Bioequivalence and Bioavailability Forum

Dear drplacebo,

❝ Will this be acceptable from regulatory point of view?

Unless you intend to submit your data to Denmark, where such a ratio may lead to difficulties, all which matters to the regulators is your 90 % CI. The result of the point estimate is not taken into consideration in the guidelines to accept or reject bioequivalence.

The question is more whether such a difference is acceptable from the sponsor's point of view, and whether they should take the chance, or rather re-formulate the product. The decision would depend on the number of subjects in the pilot study (and therefore, how reliable your estimated ratio is), and on the intra-subject CV (little chances to demonstrate bioequivalence with a point estimate at 112 % and a high CV).

Regards
Ohlbe

Dear drplacebo!

Although the new European BE-Guideline was announced as a kind of
  Cookbook
let's see was has changed:

EMEA (2001):
The number of subjects required is determined by

1. the error variance associated with the primary characteristic to be studied as estimated from a pilot experiment, previous studies, or from published data,
   
2. the significance level desired,
   
3. the expected deviation (delta) from the reference product compatible with BE and,
   
4. the required power.

So if you expect +12% from your pilot study, and variability + budget allows, why not?

EMEA (2008 draft):
The number of subjects to be included in the study should be based on an appropriate (sic!) sample size calculation.

I see!