Simulation Study on Bioequivalence Tests Under Several Variability Conditions

• Activity Number: 522
• Type: Contributed
• Date/Time: Wednesday, August 1, 2012 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Denka Markova*+ and Dean Young
• Companies: Axio Research Inc. and Baylor University
• Keywords: bioequivalence ; within-subject variability ; between-subject variability ; generic drugs ; test and reference formulations ; mean ratio difference

Abstract

We eliminate the effect of several parameters on a bioequivalence testing procedure that plays an important role in the development of generic drugs. The current FDA criteria are not flexible with respect to highly variable drugs, and this characteristic has caused many good drugs to be rejected. Most often in the literature, we find studies examining the sample size or the within-subject variability as the main factors affecting the outcome of a bioequivalence test. Frequently, pharmaceutical companies have tried to convince the FDA that their product would meet the bioequivalence criteria just by increasing the sample size. Here we examine the effect of the between-subject variability as well as the effect of the mean ratio difference between the test and reference formulations. We use a Monte Carlo simulation to draw conclusions based on the importance of these two sources of variability and to show that simply increasing the sample size is insufficient to meet the bioequivalence criteria.