Bioequivalence and Variability

• Activity Number: 47
• Type: Invited
• Date/Time: Sunday, August 1, 2010 : 4:00 PM to 5:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Donald Schuirmann*+
• Companies: FDA
• Keywords: bioequivalence

Abstract

Variability has always been a concern in bioequivalence (BE) assessment as a nuisance parameter. For the standard Average Bioequivalence approach to BE assessment, the more variable the response (within a subject), the more subjects are needed to have desired power to conclude BE. More recently there has been a realization that the level of variability for the Reference product is relevant to the acceptable average difference between the Reference and Test products. This has led to the use of Scaled Average Bioequivalence for BE assessment of highly variable drugs. Currently, CDER does not require a comparison of variabilities between the Test and Reference products in assessing BE. If desired, it is possible to formulate such a comparison statistically. However, determination of the allowable difference between product variabilities may be a difficult regulatory challenge.