Regulatory utility of physiologically-based pharmacokinetic modeling to support alternative bioequivalence approaches and risk assessment: A workshop summary report

This report summarizes the proceedings for day 2 sessions 1 and 3 of the 2-day public workshop entitled Regulatory Utility of Mechanistic Modeling to Support Alternative Bioequivalence Approaches, a jointly sponsored workshop by the US Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG). The aims of this workshop were: (1) to discuss how mechanistic modeling, including physiologically-based pharmacokinetic (PBPK) modeling and simulation, can support product development, and regulatory submissions; (2) to share the current state of mechanistic modeling for bioequivalence (BE) assessment through case studies; (3) to establish a consensus on best practices for using PBPK modeling for BE assessment to help drive further investment by the generic drug industry into mechanistic modeling and simulation; and (4) to introduce the concept of a Model Master File to improve model-sharing. The theme of day 2 covered PBPK absorption model for oral products as an alternative BE approach and a tool for supporting risk assessment and biowaiver (session 1), oral PBPK for evaluating the impact of food on BE (session 2), successful cases, and challenges for oral PBPK (session 3). This report summarizes the topics of the presentations of day 2 sessions 1 and session 3 from FDA, academia, and pharmaceutical industry, including the current status of oral PBPK, case examples as well as the challenges and opportunities in this area. In addition, panel discussions on the utility of oral PBPK in both new drugs and generic drugs from regulatory and industry perspective are also summarized.

Automated summary

This report summarizes the proceedings of day 2 sessions 1 and 3 of a 2-day public workshop titled Regulatory Utility of Mechanistic Modeling to Support Alternative Bioequivalence Approaches, sponsored by the FDA and CRCG. The workshop aimed to discuss the role of mechanistic modeling, particularly PBPK modeling and simulation, in product development and regulatory submissions. It also aimed to showcase case studies on the use of mechanistic modeling for bioequivalence assessment and establish best practices for its application. The report highlights the topics covered, including PBPK absorption models for oral products, the impact of food on bioequivalence, successful cases, challenges, and opportunities in the field.