Bioequivalence and Bioavailability Forum

Dear all,

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.

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.

All these pre-dose values (except for one subject) are lower than 5% of the respective Cmax.
Since the EMA guideline on BE reports that, if the pre-dose concentration is greater than 5 % of the Cmax value, the subject being removed from the analysis, we cannot exclude these data from the statistical analysis.

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?

Thank you in advance for your answer.

best regards,
Paola

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Edit: Category changed. [Helmut]