Bioequivalence and Bioavailability Forum

Dear Ratnakar,

❝ [...] but as per FDA (if it is 2 times median Tmax) we have to continue the subject in the study even if he had vomiting in period 1 as we are not aware of the median Tmax of the study drug at that point of time and we get the data only after analyzing the samples and then we take the decision whether to exclude the subject or not.

The FDA guidance recommends not to use data from subjects who vomited at or before 2 times median Tmax. However:

• the guidance does not say you should refer to the median Tmax in your study, rather than, for instance, the Tmax described in the labelling of the reference product,
  
• the guidance does not forbid to exclude subjects who have vomited, based on your medical judgement or on objective criteria described in the protocol (at least, if the decision is taken before sample analysis).

If a subjects vomits in Period 1 at or before Tmax described in the labelling (or a time pre-defined in the protocol), I would discontinue him from the study and certainly not have him go through Period 2. If an FDA guy starts discussing I would refer him to the Declaration of Helsinki, § 4, 6, and to ICH GCP § 2.1, 2.3.

❝ But my query is as per EU guideline, the decision of exclusion of the subject to be taken before Bioanalysis and if we take the decision to exclude him should we analyze the samples?

Not discussed in the guideline. I may analyse samples collected before the subject vomits and the decision to exclude him is taken by the investigator. But I would stop collecting samples once the decision to withdraw him is taken.

Regards
Ohlbe