Bioequivalence and Bioavailability Forum

Hi Helmut,

❝ By “much more” you mean that the 90% CI is entirely outside the 80-125% limits, right?

Not necessarily. Yesterday when I was asking the question I was thinking about 90% CI partially out, e.g., T fed/T fasting is 60%--85%, and R fed/R fasting is 115%--130%. So food increase the reference but decrease the test absorption. Or vice versa.

But what if 90% CIs are within 80%--125%? e.g., T fed/T fasting 80.1%--90% (which is statistically significant different but is BE) and R fed/R fast about 115%--124% (similarly, there's statistically significant difference but is BE), or vice versa. Clearly, food effect is huge and there's something wrong here...

Of course, this is just pure speculation. I'm not even sure if the scenario is remotely possible given that T fed/R fed and T fast/R fast are assumed within 80%--125% ...

❝ Everything else (CI overlapping the limits) is indecisive and would not worry me.

If the scenario above is possible, I would worry about it... But again, maybe it's just my silliness. I cannot think straight right now.

❝ Nil – also for the “nice” case. Though the EMA stated in various conferences to welcome such a hybrid application, I haven’t seen one so far. Any experience from the members?

Yes, let's hear other opinion/experience.