Assessing bioequivalence and drug interchangeability

ABSTRACT

As indicated by the US Food and Drug Administration (FDA), approved generic drug products can be used as substitutes for their respective innovative drug products. The FDA, however, does not indicate that two generic copies of the same innovative drug can be used interchangeably, even though they have been shown to be bioequivalent to the same innovative drug product. As more and more generic drug products become available in the market place, it is a concern whether these approved generic drug products have the same quality and safety/efficacy and hence can be used interchangeably. To address the issue of drug interchangeability, several criteria such as individual bioequivalence criterion, a criterion based on the variability due to subject-by-drug interaction, and a scaled criterion for drug interchangeability (SCDI) have been proposed in the literature. In this article, the performances of these criteria, including a newly proposed reversed average bioequivalence criterion, are studied under a 2x4 replicated crossover design in terms of the percentage of passing at the best and worst possible scenarios of similarity. The goal of this paper is to investigate the interchangeability in terms of switchability between a generic (test) drug product and an originator (reference) drug product.

KEYWORDS:

• Drug interchangeability
• replicated crossover design
• reversed average bioequivalence
• scaled criterion for drug interchangeability (SCDI)
• variability due to subject-by-drug interaction