Bioequivalence and Bioavailability Forum • inter-batch variability?

inter-batch variability? [Regulatives / Guidelines]

posted by Dr_Dan – Germany, 2010-08-04 12:29 (5799 d 23:13 ago) – Posting: # 5713
Views: 22,851

Dear all
I need your help regarding following problem: we performed 2 BA (pilot) and 2 BE (pivotal, one 2 way cross-over and one replicate design) studies with the same test formulation.
The batches we used were:
Study 1 (pilot): test 1 (lab scale), ref. 1, study centre 1
Study 2 (pilot): test 2, ref. 2, study centre 1
Study 3 (pivotal): test 2, ref. 1, study centre 2
Study 4 (pivotal): test 3, ref. 3, study centre 3
Both pivotal studies show bioequivalence, the pilot studies were not powered adequately to demonstrate bioequivalence but the results hint in this direction. The drug is highly variable.
The point estimator (AUC/Cmax) differ between the studies:
Study 1: 111/116
Study 2: 84/95
Study 3: 111/114
Study 4: 98/97
The assessor concludes that these different point estimators hint at inter batch variability of the test product (why not the reference?) and therefore a marketing authorisation can not be granted.
What should be our response, which argumentation could help to safe our product?
Your input is very much appreciated.
Kind regards
Dan

—
Kind regards and have a nice day
Dr_Dan

Complete thread:

inter-batch variability?Dr_Dan 2010-08-04 10:29
- inter-batch variability? Pavidus 2010-08-04 11:57
- inter-batch variability? d_labes 2010-08-04 13:58
- inter-batch variability? ElMaestro 2010-08-04 17:09
  - Between study variability common for HVDs Helmut 2010-08-04 19:45
    - Between study variability common for HVDs ElMaestro 2010-08-04 21:01
      - Representative batches? Helmut 2010-08-04 23:42
        
        Representative batches? ElMaestro 2010-08-05 08:40
        
        Representative batches? Helmut 2010-08-05 12:30
        
        Representative batches? Dr_Dan 2010-08-05 08:58
        
        Representative batches? Helmut 2010-08-05 12:45
        
        Confidence intervals vs. point estimators Dr_Dan 2010-08-06 09:55
        
        Confidence intervals vs. point estimators ElMaestro 2010-08-06 12:34
        
        Confidence intervals vs. point estimates Helmut 2010-08-06 13:20
        Confidence intervals vs. point estimators Dr_Dan 2010-08-06 14:44
        
        Confidence intervals vs. point estimators ElMaestro 2010-08-06 15:01
        
        meta analysis? martin 2010-08-06 17:25
        
        meta analysis? ElMaestro 2010-08-06 17:57
        
        meta analysis? Helmut 2010-08-06 18:31
        
        meta analysis? Ohlbe 2010-08-06 23:21
        
        No chance against RMS? Dr_Dan 2010-08-10 12:27
        
        No chance against RMS? ElMaestro 2010-08-10 16:26
  - Batch-to-Batch Pharmacokinetic Variability kumarnaidu 2016-07-20 07:16
    - tlast (Common) Helmut 2016-07-20 10:48
      - tlast (Common) nobody 2019-02-21 15:20
        
        tlast (Common) ElMaestro 2019-02-21 16:32
        
        tlast (Common) nobody 2019-02-21 17:02
        
        tlast (Common) ElMaestro 2019-02-21 18:02
        
        tlast (Common) nobody 2019-02-21 18:17