Bioequivalence and Bioavailability Forum

Dear bjkim97!

The EMA allows widening of the BE acceptance limits based on the CVintra of the Reference according to the formula

[U, L] = exp [±k·sWR] with k=0.760
sWR = sqrt(log(1.0 + CV^2)) with CV is given ratio

This widening is allowed for Cmax only and if CVintra_R>30%.
If CVintra_R≤30% the usual acceptance limits 80 ... 125% apply.
If CVintra_R>50% a cap is imposed on the BE limits and they are held at 69.84 ... 143.19%, the values for CVintra_R=50%.

That was what I'm talking about in stating "widest acceptance range allowed in the EMA guidance".

An additional requirement for scaled ABE is the constraint to the point estimate (ratio T/R) to be within the range 80.00 ... 125.00%.

Hope this helps against confusion.

BTW: Such a cap is not imposed in the FDA approach