Free analyte QC concept: a novel approach to prove correct quantification of free therapeutic protein drug/biomarker concentrations.

Quantification of free drug concentrations is highly challenging due to the dynamic drug-ligand equilibrium, which may result in incorrect results. Current QC concepts do not adequately cover all of the important influencing factors: the assay itself (format and procedure); the calibration concept; the sample preparation; and the sample storage. Here, we propose a 'free analyte QC concept' that enables quantitative testing of these four factors and, thus, provides best possible proof of correct free drug quantification. The principle of the free analyte QC concept and an example of its application for a free drug assay is described. A comparison of this novel approach with current approaches and how the new concept fits (or does not fit) with current regulatory guidelines is discussed.