Enhancing efficiency and quality of statistical estimation of immunogenicity assay cut points through standardization and automation

•A web-based customized assay statistical tool (CAST) is developed to automate statistical analysis for anti-drug antibody assays.•CAST provides a tool to assess assay cut point at a click of the button during validation and in-study sample analysis.•CAST takes into account multiple assay factors in cut point analysis for various experimental designs.•Prediction limit approach, along with automated outlier detection and data transformation, is utilized to compute cut point.•Equivalence evaluation is applied to assess the need for a group-specific cut point.

Biotherapeutics can elicit immune responses, which can alter the exposure, safety, and efficacy of the therapeutics. A well-designed and robust bioanalytical method is critical for the detection and characterization of relevant anti-drug antibody (ADA) and the success of an immunogenicity study. As a fundamental criterion in immunogenicity testing, assay cut points need to be statistically established with a risk-based approach to reduce subjectivity. This manuscript describes the development of a validated, web-based, multi-tier customized assay statistical tool (CAST) for assessing cut points of ADA assays. The tool provides an intuitive web interface that allows users to import experimental data generated from a standardized experimental design, select the assay factors, run the standardized analysis algorithms, and generate tables, figures, and listings (TFL). It allows bioanalytical scientists to perform complex statistical analysis at a click of the button to produce reliable assay parameters in support of immunogenicity studies.