A PAT-based qualification of pharmaceutical excipients produced by batch or continuous processing.
Pharmaceutical excipients have an influence on the main requirements for medicinal products (viz., quality, safety and efficacy) but also on their manufacturability. During product lifecycle it may become necessary to introduce minor changes (e.g., to continuously improve it) or major changes in the validated process (e.g., moving it to a new production site, replacing process version or even disruptively changing processing type). Those changes can influence the critical to quality attributes of the product. Therefore, it is important to enhance process understanding to avoid the risk of any significant quality changes. Process analytical technology can support better decision making and risk-management as required in quality by design - viz., by many pharmaceutical regulatory authorities. This study compares the quality of the pharmaceutical excipient sodium carbonate (anhydrous) produced either in a batch or a continuous process. For continuous processing two different production lines were available that differed on the dryer and crystallizer types used. Therefore their influence on critical to quality attributes of sodium carbonate was investigated for each of the three processing alternatives. The overall goal was to identify which of the continuous processes ensures a similar product quality to batch processing. Namely, changes on chemical and physical attributes of the product were investigated with Raman spectroscopy, laser diffraction and X-ray powder diffraction. Principal component analysis, a very common multivariate analysis technique, was applied to extract relevant information from small differences at multiple spectral regions from samples from each process type and from each analytical technique used. Changing processing from batch to continuous improved consistency of certain attributes (e.g., particle size distribution) but affected others. However, the increased process/product knowledge gained can lead to an enhanced control strategy and ensure a similar product quality is obtained from distinct process versions.
['Hertrampf|A|A|', 'Müller|H|H|', 'Menezes|J C|JC|', 'Herdling|T|T|']
D002626:Chemistry, Pharmaceutical D016002:Discriminant Analysis D005079:Excipients D007834:Lasers D016014:Linear Models D008855:Microscopy, Electron, Scanning D015999:Multivariate Analysis D010316:Particle Size D004364:Pharmaceutical Preparations D011208:Powders D011786:Quality Control D013059:Spectrum Analysis, Raman D013678:Technology, Pharmaceutical D014961:X-Ray Diffraction
Pharmaceutical excipients Process analytical technology Multivariate data analysis Pharmaceutical engineering Quality control strategy Supplier qualification