Advances in Physiologically Based Pharmacokinetic (PBPK) Modeling and its Regulatory Utility to Support Oral Drug Product Development and Harmonization.

This report summarizes the proceedings of Session 1 of the one-day public workshop titled "Advances in PBPK Modeling and its Regulatory Utility for Oral Drug Product Development" hosted by the U.S. Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) on October 12, 2023. This report focuses on cutting-edge developments, ongoing challenges, and potential solutions in the field of physiologically based pharmacokinetic (PBPK) absorption modeling for systemic and gastrointestinal (GI) locally acting oral drug products, as well as exploring opportunities to enhance global harmonization for generic drug development. Despite significant advancements and several successful case studies of utilizing PBPK models in generic drug development, developing patient-centric dissolution quality standards using PBPK modeling that account for food effects or different disease states remains challenging. Combining multiple dissolution studies at different pH ranges can aid in developing patient-centric dissolution specifications. Additionally, a major challenge for GI locally acting drug products is the inability to validate the PBPK model for local bioavailability due to the lack of measured data for local drug concentration along the different sections of the GI tract. A totality of evidence-based approach, taking account of all available data in addition to PBPK modeling-based evidence, should be considered. Moving forward, it is crucial to promote global collaboration and research by sharing knowledge and experiences for utilizing PBPK models in regulatory contexts to advance both internal and international harmonization.