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Mauricio Sampaio
Regular

Brazil,
2018-01-08 19:59

Posting: # 18150
Views: 1,680
 

 If the reference product does not pass in BCS ?? [Dissolution / BCS / IVIVC]

How can I proceed with a biowaiver if the reference product does not pass in all conditions of dissolution required to BCS?
ElMaestro
Hero

Denmark,
2018-01-09 05:35

@ Mauricio Sampaio
Posting: # 18151
Views: 1,461
 

 If the reference product does not pass in BCS ??

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?

if (3) 4

Best regards,
ElMaestro

"(...) targeted cancer therapies will benefit fewer than 2 percent of the cancer patients they’re aimed at. That reality is often lost on consumers, who are being fed a steady diet of winning anecdotes about miracle cures." New York Times (ed.), June 9, 2018.
Mauricio Sampaio
Regular

Brazil,
2018-01-10 13:52

@ ElMaestro
Posting: # 18159
Views: 1,337
 

 If the reference product does not pass in BCS ??

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?:confused:
Relaxation
Junior

Germany,
2018-01-09 16:20

@ Mauricio Sampaio
Posting: # 18154
Views: 1,414
 

 If the reference product does not pass in BCS ??

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 (:-D), 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.
Mauricio Sampaio
Regular

Brazil,
2018-01-10 13:59

@ Relaxation
Posting: # 18160
Views: 1,355
 

 If the reference product does not pass in BCS ??

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!!!!:-D

» 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!:crying:
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