Bioequivalence and Bioavailability Forum

Dear Amalia,

» what I guess I should have clarified is that the reason we are trying to use this justification is because the lower strength is not proportional in terms of excipients.

Okay thanks for the clarification.

Hmm, I think you are in a quagmire here. If the lower strength isn't proportional then you can't go through the Additional Strength Pathway. You can't go through the BCS-Based Biowaiver Pathway either as you mentioned that the API is BCS class II.

» The advise was given by an "external clinical expert".

Okay

» I presume this is why we were advised to follow the solubility path for a biowaiver? That is why we are wondering whether we should perform the solubility tests at the API or the final formulation.

You cannot follow both of the Biowaiver Pathways because of the reasons I mentioned above. If an API is BCS Class II, then it's not eligible for BCS Biowaiver, plain and simple.

But if you think you can perform experiments that will demonstrate the solubility (and permeability) of the API such that it is classified as BCS Class I or III, then be my guest. However you will have to explain to the regulators why you didn't follow he same pathway for the higher strength.

» What do you think?

If you ask me, I'd recommend you conduct an Invivo BE study. The solubility and permeability experiment on the lower strength API is a waste of energy and resources IMHO. But if asked, don't quote me as the "external clinical expert." I'm just me .

Regards,