Bioequivalence and Bioavailability Forum

Dear Vijay!

❝ 4. Finally, I may be totally naïve in asking this question but I still need to clarify . Does one use the actual AUC and Cmax parameters or the dose normalized AUC and Cmax parameters while assessing bioequivalence.

The former.

❝ Is there any difference?

The definition of bioequivalence (for different wordings see the Guidelines) includes the same molar dose giving the same rate and extent of bioavailability.

❝ If we consider a scenario where a lesser dose of a new formulation (say 7.5 mg) is being tested against an old formulation (say 10mg), then we do not need to dose normalize on the presumption that the new formulation is designed to perform as good as theold formulation but with a lesser dose due to better bioavailability.

Wonderful, that’s an improvement! The technical term is “Suprabioavailability” (see the EMEA’s NfG Section 5.5). If you succeed, most likely you have to run additionally a (small) clinical study to show safety/efficacy as well. IIRC, an example was glibenclamide, where a formulation of 3.5 mg with micronized particles gave a similar BA as the conventional formulation with 5 mg.