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Registerinter-batch variability? [Regulatives / Guidelines]
Dear Dan!
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.
❝ 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.
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.
—
Regards,
Detlew
Regards,
Detlew
Complete thread:
- inter-batch variability? Dr_Dan 2010-08-04 10:29 [Regulatives / Guidelines]
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- 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
- No chance against RMS? Dr_Dan 2010-08-10 12:27
- meta analysis? ElMaestro 2010-08-06 17:57
- meta analysis? martin 2010-08-06 17:25
- Confidence intervals vs. point estimators ElMaestro 2010-08-06 15:01
- Confidence intervals vs. point estimators ElMaestro 2010-08-06 12:34
- Confidence intervals vs. point estimators Dr_Dan 2010-08-06 09:55
- Representative batches? Helmut 2010-08-05 12:45
- Representative batches? ElMaestro 2010-08-05 08:40
- Representative batches? Helmut 2010-08-04 23:42
- Between study variability common for HVDs ElMaestro 2010-08-04 21:01
- 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
- tlast (Common) ElMaestro 2019-02-21 18:02
- tlast (Common) nobody 2019-02-21 17:02
- tlast (Common) ElMaestro 2019-02-21 16:32
- tlast (Common) nobody 2019-02-21 15:20
- tlast (Common) Helmut 2016-07-20 10:48
- Between study variability common for HVDs Helmut 2010-08-04 19:45
Ing. Helmut Schütz