Biowaivers: Criteria and Requirements

A Biowaiver means that in vivo bioavailability and/or bioequivalence studies may be waived (not considered necessary for product approval). Instead of conducting expensive and time consuming in vivo studies, a dissolution test could be adopted as the surrogate basis for the decision as to whether the two pharmaceutical products are equivalent. The risk of therapeutic inequivalence of two immediate release products can never be reduced to zero, even if a full clinical study is performed.

The conclusion of comparative clinical studies, in vivo bioequivalence studies, in vitro equivalence tests and biowaivers is based on statistics and scientific data that are assumed to be representative for the products at issue. The aim of biowaiver guidance is to reduce the risk of bioinequivalence to an acceptable level. Pharmaceutical development work aims at reducing the probability of manufacturing inequivalent formulations taking into account the critical aspects of the product at issue. In this context, the absorption phase is regarded as the critical process determining the equivalence of the pharmacokinetic profiles and thereby the therapeutic equivalence of the test and reference product.
In this report we will focus on BCS-based Biowaivers. However, other type of biowaivers had been discussed in regulation.