Bioequivalence and Bioavailability Forum

❝ 1. Although ICH M13A was adopted by the CHMP on 25 July 2024, it will come into effect on 25 January 2025. A six month transition period is common for the EMA in order to give applicants the opportunity to adapt the design of studies to the new requirements.

❝ Tell the assessor in a polite way that (a) at the time being ICH M13A is not in effect and (b) you had no crystal ball and thus, performed the study according to the (then) applicable guideline of 2010.

❝ 2. For high-risk products the clinical use of the comparator is not relevant, sorry. You were aware of the Q&A document. Read #2.4 and #2.5 again. We are dealing with an IR product. Why should it be administered with food? Bad tolerability in fasting state? If yes, you can try to give that as a justification for not performing another study in fasting state. Or did the originator some evergreening to make your life miserable? See the GL 2.1.5, second paragraph for alternatives. IMHO, belonging to the realm of science fiction.

❝ If all (esp. idea #1) fails, I’m afraid you have to reformulate in order to pass in fasting state as well.

Thanks Helmut for your swift reply!

We will indeed try to answer that the study was performed according to the guideline in force at that time but not sure it will convince the assessor

Concerning your comment that the clinical use of the comparator is not relevant, you mean that even if the comparator is labelled to be taken only with food, we have to perform two PK studies in both conditions (fed and fasting). In our case, the comparator should be administered with food according to its SMPC as it is a low solubility drug. Then, there is a clinically relevant food effect observed in PK. However, the manufacturing technology used in the test and the comparator are different leading to a more food effect for the test and then, a lower BA observed for the test in fasting conditions.
To be honest, I still not understand why we should be BE in fasting condition if the products shoudl be taken with food in clinical practice.