Bioequivalence and Bioavailability Forum

❝ 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 […]

• calibrators are used to calculate all concentrations in your run (subject samples and QCs). A problem with a single calibrator will directly and negatively affect all results in the run. And what you're trying to measure is not the back-calculated concentration of your calibrators (which you fundamentally don't care about) but the concentration of your subject samples.
  
• 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. You don't have an expected concentration for subject samples, you don't do any outlier test or whatever on them, and many Agencies unfortunately hate to hear about "PK repeats". So unless you have a clear analytical reason, you will accept all subject samples in a validated analytical run. The same goes with QC samples...