inter-batch variability? [Regulatives / Guidelines]

posted by Dr_Dan  – 2010-08-04 10:29  – Posting: # 5713
Views: 11,467

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

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