Assessing Impact of Food on Oral Drug Bioequivalence Supporting ICH M13 A with the Advancements of Physiologically Based Pharmacokinetic Modeling.

Abstract

On October 12, 2023, the U.S. Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) hosted a public workshop on "Advances in PBPK Modeling and its Regulatory Utility for Oral Drug Product Development", which highlighted significant strides in physiologically based pharmacokinetic (PBPK) modeling, particularly its application in the regulatory decision-making processes. This manuscript provides a comprehensive overview from the second session of the workshop titled "PBPK Modeling to Evaluate Food Impact on Bioequivalence Supporting ICH M13A", focusing on the critical role of PBPK modeling to evaluate the influence of food on drug bioequivalence (BE). Presentations and panel discussions from this session addressed the application of PBPK modeling for potential biowaiver of certain fed BE studies, thereby enhancing drug development efficiency and reducing costs. Presented case studies highlighted that PBPK modeling can be used to recapitulate formulation-dependent food impact, assist in the selection of biopredictive dissolution method and provide support for justifying the waiver of fed BE studies. The discussions also explored advanced methodologies for simulating the gastrointestinal environment more accurately and the operational insights from companies integrating PBPK modeling into their drug development program. Challenges such as the need for robust model validation and the integration of biopredictive dissolution testing results into the PBPK model were emphasized. Overall, the workshop session underscored the burgeoning confidence in PBPK modeling as a tool to refine regulatory pathways and optimize drug product evaluations, support future advancements in the field and harmonization across different regulatory agencies.