Bioequivalence and Bioavailability Forum

Hi Samar,

❝ 1. Is there a limit for Upper/Lower ratio for setting the range?.

As far as I know there's no such requirement, at least not in the guidelines that I know of.

But just for my curiosity, why do you want to set limit for U/L ratio?

Usually, upper limit should be determined based on information of expected Cmax of your product. Consider the variability of Cmax (do not use the reported mean Cmax from literature) when choosing the suitable upper limit. I would choose at least mean + 2sd, preferably mean+3sd, as upper limit.

As for lower limit, minimum requirement is <5% of Cmax though personally I usually choose a bit lower than that. In this case, the Cmax I prefer is mean-3sd.

Also, I'd check various sources for a better idea of what the "expected maximum concentration" will be. For the same strength and formulation, you might be surprised to find very different Cmax in different sources.

❝ 2. Should we consider the Linear Model as the simplist regression method?

Again, I don't think there's guidance requiring only linear model, though the simplest method is preferable. I vaguely recall there's certain guideline mentioned that if the simpler model is ok, then you should not use more complicated model. If you cannot find linear model in the minimum range as mentioned above, I think other model is OK.

Let's see if other members have different opinion.