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Beholder
Regular

Russia,
2018-09-04 11:12

Posting: # 19234
Views: 640
 

 Generic FDC drug vs two monoproduct drug or vs "originator" FDC drug? [Design Issues]

Hello to everybody!

There is generic FDC drug named AB which is intended to be studied in BE 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.
Which drug (s) to choose as reference drug (s)? What would be your opinion?
THX in advance.

Best regards
Beholder
Helmut
Hero
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Homepage
Vienna, Austria,
2018-09-04 13:04

@ Beholder
Posting: # 19235
Views: 557
 

 Generic FDC: EMA-approach

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 for
  • BE of all components the new FDC to the originator FDC and
  • BE of the components of the FDC to the monoproducts.
The 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:
  • PE close to 100% and
  • narrow 90% CI.
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.

Cheers,
Helmut Schütz
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Beholder
Regular

Russia,
2018-09-04 13:27

@ Helmut
Posting: # 19236
Views: 546
 

 Generic FDC: EMA-approach

Hi Helmut,

» I don’t know the state of affairs in Russia and/or the EEU but

Looks like there is no GL for FDC in Russia but there is in EEC (under development).

» scientific advice (Russia: :lookaround:)

Scientific advice in Russia now can be described only as :lookaround: . Joke.

THX one more time for valuable info.

Best regards
Beholder
Helmut
Hero
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Homepage
Vienna, Austria,
2018-09-04 13:38

@ Beholder
Posting: # 19237
Views: 526
 

 Generic FDC: EMA-approach

Hi Beholder,

I forgot that at last year’s BioBridges Marina Feřtek of the Czech State institute for drug control (SÚKL) gave a presentation about FDCs.
To download: Navigate to the archive, password: Bridges2017

Cheers,
Helmut Schütz
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The quality of responses received is directly proportional to the quality of the question asked. ☼
Science Quotes
Beholder
Regular

Russia,
2018-09-04 15:23

@ Helmut
Posting: # 19238
Views: 511
 

 Generic FDC: EMA-approach

Dear Helmut,

» I forgot that at last year’s BioBridges Marina Feřtek of the Czech State institute for drug control (SÚKL) gave a presentation about FDCs.

Yes, saw that the conference took place and wanted to go throght the presentations. Good occasion now. Thank you.

Best regards
Beholder
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