Bioequivalence and Bioavailability Forum

Hi Helmut,

❝ What do you think a regulator would prefer?

1. Excluding the subject and assess BE based on valid data only.
   

   ❝

2. Keep the subject though the reanalysed C_max in one period is not valid.

Please don't misunderstand what I mean. I'm certainly not pleading to use data which were not demonstrated to be valid during method validation. I would not extrapolate above the ULOQ and I would not analyse a sample beyond its stability period. But let me play the devil's advocate too. Let's imagine your subject had a Cmax at midrange of the calibration curve in Period 1 and is at least 5 x ULOQ in Period 2 (still ULOQ after a 1/5 dilution). Regulators would not be happy with the exclusion of the subject. Which doesn't mean that they would like possibly unreliable data to be used instead: rather that they may reject the study as a whole . Regulators don't wear Armani suits.

OK, we're discussing rather extreme situations. Let's remain optimistic and hope that Anand still has enough plasma for re-analysis, that the analyte is stable, and that the validation of the higher dilution factor will pass