A Study to Compare Bioequivalence Approach Between FDA and EMA in a Highly Variable Drug: Pinaverium Bromide Film Tablets

The aim of this study is to investigate pharmacokinetic parameters of test and reference film tablet formulations of a highly variable drug, pinaverium bromide, under fasting conditions and to assess their bioequivalence in accordance with the FDA and EMA criteria. A randomised open-label, single oral dose, three-sequence, three-period, semi-replicated, cross-over trial was conducted with 36 healthy subjects. The intrasubject variability of reference products for Cmax and AUC0-tlast was found to be more than 50%. While bioequivalence was proven according to the FDA reference scaled average bioequivalence approach with only 36 subjects, more than 200 subjects are required to demonstrate bioequivalence in accordance with the EMA bioequivalence guideline. It is believed that the EMA bioequivalence criteria are too stringent for highly variable drugs whose intrasubject variability are more than 30% for both Cmax and AUC0-tlast and that in consequence the EMA ought to revise their bioequivalence guidelines for such drugs in the future.