Bioequivalence and Bioavailability Forum

Dear rafimmc!

❝ Can we expect a multiple dose study with 64 subjects to give lesser

❝ variablity ...

Yes, you are right.
There are just a few examples were variability in steady state was not lower than after a single dose.

❝ ... and thus increasing the chances of demonstrating bioequivalence?

No. Multiple dose studies to decrease variability were suggested at the BioInternational Conference 1992; although common practice (EU, Australia,...) for many years, according to current practice single dose studies are mandatory because of their higher discriminatory power (especially for C_max).
I've seen many deficiency letters in the last years where sponsors were asked for single dose BE after submitting MD only. These sponsors are in the uncomfortable situation, that they have forseen problems - if not infeasibility - in demonstrating BE in single dose; seeking help in MD now they are pushed back to start...