Bioequivalence and Bioavailability Forum

Dear Clare,

❝ If I have understood the current EMA guidelines correctly, the acceptance limits can only be widened if the intra-subject CV > 30% in the BE study

As per EMA's Guideline on the Investigation of Bioequivalence, "For the acceptance interval to be widened the bioequivalence study must be of a replicate design where it has been demonstrated that the within-subject variability for Cmax of the reference compound in the study is >30%. EMA will accepts Expandable BE limits only for replicate design if the intrasubject variability for Cmax of the reference is more than 30%.

❝ Nevertheless, there are UKPARs showing that widened acceptance limits have been allowed without a replicate study design.

May be EMA would have accepted expandable limits without replicate design before, but as per the recent guidance, expansion of BE limits are allowed only in the replicate design.