Abstract
After tier 1 and 2 cut points for anti-drug antibody (ADA) assays are derived during pre-study assay validation in a population, there is a need to verify the continued appropriateness of the previously derived cut points during sample analysis in the same or different populations, per FDA guidance (US HHS, FDA, CDER, CBER, 2019). Proper sample size–dependent criteria with statistical underpinning were derived and presented in this technical note to aid in assessing the appropriateness of tier 1 and tier 2 cut points, respectively.
References
US HHS, FDA, CDER, CBER Immunogenicity testing of therapeutic protein products—developing and validating assays for anti-drug antibody detection, Guidance for Industry, January 2019, page 28. https://www.fda.gov/media/119788/download
Devanarayan V, Smith WC, Brunelle RL, Seger ME, Krug K, Bowsher RR. Recommendations for systematic statistical computation of immunogenicity cut points. AAPS J. 2017;19:1487–98. https://doi.org/10.1208/s12248-017-0107-3.
Amaravadi L, et al. White paper on recent issues in bioanalysis: focus on new technologies and biomarkers (part 3--LBA, biomarkers and immunogenicity). Bioanalysis. 2015;7(24):3107–24. https://doi.org/10.4155/bio.15.226.
Song S, Yang L, Trepicchio WL, Wyant T. Understanding the supersensitive anti-drug antibody assay: unexpected high anti-drug antibody incidence and its clinical relevance. J Immunol Res. 2016. https://doi.org/10.1155/2016/3072586.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Tan, C.Y., Steeno, G.S., You, Z. et al. Criteria to Reevaluate Anti-drug Antibody Assay Cut Point Suitability in the Target Population. AAPS J 22, 19 (2020). https://doi.org/10.1208/s12248-019-0400-4
Received:
Accepted:
Published:
DOI: https://doi.org/10.1208/s12248-019-0400-4