inter-batch variability? [Regulatives / Guidelines]

posted by d_labes  – Berlin, Germany, 2010-08-04 15:58 (5007 d 20:48 ago) – Posting: # 5715
Views: 15,480

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)

:not really:
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

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