ABSTRACT
No topic seems so simple but stimulates such intense controversy and misunderstanding as the topic of bioequivalence. The apparent simplicity of comparing in vivo performance of two drug products is an illusion that is quickly dispelled when one considers the di⁄culties and general public misunderstanding of the accepted regulatory methodology. In the US 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 regarding the determination of therapeutic equivalence of these products to the approved reference. These misconceptions include the belief that the US Food and Drug Administration (FDA) approves generic products that have mean di¡erences from the reference product of 20^25% and that generic products can di¡er 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 re£ect bioequivalence and therefore therapeutic equivalence in patients. When the current bioequivalence methods and statistical criteria are clearly understood it becomes apparent that these methods constitute a
strict and robust system that provides assurance of therapeutic equivalence. In this chapter we will discuss the history, rationale and methods utilized for the demonstration of bioequivalence for regulatory purposes in the US as well as brie£y reviewing the bioequivalence requirements in other countries. In addition, we will touch on some of the controversial issues and di⁄culties in demonstrating bioequivalence for locally acting drug products.
