Generic FDC: EMA-approach [Design Issues]

posted by Helmut Homepage – Vienna, Austria, 2018-09-04 11:04 (786 d 08:15 ago) – Posting: # 19235
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Hi Beholder,

» […] There are two options to choose reference drug (s) for that study:
» 1. two separate monoproducts - named drug A and drug B. Both drugs considered as reference drugs
» 2. "original" FDC drug named AB which is also considered as reference drug.

I don’t know the state of affairs in Russia and/or the EEU but according to the EMA’s GL your second option is the most important one (since the originator already demonstrated BE of the FDC’s components to the monoproducts).
However, there is a trap: “BE-drift”. Imagine that (say for component A) the originator passed BE of the FDC with a PE of 90% (bridging to the efficacy/safety data of the monoproduct A). Now you pass BE to the FDC’s A also with a PE of 90%. The link to the originator’s efficacy/safety data of the monoproduct A is just 81%. Oops!

Hence, the GL asks forThe GL provides a way out:

A justification should be provided why ‘drifting’ of bioavailability is not considered relevant and hence why the original demonstration of efficacy and safety is relevant to the generic.


A simple justification could be:I would perform the study of the FDC first (assessing BE of all components) and – if results are promising – go for a scientific advice (Russia: :lookaround:) asking for waiving the bridging study.

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Helmut Schütz
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