Using mechanistic models to support development of complex generic drug products: European Medicines Agency perspective

Authors: Manolis E, Garcia-Arieta A, Lindahl A, Kotzagiorgis E, Limberg J, Holte O, Paixao P, Versantvoort C, Tshinanu FM, Blake K, Van Den Heuvel M
Publication: CPT Pharmacometrics Syst Pharmacol
Keywords: bioequivalence (BE), European Medicines Agency (EMA), model‐informed drug development, PBPK modeling

Abstract

Model‐informed drug development (MIDD) approaches receive wide regulatory acceptance in the European Medicines Agency (EMA) to support new drug development. For generic drugs, the European regulators have not reached a common position on how to use these methods. This commentary expands on the existing EMA regulatory framework for bioequivalence and physiological based pharmacokinetic (PBPK) modeling to propose conditions where mechanistic models could support or potentially waive clinical bioequivalence (BE)/bioavailability (BA) studies.

By Efthymios Manolis, Alfredo García Arieta, Anders Lindahl, Evangelos Kotzagiorgis, Jobst Limberg, Øyvind Holte, Paulo Paixao, Carolien Versantvoort, Flora Musuamba Tshinanu, Kevin Blake, Michiel Van Den Heuvel