FDA Workshop Advances PBPK Modeling for Bioequivalence

Regulatory affairs leads preparing bioequivalence submissions have a sharper set of modeling tools to work with: the FDA, in collaboration with the Center for Research on Complex Generics, convened a full-day workshop on October 12, 2023, dedicated to the regulatory utility of physiologically-based pharmacokinetic (PBPK) absorption modeling and simulation for oral drug product development.

The scope of the workshop reflects how broadly PBPK absorption modeling has penetrated the BE review process. Applications now span alcohol dose dumping risk assessment, single-sex BE study justifications, formulation excipient impact evaluations, local bioavailability predictions for locally-acting products, and pediatric BA/BE assessments. For regulatory teams, the practical implication is that FDA reviewers are increasingly receptive to model-supported scientific rationales in place of, or alongside, conventional in vivo study data.

The regulatory footing for these approaches is documented. Recent FDA Guidances for Industry covering food-effect assessments and gastric pH-dependent drug interactions with acid-reducing agents explicitly reference PBPK modeling as a supporting methodology. The draft ICH M13A guideline on BE for immediate-release solid oral dosage forms extends that recognition to the harmonization context, a signal that PBPK-supported submissions will face consistent expectations across major regulatory jurisdictions.

Workshop sessions addressed four operational areas most relevant to submission teams: advances in PBPK modeling within regulatory contexts and harmonization efforts; food-impact modeling to support BE under ICH M13A; BA and BE assessments in pediatric populations; and the use of virtual BE analysis to underpin BCS-based biowaivers and risk-based extrapolations, including fasting-to-fed and normal-to-elevated gastric pH scenarios. Round-table discussions among industry, academic, and regulatory experts were structured to surface best-practice consensus on the most contested methodological questions.

For QA directors and regulatory leads working on complex generics, the bio-predictive dissolution angle carries direct process validation implications: establishing in vitro dissolution methods that are mechanistically linked to in vivo performance through validated PBPK models strengthens the scientific rationale for biowaivers and reduces exposure to costly late-stage in vivo study requirements.

The Center for Research on Complex Generics, a joint program between the University of Maryland School of Pharmacy and the University of Michigan College of Pharmacy, co-organized the event alongside FDA, reflecting the agency's ongoing investment in building shared scientific infrastructure around complex generic development.

Regulatory teams tracking the evolution of PBPK acceptance criteria should monitor the finalization of ICH M13A as the clearest near-term indicator of how model-supported BE submissions will be evaluated across participating regulatory authorities.

Source: FDA via What's New: Drugs RSS Feed, published 2026-08-28; event date October 12, 2023, 8:30 a.m. – 5:30 p.m. ET, Universities at Shady Grove, Rockville, Maryland. Hybrid attendance offered; virtual attendance free, in-person registration $250.