Bioequivalence and Bioavailability Forum

Hello AB,

❝ how can we calculate the sample size for the bioequivalence studies which require clinical endpoints especially Gel & cream formulations.

Depends on what your design is.
If the product is absorbed to the blood stream and acting thereafter then ordinary PK considerations usually apply.
If the product is locally acting then you face challenges for submission in several territories, e.g. EU, US.

❝ where do we get the information on the variability and other parameters like mean difference values of test and reference etc. required to calculate sample size.

Forget about this. You may be able to look up something but it is not necessarily applicable to your formulation. These things sometimes work completely different from ordinary tablet generics where a CV often can be reliably looked up by FOI, SPCs, Prescr. info or publications. Several companies fail here because they trust something found in the literature. It adds "50% risk"

❝ what are the formulas & softwares usually used?

You did not name your API, and the required design could imply anything from a PD endpoint with 12-week dosing in two arm to to a four-point bioassay with single dose. For inspiration, try and look up vasoconstrictor assays (topical corticosteroids), FDA's clindamycin guidance, or try to have a look at relative potency and bioassay approaches in EU and US. DEpending on your API this may very well go very much beyond the formulae you know from ordinary equivalence by PK.

❝ Do we have to do a pilot study to estimate the parameters, if so how may subjects should be considered in pilot study?

This will be guess-working because you really don't know anything about the in vivo properties of your formulation prior to the study. Pilot studies with less than 20-24 subjects are not often too useful.

Good luck.