Bioequivalence and Bioavailability Forum • EMA: generally no product-specific GLs

EMA: generally no product-specific GLs [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2013-09-19 13:48 (4658 d 15:09 ago) – Posting: # 11524
Views: 32,848

Hi CR,

❝ Do we get Bioequivalence Recommendations for Specific Products on EMA site…

Nope. Apart from biosimilars and a few drugs/formulations in the Q&A-document EMA hasn’t published product specific guidelines so far – though considering for the future.

❝ My requirement is, per FDA recommendations for Spironolactone, analytes to be measured for showing BE is just the parent compound. But as we are planning for MHRA submission, I am not sure if MHRA insists on metabolites as well.

Spironolactone it tough, but possible. Therefore, that’s the way to go. Personally I’m not sure whether spironolactone cannot be classified as a pro-drug. Did you search MHRA’s PARs?

❝ […] Spironolactone is extensively metabolized; it has three known active metabolites: canrenone, 7-thiomethylspironolactone, and 6-hydroxy-7-thiomethylspironolactone.

Yep. As usual metabolites show nicer variability; my studies (CV%):

                       AUC              C_max        n

                  x    min   max    x   min   max

Spironolactone  28.9  19.8  43.0  28.0 23.6  34.1   4 

Canrenone        9.49  6.98 12.2  13.1  9.09 17.8  10

7-α-TMS         14.4  11.8  21.2  18.3 15.3  16.0   3

If you succeed in convincing MHRA that spironolactone is a pro-drug, you would have to show BE only for one metabolite (active or not). I would opt for canrenone.

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Complete thread:

Bioequivalence Recommendations for Specific Products cr.maroj 2013-09-19 11:00
- 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 GLsHelmut 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
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        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
        
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