Bioequivalence and Bioavailability Forum

Dear Ohlbe!

❝ ❝ Again, what’s your rationale of “excluding a standard sample” – calibrators and QCs are prepared in exactly the same way? Both are spiked samples of known concentrations. If you ask for an “excellent and documented analytical reason” to exclude a QC, why do you not require the same for standards? Or do you? To paraphrase your statement:

❝ ❝ Your calibrator is an experimental result […]

❝

❝ True. But calibrators and QCs have a different aim in your run:

❝ - calibrators are used to calculate all concentrations in your run (subject samples and QCs).

ACK.

❝ A problem with a single calibrator will directly and negatively affect all results in the run.

Sidenote: As may a single QC.

❝ And what you're trying to measure is not the back-calculated concentration of your calibrators (which you fundamentally don't care about)…

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. 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?

❝ … but the concentration of your subject samples.

Right, that’s the primary objective.

❝ - QCs are there to monitor the precision and accuracy of your method, as applied to your subject samples. Treating them differently from your subject samples would therefore introduce a bias in that estimation.

I didn’t ask for that. I got the impression that you would treat calibrators and QCs differently.

❝ […] many Agencies unfortunately hate to hear about "PK repeats".

Yes, you know my opinion about that: It’s not only bad science, but in contra­diction to many authorities as well (FDA, HPB/TGD, ANVISA,…). So much about harmonization.

❝ So unless you have a clear analytical reason, you will accept all subject samples in a validated analytical run.

Sure.

❝ The same goes with QC samples…

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

P.S.: Interesting thread.