibility by creating CLINICAL \nPERFORMANCE  metrics, taking into account sensitivity, specificity and confidence intervals. \n- Any claims regarding CLINICAL BENEFIT  should be supported by sufficient clinical performance \ndata.   \n- USABILITY  should be confirmed by the manufacturer.   \nPage 21 of 21 \n d) Active devices containing MDSW to enable their intended purpose  \nActive devices, such as diagnostic or therapeutic devices, that include MDSW which drives the device in a \nway that, without the software it would not be able to fulfil its intended purpose. This software does not \nperform a medical purpose on its own.    \nThe CLINICAL EVALUATION  of the MDSW should not be performed independently but should be performed \ntogether with the driven device.  \ne) MDSW which provides an additional user-interface to control an insulin pump \nA MDSW intended to virtualise controls of an insulin pump additionally on a smartphone app by connecting \nto it.  \nAs the software is driving the insulin pump, it is not performing a medical purpose on its own, nor is it \ncreating information on its own for medical purposes.  \nThe CLINICAL EVALUATION  of the MDSW app should not be performed independently but should be \nperformed together with the driven insulin pump.  \nf) MDSW intended to analyse exhaled CO2 in a life-sustaining device in order to control \nventilator settings \nThe MDSW uses physiological data of the patient (e.g. exhaled CO 2, blood oxygen saturation) to control a \nventilation device (e.g. frequency, volume and pressure). \nThe MDSW allows the device to maintain the pre-set value at a desired target (defined by the clinician) \nwithout periodic user adjustments needed. This MDSW is part of a closed-loop system.  \nThe CLINICAL EVALUATION  should not be limited to the MDSW and should include pre-clinical and clinical \ninvestigations, encompassing the entire closed-loop system."}, {"title": "mdcg_2019_9_sscp_en.pdf.txt", "text": "Medical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  1(24)  \n \n \nMDCG  2019-9 \n \nSummary of safety and clinical performance \nA guide for manufacturers and notified bodies \n                \n \n \nAugust  2019 \n \n \n  \n \n \n  This document has been endorsed by the Medical Device Coordination Group (MDCG) established by Article 103 of Regulation (EU) 2017/745. The MDCG is composed of representatives of all Member States and it is chaired by a representative of the European Commission. The document is not a European Commission document and it cannot be regarded as reflecting the official position of the European Commission. Any views expressed in this document are not legally binding and only the Court of Justice of the European Union can give binding interpretations of Union law.  \n \n \n   \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  2(24)  \n \n \n \n \n \n \nMDCG 2019-9 \nSummary of safety and clinical performance  \nA guide for manufacturers and notified bodies  \n \nAugust 2019 \n \nTable of contents  \nIntroduction  .............................................................................................................................. ...............................3  \nAbbreviations  .............................................................................................................................. ...........................3  \nGeneral requirements and recommendations for the SSCP  ..........................................................................4  \nValidation and uploading of the SSCP  ...............................................................................................................7  \nGuidance for each of the required sections of the SSCP document  ...........................................................10  \n1. The identification of the device and the manufacturer, including the Basic UDI-DI and, if  \nalready issued, the SRN  .........................................................................................................................10  \n2. The intended purpose of the device and any indications, contraindications and target \npopulations  .............................................................................................................................. ..................11  \n3. A description of the device, including a reference to previous generation(s) or variants if      \nsuch exist, and a description of the differences, as well as, where relevant, a description of any accessories, other devices and products, which are intended to be used in combination with      \nthe device  .............................................................................................................................. ....................11\n \n4. Information on any residual risks and any undesirable effects,  warnings and precautions  ......12  \n5. The summary of clinical evaluation as referred to in Annex XIV, and relevant information on \npost-market clinical follow-up  .................................................................................................................15  \n6. Possible diagnostic or therapeutic alternatives  ...............................................................................18  \n7. Suggested profile and training for users  ...........................................................................................19  \n8. Reference to any harmonised standards and CS applied  .............................................................19  \n9. Revision history  .............................................................................................................................. ......19  \nReferences  .............................................................................................................................. .............................20  \nAppendix: Template for the SSCP  ....................................................................................................................21   \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  3(24)  \nIntroduction \n \nThe Regulation (EU) 2017/745 on medical devices (1) requires that the \nmanufacturer shall draw up a summary of safety and clinical performance (SSCP) for implantable devices and for class III devices, other than custom-made or \ninvestigational devices. The SSCP shall be validated by a notified body (NB) and made available to the public via the European database on medical devices (Eudamed)\n1. \n The SSCP is intended to provide public access to an updated summary of clinical data\n2 and other information about the safety and clinical performance of the medical \ndevice. The SSCP will be an important source of information for intended users \u2013 both healthcare professionals and if relevant for patients. It is one of several means intended to fulfil the objectives of the Medical Device Regulation (MDR) to enhance transparency and provide adequate access to information\n3. \n The SSCP is not intended to: \n\u0081 give general advice on the diagnosis or treatment of particular medical \nconditions, nor \n\u0081 replace the instructions for use (IFU) as the main document that will be \nprovided to ensure the safe use of a particular device, nor \n\u0081 replace the mandatory information on implant cards\n4 or in any other \nmandatory documents. \n The main purpose of this document is to provide guidance on the presentation, content and validation of the SSCP. The word \u201cshall\u201d is used when there is a corresponding \u201cshall\u201d in the MDR, otherwise \u201cshould\u201d or \u201crecommended\u201d etc. is used indicating the interpretation of the MDR.  \nAbbreviations \n \nCIV ID clinical investigation identification number, generated by Eudamed for  \nclinical investigations under the Medical Device Directives (2) (3) \nCMR carcinogenic, mutagenic or toxic to reproduction CS \u2018common specifications\u2019 as defined in the MDR\n5 \nEU European Union  Eudamed European database on medical devices FSCA field safety corrective action\n6 \nFSN field safety notice7 \n                                                 \n1 MDR, Article 32 (1) \n2 MDR, Article 32 (2)(f) , Article 61 (11) and Article 83 (3)(d) \n3 MDR, Recital (43) \n4 MDR, Article 18 \n5 MDR, Article 2 (71) \n6 MDR, Article 2 (68)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  4(24) IFU instructions for use \nMDR Medical Device Regulation (1) NB notified body\n8 \nPMCF post-market clinical follow-up9 \nPMS post-market surveillance10 \nPSUR periodic safety update report11 \nSRN single registration number for an economic operator12 \nSSCP summary of safety and clinical performance TD technical documentation\n13 \nUDI-DI Unique Device Identification - device identifier14 \nURL Uniform Resource Locator (internet address)  \nGeneral requirements and re commendations for the SSCP \n \nThe information in the SSCP should be sourced entirely from the technical documentation (TD) of the device\n15. Examples of such documents are design \nverification/validation reports, the risk management report/file, the clinical evaluation report, and post-market surveillance (P MS) and post-market clinical follow-up \n(PMCF) plans and reports. The IFU includes information extracted from the same sources as the SSCP, but may itself be used as a source for the SSCP if appropriate.  The SSCP shall be kept updated in Eudamed\n16. When the PMCF evaluation report17 \nand the periodic safety update report (PSUR)18 are updated at least annually19, the \nSSCP shall be reviewed and updated20 if needed to ensure that any clinical and/or \nsafety information in the SSCP remains correct and complete. When updating the SSCP, all sections of the document shall be updated if needed so that they are in alignment with the most current version of the relevant parts of the TD of the device.  This guide outlines the minimum content of the SSCP. The manufacturer may add further information from the TD of the device to enhance the comprehension of the mandatory information providing: \n\u0081 it does not affect the readability of the SSCP and \n\u0081 it excludes any element of a promotional nature. \n                                                                                                                                                           \n7 MDR, Article 2(69) \n8 MDR, Article 2 (42) \n9 MDR, Annex XIV Part B \n10 MDR, Article 2 (60) \n11 MDR, Article 86 Periodic safety update report \n12 MDR, Article 31(2) \n13 MDR, as specified in Annexes II and III. \n14 MDR, Article 2 (15) and Article 27 \n15 MDR, Annex II and III \n16 MDR, Article 29 (4) and Annex VI Part A 2.14 \n17 MDR, Article 61 (11) \n18 MDR, Article 86 (1) \n19 MDR Article 86 (1); PSUR for class IIa devices shall be updated when necessary and at least every two years \n20 MDR, Article 61 (11) and Article 83 (3)(d)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  5(24)  \nThe SSCP shall be objective  and adequately summarise  both favourable and \nunfavourable data21.  \n For further guidance on the contents of the SSCP, please refer to sections 1-8 of this document and to the template in the Appendix. The format and structure of this template is recommended. It addresses all of the SSCP content requirements of the MDR\n22, but the order has been revised to enhance its presentation. \n The IFU shall contain all that is needed to directly find the SSCP in Eudamed. The following applies to the IFU\n23. \n\u0081 It shall state that the SSCP is available in the European database on medical \ndevices (Eudamed), where it is linked to the Basic UDI-DI. \n\u0081 It should provide the URL to the Eudamed public website:  \nhttps://ec.europa.eu/tools/eudamed  \n\u0081 It should state the value of the Basic UDI-DI. Alternatively, another metadata \ncan be stated provided it can be used to unambiguously search and find the intended SSCP in Eudamed.  \n Translations to other EU languages No single language will be understood by all intended users and patients in the EU \u2013 see the European Survey on Language Competences initiated by the European Commission (4). In order to meet the requirement in the MDR that the SSCP shall be written in a way that is clear to the intended user and, if relevant, to the patient\n24, \nthe SSCP should be translated into the languages accepted in the Member States where the device is envisaged to be sold. This is by analogy with the requirement for an IFU\n25. Note that Member States may have different language requirements for an \nIFU depending on whether the information is intended for health care professionals or for patients. The SSCP part intended for patients should be provided in all the languages required for IFUs intended for patients in the Member States concerned.  If the selection of European languages for the SSCP does not include English, then an English translation of the document should also be provided. English is the most common language used in medical scientific publications and is understood by many healthcare professionals in the EU. Always providing an English-language version of the SSCP further enhances access to information\n26 about devices available on the \nEU market.   There should be one SSCP document for each language. Each SSCP document should state in which language the SSCP was validated by the NB. The manufacturer should ensure, through their quality management system, that the translations are correct. \n                                                 \n21 MDR, Annex XIV, Part A Clinical evaluation, (2) \n22 MDR, Article 32 (2) \n23 MDR, Article 32 (1) and Annex I, 23.4 (d) \n24 MDR, Article 32 (1) and Recital (43) \n25 MDR, Annex II (2), Article 10 (11) \n26 MDR, Recital (43)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  6(24)  \nRelevant SSCP information for patients The MDR indicates that patients are also intended recipients of the information in the SSCP, \u201cif relevant\u201d\n27. Devices for which information will be especially relevant for \npatients include: \n\u0081 implantable devices for which patients will be given implant cards28, and \n\u0081 class III devices that are intended to be used directly by patients. \n \nFor these devices, a part of the SSCP specifically intended for patients should be provided.  Note: Devices listed in MDR Annex XVI, and eligible for a SSCP, should always be considered as relevant for patient information.  For devices other than the two groups listed above, including any devices listed in Annex XVI and eligible for a SSCP, the manufacturer may consider whether it is relevant to provide specific information intended for patients. This can be based on the manufacturer\u2019s analysis of the device in question.  