Recent Developments in Scaled Average Bioequivalence

• Activity Number: 547
• Type: Contributed
• Date/Time: Wednesday, August 7, 2013 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Pascal Guibord*+
• Companies: Algorithme Pharma
• Keywords: scaling ; bioequivalence ; average ; clinical trials ; sample size ; expanding limits

Abstract

The approach of the one size-fits-all criterion for the assessment of average bioequivalence began to dissipate in the past years as it has been challenged and criticized. It was suggested that flexible criteria be developed based on the characteristics of the drug, its therapeutic window and intra-subject variability (ISV). This has led to the use of Scaled Average Bioequivalence (SABE) for bioequivalence assessment of highly variable drugs (HVD), as it has been otherwise very difficult to determine BE for this class of drugs. Regulatory authorities such as FDA and EMA have since adopted the use of scalable bioequivalence limits for drugs with wide therapeutic windows; recently the FDA also proposed a scaling method for drugs with a narrow therapeutic window. A review of the recent developments in the implementation of SABE and its impact on the sample size, statistical analysis and interpretation of the study results will be presented and discussed. More specifically, the impact of the type of implementation (EMA, FDA), the regulatory constraints (switching variation, GMR), the study design (partially- or fully-replicated), and the selection of subjects will be evaluated.