ABSTRACT
As demonstrated in the previous chapter, the key assay performance parameters during assay validation are the cut points for screening, confirmatory, and neutralizing assays. Due to the product-, process-, and patient-related factors that can contribute to the variability of immunogenicity data, determination of cut point is not straightforward. According to regulatory guidances and white papers FDA (2009), USP<1106>, and Shankar et al. (2008), cut points should be statistically derived from data generated during pre-study validation. According to Shankar et al. (2008), for the screening assay validation, typically 50 samples are needed for the screening cut point determination. The experimental design for the establishment of cut point is described in section 3.2. In section 3.3, statistical details for the determination of cut points are introduced, with an emphasis on screening cut point determination. The “white
paper” approach by Shankar et al. (2008) will be introduced followed by some recent advancements in research community on cut point determination.