Readability The SSCP should always have one part for intended users/healthcare professionals, and when it is relevant (see above) a second part for patients. Both should be clear and provide information at an appropriate depth to reflect the healthcare professionals\u2019 and the patients\u2019 different levels of knowledge\n29. \n For further guidance, see references (5) and (6) in this guide. It should not be assumed that the patient has any formal education in a medical discipline or any prior knowledge of medical terminology or clinical research. It is recommended that the readability of the part of the SSCP intended for patients is assessed for example by a test given to lay persons. The manufacturer may use a method it finds adequate for the readability test to confirm that the SSCP is written in a way that is clear to the patient\n30. \n Medical terminology, relevant for the medical device and the clinical context, should be used consistently throughout the part of the SSCP that is intended for healthcare professionals.  Stylistic recommendations The SSCP should be presented in an organised and unambiguous manner.   Usually, abbreviations and acronyms should not be used; if they are, then in the text, the abbreviation or acronym should follow the full phrase it is intended to replace. It may then be used thereafter throughout the document.  \n                                                 \n27 MDR, Article 32 (1) \n28 MDR, Article 18 \n29 MDR, Article 32 (1) and Recital (43) \n30 MDR, Article 32(1), Article 2 (38)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  7(24) Medical terms should be explained in simple language in the parts intended for \npatients. Consistency should be assured by giving the lay term with a description first, and then the medical term immediately afterwards (in brackets). On a case-by-case basis the lay or medical term (but preferably the lay term) may then be used throughout the part intended for patients.  It is recommended to keep the information for patients/lay persons and for intended users/healthcare professionals in two separate parts of the SSCP, separated by a \u201cpage break\u201d. This enhances their readability and facilitates printing of each part \nseparately. See the template in the Appendix of this document.   The SSCP should be written in a font type and size which allow easy reading. Since the SSCP is intended for the public, it needs to be in a format that everyone can read (and that is not editable) without the need for a license. Therefore the SSCP file uploaded in Eudamed should be in PDF format. When downloaded, the PDF file should be printable and searchable with t he search function in the program used to \nview the file, for example the Adobe Reader. \nValidation and uploading of the SSCP \n \nValidation of the initial SSCP by the NB When the NB has assessed that all the required elements\n31 are included in the draft \nSSCP, accurately presented and in alignment with the most current version of \nrelevant documents in the TD, the SSCP has been validated  by the NB. \n \nIn the circumstance that the conformity assessment is performed according to Annex X and XI in the MDR and there are two NBs involved, it is the NB which assesses the TD according to Annex X that shall validate the SSCP.  The validation of the SSCP by the NB covers only one of the language(s) accepted by the NB and agreed with the manufacturer. The manufacturer should state in the revision history in each SSCP document in which language the SSCP was validated by the NB.  The timing of the SSCP validation may depend on the class of device and the conformity assessment routes: \n\u0081 For class III devices and class IIb im plantable devices, except  sutures and \nstaples etc.\n32, the validation is performed when a draft SSCP as a part of the \napplication documents is submitted to the NB involved in the conformity assessment\n33, prior to issuing the certificate. \n\u0081 For class IIa implantable and some IIb implantable devices such as sutures \nand staples etc34, a draft SSCP as a part of the application documents shall \nbe submitted to the NB involved in the conformity assessment. The draft \n                                                 \n31 MDR, Article 32 (2), Article 61 (11), and Article 83 (3) (d) \n32 MDR, Article 52 (4) 2nd paragraph \n33 MDR, Article 32 (1) \n34 MDR, Article 52 (4) 2nd paragraph  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  8(24) SSCP shall be validated by the NB35.  \n In the circumstance if more than one device is covered by the relevant certificate, at least one draft SSCP shall be validated against relevant documents in the TD during the initial conformity assessment, prior to issuing the certificate.   Draft SSCPs that are not validated at the initial conformity assessment, shall be validated against relevant documents in the TD at least once during the period of validity of the certificate. \n Validation of updates of the SSCP between certifica tion activities \nThe manufacturer has an obligation to keep the SSCP updated; for further details see the section \u201cGeneral requirements and recommendations for the SSCP\u201d in this guide. Furthermore the manufacturer shall prepare a periodic safety update report (PSUR) that includes data gathered as a result of the post-market surveillance plan, description of any preventive and corrective actions taken, conclusions of the benefit-risk determination, and the main findings of the PMCF\n36.  \nIf the PSUR contains information rendering any information in the SSCP incorrect or incomplete, the SSCP shall be updated\n37 to be in line with the information in the \nmost recent PSUR.  The manufacturer shall submit a PSUR to the NB at least annually, or for class IIa implantable devices\n38 at least every two years39.  \nIf the SSCP has been updated with new/changed information, except for strictly editorial modifications, the manufacturer should submit the updated SSCP to the NB when submitting the required PSUR.  \n\u0081 If the SSCP has been previously validated, the NB should validate the updated \nSSCP against the submitted and evaluated PSUR. Both the NB and the \nmanufacturer should make an effort to keep the validation time short in order to meet the MDR requirement of an update of the SSCP at least annually if indicated\n40.  \n\u0081 If the SSCP has not previously been validated41, the NB may defer the \nvalidation until a validation against the relevant documents in the TD is planned during the period of validity of the certificate.  \n In addition, as part of its surveillance activities, the NB shall verify that the manufacturer has appropriately updated the SSCP. The NB should take into consideration its assessment of the PMS plan and PSUR, the PMCF plan and its evaluation report, and/or other relevant information. \n                                                 \n35 MDR, Article 32 (1) \n36 MDR, Article 86 (1) \n37 MDR, Article 29 (4) and Annex VI Part A 2.14, and Article 61 (11) and Article 83 (3)(d) \n38 In this context applicable for implantable devices intend ed to be placed in the teeth, MDR Annex VIII, 5.4. Rule \n8) \n39 MDR, Article 86 (1) \n40 MDR, Article 61 (11) \n41 May only be applicable for class IIa implantable devices and some IIb implantable devices such as sutures, \nstaples etc. as listed in MDR, Article 52 (4) 2nd paragraph  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  9(24)  \nValidation of SSCP at certificate renewal With each certificate renewal application, the manufacturer should: \n\u0081 For class III devices and class IIb impl antable devices, other than sutures and \nstaples etc.