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Marcel ★ 2011-03-30 15:57 (5570 d 02:39 ago) Posting: # 6835 Views: 4,422 |
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Good afternoon, Can the "absorption/permiability" section of a BCS biowaiver application through the EMA be supported solely on a literature review (ie. information past data exclusivity or part of the public domain)? For example, if the proper studies (mass balance and/or bioavailability) have been published, do you think these can be used to circumvent doing your own BA study or even Caco-2 cells studies? This is assuming that the excipients are the same between formulations and/or those that differ don't affect absorption. Any input from those experienced with this is greatly appreciated. Marcel |
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Helmut ★★★   Vienna, Austria, 2011-03-30 16:43 (5570 d 01:54 ago) @ Marcel Posting: # 6837 Views: 3,910 |
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Hi Marcel! Definitely yes. From a presentation by Henrike Potthast (BfArM) at last year’s EGA-workshop:
Generally, sound peer-reviewed literature may be acceptable for known compounds to describe the drug substance characteristics of importance for the biowaiver concept. — 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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Marcel ★ 2011-03-30 18:02 (5570 d 00:34 ago) @ Helmut Posting: # 6840 Views: 3,746 |
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Hi Helmut, That's a pretty succinct and direct response. Thanks for the info and the link. Have a great day. |
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Dr_Dan ★★ Germany, 2011-03-31 15:13 (5569 d 03:24 ago) @ Helmut Posting: # 6843 Views: 3,699 |
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Hi Helmut do not rely on Henrike Potthast's (BfArM) words! She tends to forget what she said. Regarding complete absorption she points out in our BE BCS I waiver submission that even if you show 100% Bioavailability this will not support the waiver as long as the drug is not stable over the whole pH range. Kind regards Dan — Kind regards and have a nice day Dr_Dan |
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Marcel ★ 2011-04-11 14:10 (5558 d 04:27 ago) @ Dr_Dan Posting: # 6886 Views: 3,509 |
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❝ Regarding complete absorption she points out in our BE BCS I waiver submission that even if you show 100% Bioavailability this will not support the waiver as long as the drug is not stable over the whole pH range. Hi Dan, What do you mean by "not stable over the whole pH range." Are you talking about standard stability studies? Solubility profiles? Dissolution profiles? etc. Can you elaborate? Thanks, Marcel |
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Dr_Dan ★★ Germany, 2011-04-11 17:07 (5558 d 01:29 ago) @ Marcel Posting: # 6887 Views: 3,492 |
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Hi Marcel, I am talking about the drug properties. For example in dissolution tests some pro-drugs degrade at higher pH and convert into the active metabolite. However, the guideline CPMP/EWP/QWP/1401/98 Rev.1 does not demand that active substances have to be stable at the required pH range. Regards Dan — Kind regards and have a nice day Dr_Dan |
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Marcel ★ 2011-04-13 12:56 (5556 d 05:41 ago) @ Dr_Dan Posting: # 6892 Views: 3,492 |
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Got you. Thank you. |
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CLR ☆ Singapore, 2011-04-07 06:46 (5562 d 11:51 ago) @ Helmut Posting: # 6866 Views: 3,581 |
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Hi Helmut, The statement you refer to in the EMA guideline struck me as being somewhat vague. Would the FIP Biowaiver monographs suffice wrt the permeability requirements? Also, in your experience, how widely used are these monographs towards BCS-based biowaiver applications and what is your feeling about the success rates? It is often said that regulators have to strike a balance between being stringent about the reliability of the evidence, while not strangling the industry!  I like the EMA's stand of allowing literature sources but it would be nice to know what kind of evidence is being presented in the successful applications so that others may follow suit. We do all like to be part of the flock  — Best regards, Clare |
Ing. Helmut Schütz