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joyjac ★ Philippines, 2008-08-15 05:03 (6529 d 01:24 ago) Posting: # 2190 Views: 5,963 |
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Dear colleagues, Would you know if EMEA allows or accepts BE data that has been normalized or corrected to account for any potency differences between the reference and generic product? Thanks. |
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Helmut ★★★   Vienna, Austria, 2008-08-15 15:11 (6528 d 15:15 ago) @ joyjac Posting: # 2191 Views: 7,707 |
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Dear Joy, first see this post. A potency correction was one of the discussion points for the revison of the guideline (the draft was adopted on July 24th, 2008 by EMEA's CHMP - see this post). Since the potency correction was dropped from WHO's guideline in 2006, don't expect it in the drafted EU-guideline. From personal communications with members of the EWP/PK group I reconstruct the argument against a correction as follows: > The analytical method has some documented variability. > It's possible in a fraudulent way to reanalyse the study's IMPs after the biostudy was evaluated until by simple chance their content will come up in such a way that it would 'safe' an already failed study.Although a prerequisite of BE is GMP (including documented release of IMPs) which should prevent such a thing, that's the currenty thinking in the EU (paranoia? In practice in Canada since 1992).  For details join the party of people waiting for the draft to be published on EMEA's website. — Dif-tor heh smusma 🖖🏼 Довге життя Україна! ![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png) Helmut Schütz ![[image]](https://static.bebac.at/img/CC by.png) The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
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Helmut ★★★ Vienna, Austria, 2008-08-21 20:35 (6522 d 09:52 ago) @ Helmut Posting: # 2224 Views: 5,302 |
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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! — Dif-tor heh smusma 🖖🏼 Довге життя Україна! Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
Ing. Helmut Schütz