Bioequivalence and Bioavailability Forum

inter-batch variability? [Regulatives / Guidelines]

posted by d_labes  – Berlin, Germany, 2010-08-04 15:58 (5185 d 22:58 ago) – Posting: # 5715
Views: 16,837

Dear Dan!

❝ 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 [color:red](why not the reference?)/color:red] and therefore a marketing authorisation can not be granted.

(emphasis by me)


I never heard about a regulatory criterion requesting that the point estimators between BE studies must not varying. And that you must express articulately against the regulatory body.
I would wonder if there is no variability!

As you have told: the pivotal studies have shown bioequivalence. IMHO that was it. All other concerns are negligible (if not safety is concerned).

More over the assessors judgment is logical flawed:
Considering Study 1/Study 3 with the same reference 1 (batch?), neglecting the fact that study 1 is pilot and therefore not suitable for a reliable point estimator, there is no substantial difference in the point estimators although test 1 and test 2 (batches?) are used.
Since the other 2 studies use different test/reference (batches?) one cannot use them to judge. If judgment of inter-batch variability is ever possible from BE studies which I highly question.

But to cite myself: "Regulators ways are inscrutable!"

Eventually you can argue using not the point estimators but the mean/geometric mean values of the PK metrics themselves. Hopefully they show greater variability between the reference batches.
But IMHO this is clearly nonsense.

Complete thread:

• inter-batch variability? Dr_Dan 2010-08-04 10:29 [Regulatives / Guidelines] 
  • 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