Bioequivalence and Bioavailability Forum

Dear Helmut, dear Raghavendra!

❝ ❝ What happens when the assay percentage of Investigational product

❝ ❝ (between test and reference) is more than 5% in conducting a

❝ ❝ Bioequivalence study?

❝

❝ Not a good idea. See one of my lectures concerning the main

❝ assumptions in BE testing:

❝ AUC = Dose × Fraction absorbed / Clearance

❝ This equation holds for both test ...

❝ ... You are not allowed to perform such a calculation, but be sure

❝ that regulators will!

Helmut, full ACK with your points, especially from the teaching point of view .
But sometimes life is more complicated.
And sometimes even regulators are aware of this .

The EMA guidance states under Point 4.1.8 Evaluation page 13:

"In bioequivalence studies, the pharmacokinetic parameters should in general not be adjusted for differences in assayed content of the test and reference batch. However, in exceptional cases where a reference batch with an assay content differing less than 5% from test product cannot be found (see section 4.1.2) content correction could be accepted. If content correction is to be used, this should be pre-specified in the protocol and justified by inclusion of the results from the assay of the test and reference products in the protocol."