Regulatory Utility of Mechanistic Modeling to Support Alternative Bioequivalence Approaches: A Workshop Overview.

On September 30 and October 1, 2021, the U.S. Food and Drug Administration and the Center for Research on Complex Generics co-sponsored a live virtual workshop titled "Regulatory Utility of Mechanistic Modeling to Support Alternative Bioequivalence Approaches." The overall aims of the workshop included: (i) engaging the generic drug industry and other involved stakeholders regarding how mechanistic modeling and simulation can support their product development and regulatory submissions; (ii) sharing the current state of mechanistic modeling for bioequivalence assessment through case studies; (iii) establishing a consensus on best practices for using mechanistic modeling approaches, such as physiologically based pharmacokinetic modeling and computational fluid dynamics modeling, for bioequivalence assessment and (iv) introducing the concept of a Model Master File to improve model-sharing between model developers, industry, and FDA. More than 1500 people registered for the workshop. Based on a post-workshop survey, the majority of participants reported that their fundamental scientific understanding of mechanistic models was enhanced, there was greater consensus on model validation and verification, and regulatory expectations for mechanistic modeling submitted in abbreviated new drug applications (ANDAs) were clarified by the workshop.