Bioequivalence and Bioavailability Forum

Dear Helmut,

❝ Sidenote: As may a single QC.

Yes, sure

❝ I’m interested in the back-calculated concentrations as well. OK, to be more precise, to check the residuals (haha, is the applied weighting scheme of the curve appropriate as established in validation). I have to back-calculate concentrations first, in order to be able to exclude a point.

OK, agreed, of course. But that's not the primary goal of the study.

❝ Again, would you allow that without justification (in my limited experience FDA does), or would you like to see the same justifications you required for QCs?

Yes, I would accept the exclusion of a calibration sample without any "assignable cause", as the FDA would put it.

❝ I got the impression that you would treat calibrators and QCs differently.

I do. I accept calibrators to be excluded from the calibration curve without an "assignable cause", if they are more than 15 % from nominal (20 % at the LLOQ). The back-calculated concentration should be reported in the analytical report even if excluded (clearly identified as excluded), but I don't mind if it is not included in the calculation of the precision and accuracy of the results at each level of concentration (actually I don't mind if the mean and CV of the back-calculated concentration of the calibrators at each level of concentration are not calculated at all - that's not really relevant). But I do consider that all QCs should be included in the calculations, unless you had a true analytical problem (in which case I would not expect the result to be reported at all).

❝ ❝ The same goes with QC samples…

❝

❝ What do you mean by this? Sounds like an oxymoron to me.

Once again: I treat QCs the same way as unknown samples. Report them all unless you had a clear analytical problem, include them all into calculations, no exclusion from the report, or they won't be representative any more.

❝ P.S.: Interesting thread.

Yes

Best regards
Ohlbe