Bioequivalence and Bioavailability Forum

Dear Anne,

if at least one of the acceptance limits was exceeded by a CL, probably your sample size was too small - consider repeating the study.
If a point estimate (geometric mean ratio) was outside the acceptance range, I'm afraid that you will have to reformulate in such a case... (theoretically this might also happen by chance alone - but a PE outside the AR is a rather strong hint of problems with the formulation)

The only exception I remember was a task force lead by Larry Lesko (FDA/CDER) a couple of years ago.
If the BE study between the formulation used in phase III and the finally to be marketed formulation failed, FDA looked at the submitted safety and efficacy data. If the tested formulation failed due to exceeding the upper acceptance range and data of higher dose level(s) supported no safety problems, the MA was granted. An analogous procedure was applied to the lower acceptance range and efficacy data of lower dose level(s). These decisions were made on a case-by-case basis.