Increasing impact of quantitative methods and modeling in establishment of bioequivalence and characterization of drug delivery

Advances in quantitative methods and modeling for complex generic drugs and opportunities to hybridize learnings between innovator and generic drug developers

“…7 For complex generics, MIE can use virtual BE simulations that in combination with in vitro BE testing can support alternative approaches to conventional in vivo BE studies. [4][5][6] The FDA has pioneered advancements in QMM for complex generics to offer developers MIE-driven frameworks to establish BE. The widening impact of QMM and MIE to demonstrate BE and characterize drug delivery for complex generics is spotlighted extensively in this mini-themed issue.…”

“…MIE integrates evidence from empirical studies with computational models, extending the continuum of knowledge acquired through model-informed drug development (MIDD) for a new drug application (NDA) with emerging post-NDA knowledge. [4][5][6] Mechanistic modeling approaches like physiologically-based pharmacokinetic (PBPK) and computational fluid dynamics models are extensively applied to assess substitutability. They are used by generics developers to address BE issues within abbreviated new drug applications (ANDAs) and by OGD scientists to review ANDAs and make regulatory decisions.…”

“…15 Under the GDUFA III (2023 to 2027), utilizing QMM for complex generics to establish BE in place of clinical end point BE studies has the potential to lower development costs and accelerate access to generic drugs. A recent rise in MIE alternative BE approaches in pre-ANDA and ANDA interactions between the generic drug industry and the FDA is signaling an industry shift from MIE development to implementation; Yoon et al 5 provided a forward-looking perspective on how QMM will be pivotal to drive innovation for complex generics during this transition. The rollout of a model master file (MMF) by the OGD as a framework to communicate model practices between developers (model and product) and regulators has extraordinary potential to standardize MIE approaches and streamline regulatory review globally; consensus with the European Medicines Agency (EMA) may serve as a starting point.…”

“…They are used by generics developers to address BE issues within abbreviated new drug applications (ANDAs) and by OGD scientists to review ANDAs and make regulatory decisions 7 . For complex generics, MIE can use virtual BE simulations that in combination with in vitro BE testing can support alternative approaches to conventional in vivo BE studies 4–6 …”

“…Central to the success of the initiative is the burgeoning integration and adoption of model‐integrated evidence (MIE) by generic drug developers and the FDA. MIE integrates evidence from empirical studies with computational models, extending the continuum of knowledge acquired through model‐informed drug development (MIDD) for a new drug application (NDA) with emerging post‐NDA knowledge 4–6 . Mechanistic modeling approaches like physiologically‐based pharmacokinetic (PBPK) and computational fluid dynamics models are extensively applied to assess substitutability.…”