Bioequivalence and Bioavailability Forum

Hi Tina!

❝ Should a European Reference Product be always used for MRP/DCP?

Yes – or more precise: “must” not “should”.

❝ If the innovator is the European Reference Product…

There is no “European Reference Product” – unless the innovator product was authorized by the Centralized Procedure. In an MRP/DCP the reference marketed in any country of the EEA can be used.

❝ … and is not available in a member state, can the generic (which had compared itself with the ERP) available in the member state be used for MRP/DCP application with the member state as the RMS?

No way.*

❝ If the generic is marketed only in one member state, it would have been the company's decision to market in that MS. However, they have still compared with the innovator?

❝ Does EMA require only a innovator to be compared as the reference?

Yes. For details see Section 4.1.2 of the BE GL.

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• A crazy story for the records: The innovator was approved in the UK in the early 1960s. In the 1970s a generic (with the same brand name!) was approved in the UK. The innovator removed his product from the market shortly after. In 2009 one of my sponsors wanted to apply for a generic application in Germany and asked the BfArM whether the UK-product (the only one on the market in the EU for decades) is the innovator. The BfArM asked MHRA and got the answer “yes”! We ran the study – nicely BE – and submitted it in Germany. Now the BfArM had another conversation with MHRA and it turned out that the reference was actually a generic (see above). Oops! In 2011 the BfArM accepted the study (BE of a generic vs. a generic…), but based the decision mainly on “well established use” of the pseudo-reference. No idea whether the sponsor will go for an MRP and what might happen then.