Bioequivalence and Bioavailability Forum

Dear all,

in the meantime I have received the May 2012 draft from Jiři (THX!). Section 3.1.8 is 1:1 with EMA’s 4.1.8. Crazy that they carried over the ±20% expected deviation from the 2009 Q&A v2 (see also this thread) to Section 3.1.3, which reads:

The number of subjects to be included in the study should be based on an appropriate sample size calculation.

The number of subjects required is determined by:

1. the intra-subject coefficient of variation of the drug to be studied either estimated from a pilot study, results of previous clinical studies or from published literature
   
2. the significance level desired (α=0.05)
   
3. the expected deviation from the reference product compatible with bioequivalence (delta, ie percentage difference from 100 % ie. ±20%)
   
4. the required power should be at least 80%

The clinical and analytical standards imposed may also influence the statistically determined number of subjects. However, generally the minimum number of subjects should not be smaller than 12.

Funny that the Q2 from above is not answered at all. Still interested in the URL which I could add to the Guidelines.