Bioequivalence and Bioavailability Forum

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.