Bioequivalence and Bioavailability Forum

❝ Recently (Before the finalisation of the ICHM13A), we performed a study comparing two high-risk products and the reference product should be administered with according to its SPC. Therefore, the study was performed in fed conditions and the BE was concluded.

❝ Following a DCP, the assessor request a study in fasting condition according to the ICHM13A. My question is do we have to demonstrate the BE for this study even if the two products will have to be administered with food in clinical use?

❝ (SPOILER ALERT, we will be not BE in that conditions and most probably we will have a lower BA).

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.