ABSTRACT
When a brand-name drug is going off patent, the innovator drug company will usually develop a new formulation to extend its exclusivity in the marketplace. At the same time, generic drug companies may file abbreviated new drug applications (ANDA) for generic drug approval. An approved generic drug can be used as a substitute for the brand-name drug. In 1984, the FDA was authorized to approve generic drugs through bioavailability and bioequivalence studies under the Drug Price and Patent Term Restoration Act. As defined in 21 CFR 320.1, bioavailability refers to the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action. In vivo bioequivalence testing is usually considered as a surrogate for clinical evaluation of drug products based on the Fundamental Bioequivalence Assumption that when two formulations of the same drug product or two drug products (e.g., a brand-name drug and its generic copy) are equivalent in bioavailability, they will reach the same therapeutic effect or they are therapeutically equivalent (Chow and Liu, 1999a). Pharmacokinetic (PK) responses such as area under the blood or plasma concentration-time curve (AUC) and maximum concentration (Cmax) are usually considered the primary measures for bioavailability. In vivo bioequivalence testing is commonly conducted with a crossover design on healthy volunteers to assess bioavailability through PK responses. The PK responses are then analyzed with appropriate statistical method to determine whether bioequivalence criterion is met according to the regulatory requirement for bioequivalence review. Throughout this chapter, the brand-name drug is referred to as a the reference product (formulation) whereas its new dosage form or generic copy is called a test product (formulation).
