Bioequivalence and Bioavailability Forum

Dear All,

Recently FDA has rejected one of the our Narrow Therapeutic study by stating following:

"Fed study is not acceptable due to the substantial difference in Tmax between test product and the reference listed drug product. Recommendation of the medical reviewer of the division of clinical reviewer of the office of generic drug. The reviewer stated that “there is a large difference in the median Tmax between the test and reference (6 hrs for test treatment versus 8 hrs for the RLD treatmement or 25% difference) is accompanied by also relatively large difference in the Cmax (with the point estimate of 1.15 hrs) under fed condition. These differences are unacceptable as they may adversely impact the anticipated safety and efficacy of the product when interchanged with the reference listed drug product. Patient used to taking one ER formulation preparation would at risk of having a different safety profile from the standard of on set of adverse effects."

In this case i could not get any kind of clarity in the present regulation (as per my understanding) about the consideration of median Tmax during the estimation of BE for narrow therapeutic drugs.

Kindly help me to come out of this issue and our study get accepted by the agency.

Awaiting for your answer which may guide me to prepare my justification.

Regards,

Compliance