Sensitivity and Drug Tolerance of Antidrug Antibody Assays in Relation to Positive Control Characteristics

Abstract

Assay sensitivity and drug tolerance as studied here, are likely driven by multiple factors such as cut point confidence level, stoichiometry of PC-drug complexes and presentation of epitopes.

Toward Comparability of Anti-Drug Antibody Assays: Is the Amount of Anti-Drug Antibody–Reagent Complexes at Cut-Point (CP-ARC) the Missing Piece?

“…The apparent assay performance parameters especially assay sensitivity and also drug tolerance, depend on the used ADA-positive control [13], which can have different binding properties. There are a few studies reporting the impact of differences in ADA affinity on assay sensitivity on different technology platforms [7,[14][15][16][17][18]. The difficulties in understanding and interpretation of assay results is discussed in the scientific community [19], most notably the potential overestimation of the sensitivity due to use of high affinity ADA-positive controls [4,5].…”

“…The critical role of the binding kinetic properties of the used ADA-positive control for assay development and validation is well understood [7,8,[14][15][16][17]. Egging et al performed a detailed investigation into the correlation of apparent assay sensitivity and drug tolerance in relation to the binding properties of the ADA-positive control antibody preparation [14]. However, in contrast to the theory that this is the key to understand ADA assay performance, no relation between affinity of the positive control and sensitivity or drug tolerance was found in this study.…”