Bioequivalence and Bioavailability Forum

Dear Amalia

❝ Basically it is an additional strength biowaiver.

Okay

❝ The molecule is classified as BCS Class II.

Okay. I'll like to point out that BCS classification is irrelevant when following the Additional Strength Biowaiver pathway. What's relevant is to confirm if Invivo Bioequivalence was established for the Highest Strength of your formulation. And that both strengths are in the same proportion in terms of excipients.

❝ However we were advised that considering solely the lowest strength, it is very close to being considered as highly soluble.

Who gave the advice? A Regulatory Agency? A CRO?

❝ As per the Guideline of BE "the drug substance i considered highly soluble if the highest single dose administered as immediate release formulation is completely dissolved in 250ml of buffers within certain pH range". In other words for a highly soluble drug, the dose number (D0) is equal or lower than 1.

Again I'll reiterate that solubility of the drug substance is irrelevant. See above.

❝ Therefore, my question here is whether the solubility test should be done at the API or the final formulation (lowest strength) in order to support a biowaiver for the lowest stength.

Following the Additional Strength Biowaivers pathway, you don't need to perform solubility test for the API. what you do is to perform a comparative dissolution profile study for your low strength formulation against the high strength formulation after you've ensured that the requirements I stated above have been met.

❝ I hope I have not confused you more!

Lol, I think not. I hope i haven't confused you as well.

Regards,