Bioequivalence and Bioavailability Forum

Dear Helmut:
Can we use 10% formulation difference or more for sample size estimate. I have a failed BE study and now we want to plan another BE study with the sample size based on the mean ratio (T/R)=112% (from the failed BE study). Is it appropriate to consider this much difference. In FDA guidance "Statistical Approaches to Establishing Bioequivalence" they have written the below line in sample size consideration section.
Sample sizes for average BE should be obtained using published formulas. Sample sizes for population and individual BE should be based on simulated data. The simulations should be conducted using a default situation allowing the two formulations to vary as much as 5% in average BA with equal variances and certain magnitude of subject-by-formulation interaction. The study should have 80 or 90% power to conclude BE between these two formulations. Sample size also depends on the magnitude of variability and the design of the study. Variance estimates to determine the number of subjects for a specific drug can be obtained from the biomedical literature and/or pilot studies.

Looking forward to your reply!
Best Regards!