Statistical methods and tool for cut point analysis in immunogenicity assays.

Administration of biopharmaceutical products can generate immune response that may severely impact the safety or efficacy of the products. Immunogenicity evaluation, required by regulatory agencies, relies on well developed and validated assays. Key to such assay development is the determination of a cut point during assay validation. Although many methods have been suggested in literature, they are either too complicated to be of practical use by scientists without ready assistance of statisticians or lacking statistical justification. In this paper, we discuss statistical considerations on cut point analysis in immunogenicity assay validation, with a focus on data normalization, outlier detection, and cut point calculation. Also provided is a statistical procedure for cut point determination which maintains a good balance between statistical rigor and implementation simplicity. To facilitate the implementation of the procedure, a software tool is developed, using R language, to automate the proposed process. Taken together the proposed approach renders scientists a practical guide for cut point determination.