Bioequivalence and Bioavailability Forum

Hi Outlaw,

❝ […] 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.

See the plot I added to my previous post in the meantime. Ratios of 0.5 or 2 are extreme, but the bias for e.g., ±30% (which we commonly see) would be still substantial.

❝ ❝ 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.

It will. C_min is mandatory and – especially if you only have limited accumulation – it might be variable as hell. See also this post about EMA’s current thinking on SD/MD.