\n42, submit a draft SSCP which has been updated within the previous \n12 months, regardless of whether there are new data or conclusions. \n\u0081 For class IIa implantable and IIb implantable devices, such as sutures and \nstaples etc.43, confirm that the SSCP in Eudamed is in alignment with the \ncurrent version of the TD, or provide an updated SSCP where required. \n \nAt certificate renewal, the same principles should apply for the validation of the SSCP documents as at the initial certification.  Uploading of the SSCP in Eudamed The SSCP shall be uploaded in Eudamed by the NB\n44, which is the only actor that \ncan manage the SSCPs in Eudamed. Timelines for uploading of the SSCP documents in Eudamed: \n\u0081 The NB shall upload the SSCP validated in conjunction with an initial \nconformity assessment at the same time that it uploads the issued certificate. \n\u0081 For class IIa implantable and IIb implantable devices, such as sutures and \nstaples etc.\n45, the NB shall upload the SSCPs of all the devices covered by \nthe issued certificate at the same time that it uploads the issued certificate, even if some of the SSCPs have not been validated yet, and are to be validated during the period of validity of the certificate.  The manufacturer should state in a revision history in the SSCP document whether that revision was validated by the NB. It is important and should be transparent to the public\n46 whether the SSCP document has been validated \nyet by the NB. See the example of a revision history in section 9 and in the template in the Appendix of this guide. \n\u0081 The NB shall upload a SSCP whenever it has been validated against relevant \ndocuments in the TD, and thus replacing the SSCP uploaded at the initial \ncertification with the currently validated revision. \n\u0081 The manufacturer is responsible for the translations of the SSCP into other \nlanguages\n47, once the \u201cmaster\u201d SSCP has been uploaded by the NB.  \nIf the \u201cmaster\u201d SSCP is in a language other than English, then an English translation should be provided by the manufacturer within 90 days of the upload of the \u201cmaster\u201d SSCP. The NB should upload the English translation within 15 days of receiving this from the manufacturer. \n\u0081 The manufacturer decides when it translates the initial \u201cmaster\u201d SSCP into \nother languages in the Member States depending on when/if they plan to place the product on that market. \n                                                 \n42 MDR, Article 52 (4) 2nd paragraph \n43 MDR, Article 52 (4) 2nd paragraph \n44 MDR, Article 32 (1) \n45 MDR, Article 52 (4) 2nd paragraph \n46 MDR, Recital (43) \n47 See page 4 in this guide, Translations to other EU languages; The manufacturer should ensure, through their \nquality management system, that the translations are correct.  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  10(24) The NB does not validate the translated SSCP documents. It should upload \nthem in Eudamed within 15 days of receiving them. \n The manufacturer shall verify that the SSCP, and any translations needed for any single Member State, have been uploaded in Eudamed before placing a device on that market\n48. \n \n\u0081 When receiving an updated SSCP document in conjunction with the PSUR, \nthe NB should upload the updated SSCP document within 15 days after it is validated, or within 15 days after deeming the validation to be deferred\n49 until \na validation against the relevant documents in the TD is planned during the period of validity of the certificate.  \n\u0081 At certificate renewal, the NB shall upload any updated SSCPs of all the \ndevices covered by the reissued certificate at the same time that it uploads \nthe reissued certificate. The NB should ensure the revision history indicates whether or not these have been validated by the NB. \n\u0081 The manufacturer should provide updated translations to the NB within 90 \ndays of the upload of the updated \u201cmaster\u201d SSCP.  The NB should upload these translations within 15 days of receiving them from the manufacturer. \n \nGuidance for each of the required sections of the SSCP document \n \n1. The identification of the device and the manufacturer, including the Basic \nUDI-DI and, if already issued, the SRN \n \nThe first section of the SSCP shall ident ify the device and the manufacturer, and \nshould also contain some general information related to the device:  \n1.1. Device trade name(s) (this include all trade names the device may have on \nthe market in different Member States) \n1.2. Manufacturer\u2019s name and address 1.3. Manufacturer\u2019s SRN (single registration number) 1.4. Basic UDI-DI 1.5. Medical device nomenclature\n50 description / text  \n1.6. Class of device51 \n1.7. Year when the first certificate (CE) was issued covering the device 1.8. Authorised representative if applicable; name and the SRN 1.9. NB\u2019s name (the NB that will va lidate the SSCP) and the NB\u2019s single \nidentification number\n52 \n \n                                                 \n48 MDR, Article 29 (4) and Section 2 of Part A of Annex VI (2.14) \n49 May only be applicable for class IIa implantable devices and some IIb implantable devices as listed in MDR, \nArticle 52 (4) 2nd paragraph \n50 MDR, Article 26 \n51 MDR, Annex VIII \n52 MDR, Article 43 (1)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  11(24) 2. The intended purpose of the device and any indications, contraindications \nand target populations \n \n2.1. The device's intended purpose(s) shall be described.  \n \n2.2. The indications shall be described. This includes the stages and/or severities \nof the pathologies, the specific medical conditions, and the specific anatomical locations or confirmation that no anatomical locations are contraindicated, as applicable. The target population(s) shall be specified, for example if the device is intended for adults and/or children and/or infants/neonates. \n \n2.3. Any contraindications or restrictions for use or limitations of the device shall \nbe included. \n The information can be sourced from the IFU, or from the clinical evaluation report. \n3. A description of the device, including a reference to previous generation(s) \nor variants if such exist, and a description of the differences, as well as, where relevant, a description of any accessories, other devices and products, which are intende d to be used in comb ination with the device \n \n3.1. A description of the device shall be presented, including its operating \nprinciples and mode(s) of action. Design characteristics should be included, for example key functional elements and any materials or substances in contact with the patient\u2019s tissues. Include information on whether the device is for single use, and its method of  sterilisation. For absorbable implants the \nstability retention profile, including time  to loss of stability and the absorption \ntime, should be provided.  A picture or drawing can be added accompanied by text.  \n \nInformation about the constituents should be provided, as required for the IFU\n53, if the device incorporates \n\u0081 a medicinal substance (including a human blood or plasma derivative), or  \n\u0081 tissue(s) or cells of human or animal origin, or their derivatives, or \n\u0081 substances or combinations of subs tances that are absorbed by or locally \ndispersed in the human body, or \n\u0081 materials incorporated into the device that contain or consist of CMR \n(carcinogenic, mutagenic or toxic to reproduction) substances or \nendocrine-disrupting substances, or  \n\u0081 materials that could result in sensitisation or an allergic reaction by the \npatient or user. \n \nIn Eudamed, the SSCP is associated to one unique Basic UDI-DI. All UDI-DIs/devices associated to this Basic UDI-DI will be seen as having the same \n                                                 \n53 MDR, Annex I (23.2) (e) and (r), and (23.4) (s)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  12(24) SSCP (a UDI-DI/device must always be associated with one and only one \nBasic UDI-DI).  If the device is a system of several components/devices, each device in the system should have a Basic UDI-DI but also one Basic UDI-DI for the system. It is the Basic UDI-DI for the system that is intended to be provided in section 1.4 in the template, and that will be associated with the SSCP in Eudamed. The device system, and any Basic UDI-DIs of included devices, should be described in section 3.1.  The device description in the SSCP shall therefore include all the device(s)/device system associated  with the same Basic UDI-DI. The \ndescription of the device(s)/device system should be comprehensive and can be presented in different ways to include, if such exist, any configurations / combinations / different sizes / specification of any soft-ware versions that can be related to safety and/or performance and their release dates / etc.  The description should also include any model number or similar designation used to identify the device(s)/device system.  \n \n3.2. A reference to previous generation(s) or variants shall be provided, if such \nexist. This applies both to changes/variants of the device itself (same Basic UDI-DI) and to previous generation(s) or variants associated with other Basic UDI-DIs, if available. A description of the differences shall be provided, highlighting the reasons for the change; for example changes to the intended clinical benefits, changes to reduce iden tified clinical risks, or changes for \nmanufacturing reasons etc.  \n 3.3. If there are any accessories\n54 that are not themselves devices, but are \nintended by the manufacturer to be used in combination with the device, they shall be described or listed. The list of accessories should include all those that are essential for the safe and correct use of the device.  \n \n3.4. If there are any other devices and products intended to be used in \ncombination with the device, they shall be described or listed. However, generic surgical equipment and/or other generic devices do not need to be listed. \n In the part of the SSCP that is intended for patients, section 3 may be limited to the device(s) in question (Basic UDI-DI) including relevant and necessary accessories from a patient\u2019s perspective; see suggested headings for section 3 in the template in the Appendix.  \n4. Information on any residual risks and any undesirable effects, warnings \nand precautions \n \n                                                 \n54 MDR, Article 2 (2)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  13(24) 4.1. Residual risks and undesirable effects \n This section of the SSCP guide and template includes residual risks\n55, other \nthan those contraindications, limitations, warnings and precautions that are included in sections 2.3 and 4.2.   Description of residual risks and undesirable effects Risk is defined in the MDR\n56 as the combination of the probability of \noccurrence of harm and the severity of that harm. Harm is defined in the standard ISO 14971:2012\n57 as physical injury or damage to the health of \npeople, or damage to property or the environment. Thus the term \u2018risk\u2019 includes both clinical and non-clinical harms.   The term \u2018residual risk\u2019 is defined in the standard ISO 14971:2012\n58 as \u201crisk \nremaining after risk control measures have been taken\u201d.  \nThere is a requirement in the MDR that the IFU shall contain information on \nany residual risks and any  undesirable side-effects\n59, i.e. no sort of residual \nrisk or undesirable side-effect related to the device is excluded from \ndisclosure. The SSCP should contain information on at least the same residual risks and undesirable side-e ffects as included in the IFU. \n \nFor the purpose of the SSCP, an undesirable effect\n60 can be understood as \nany undesirable side-effect related to the device and that is experienced by the patient and/or can be diagnosed and/or measured in the patient. \n  For the clarity of the SSCP, undesirable side-effects can be annotated also in other terms as appropriate, to present any undesirable side-effects related to the device in question. There may be device-specific terminology for describing side-effects and risks in device -specific ISO standards or scientific \nliterature that is important to use to allow comparison of clinical data.  For example, some events indicated in the MDR by the terms \u2018adverse events\u2019\n61, \u2018undesirable side-effects\u2019 or \u2018incidents\u201962, may all be annotated as \n\u2018adverse events\u2019 in the scientific literature.  Any further discussion on risks can be included in the SSCP if needed for clarity or comprehension.  \nQuantitative data The definition of risk\n63 includes the probability of occurrence of harm. \nTherefore the information in the SSCP on risks shall also include \n                                                 \n55 MDR, Annex I, (23.1) (g) \n56 MDR, Article 2 (23) \n57 EN ISO 14971:2012 Medical devices \u2013 Application of risk management to medical devices, section 2.2 \n58 EN ISO 14971:2012 Medical devices \u2013 Application of risk management to medical devices, section 2.15 \n59 MDR, Annex I , 23.4 (g) \n60 MDR, Article 32 (2) (h) \n61 MDR, Article 2 (57) \n62 MDR, Article 2 (64)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  14(24) quantifications. This information can be sourced from the clinical evaluation \nreport where an updated examination of qualitative and quantitative aspects of clinical safety is available, with clear reference to the determination of residual risks and side-effects\n64. \n It should also be clarified in the SSCP whether quantitative data on side-effects or residual risks rela te to clinical data that were obtained proactively, \nfor example from a structured prospective follow-up study of the device itself, or if the expected frequencies\n65 come from a systematic review of the \nscientific literature. It should be disclosed in the SSCP if data from spontaneously reported incidents or serious incidents\n66 are used as one of \nthe sources for estimating quantitative data on side-effects or residual risks, in which case significant under-reporting needs to be considered.   A relation to time should also be included when presenting the quantitative data, for example during five or ten years of use from implantation, or adverse events per 100 patient-years for implantable devices with constant hazards, etc. The quantitative data and the relation to time should always be presented together.  \nTo use tabulated lists for the presentation of side-effects and residual risks with quantitative data and a relation to time, may enhance the readability.   In the part of the SSCP that is intended for patients, residual risks and side-effects should be explained and quantified in a way that patients and lay persons can understand. A statement should be included about how potential risks have been controlled or managed, and also a statement on what to do if the patient believes that he/she is experiencing side-effects related to the device or its use. See the example in the template in the Appendix.  \n \n4.2. All warnings and precautions pertaining to the device should be presented. \nHowever warnings and precautions solely related to for example installation/preparation of a device or relating to special procedural steps can be discussed on a general level in the SSCP if a link (URL) to the IFU on the manufacturer\u2019s website is provided.  Always include any warnings, precautions or measures to be taken by the patient or a healthcare professional with regard to reciprocal interference with reasonably foreseeable external influences, medical examinations or environmental conditions.   If any particular clinical follow-up is necessary and mentioned in the IFU, that information should also be included in the SSCP.  \n                                                                                                                                                           \n63 MDR, Article 2 (23) \n64 MDR, Annex XIV, Part A Clinical evaluation, (1) \n65 MDR, Article 88 (1) \n66 MDR, Article 2 (64) and (65)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  15(24) 4.3. Other relevant aspects of safety s hould be described. If the device  has been \nsubject to any field safety corrective action (FSCA including FSN), the date of the FSCA and a summary of the associated circumstances and any actions undertaken should also be included.   \n5. The summary of clinical evaluation as referred to in Annex XIV, and relevant \ninformation on post-market clinical follow-up \n \nThis part of section 5 relates to content intended for the user/healthcare professional.  This section is intended to summarise, in a comprehensive manner, the clinical evaluation results and the clinical data\n67 forming the clinical evidence68 for the \nconfirmation of conformity with relevant general safety and performance requirements\n69, the evaluation of undesirable si de-effects and the acceptability of \nthe benefit-risk ratio70. \n It shall be an objective and balanced summary of the clinical evaluation\n71 results \nof all the available clinical data related to the device in question, whether favourable, unfavourable, and/or inconclusive.  See suggested headings for this section in the Appendix of this document.   \n5.1. The SSCP should include a statement if conformity of the device was \nassessed and endorsed by the NB on the basis of equivalence. If equivalence was used, t hen the device(s) for whic h equivalenc e has been \ndemonstrated should be identified by name and Basic UDI-DI if available, together with the name(s) of its/their manufacturer(s). \n \nThe SSCP should also include a statement whether the equivalent device\u2019s SSCP is available in Eudamed. If not available in Eudamed, the SSCP should include a summary of the clinical data pertaining to the equivalent device, written in accordance with the recommendations of this section 5, with a clear note that it relates to the equivalent device. It should be evident from the summary what the clinical evidence for the equivalent device was based on: whether it was clinical investigations of that device itself, or if any other data were used and then the sources of that data. Also include a summary of how long-term safety and performance of the equivalent device has been confirmed. \n \n5.2. All clinical investigations of the device in question, conducted before the CE-\nmarking, should be summarised. It is recommended to keep the format clear \n                                                 \n67 MDR, Article 61 (11) and Article 2 (48) \n68 MDR, Article 2 (51) \n69 MDR, Annex I \n70 MDR, Article 61 (1) and Annex XIV, Part A (1) \n71 MDR, Annex XIV, Part A (2)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  16(24) by grouping the information for each study. The summary of each \ninvestigation should include the following non-exclusive list: \n\u0081 Identity of the investigation/study: If performed under the Medical Device \nDirectives or the MDR, then give the CIV ID or single identification number.  Add reference details if the clinical investigation report is available in Eudamed\n72. For other studies, the title of the study and a clear \nreference to a clinical trials database or publication where detailed data on the study can be found (7)\n73 should be included. In the circumstance that \nthe investigation/study was conducted outside EU, identify the country/-ies where it was performed. \n\u0081 Identity of the device including any model number/version \n\u0081 Intended use of the device in the investigation \n\u0081 Objectives of the study \n\u0081 Study design: randomised controlled trial, other pivotal trial, short-term \nfeasibility study, other; and the duration of the follow-up \n\u0081 Primary and secondary endpoint(s) \n\u0081 Inclusion/exclusion criteria for subject selection \n\u0081 Number of enrolled subjects, including if applicable in different treatment \narms \n\u0081 Study population: main baseline characteristics of each study group, \nincluding gender and age of enrolled subjects \n\u0081 Summary of study methods  \n\u0081 Summary of results: any clinical benefits\n74; any undesirable side-effects or \nadverse events, and their frequency in relation to time; any results on long-term benefits or risks, for exampl e implant survival rates at 5 or 10 \nyears and/or cumulative experience in patient-years. A statement of percentage completeness of follow-up should be provided. Add a note if the study is still ongoing for long-term follow up. \n\u0081 Any limitations of the study, such as high loss to follow-up, or potential \nconfounding factors that may question the results. \n\u0081 Any device deficiency and any device replacements related to safety \nand/or performance during the study. \n \n5.3. Summary of other clinical data and the main findings pertaining to the device \nitself should be included if available.  This can be sourced\n75 for example from: \n\u0081 A systematic literature review yielding articles in which the device in \nquestion was used. References to these articles should be provided. A bibliography can be added at the end of the SSCP document if there are many references. \n\u0081 Clinically relevant information based on clinical data obtained from the \nimplementation of the manufacturer\u2019s PMCF and PMS plans, such as: \n                                                 \n72 MDR, Article 77 (7) \n73 WMA Declaration of Helsinki, sections 35, 36, MDR Recital (64) \n74 MDR, Article 2 (53) \n75 MDR, Article 2 (48)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  17(24) - Conducted PMCF investigation(s)76; include information on each study \nas outlined in section 5.2 in this guide. \n- New or changed likelihood of an undesirable side-effect(s), or \nsignificant increase in the frequency or severity of incidents, or any \nidentified trends77, or any other main findings from the PMCF \nevaluation report or PSUR78. \n\u0081 Analysis of clinical data from medical device registries. Any known \nlimitations such as incomplete follow-up should be disclosed. \n \n5.4. An overall summary of the clinical performance79 and safety should be \nprovided, and that is supported by clinical evidence80, based on clinical data \nand the clinical evaluation results pertaining to the device in question. It is recommended that the overall summary should include the following: \n\u0081 The clinical performance normally leads to clinical benefits for the patient. \nGive a description of the documented clinical benefits\n81 for patients with \nrelevant and specified clinical outcome measures, and the success rate for achieving the outcome measures. This should be described for all clinical claims the manufacturer presents in the IFU, and in any information, marketing, or promotional material that it distributes. For a non-absorbable implant, there should also be information about the expected lifetime of the device including data on implant survival rates. \n\u0081 Benefit-risk assessment for the various indications including the \nacceptability of the benefit-risk ratio\n82. This includes a summary of the \nevaluation of undesirable side-effects.  \nIn the case of a device without an intended medical purpose\n83, the \nrequirement to demonstrate clinical benefit shall be understood as a requirement to demonstrate the performance of the device. The summary of the clinical evaluation shall be based on relevant data concerning safety and performance\n84. \n \n5.5. The SSCP shall have a section on planned or ongoing PMCF85 that should \ninclude the following (non-exclusive list): \n\u0081 Summary of the latest approved PMCF plan for the device. Include any \nplanned or ongoing studies (brief description), and if there are any unanswered questions relating to the use of the device and how they will be investigated. \n                                                 \n76 MDR, Article 74 (1) \n77 MDR, Article 88 (1) and Annex XIV Part B (6.1) (b) \n78 MDR, Article 61 (11), Article 83 (3) (d) \n79 MDR, Article 2 (52) \n80 MDR, Article 61 (1) and Article 2 (51) \n81 MDR, Article 2 (53) \n82 MDR, Article 61 (1) and Annex I Sections 1 and 8 \n83 MDR, Annex XVI \n84 MDR, Article 61 (9) \n85 MDR, Annex XIV Part B  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  18(24) \u0081 If any emerging risks, complicati ons or unexpected device failures have \nbeen detected, and how these will be followed up. \n  The information on clinical evaluation and PMCF intended for patients, in \nsection 5 The part of the SSCP intended for patients should be provided with a brief summary which enables the patient to understand the basis upon which clinical safety and perform ance has been de monstrated. The su mmary shoul d include \nthe following (non-exclusive list): \n\u0081 Clinical background of the device \nA description of the relative novelty of the device: if the product has a \nproven clinical track record of safety and performance, or if there are one or more novel design features. \n\u0081 The clinical evidence for the CE marking \nA description whether clinical evidence is based on data concerning an equivalent device, on data collected during a clinical investigation of the device itself, or on a combination of the two. A short lay-summary of the clinical investigations performed on the device itself should be given, if such exist. If there are clinical investigation reports on the device itself available in Eudamed, this should be stated and identification numbers should be given\n86 (CIV ID or single identification number). The summary \nshould not make misleading claims regarding the strength of clinical evidence, either by direct reporting or omission. \n\u0081 Safety \n- A description of the benefit-risk a ssessments related to safety and \nperformance for each indication claimed by the manufacturer, including \ninformation to address benefit-risk issues of interest to specific patient populations, if applicable.  \n- A description of how the manufacturer continuously collects information \non safety and performance and in particular if any clinical studies \n(PMCF) are ongoing or planned. A description of the purpose of any such studies, for example to corroborate safety and performance claims based on equivalence data, or to demonstrate long-term safety.  \n \n6. Possible diagnostic or therapeutic alternatives \n \nThis part of the SSCP document should contain a review of how the device relates, in terms of benefit-risk, to diagnostic or therapeutic alternatives and the specific conditions under which the device and its alternatives can be considered\n87. \n \n                                                 \n86 MDR, Article 77 (7) \n87 MDR, Recital 49  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  19(24) If reference is made to the \u201cstate of the art\u201d, that statement should be supported \nfor example by referring to relevant recognised guidance documents generated by specialty medical societies or educational bodies.  In the part of the SSCP intended for patients the text should include a recommendation to discuss any possible diagnostic or therapeutic alternatives with a healthcare professional who can take into consideration the individual patient\u2019s situation. See the proposed text in the template in the Appendix.  \n7. Suggested profile and training for users \n \nThe experience, education and/or training of the intended user(s) shall be described\n88. This includes any specific mandatory training before using the \ndevice, and any update training for continued safe use of the device.  If the device is intended to be handled directly by the patient, section 7 should be included in the SSCP part intended for patients and any required training should be described.  \n8. Reference to any harmonised standards and CS applied \n \nA list with all applied common specifications (CS), international standards harmonised under the Medical Device Directives (2)(3) and/or the MDR, and relevant adopted monographs of the European Pharmacopoeia\n89 shall be \nprovided.   The year/revision of the applied CS, standard or monograph, should be listed together with information whether it was applied in full or in part.  The year/revision of an applied harmonised standard or CS may change in the technical documentation for the device. However, an update of the SSCP concerning this change can wait until the next revision of the SSCP is issued.  This list in section 8 does not need to be included in the part of the SSCP that is intended for patients. \n \n9. Revision history \n \nThe SSCP document should include a revision history. The purpose is to include the following information: \n\u0081 The SSCP revision number \n\u0081 Date when the revision was issued \n                                                 \n88 By analogy with the IFU, see MDR, Annex I, 23.1 (a) \n89 MDR, Article 8 (2)  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  20(24) \u0081 Description of the main changes \n\u0081 In which language the SSCP was validated by the NB \n\u0081 In case of a SSCP on class IIa implantable or some90 IIb implantable \ndevices; whether the SSCP revision has been validated yet or not by the NB \n See an example of a table for a Revision history in the Appendix of this guide. \nReferences \n1. Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April \n2017 on medical devices http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=OJ:L:2017:117:TOC \n \n2. Council Directive 93/42/EEC of 14 June 1993 concerning medical devices \nhttp://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:01993L0042-20071011  \n \n3. Council Directive of 20 June 1990 on the approximation of the laws of the Member \nStates relating to active implantable medical devices (90/385/EEC) http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:01990L0385-20071011  \n \n4. The European Survey on Language Competences: measuring foreign language \nstudent proficiency.  