ABSTRACT
In the United States, for traditional chemical (small-molecule) drug products, when an innovative (brand-name) drug product is going off patent, pharmaceutical and/or generic companies may file an abbreviated new drug application (ANDA) for the approval of generic copies of the brandname drug product. In 1984, the U.S. Food and Drug Administration (FDA) was authorized to approve generic drug products under the Drug Price Competition and Patent Term Restoration Act, which is known as the HatchWaxman Act. For the approval of small-molecule generic drug products, the FDA requires that evidence of the average bioavailability be provided in terms of the rate and extent of drug absorption. As indicated earlier, the assessment of bioequivalence as a surrogate endpoint for the quantitative evaluation of drug safety and efficacy is based on the Fundamental Bioequivalence Assumption. It states that if two drug products are shown to be bioequivalent in terms of average bioavailability, then it is assumed that they will reach the same therapeutic effect or that they are therapeutically equivalent and hence can be used interchangeably. Under the Fundamental Bioequivalence Assumption, regulatory requirements, study design, criteria, and statistical methods for assessment of bioequivalence have been well established (see, e.g., Schuirmann, 1987; EMA, 2001; FDA, 2001, 2003; WHO, 2005; Chow and Liu, 2008).
