An Alternative Approach for the Assessment of Bioequivalence Between Two Formulations of a Drug

The problem of the assessment of bioequivalence between a test formulation ( T ) and a reference formulation ( R ) of a drug using a two‐way crossover experiment is considered. To claim bioequivalence between two formulations, it is required by the United States Food and Drug Administration (FDA) to demonstrate that the true ratio of means μ T /μ R of pharmacokinetic parameters of concern falls within some reasonable limits (e.g., (80%, 120%)) with certain assurance. A commonly used approach is to construct an approximate 90% confidence interval for μ T /μ R and compare it with (80%, 120%). In this paper, an exact approach according to the FDA's criteria is proposed. The proposed procedure is derived by constructing an exact confidence region (an ellipse) for (μ R , μ T ) and comparing it with the region bounded by μ T = 0.8 μ R and μ T = 1.2 μ R . Bioequivalence is concluded if the ellipse is within the critical region.