Bioequivalence and Bioavailability Forum

Dear Helmut, hi ElMaestro,

❝ THX for your explanation (especially the lucid last sentence).

THX from me too .

❝ I was puzzled by the “appropriate sample size calculation” [sic] in 4.1.3. If there are no safety issues I don’t see a reason why not any Xover BE study could be performed in a replicate design.¹ Sometimes the clinical capacity might come into play.²

Beside the statement of our Capt'n I see also no reason why not.

IMHO "... replicate designs e.g. for substances with highly variable pharmacokinetic characteristics ..." doesn't mean only for that example. And if even the Spanish agreed - why to worry? Paranoia after all the bizarrness or curiosities known from regulatory bodies like this last one?

With the advent of PowerTOST every body has the ability to do an "appropriate sample size estimation (!)" for nearly all designs imaginable in BE studies. Thus choose the design which best fit your needs and go on. You can't protect yourself against regulatory curiosities.