Challenges in developing antidrug antibody screening assays.

Robert Dodge is the Laboratory Director for Immunochemistry and Cell Biology at Taylor Technology, a Pharmanet company in Princeton, NJ, USA. Taylor Technology is a contract research laboratory specializing in assay development and sample testing in a good laboratory practice environment. Robert oversees a staff of scientists responsible for the development of assays for use in protein drug quantitation, antidrug antibody screening and biomarker detection. Protein drugs may elicit an immune response in the form of production of antidrug antibodies (ADAs) by a subject. This ADA response may have serious safety implications for subjects or, at a minimum, may affect drug efficacy. Bioanalytical testing for antidrug antibodies has therefore become a required part of safety testing for subjects receiving protein drugs. Regulatory guidance and scientific white papers recommend a tiered approach for bioanalytical ADA testing. The first assay in the tiered testing scheme is a screening assay, which tests all subjects in the study for the presence of ADAs. The screening assay is quasiquantitative, typically lacks a specific positive control and must be designed to detect numerous isotypes and subclasses of antibodies. These characteristics of an ADA screening assay differ from a those of a standard immunoassay designed to quantitate a specific protein in matrix and thus present unique challenges. This article reviews the unique challenges encountered during the development of an ADA assay.