Bioequivalence and Bioavailability Forum • FDA: Alternative approaches…

FDA: Alternative approaches… [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2013-12-24 15:15 (4562 d 07:32 ago) – Posting: # 12103
Views: 30,912

Hi intuitivepharma,

❝ […] In such a precarious situation my only hope to defend the ANDA would be based on the following assumptions.

❝ The guidance recommendations are nonbinding

Yes, but:

“You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the Office of Generic Drugs.”

The guidance was already published in March 2011. What does your protocol state?

If you targeted the active R-138727 (contrary to the guidance), why didn’t you contact the OGD beforehand?
If you stated the inactive R-95913, you cannot switch to R-138727 only because you don’t like the outcome.

❝ The demonstration of bioequivalence to an active metabolite is more “closer” to the actual clinical situation than demonstration of bioequivalence to an inactive metabolite.

❝ Can any one let know why for Prasugrel, bioequivalence is based on inactive metabolite and active metabolite PK is submitted as supportive data.

[image]
© Anypodetos @ Wikimedia Commons

We had this discussion ∞ times. Current thinking at most regulatory authorities is to demonstrate similarity of the in vivo performance of formulations. Since prasugrel is a pro-drug the inactive R-95913 is closer related to the drug release than the active – but secondary! – R-138727. Regulators are not interested any more in the “clinical situation” – which would call for the most active metabolite with the longest half-life in steady state in many cases.
That’s history.

❝ The condition that data on active metabolite is required implies that it can be quantified.

Yes, but only as supportive data.
Face it: According to the guidance your study failed.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

Complete thread:

Bioequivalence Recommendations for Specific Products cr.maroj 2013-09-19 11:00 [Regulatives / Guidelines]
- Bioequivalence Recommendations for Specific Products Ohlbe 2013-09-19 11:45
  - EMA: Draft product-specific guidances ♬ Helmut 2013-11-15 15:45
    - EMA: Draft product-specific guidances ♬ luvblooms 2013-11-19 06:35
    - EMA: Capecitabine product-specific guidance ♬ mittyri 2013-12-10 15:33
      - EMA: Capecitabine product-specific guidance ♬ Helmut 2013-12-10 16:11
        
        Russian GL 2013: harmonisation to EMA mittyri 2013-12-14 11:57
    - EMA: Draft product-specific guidances ♬ pash413 2013-12-18 12:35
      - EMA: Use of AUC72 not dependent on t½ Helmut 2013-12-18 14:35
    - End of consultation approaching‼ Helmut 2014-02-10 18:33
      - End of consultation approaching‼ Dr_Dan 2016-01-28 09:27
        
        Guesstimates Helmut 2016-01-28 13:32
- EMA: generally no product-specific GLs Helmut 2013-09-19 11:48
  - Thank you cr.maroj 2013-09-19 13:03
  - EMA: generally no product-specific GLs The Outlaw Torn 2013-09-20 07:52
    - EMA: parent whenever possible Helmut 2013-09-20 09:02
      - EMA: parent whenever possible cr.maroj 2013-09-20 10:14
        
        EMA: parent whenever possible Helmut 2013-09-20 12:53
        
        EMA: parent whenever possible Ohlbe 2013-09-20 13:52
        
        EMA: parent whenever possible mittyri 2013-09-20 14:55
        
        EMA vs. Russia Helmut 2013-09-20 19:21
        
        FDA: Prasugrel intuitivepharma 2013-12-20 07:36
        
        FDA: Prasugrel Helmut 2013-12-20 13:46
        
        FDA: Prasugrel intuitivepharma 2013-12-24 06:38
        
        FDA: Alternative approaches…Helmut 2013-12-24 14:15
        
        FDA: Alternative approaches… intuitivepharma 2013-12-26 05:11
        
        FDA: RTR Helmut 2013-12-26 14:35
        
        FDA: RTR intuitivepharma 2013-12-31 05:34
        FDA: RTR meghalvakil20 2015-07-23 16:32
        
        WayBack Machine Helmut 2015-07-23 16:58
        
        WayBack Machine meghalvakil20 2015-07-23 17:03
        
        Old stuff Helmut 2015-07-23 17:28
        
        EMA: parent whenever possible ElMaestro 2013-09-20 19:35
        
        EMA: Sirolimus product-specific GL luvblooms 2013-11-19 13:00