ABSTRACT
The topic of bioequivalence evaluation of generic drug products seems simple but stimulates intense controversy and misunderstanding. For example, one often hears members of the public and medical experts alike stating various opinions on the unacceptability of approved generic drug products based on misconceptions about the determination of therapeutic equivalence of these products to the approved reference. These misconceptions include the belief that the Food and Drug Administration (FDA) approves generic products that have mean differences from the reference product of 2025% and that generic products can differ from each other by as much as 45%. In addition, some incorrectly assume that, since most bioequivalence testing is carried out in normal volunteers, it does not adequately reflect bioequivalence and therefore therapeutic equivalence in patients. When the current bioequivalence methods and statistical criteria are clearly understood it becomes apparent that these methods provide a strict and robust system that provides assurance of therapeutic equivalence. In this chapter we will discuss the rationale and methods utilized for the demonstration of bioequivalence for regulatory purposes in the United States. In addition, we will touch on some controversial issues and difficulties in demonstrating bioequivalence for certain classes of drug products.
