Bioequivalence and Bioavailability Forum

Hello Samaya,

❝ We are developing a topical ointment (5-Fluorouracil) for US and EU.

❝ As of now we plan to conduct three arm study (Test product, US reference product, Placebo) to file in US. Is there any chance that MHRA (EU regulatory authority) will accept this study?? or we should include EU reference product as well i.e. four arm study (Test product, US reference product, EU reference product, Placebo)?

Almost zero chance for EU approval without an EU-sourced ref. product, I think.

❝ Secondly, if four arm study is conducted then MHRA and FDA would accept the statistical significance of clinical data?

Likely, yes. But you should get sc. advice first to have confirmed that they will accept the US-inspired protocol. Or you should submit in a non-UK country country as RMS in a DCP - this can radically increase your chance of success even in the UK., even if this sounds a bit counter-intuitive to you.

❝ Lastly, whether study should include subjects from different parts of India / US /EU or only Indian population would suffice??

I don't think that populations should affect the success proportion of T vs R. So my guess -and I stress: this is a guess- is that Indian subjects would be OK for approval in both US and EU. As I read the US guidance, little is dictated re. the origin of the subjects.