Bioequivalence and Bioavailability Forum

Dear Joy!

The draft was published today; as expected no poteny correction.
See (4.1.2 Reference and test product, page 6, lines 202-207):
'Batch control results of the test and reference products should be reported. The assayed content of the batch used as test product should not differ more than 5% from that of the batch used as reference product determined with the test procedure proposed for routine quality testing of the test product. In order to demonstrate that a representative batch of the reference product with regards to dissolution and assay content has been selected, the applicant should present dissolution profiles and content analysis of at least 3 batches of the reference product, unless otherwise justified.'

and 4.1.8 Evaluation (page 13, lines 492-494):
'The pharmacokinetic parameters should not be adjusted for differences in analysed content of the test and reference batch, i.e. content correction is not accepted, in the evaluation of bioequivalence studies included in applications for generic products.'

In short batches of test and reference should selected in such way, that their contents do not differ by more than 5%. Interestingly Section 4.1.3 (Subjects / Number of subjects, page 7, lines 221-224) was reduced from one paragraph in the 'old' Note for Guidance to one sentence:
'The number of subjects to be included in the study should be based on an appropriate sample size calculation.'
In other words if the difference in contents (= expected difference in the BE study) is limited to 5%, this means reformulation if you fail to find suitable batches!