Bioequivalence and Bioavailability Forum • Final version published

Final version published [Regulatives / Guidelines]

posted by Helmut – Vienna, Austria, 2010-01-29 15:29 (5619 d 12:34 ago) – Posting: # 4659
Views: 25,443

Dear all!

The eagle has landed. The final BE-Guideline was published today.
The Guideline will be effective with 1 August 2010.

Fascinating!

[…] the 90% confidence interval for the ratio of the test and reference products should be contained within the acceptance interval of 80.00-125.00%. To be inside the acceptance interval the lower bound should be ≥80.00% when rounded to two decimal places and the upper bound should be ≤125.00% when rounded to two decimal places.
Funny. 79.995%-125.004% is bioequivalent, but your software will print out “Bioequivalence not shown.” Time for a revision of Phoenix/WinNonlin.
No statistical test for any effect (carry-over, period, treatment), as well as no confidence intervals.
Two-stage design: 94.12% confidence interval given as an example for the combined analysis. That’s the one of Potvin et al. (based on Pocock’s).
Interesting section on exclusion of subjects.
Scaling for C_max made it, but the widening of the acceptance range is limited to a maximum of 69.84–143.19% (CV_ref≤50%).The suggested method is (following the terminology of Tóthfalusi et al.) ABEL (Average Bioquivalence with Expanding Limits). Like in the U.S. a constraint of 80.00%-125.00% is set to the GMR.
t_max is back (instead of partial AUC truncated at t_max,ref) – but no statistical analysis (“no apparent difference in median t_max and its variability”).
C_ss,min has vanished.

Edit: Link corrected for new EMA’s website. 2010-07-16 [Helmut]

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Complete thread:

EMA BE guideline - final version Ohlbe 2010-01-28 18:31 [Regulatives / Guidelines]
- Final version publishedHelmut 2010-01-29 14:29
  - Final version published ElMaestro 2010-01-29 17:02
    - Statistix Helmut 2010-01-29 17:30
      - Statistix ElMaestro 2010-01-29 18:11
    - Calories ;-) Helmut 2010-01-29 19:22
      - Calories ;-) ElMaestro 2010-01-29 20:43
        
        Calories ;-) Helmut 2010-01-29 21:08
      - Variable calories d_labes 2010-02-01 12:05
    - ANOVA only - no doubts Helmut 2010-02-10 23:41
      - ANOVA only - no doubts ElMaestro 2010-02-12 21:09
  - Final EMA oracle d_labes 2010-02-01 11:53
    - Final EMA oracle Helmut 2010-02-01 12:28
    - Final EMA oracle ElMaestro 2010-02-01 12:50
      - More then two EMA oracles d_labes 2010-02-01 13:30
        
        Less of an issue ElMaestro 2010-02-01 15:29
        
        Less or More of an issue d_labes 2010-02-01 16:53
        
        Less or More of an issue ElMaestro 2010-02-01 17:22
        
        Effective with 1 Aug 2010 Helmut 2010-02-02 00:55
        Bias? ElMaestro 2010-02-04 11:27
        
        Bias? Helmut 2010-02-05 02:03
        
        Bias? ElMaestro 2010-02-05 09:33
        
        Bias? Helmut 2010-02-05 10:21
        
        Bias? d_labes 2010-02-05 13:59
        Bias? ElMaestro 2010-02-05 16:00
        
        Bias? Helmut 2010-02-05 19:14
      - Final EMA oracle Helmut 2010-02-01 13:43
        
        Final EMA oracle ElMaestro 2010-02-01 14:54
        
        Final EMA oracle d_labes 2010-02-01 15:20
        
        Teaching Helmut 2010-02-01 16:07
  - Cmin really gone? tmax reappeared? d_labes 2010-02-01 14:02
    - Cmin really gone. tmax reappeared - but how? Helmut 2010-02-01 23:30
  - Interpol or not d_labes 2010-02-01 14:52
    - Interpol! Helmut 2010-02-02 00:02
      - Interpol! ray_be 2010-02-03 18:31
        
        WinNonlin/Phoenix extrapolation to t=tau Helmut 2010-02-03 20:26
  - Meta-analysis Helmut 2010-02-07 17:41
  - Final version published Panks.79 2010-03-08 07:22
    - Cmin for MR-formulations? Helmut 2010-03-08 18:16
      - Cmin for MR-formulations? Marcel 2010-04-23 10:09
        
        MR-Guideline? Helmut 2010-04-23 12:34
- Overview of comments published Helmut 2010-02-10 18:33
  - Comments commented d_labes 2010-02-11 08:19
  - Definition of Cmin by EMEA Ravi 2010-03-13 12:05
    - The EMA’s Cmin & WinNonlin Helmut 2010-03-13 12:52