Bioequivalence and Bioavailability Forum • EMA: Capecitabine product-specific guidance ♬

EMA: Capecitabine product-specific guidance ♬ [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2013-12-10 17:11 (4584 d 14:09 ago) – Posting: # 12031
Views: 31,514

Hi Mittyri,

❝ Could you explain, why does Capecitabine draft have no scaling at least for Cmax?

Very, very unlikely that EMA currently accepts scaling for anything else than C_max. The only case I know is the first partial AUC for ER methylphenidate. Early pAUC and C_min are under discussion (draft MR GL).

Scaling for C_max would only be acceptable if CV_WR >30% is demonstrated in a replicate design and “a wider difference in C_max is considered clinically irrelevant”. Since the PKWP classified capecitabine as a “critical dose” drug, end of story. Be happy that they didn’t classify it as an NTID.
From your reference one cannot conclude CV_WR >30%. C_max in a 2×2 cross-over showed a CV_intra of ~38%. That’s only a hint.
For many drugs the effect primarily correlates with AUC, not C_max. Sometimes C_max correlates with AEs. However, EMA is interested in the biopharmaceutical performance of the formulations (in vivo release in ”human test-tubes”).
BTW, in Russia an AR of 75–133% for C_max is acceptable for all drugs without a clinical justification, right?

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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