Clinical immunogenicity specificity assessments: a platform evaluation.

Immunogenicity assessment is an integral part of the evaluation of the safety and efficacy for protein therapeutics during drug development, and is required by the regulatory authorities. A tiered strategy is typically utilized to assess immunogenicity and is often comprised of a screening method, a confirmation/specificity step and a characterization step. To ensure methods with appropriate sensitivity are utilized, the threshold for screening assays is set to minimize false negatives resulting in a certain rate of false positivity. The confirmatory step is critical for determining assay specificity and eliminating false positives identified in the screening assay. Using a widely implemented technology and bridging assay format commonly used for immunogenicity assessments, unacceptably poor specificity was observed for the confirmatory/specificity step for a subset of monoclonal antibodies in our group. Therefore, we believe that this challenge will be relevant to others in the field. In this paper, we will describe our challenges with one of these antibodies, monoclonal antibody therapeutic X (rhuMAb X). This paper presents extensive evaluation of two technology platforms and various conditions to evaluate and provide solutions to improving the assay specificity in the immunogenicity assessment of antibody therapeutics.