Bioequivalence and Bioavailability Forum

Hi Ohlbe,

❝ […] I think that regulators would not see with a very positive eye the exclusion of the one subject with the highest Cmax in the whole study. Particularly if his Cmax was within range in the other period.

Let me play the devil’s advocate. I think there are two worst case scenarios. (1) Further dilution fails A&P or (2) the storage cannot be extended (fails as well). Now what? All reanalysed concentrations (>ULOQ is mentioned as a reason in the BMV-GL) are not valid. Given the high variability generally observed for C_max, the value in the other period is not relevant. Even with true F=1, C_max might be ≤ULOQ in one period and >ULOQ in the other.

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.

I’m not a regulator () but (a) would not bias the treatment comparison. Only the producer’s risk increases. IMHO, (b) contradicts all rules about using valid data only and the treatment comparison might be biased.