Bioavailability and Bioequivalence
A brief history of regulatory development using bioavailability and bioequivalence studies for approving generic drug products is provided. Concepts of drug exchangeability and switchability are illustrated and their relationship with average bioequivalence, population bioequivalence, and individual bioequivalence is elucidated. The commonly used crossover designs for bioavailability and bioequivalence studies are presented. They include the standard two-sequence two-period crossover design, some higher-order crossover designs for comparing two treatments, and Williams design. Statistical methods for evaluation of average bioequivalence, including the confidence interval and two one-sided tests approaches, are illustrated with reference to sample size determination. Current issues and future challenges for bioavailability and bioequivalence studies are also given.
