Prediction of fasted and fed bioequivalence for immediate release drug products using physiologically based biopharmaceutics modeling (PBBM).

Bioequivalence studies are an integral part of clinical pharmacology strategy for drug development. Physiologically based biopharmaceutics modeling (PBBM) can be a helpful tool to assess potential bioequivalence risks and predict the outcome of bioequivalence studies. In this study, GastroPlus™ was used for virtual bioequivalence (VBE) assessment of 6 case studies which includes four BCS 2, and one each of BCS 1 and 3 molecules. The purpose was to investigate if bioequivalence in fed state can be accurately predicted based on model developed on data from bioequivalence study in fasted state and known food effect from clinical studies. Our results show that we were able to successfully predict passing (5 cases) and failed (1 case) bioequivalence studies. Ultimately, if there is confidence in such models, a case can be made to waive fed bioequivalence study, on a case-by-case basis (e.g. for BCS class 1 and 2 molecules with known food effect mechanism, reliable estimate of human pharmacokinetic parameters, and available in vivo data in fasted state for model verification). This has the potential to reduce clinical burden in drug development, increase confidence in pivotal BE studies and support regulatory applications such as justify waiving of BE study for Scale-Up and Post Approval Changes (SUPAC). Hence VBE can significantly reduce time and cost of drug development, as well as minimize drug exposure to healthy volunteers.