ABSTRACT
In 1984, the FDA was authorized to approve generic drugs through bioavailability and bioequivalence studies under the Drug Price and Patent Term Restoration Act. In vivo bioequivalence testing is commonly conducted with a crossover design on healthy volunteers to assess bioavailability through PK responses such as area under the blood or plasma concentration-time curve and maximum concentration. This chapter introduces various bioequivalence criteria and describes sample size calculation for the average bioequivalence. It provides sample size formulas for population bioequivalence and individual bioequivalence. The chapter focuses on sample size calculation for in vitro bioequivalence. It discusses sample size requirement for similarity assessment of critical quality attributes (CQAs) in analytical studies for the demonstration of a proposed biosimilar product as compared to its originator product. The FDA recommends a stepwise approach for obtaining the totality of the evidence for demonstrating biosimilarity between a proposed biosimilar product and an innovative biological product.
