Bioequivalence and Bioavailability Forum

Dear Bab.

❝ In method validation dilution integrity experiment was established with

❝ 1/5 and 1/10 dilution. But in the study sample analysis samples were

❝ diluted with 1/2 dilution only.

According to common sense, if the method was validated for no dilution, 1:5 and 1:10 dilution it should be possible to go with 1:2 also. But: regulators want to see data, not common sense.

❝ Is it acceptable?

It casts a damning light on both the analytical performance and the QAU (why was the 1:2 dilution performed ouside the validated method?). I would go with a partial validation and

1. report the non-adherence to the SOP as a protocol deviation in the analytical report, and
   
2. present results of the revalidation supporting a claim that no influence on the study's outcome is likely.