Calibrators have a known concentration of analyte which has to be defined by the manufacturer of that calibrator. There are multiple ways that manufacturers identify appropriate calibrator set points.
This process may involve testing new calibrator lots as unknowns using a previously established set of calibrators. The process could also involve the gravimetric addition of the analyte of interest to an analyte-deficient matrix in which the set points are defined by the weight of the analyte added divided by the volume of matrix.
Verification of proper calibrator set points can involve using the newly set calibrators to test proficiency material, other assay standards, or even NIST traceable standards. If verification passes pre-established analytical criteria, the calibrator set points can be released for that lot of calibrator.
These same techniques can apply to Laboratory Developed Tests (LDTs) that individual laboratories create, such as laboratory-prepared calibrator material that is sent to a reference laboratory for quantitation.
Ultimately, all calibration materials are themselves made from other calibrators or materials with known concentrations. Following best practice, every 'calibrated calibrator' should be traceable back to a precisely-defined standard reference material.
