Bioequivalence and Bioavailability Forum

Hi Hiren,

❝ ❝ are you aware of FDA’s guidance?

❝

❝ Yes I saw that but since it is still in draft phase (old-2006) wanted to confirm with practical experience

Didn’t you bother following the link? The guidance is from February 2012. Practically the FDA does not distinguish between drafts and final versions.

❝ ❝ ❝ 4. Since all the three products are developed by us on the same platform, we can assume zero / minimal variability associated with formulation difference.

❝ ❝

❝ We are sure that there shall be no/very less variability due to formulation as all the three products are manufactured by us on same platform with same excipients/process/manufacturing location, which is not the case in BE study as Test and reference product are based on different platforms/manufacturing process/location etc. Hence we want to remove this variability part from total variability while calculating sample size.

Please don’t mix up variability with the expected deviations of test from references. F.i. in line extensions I generally assume a ratio of 1 – and not ±5%. The problem here is that DDI depend mainly on the properties of the active moieties, not the formulations. Do you have any hints (in vitro cocktail studies, PK/PD, …) suggesting that you should not expect a relevant interaction?

❝ ❝ ❝ Is there any method to calculate the sample size based on true intrinsic variability of molecule only? This can reduce our sample size to some extent.

❝ ❝ Doesn’t make sense. You administer formulations, not the APIs in solution.

❝ Explained above

Nope.