Bioequivalence and Bioavailability Forum

Hi Helmut and Beholder,

Let's take a hypothetical example
Due to high intersubject variability we got some periods for some (not many) subjects less than 5% of LLOQ.
1. Would you ask analytical lab to revalidate the method and reanalyze those profiles again or since analytical part is over, there's no way to change the method when playing part starts (Cmax estimation is PK part, right?)

2. Do you think the reasons to exclude that subjects are feasible enough?
Have you ever been asked to do that?

For me this is mind-blowing since the applicants should invest money not only in dropouts, but in extreme metabolizes too! The power loss for replicate designs is more significant (double the subject data)

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PS: moreover, that criterion (Cmax< 20*LLOQ) is not listed in EMA GL as a reason for subject exclusion