Abstract

The approach of scaled average bioequivalence (SABE) standardizes, by the within-subject standard deviation, the more frequently applied method of unscaled average bioequivalence. The US Food and Drug Administration recommends that SABE be applied for determining bioequivalence (BE) for drugs that have large within-subject variation and also for those that have a narrow therapeutic index. The European Medicines Agency suggests another procedure for the evaluation of BE of highly variable drug products. Average BE with expanding limits (ABEL) is closely related to SABE and has similar characteristics. Both SABE and ABEL require fewer subjects than unscaled average BE with highly variable drugs. The contribution discusses their background as well as their statistical and regulatory features and presents procedures for their implementation.