gtomer ☆ Israel, 2014-04-09 16:40 (3641 d 08:49 ago) Posting: # 12799 Views: 5,007 |
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Hi All, Would value your opinion: The bioequivalence guide (CPMP/EWP/QWP/1401 Rev 1) requests to perform a dissolution profile comparison at 3 pHs between the test and reference products used in the BE study. It gives superiority to the BE study results, should the dissolution profiles will not be similar, "However, possible reasons for the discrepancy should be addressed and justified.". Does anyone know of any investigatory methods or justifications found for such discrepancy, i.e. where reference vs. test found similar in BE study but F2>50 in dissolution? Many thanks. |
Helmut ★★★ Vienna, Austria, 2014-04-10 14:31 (3640 d 10:58 ago) @ gtomer Posting: # 12805 Views: 4,173 |
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Hi gtomer, in vivo BE overrules any in vitro dissimilarity (as a successful therapeutic equivalence study would overrule in vivo inequivalence). You should perform the comparative dissolution, but demonstrating in vitro similarity is not necessary. See also this thread. ❝ Does anyone know of any investigatory methods or justifications found for such discrepancy, i.e. where reference vs. test found similar in BE study but F2>50 in dissolution? I guess you mean ƒ2 <50? Either the dissolution media are not biorelevant (i.e., overdiscriminatory, since BE was proven in vivo) or dissolution is not the driving force for absorption at all (e.g., BCS classes I/IV). — 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 |
jag009 ★★★ NJ, 2014-04-11 17:14 (3639 d 08:14 ago) @ Helmut Posting: # 12812 Views: 4,070 |
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Hi Helmut, ❝ ...dissolution is not the driving force for absorption at all (e.g., BCS classes I/IV). Does it mean that you would have to run experiments to demonstrate the drug is class IV (run both solubility and permeability) assuming no/insufficient literature supports. Thanks John |
Helmut ★★★ Vienna, Austria, 2014-04-11 17:22 (3639 d 08:07 ago) @ jag009 Posting: # 12813 Views: 4,136 |
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Hi John, ❝ Does it mean that you would have to run experiments to demonstrate the drug is class IV (run both solubility and permeability) assuming no/insufficient literature supports. I don’t think so – at least I never got a question from a European agency in my studies (passing BE). I simply reported the dissolution at three pHs. I neither calculated ƒ2 nor did I discuss anything. Other experiences? — 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 |
jag009 ★★★ NJ, 2014-04-11 19:58 (3639 d 05:30 ago) @ Helmut Posting: # 12819 Views: 4,042 |
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Hi Helmut, ❝ I don’t think so – at least I never got a question from a European agency in my studies (passing BE). I simply reported the dissolution at three pHs. I neither calculated ƒ2 nor did I discuss anything. ❝ ❝ Other experiences? Yes but I need to dig it up Will get back to you. Not class 4 though We did it just to protect our butt. John |