Patr\u00edcia Costa and Patr\u00edcia Albergaria-Almeida / Procedia - Social and Behavioral Sciences 191 (2015) 2369 \u2013 2373 https://www.sciencedirect.com/science/article/pii/S187704281502515X \n \n5. Summaries of Clinical Trials Results for Laypersons \nhttps://ec.europa.eu/health/sites/health/files/files/eudralex/vol-\n10/2017_01_26_summaries_of_ct_results_for_laypersons.pdf  \n \n6. Common European Framework of Reference for Languages: Learning, teaching, \nassessment (CEFR) https://www.coe.int/en/web/common-european-framework-reference-\nlanguages/home  \n \n7. WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving \nHuman Subjects https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-\nfor-medical-research-involving-human-subjects/  \n \n                                                 \n90 MDR, Article 52 (4) 2nd paragraph  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  21(24) Appendix: Template for the SSCP \nTexts in italic in the template are general information texts proposed to be included in \nthe SSCP document.  \n Note that there shall always be SSCP information dedicated to users/healthcare professionals for all implantable devices and for all class III devices, other than custom-made or investigational devices. When relevant, a second part dedicated to patients/lay persons should be added. See further recommendations on relevant SSCP information for patients in this guide.  Summary of safety and clinical performance  \nThis Summary of Safety and Clinical Perform ance (SSCP) is intend ed to provide public \naccess to an updated summary of the main aspects of the safety and clinical performance of the device.  The SSCP is not intended to replace the Instructions For Use as the main document to ensure the safe use of the device, nor is it intended to provide diagnostic or therapeutic suggestions to intended users or patients.  The following information is intended for users/healthcare professionals. \n \nIf the SSCP includes a part intended for patients, the following can be added:  \nFollowing this information there is a summary intended for patients . \n \n1. Device identification and general information \n1.1. Device trade name(s) 1.2. Manufacturer\u2019s name and address 1.3. Manufacturer\u2019s single registration number (SRN) 1.4. Basic UDI-DI 1.5. Medical device nomenclature description / text  1.6. Class of device 1.7. Year when the first certificate (CE) was issued covering the device 1.8. Authorised representative if applicable; name and the SRN 1.9. NB\u2019s name (the NB that will validate the SSCP) and the NB\u2019s single \nidentification number  \n 2. Intended use of the device  \n2.1. Intended purpose 2.2. Indication(s) and target population(s)  2.3. Contraindications and/or limitations \n  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  22(24) 3. Device description \n3.1. Description of the device 3.2. A reference to previous generation(s) or variants if such exist, and a \ndescription of the differences \n3.3. Description of any accessories which are intended to be used in combination \nwith the device \n3.4. Description of any other devices and products which are intended to be used \nin combination with the device \n 4. Risks and warnings \n4.1. Residual risks and undesirable effects \n4.2. Warnings and precautions 4.3. Other relevant aspects of safety, including a summary of any field safety \ncorrective action (FSCA including FSN) if applicable \n 5. Summary of clinical evaluation and post-market clinical follow-up (PMCF) \n5.1. Summary of clinical data related to equivalent device, if applicable 5.2. Summary of clinical data from conducted investigations of the device before \nthe CE-marking, if applicable \n5.3. Summary of clinical data from other sources, if applicable 5.4. An overall summary of the clinical performance and safety 5.5. Ongoing or planned post-market clinical follow-up \n 6. Possible diagnostic or therapeutic alternatives  7. Suggested profile and training for users  8. Reference to any harmonised standards and CS applied  9. Revision history  \nSSCP  \nrevision \nnumber Date  \nissued  \n Change description  Revision validated by the Notified \nBody \n      Yes  \n        Validation language: \n  No (only applicable for class IIa or \nsome IIb implantable devices (MDR, Article 52 (4) 2\nnd paragraph) for which \nthe SSCP is not yet validated by the NB) \n \n      Yes  \n        Validation language: \n  No \n \n \nIf the SSCP concerns a device for which it is relevant to provide information to patients in lay man\u2019s language, the following text can be included and then followed by a \u201cpage break\u201d:   \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  23(24) A summary of the safety and clinical performance of the device, intended for patients, \nis given below.  \n \nSummary of safety and clinical performance Document revision: Date issued:  \nThis Summary of Safety and Clinical Perform ance (SSCP) is intend ed to provide public \naccess to an updated summary of the main aspects of the safety and clinical performance of the device. The information presented below is intended for patients or lay persons. A more extensive summary of its safety and clinical performance prepared for healthcare professionals is found in the first part of this document.   The SSCP is not intended to give general advice on the treatment of a medical condition. Please contact your healthcare professional in case you have questions about your medical condition or about the us e of the device in your situation. This \nSSCP is not intended to replace an Implant card or the Instructions For Use to provide information on the safe use of the device. \n \n1. Device identification and general information \no Device trade name \no Manufacturer; name and address \no Basic UDI-DI \no Year when the device was first CE-marked \n 2. Intended use of the device  \no Intended purpose \no Indications and intended patient groups  \no Contraindications \n 3. Device description \no Device description and material/substances in contact with patient tissues \no Information about medicinal substances in the device, if any \no Description of how the device is achieving its intended mode of action  \no Description of accessories, if any \n 4. Risks and warnings \nContact your healthcare professional if you believe that you are experiencing side-\neffects related to the device or its use or  if you are concerned about risks. This \ndocument is not intended to replace a consultation with your healthcare professional if needed. \n \no How potential risks have been controlled or managed \no Remaining risks and undesirable effects \no Warnings and precautions \no Summary of any field safety corrective action, (FSCA including FSN) if \napplicable \n  \nMedical Device       \nMedical Device Coordination Group Document   MDCG  2019-9  \n  \n \n \n  24(24) 5. Summary of clinical evaluation and post-market clinical follow-up \no Clinical background of the device \no The clinical evidence for the CE-marking \no Safety \n 6. Possible diagnostic or therapeutic alternatives \nWhen considering alternative treatments, it is recommended to contact your \nhealthcare professional who can take into account your individual situation.  \no General description of therapeutic alternatives \n 7. Suggested training for users"}]