Bioequivalence and Bioavailability Forum

Hi Hiren,

are you aware of FDA’s guidance?

❝ 1. Is it mandatory for USFDA that Cmax, AUC meet the traditional BE limits of 80 - 125 for claiming no DDI?

1. If you have a PK/PD model you can set the “no effect boundaries” on it.
   
2. If not, 80–125% apply.

❝ 2. If the study fails for meet 80-125 limits, is it possible to justify on clinical grounds that such an effect is of no clinical relevance?

If you follow approach 2 above you should design the study with a sufficiently large samples size.

❝ 3. How to calculate sample size of DDI studies?

Based on the drug with the larger CV_intra and the “no effect boundaries”.

❝ 4. Since all the three products are developed by us on the same platform, we can assume zero / minimal variability associated with formulation difference.

❝ Is there any method to calculate the sample size based on true intrinsic variability of molecule only? This can reduce our sample size to some extent.

Doesn’t make sense. You administer formulations, not the APIs in solution.