USA – FDA updates statistical approaches for assessing bioequivalence

The US Food and Drug Administration (FDA) has published a draft guidance updating its principles for assessing in vivo or in vitro bioequivalence studies (BE) for investigational new drugs (INDs), new drug applications (NDAs), abbreviated new drug applications (ANDAs) and supplements to these applications.

The update replaces a previous version in February 2001 and adds new topics such as assessing the bioequivalence for narrow therapeutic index (NTI) drugs and highly variable drugs, using adaptive trial designs, and statistical approaches for filling in missing patient data.

The guidance intends to “help applicants plan and analyze their BE studies with the goal of minimizing the number of assessment cycles necessary for approval.”

FDA defines BE as the “comparison between a test (T) and reference (R) drug product, where T and R can vary depending on the comparison to be performed” such as whether the comparison involves a marketed formulation versus clinical trial formulation, a generic drug versus reference listed drug (RLD), or originally approved formulation versus post approval formulation change…