Bioequivalence and Bioavailability Forum

Dear Swapnil!

❝ Due to one outlier subject one of our pivotal study is failing.

How did you judge that the subject was an outlier?

❝ In such case can we perform redosing for approximately 20% (of original sample size) subjects to confirm the results and to support our application (MA).

Sometimes. You are aware that FDA hates such an approach and it should not be considered standard?

❝ Nowadays this approach is used for USFDA but can you please update me regarding EU view on the same.

Re-dosing is not acceptable in the EU. Sorry.

Reasons for exclusion must be pre-specified in the protocol. Besides clinical events (vomiting, diarrhoea,…), PK reasons are:

• […] subjects in a crossover trial who do not provide evaluable data for both of the test and reference products […] should not be included.
  
• A subject with lack of any measurable concentrations or only very low plasma concentrations for reference medicinal product [may be excluded]. A subject is considered to have very low plasma concentrations if its AUC is less than 5% of reference medicinal product geometric mean AUC (which should be calculated without inclusion of data from the outlying subject). The exclusion of data due to this reason will only be accepted in exceptional cases and may question the validity of the trial.

(my emphases)