Bioequivalence and Bioavailability Forum

Hi Mikalai,

❝ I thought that something like clinical pharmacology of the drug may, to some extent, reassure our NCA that safety and efficacy are not at risk?

OK, you missed the lower limit of C_max for one API. It depends on the drug whether this imposes a risk to the patients. Efficacy is in many cases more related to AUC than to C_max. Exceptions are f.i. painkillers where C_max (and t_max!) is important. Safety is generally related to the upper limit of C_max.

Now for the big but: If you consider the conventional limits of 80–125% C_max being too strict, you should have stated wider limits (or aim at reference-scaling in a replicate design if CV_wR >30%) already in the protocol and discussed that with the agency before performing the study.
It smells of cherry-picking if you fail to show BE according to the protocol and afterwards about a patient’s risk which you consider not relevant for any reason.