Bioequivalence and Bioavailability Forum

Dear Compliance,

❝ Can anyone tell me the FDA concern if we conduct the study sample analysis immediately after completion of respective period instead of conducting analysis of all periods together.

No personal experience with the FDA in this respect. Their guidance is not specific in this respect but rather outdated. EMA’s is more clear (Section 5.1)

For bioequivalence studies it is advised to analyse all samples of one subject together in one analytical run to reduce the variability in outcome. The QC samples should be divided over the run in such a way that the accuracy and precision of the whole run is ensured.

(Note: advised, not required)

❝ We want to do this because we want to expiated our submission process. However there is no stability issue.

I wouldn’t say this a justification welcomed by any authority. We once had the case of a very instable compound, where we analysed samples immediately after each period. But we had hard data showing stability problems. Random variability of calibration curves will directly influence the study’s variability. At least if the study is not too imbalanced the overall T/R should not be influenced to much, but your power will decrease. Did you get approval for this procedure by the IEC and the authority? If the study passes, it should be OK. If the study fails due the CV expect problems with the sponsor.