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martin ★★ Austria, 2008-08-26 15:51 (6518 d 10:36 ago) Posting: # 2255 Views: 5,905 |
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dear colleagues ! I do have a question regarding the difference between the two terms "bioequivalence" and "(bio) comparability". in the language of statistics, I suppose that both terms refer to testing for equivalence with pre-specified margins. bioequivalence usually implies using the conventional margins for ratios ranging from 0.8 to 1.25 whereas (bio) comparability is based on pre-specified margins justified by clinical relevance. any comments would be highly appreciated ! best regards martin |
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Jaime_R ★★ Barcelona, 2008-08-27 14:12 (6517 d 12:15 ago) @ martin Posting: # 2259 Views: 4,950 |
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Dear Martin, I don't know the term "(bio) comparability" - which sounds like a shortened version of "comparative bioavailability". Maybe one of Helmut's posts helps? — Regards, Jaime |
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Ohlbe ★★★ France, 2008-08-27 14:20 (6517 d 12:07 ago) @ Jaime_R Posting: # 2260 Views: 5,028 |
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Dear all, I couldn't find the term "comparability" in the general FDA guideline, or in the "old" and "draft" EMEA guidelines. I didn't check other guidelines. Martin, where did you see it used ? Regards Ohlbe |
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martin ★★ Austria, 2008-08-27 16:36 (6517 d 09:51 ago) @ Ohlbe Posting: # 2262 Views: 4,916 |
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dear jaime_r and ohlbe ! thank you for your response. I found the word "comparability" in the following CHMP guideline: GUIDELINE ON SIMILAR BIOLOGICAL MEDICINAL PRODUCTS to cite a few sentences: [...] Comparability studies are needed to generate evidence substantiating the similar nature, in terms of quality, safety and efficacy, of the new similar biological medicinal product and the chosen reference medicinal product authorised in the Community [...] [...] The standard generic approach (demonstration of bioequivalence with a reference medicinal product by appropriate bioavailability studies) is normally applied to chemically derived medicinal products. Due to the complexity of biological/biotechnology-derived products the generic approach is scientifically not appropriate for these products. The ”similar biological medicinal products” approach, based on a comparability exercise, will then have to be followed. [...] I found the definition of comparability exercise in the CPMP guideline: GUIDELINE ON COMPARABILITY OF MEDICINAL PRODUCTS CONTAINING BIOTECHNOLOGY DERIVED PRODUCTS AS ACTIVE SUBSTANCE: [...] Comparability is the exercise of that will demonstrate that two products have similar profile in terms of Quality, Safety, Efficacy [...] my plain interpretation of this headache-terminology in statistical language regarding pharmacokinetics: bioequivalence: test for equivalence (using conventional margins) in rate and extent where the active ingredient becomes available at the site of drug action comparability: test for equivalence (using clinical relevant margins) for some parameters to be considered relevant what do you think ? martin |
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Ohlbe ★★★ France, 2008-08-27 16:56 (6517 d 09:31 ago) @ martin Posting: # 2264 Views: 4,955 |
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Dear Martin, OK, this is much clearer now ! I never think of these bio-generics. I am no statistician, so I am probably not the best person to answer. But I note that the definition in the guideline mentions "similar", which you translate with "equivalent" in your own definition. Does this make any difference in the stat tests used ? Regards Ohlbe |
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martin ★★ Austria, 2008-08-27 17:31 (6517 d 08:56 ago) @ Ohlbe Posting: # 2265 Views: 4,926 |
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dear ohlbe ! I found an adequate defintion in a draft guideline: Guideline on the Clinical Investigation of the Pharmacokinetics of Therapeutic Proteins (DRAFT) [...] Demonstration of comparability between two products is most often a step-wise procedure where pharmacokinetic data are an important part. The design of the pharmacokinetic study should be based on the question to be addressed by pharmacokinetic data. Often comparative pharmacokinetics is needed to establish equivalence between two products. Since not only similarity in terms of absorption/bioavailability is of interest, the standard bioequivalence design may not be optimal. In fact, the risk of differences in elimination rate may be more likely, requiring the demonstration of equivalence on clearance and/or half-life. ... Hence, the criteria used in standard bioequivalence studies may not be appropriate and the equivalence limits should be defined and justified prior to conducting the study [...]. my summary on showing comparability in pharamcokinetics: testing for equivalence in relevant PK paramters using clinical relevant margins which may be wider than the conventional margins for ratios ranging from 0.8 to 1.25. best regards martin |
Ing. Helmut Schütz