ABSTRACT
When an innovative (brand-name) drug product is going off patent, pharmaceutical and generic companies may Œle an abbreviated new drug application (ANDA) for approval of generic copies of the innovative drug product. In 1984, the United States Food and Drug Administration (FDA) was authorized to approve generic drug products under the Drug Price Competition and Patent Term Restoration Act (which is also known as the Hatch and Waxman Act). For the approval of generic drug products, the FDA requires that evidence in average bioavailability (in terms of rate and extent of drug absorption) be provided through the conduct of bioavailability and bioequivalence studies. As indicated by Chow and Liu (2008), the assessment of bioequivalence as a surrogate for the evaluation of drug safety and efŒcacy is based on the Fundamental Bioequivalence Assumption that if two drug products are shown to be bioequivalent in average bioavailability, it is assumed that they will reach the same therapeutic effect or they are therapeutically equivalent and can be used interchangeably. Under the Fundamental Bioequivalence Assumption, regulatory requirements, study design (e.g., a two-sequence, two-period crossover design or a replicated crossover design), criteria (e.g., 80/125 rule based on log-transformed data), and statistical methods (e.g., Shuirmann’s two one-sided tests or conŒdence interval approach) for assessment of bioequivalence have been well established (see, e.g., Schuirmann, 1987; FDA 2001, 2003b; Chow and Liu, 2008).
