Abstract

This article summarizes historic developments, recent expert opinions and (currently) unresolved challenges concerning the Biopharmaceutics Classification System (BCS) based biowaiver. An overview of approval statistics and application potential, case examples addressing the discriminatory power of the procedure as well as an outlook on possible refinements in the future are provided and critically discussed. Over the last decade, regulatory guidance documents have been harmonized, e.g. following scientific consent on allowing biowaivers for BCS class III drugs, making over 50% of orally administered drugs on the World Health Organization (WHO) Essential Medicines List (EML) eligible for an abbreviated approval. Biowaiver monographs that present a complete risk-benefit evaluation for individual drugs have been issued by the International Pharmaceutical Federation (FIP) for more than 25% of those drugs with the long-range aim of covering all essential drugs. Unresolved issues that have emerged from reported examples of false negative and false positive outcomes in the literature demand further adjustments to the regulatory requirements. Possible solutions for resolving these issues are the use of modelling and simulation and/or refined biorelevant in vitro tests that are better able to discriminate between dosage forms with unequal performance in vivo, potentially allowing biowaivers for selected BCS II drugs.