Bioequivalence and Bioavailability Forum

Hi Chirag!

❝ We are planning to conduct a reference - replicate design study as per USFDA requirements for submission to Health Canada.

Already knowing differences in regulatory requirements what’s the point to plan a study according to country A’s guidance(s) for submission to country B?

Canada currently does not accept reference-scaling for HVDs/HVDPs – which is the main purpose of replicate designs. If you want to submit the study later on to the FDA as well you can use a replicate design (Health Canada TPD guidance Section 2.3.1)

Replicated cross-over designs may also be used, where the formulations are tested more than once in the same subjects.

and evaluate it by conventional (unscaled) ABE. Make sure to power the study for Canada’s requirements: 90% CI of AUC within 80-125%, PE of C_max within 80–125% (see also this thread).