Bioequivalence and Bioavailability Forum

Dear Members,

I have one query regarding Biowaiver criteria of fixed combination product to be marketed in Europe.
How we can apply General Biowaiver criteria for lower strengths if composition of the strengths are not quantitatively proportional. i.e. fixed combination product containing two active ingredients (A/B = 10/80mg & 5/80mg) one with quantity less than 5% (A) and other having more than 5%(B) and is a bilayer tablet.

The following general requirements are met
a)the pharmaceutical products are manufactured by the same manufacturing process,
b)the qualitative composition of the different strengths is the same,
c) the amount of A is less than 5 % of the tablet core weight \ layer
d) the amounts of the different core excipients (layer) are the same for the concerned strengths and only the amount of active substance (A) is changed.

ЕМА:"The conditions regarding proportional composition should be fulfilled for all active substances of fixed combinations. When considering the amount of each active substance in a fixed combination the other active substance(s) can be considered as excipients. In the case of bilayer tablets, each layer may be considered independently"


I would be very grateful for any information and regulatory experience, concerning whether this is enough to cover regulatory requirements for waiving 5/80 mg strength.

Best regards, Yassen