Biopharmaceutics Applications of Physiologically Based Pharmacokinetic Absorption Modeling and Simulation in Regulatory Submissions to the U.S. Food and Drug Administration for New Drugs.
Physiologically based pharmacokinetic (PBPK) absorption modeling and simulation is increasingly used as a tool in drug product development, not only in support of clinical pharmacology applications (e.g., drug-drug interaction, dose selection) but also from quality perspective, enhancing drug product understanding. This report provides a summary of the status and the application of PBPK absorption modeling and simulation in new drug application (NDA) submissions to the U.S. Food and Drug Administration to support drug product quality (e.g., clinically relevant dissolution specifications, active pharmaceutical ingredient (API) particle size distribution specifications). During the 10 years from 2008 to 2018, a total of 24 NDA submissions included the use of PBPK absorption modeling and simulations for biopharmaceutics-related assessment. In these submissions, PBPK absorption modeling and simulation served as an impactful tool in establishing the relationship of critical quality attributes (CQAs) including formulation variables, specifically in vitro dissolution, to the in vivo performance. This article also summarizes common practices in PBPK approaches and proposes future directions for the use of PBPK absorption modeling and simulation in drug product quality assessment.Graphical abstract.
['Wu|Fang|F|', 'Shah|Heta|H|', 'Li|Min|M|', 'Duan|Peng|P|', 'Zhao|Ping|P|', 'Suarez|Sandra|S|', 'Raines|Kimberly|K|', 'Zhao|Yang|Y|', 'Wang|Meng|M|', 'Lin|Ho-Pi|HP|', 'Duan|John|J|', 'Yu|Lawrence|L|', 'Seo|Paul|P|']
D002626:Chemistry, Pharmaceutical D003198:Computer Simulation D017277:Drug Approval D000076722:Drug Development D065546:Drug Liberation D065569:Gastrointestinal Absorption D006801:Humans D008657:Metabolic Clearance Rate D008954:Models, Biological D014018:Tissue Distribution D014481:United States D014486:United States Food and Drug Administration
biopharmaceutics physiologically based pharmacokinetics (PBPK) dissolution clinically relevant drug product specifications (CRDPS) quality risk assessment