A REVIEW ON GENERAL CONCEPTS OF DESIGN AND CONDUCT OF BIOEQUIVALENCE STUDIES

ABSTRACT

Bioavailability (BA) and bioequivalence (BE) studies play a major role in the drug development phase for both new drug products and their generic equivalents, and thus attract considerable attention globally. 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. The value of testing two one‐sided null hypotheses of non‐equivalence at a significance level of 0.05, and the importance of estimating a 90% confidence interval of the ratio (test/reference) of mean AUC and C_max  values, and of the difference between mean  t_max values, are now recognized and form the current standards for BE. The Study design should be based on a reasonable knowledge of the pharmacodynamics and/or the pharmacokinetics of the active substance in question.  The design and conduct of the study should follow ICH/ EU regulations on Good Clinical Practice, including reference to an Ethics Committee. This article briefly reviews the BA/BE concepts, various basic regulatory considerations, design and conduct of BA/BE studies.

Key words: Bioavailability, Bioequivalence, Generic drugs, Pharmacokinetics.