Bioequivalence and Bioavailability Forum

Hi Paola,

❝ The bioanalytical results from a BE study (crossover, 3 periods, 36 healthy volunteers) shown the concentrations at the pre-dose sampling time above the LLOQ.

❝

❝ These results occur in 20% of the subjects, and for each subject happen in more than one period, and always during the period 1, before the starting of the drug administration.

Period 1 is a little problematic, this suggests that washout isn't the issue.

❝ Following several bioanalytical check, the results seem to be correlated to an eventual contamination of the pre-dose samples during the clinical phase, rather than to a bioanalytical bias.

"Seem"? Can you say anything with certainty?
If some period 1 predose tubes were contaminated, why weren't all of them? Were some tubes with positive values likely contaminated?

❝ Which is in your opinion the most suitable approach to treat our bioanalytical results?

❝ What is the position of the regulatory authorities in these cases?

I think I would audit the whole thing. Not sure this study is of submission quality in the absence of some concrete answers re. the origin and extent of the problem. Did you ask "why" five times?