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Mauricio Sampaio ★ Brazil, 2018-01-08 20:59 (2658 d 09:26 ago) Posting: # 18150 Views: 5,232 |
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How can I proceed with a biowaiver if the reference product does not pass in all conditions of dissolution required to BCS? |
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ElMaestro ★★★ Denmark, 2018-01-09 06:35 (2657 d 23:50 ago) @ Mauricio Sampaio Posting: # 18151 Views: 4,456 |
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Hi MS, ❝ How can I proceed with a biowaiver if the reference product does not pass in all conditions of dissolution required to BCS? How about Mahalanobis or Bootstrap? — Pass or fail! ElMaestro |
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Mauricio Sampaio ★ Brazil, 2018-01-10 14:52 (2656 d 15:32 ago) @ ElMaestro Posting: # 18159 Views: 4,303 |
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Hi El Maestro ❝ How about Mahalanobis or Bootstrap? I understood that Mahalanobis and Bootstrap help to understand how the distance is not always what it seems. But, how these statistical tools could help me, if the reference product does not meets the minimum dissolution requirements to obtain a biowaiver of the test product?  |
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Relaxation ★ Germany, 2018-01-09 17:20 (2657 d 13:05 ago) @ Mauricio Sampaio Posting: # 18154 Views: 4,384 |
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Dear Mauricio. ❝ How can I proceed with a biowaiver if the reference product does not pass in all conditions of dissolution required to BCS? I think we would need to get some more information about the problem. My guess would be that the reference product does not achieve the pre-set limit of 85% at 15 or 30 minutes, if you say "does not pass"? Could that be right? Well in that case ... its hard to provide a proper advice. Bad luck due to copy-proof galenics? But, from my experience it is worthwhile to conduct a kind of root cause analysis. In BCS there should be no solubility issue (  ), but at first check that a final release of 100% is found. Then conduct experiments under supervision, which means standing next to the apparatus and watch what happens. Sticking? Coning? Clogged basket? ... Nowadays rarely anybody attends the dissolution experiments, but if they do sometimes the information is very important. For example, simple coning may be an issue. Or a capsule being too "resistant". All this can be documented and, well, you may have a rationale, e.g., for increasing the rotational speed of your dissolution test. But you will always have to discuss it and provide a convincing statement, so its hard to provide the one solution here. Best regards, Steven. |
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Mauricio Sampaio ★ Brazil, 2018-01-10 14:59 (2656 d 15:26 ago) @ Relaxation Posting: # 18160 Views: 4,322 |
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Dear Steven ❝ My guess would be that the reference product does not achieve the pre-set limit of 85% at 15 or 30 minutes, if you say "does not pass"? Could that be right? YES!!!! ❝ But you will always have to discuss it and provide a convincing statement, so its hard to provide the one solution here. Thank you for your comments Steven! I think so that a bioequivalence test in vivo is so close to be requested as a second step!  |
Ing. Helmut Schütz