Bioequivalence and Bioavailability Forum

Dear mittyri
You are right, this inconsistency is confusing. But you will find something similar also in the guideline for MR products (draft). On the one hand the EMA would like to see a study to assess the food effect (MR) or the effect of water (your case) and on the other hand EMA commits that this effect doesn't matter as long as you are bioequivalent in a simple 2 way cross over (or two 2 way for MR). My suggestion is to conduct the simple study and to discuss arguments which led to the refusal of the 3 way study in modul 2.5 Clinical Overview of the dossier.
I hope this helps
Dr_Dan