Bioequivalence and Bioavailability Forum

Hi Helmut,

» Let’s assume that the subject with concentrations >ULOQ is observed in the last batch and we are already close to the validated long-term stability. Even if we revalidate with a higher dilution, we may exhaust the storage interval – resulting in unacceptable results as well. In such a case we have to exclude the subject.

If the storage interval is limited by the duration studied during validation (e.g. stability demonstrated for 30 days, still fine at the end): I would extend the validated period (always keep some extra stability samples in the freezer, just in case !). If the stab failed at the last time point: indeed in trouble. But 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.