Bioequivalence and Bioavailability Forum

We have two IR formulations of Rivaroxaban with 10 mg & 20 mg strengths. Rivaroxan shows drug linearity upto 15 mg dose under fasting condition and shows dose proportionality between 10, 15 and 20 mg dose under fed condition. At higher dose rivaroxaban displays dissolution limited absorption with decrease bioavaibility and decreased absorption with increased dose.
SPC prescribed 10 and 15 mg dose to be administered irrespective of food and for 20 mg strength to be taken with food.

we would like to know for USFDA and EMEA submission, how many bioequivalence studies required.

EMEA; Is their have scope of waiver to lower strength (10 mg) if we conduct only one BE study at higher strength under fed condition (the composition of strengths are quantitatively proportional).

FDA: Apart from fast and fed study at higher strength (20 mg), is their required to conduct BE study for lower strength.

Regards,
Kuldeep Namdev