Generic FDC: EMA-approach [Design Issues]
Hi Beholder,
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 for
A simple justification could be:
) asking for waiving the bridging study.
❝ […] 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 for
- BE of all components the new FDC to the originator FDC and
- BE of the components of the FDC to the monoproducts.
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:
- PE close to 100% and
- narrow 90% CI.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png)
Helmut Schütz
![[image]](https://static.bebac.at/img/CC by.png)
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png)
Helmut Schütz
![[image]](https://static.bebac.at/img/CC by.png)
The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes
Complete thread:
- Generic FDC drug vs two monoproduct drug or vs "originator" FDC drug? Beholder 2018-09-04 11:12 [Design Issues]
- Generic FDC: EMA-approachHelmut 2018-09-04 13:04
- Generic FDC: EMA-approach Beholder 2018-09-04 13:27
- Generic FDC: EMA-approach Helmut 2018-09-04 13:38
- Generic FDC: EMA-approach Beholder 2018-09-04 15:23
- Generic FDC: EMA-approach Helmut 2018-09-04 13:38
- Generic FDC: EMA-approach Beholder 2018-09-04 13:27
- Generic FDC: EMA-approachHelmut 2018-09-04 13:04