Statistical Aspects of Bioequivalence in the Pharmaceutical Industry

• Activity Number: 185
• Type: Contributed
• Date/Time: Tuesday, August 13, 2002 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section*
• Author(s): Scott Patterson*+ and Byron Jones
• Affiliation(s): GlaxoSmithKline, Inc. and GlaxoSmithKline, Inc.
• Keywords: bioequivalence ; REML ; Method-of-Moments

Abstract

Since the early 1990s, average bioequivalence (ABE) has served as the international standard for demonstrating that two formulations of drug product will provide the same therapeutic benefit and safety profile. Population (PBE) and Individual (IBE) bioequivalence have been the subject of intense international debate since methods for their assessment were proposed in the late 1980s. Guidance has been proposed by the FDA for the implementation of these techniques in the pioneer and generic pharmaceutical industries. As of the year 2002, no consensus among regulators, academia, and industry has been established on the use of the IBE and PBE metrics.

The need for more stringent bioequivalence criteria has not been demonstrated, and it is known that the PBE and IBE criteria proposed by FDA are actually less stringent under certain conditions. The statistical properties of Method-of-Moments and restricted maximum likelihood modelling in replicate designs will be summarized, and the application of these techniques in the assessment of ABE, IBE, and PBE will be considered, based on a database of 51 replicate design studies and using simulation.