Bioequivalence and Bioavailability Forum

Hi Helmut,

❝ Nope. Would only work if the true relative BA is exactly (!) 100%. It needs five half-lives to practically* reach steady state (irrespective of the starting level).

If you start at concentration zero, the absolute increase is significant (0 to 100, for example). But if you are already almost at steady state (assuming a small difference in formulations) the absolute value of reaching "true steady state for the second formulation" in the build-up is likely insignificant (96 or 97 or 98 to 100, for example). So, although it's technically/theoretically true that it takes 5 or so half lives to move from 96 or 97 or 98 to 100, it's not really clinically meaningful, is what I was trying to get to initially. But I don't believe a regulator would likely be swayed by this justification, so your point is well taken.

❝ A different case are replicate designs in steady state (scaling as acceptable according to the draft MR GL).

Thanks for the feedback. Something to consider if this "concern" arises again.

Take care and have a nice weekend,
Outlaw