Bioequivalence: Issues and perspectives

The design, performance and evaluation of bioavailability and bioequivalence have evolved over the last two decades. Bioequivalence (BE) means the absence of a greater-than-allowable difference between the systemic bioavailability of a test product and that of a reference product. Due to efforts by academia, the pharmaceutical industry and health authorities, there is far-reaching consensus on essential questions of bioequivalence trials which have been reflected in the many regulatory guidelines. Despite the introduction and wide acceptance of stringent requirements for bioequivalence studies, there is, however, increasing awareness that some fundamentals of bioequivalence assessment need to be reconsidered in principal. This includes several debatable issues such as practical strategies for bioequivalence of highly variable drugs, drugs with long half life, drugs under genetic polymorphic metabolism, biopharmaceuticals and endogenous substances; single bioequivalence range for all drugs; inclusion of female volunteers; individual versus average bioequivalence; metrics of absorption; etc. This article is an attempt to highlight current thinking on issues in bioequivalence.