The premier web-based tool for Robust and Rapid Determination of Immunogenicity Cut Points
**BETA TESTING IS IN PROGRESS**
We are pleased to announce the creation of a web-based tool through the B2S Life Sciences portal for rapid and robust computation of immunogenicity cut points. In addition to determination of Screening (tier 1), confirmation (tier 2) and titer (tier 3) cut points, the menu-driven tool provides statistical estimations of sensitivity, recommendation for low positive controls, drug tolerance, prozone, stability, selectivity, and precision. The new tool is ideal to support validation and In-study cut points for both nonclinical & clinical research.
Offers an intuitive user-interface to guide selections relevant to each analysis. Options are available for screening and titer cut points based on S/N and confirmatory cut points based on percent inhibition.
The user will upload data from a CSV file following B2S’s template. Results are provided in tables and figures along with brief summary report and recommendations.
Statistical methods used for the analyses are consistent with the FDA Guidance for industry (1) and follow the robust procedures recommended by Devanarayan V, et al (2) and Shankar G, et al (3).
Outliers are removed using Tukey’s box-plot method. Normality of the S/N ratio or log-transformed S/N ratio values is evaluated by the Shapiro-Wilk test and includes an evaluation of the skewness coefficient as a relative measure of symmetry.
Screening cut point (SCP) factors are established at the 5% false positive rate. In addition to the screening cut point estimate, the 90% one-sided lower confidence limit (LCL) for the parametric 5% FPER screening cut point factor is computed to assure at least a 5% FPER with a 90% confidence level.
Confirmatory cut point (CCP) values are established at the 1% and 0.1% false positive rates. In addition to the confirmatory cut point, the 80% one-sided LCL for the parametric 1% FPER confirmatory cut point is computed to assure at least a 1% FPER with an 80% confidence level (6).
Titration cut point (TCP) values are established at the 1% and 0.1% false positive rates.
Available Soon – sample analysis module to streamline reporting of results from tiered testing
- US Food and Drug Administration. Guidance for industry: Assay development and validation for immunogenicity testing of therapeutic protein products. 2019.
- Devanarayan V, Smith WC, Brunelle RL, Seger ME, Krug K, and Bowsher, RR. Recommendations for Systematic Statistical Computation of Immunogenicity Cut Points. The AAPS Journal. 2017;19(5):1487-98.
- Shankar G, Devanarayan V, Amaravadi L, Barrett YC, Bowsher R, Finco-Kent D, et al. Recommendations for the validation of immunoassays used for detection of host antibodies against biotechnology products. Journal of Pharmaceutical and Biomedical Analysis. 2008 Dec 15;48(5):1267–81.