Bioequivalence and Bioavailability Forum

Hi Ratnakar,

❝ ❝ Guidelines require the actual time, not the scheduled one.

❝ I know it has been mentioned in the EMA guideline but could not locate in any of the FDA guideline.

Well, FDA’s guidance is from 2003. Expect assessors to look beyond their own nose.

❝ ❝ Why not calculate AUC₇₂ for both? […]

❝ Is the use of partial area, the best solution for the truncated study?

IMHO, yes. See also the discussion in WHO’s GL, Section 6.11.4. See also this post and follow the linked posts within.

❝ If yes, what about the non truncated study having primary PK parameters as Cmax and AUCt, where samples up to 36 hrs were collected, but in 20 % of the subjects last measurable concentration appeared at 18 hrs (in fact in couple of subject it was only 8 hrs) and majority of the subjects got measurable concentration at 24 hrs and again few subjects got concentration at 36 hrs post dose.

Good question, next question. Note that “t” is defined as the time point of the last quantifiable concentration. Your primary metric is not AUC₃₆. But it’s true that missing values / <LLOQ will also lead to “apples-and-oranges” (old story). BTW, have you ever seen in a steady-state study Phoenix/WinNonlin reporting AUClast ≠ AUCtau? If yes, can you guess why?

❝ I can very well implement your suggestion of the partial area, provided it is the best approach for truncated study.

I’m using it for a couple of years now and like Sam never received a deficieny letter. I always described the method in great detail in the protocol (even a plot similar to that one) and don’t hide it in an SOP.

Don’t forget to give it a nice label. Shines the output.