Toward comparability of anti-drug antibody assays: is the amount of anti-drug antibody–reagent complexes at cut-point (CP-ARC) the missing piece?

Abstract

Immunogenicity testing is a mandatory and critical activity during the development of therapeutic proteins. Multiple regulatory guidelines provide clear recommendations on appropriate immunogenicity testing strategies and required bioanalytical assay performances. Unfortunately, it is still generally accepted that a comparison of the immunogenicity of different compounds is not possible due to apparent performance differences of the used bioanalytical methods. In this perspective, we propose the ‘cut-point anti-drug antibody–reagents complex’ (CP-ARC) concept for technical comparability of the bioanalytical methods. The feasibility and implementation in routine assay development is discussed as well as the potential improvement of reporting of bioanalytical immunogenicity data to allow comparison across drugs. Scientific sound comparability of the bioanalytical methods is the first step toward comparability of clinical immunogenicity.