Bioequivalence and Bioavailability Forum

Hi Jay,

❝ Any idea about which truncation point to be considered for pAUC?

Until the GL gets finalized, we are fishing in foul water. The FDA clearly prefers a clinical justification (based on PD), whereas the EMA seems to prefer PK. However, in my studies I succeeded with the former. As said before, go for a [e]scientific[/e] regulatory advice. Carry clinical data as ammunition with you. Don’t simply ask them. One company doing so went back home from London with AUC_0–2 for methlyphenidate in their backpack.

❝ As pAUC is considered to be more variable as compared to Cmax and AUC.

Likely.

❝ Thus should Sample Size be considered accourdingly?

Sure. You have to show BE for pAUC as well.

❝ […] more subjects may be required.

Yes.

❝ […] for pAUC which literature should we consider for calculation of Sample Size?

The only published data on pAUCs are for methlyphenidate and zolpidem. I’m afraid you have to perform a pilot study – if you assume high variability, in a replicate design.