Posting: # 19548
I have already googled around the web but couldn't find any answers thus I'll see if anyone can help here!
ICH M9 draft guidance states that “BCS-based biowaivers are applicable to drug products where the drug substance(s) (thus APIs) in test and reference products are identical (e.g. same salt, ester, isomer or mixture of isomers from that in the reference product).
My question now is, what about different API doses/amount between test and reference though?
More specifically our test product contains the exact double amount of APIs (both BCS Class I drugs) of the reference product (1000/130mg of paracetamol/caffeine TEST vs 500/65mg REFERENCE).
Given the API amount difference between T and R do you think a BCS based biowaiver application would still be applicable?
Thanks a lot in advance for the great support
Posting: # 19560
» Given the API amount difference between T and R do you think a BCS based biowaiver application would still be applicable?
No I don't think so. This is because they are not pharmaceutically equivalent.
This is even stated on the draft ICH M9 Guideline that you referenced. It can be found on lines 121 - 124 where eligibility for BCS based Biowaivers was discussed. Here's the excerpt:
A drug product is eligible for a BCS-based biowaiver provided that the drug substance(s) satisfy the criteria regarding solubility and permeability (BCS Class I and III), the drug product is an immediate-release oral dosage form with systemic action, and the drug product is a dosage form that is pharmaceutically equivalent to the reference product
For two products to be pharmaceutically equivalent, they must be of the same amount. I think some regulatory authorities allow a difference of 5% in the amount. But for 100% difference, no way.
The route you can go would be multiple strength biowaiver. However you have to check that the excipients are in the same proportion with the actives.
Posting: # 19565
thanks a lot for clarifying it this was really helpful!