Bioequivalence and Bioavailability Forum

Dear ElMaestro,

thank you for your answer.

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

Yes, we exclude the wash-out as a source of the problem.

❝ ❝ 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?

Since we are excluding that the concentration > LLOQ at pre-dose time could be due to bioanalytical issue, we think that the source of the problem could be the contamination of some tubes, probably following the contamination of the head of the pipettes.
It could be possible that not all tubes were contaminated, because both the operators that handle the blood samples and the pipettes used are not always the same during each treatment period.

However I used "seem" because it is not easy to demonstrate this kind of contamination.

❝ ❝ 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?

Unfortunately, excluding a bioanalytical bias, it is difficult for us to demonstrate that a contamination was made.

Best regards,
Paola