Bioequivalence and Bioavailability Forum • Bioequivalence concluded only in AUC

Brus
★

Spain,
2026-02-25 14:39
(98 d 14:09 ago)

Posting: # 24578
Views: 1,167

Bioequivalence concluded only in AUC [Regulatives / Guidelines]

Dear All,

I have one product (NDA approved) and now I want to develop a new pharmaceutical form of the same, as a extension line. But the new pharmaceutical form is expected to have a higher bioavailability, so a strength reduction will be proposed in order to find the dose which match with the previous formulation in terms of exposure.

But since the exposure change between formulation is not proportional (i.e. 25% change in Cmax and 90% in AUC), and dose adjustement to achieve at the same time both parameters near to T/R ratio of 100% is not possible. So, a way proposed is to select the dose to obtain the AUC T/R ratio of 100% and to justify the no relevance of Cmax for efficacy and the high relevance of AUC.

Has anyone had experience with a similar case?

What do you think?

Thank you so much

Best regards,

dshah
★★

India,
2026-02-26 09:44
(97 d 19:03 ago)

@ Brus
Posting: # 24579
Views: 975

Bioequivalence concluded only in AUC

Post reply

Hi Brus!

❝ But since the exposure change between formulation is not proportional (i.e. 25% change in Cmax and 90% in AUC), and dose adjustement to achieve at the same time both parameters near to T/R ratio of 100% is not possible. So, a way proposed is to select the dose to obtain the AUC T/R ratio of 100% and to justify the no relevance of Cmax for efficacy and the high relevance of AUC.

This is an interesting one. As a NDA holder, if you have already proved PK-PD relationship using AUC, then it could be advantageous.

Generally this approach is considered safe for regulatory application and lot of cases can be found in history for this. Even IR vs MR also mainly focuses on AUC and not Cmax.

Hope this helps.

Divyen