Anti-Drug Antibody (ADA) Assays

Following FDA guidance, ADA assays take a risk-based and tiered approach to evaluating immune responses. Primarily, ADA assays are divided into four phases: screening, confirmatory, titer, and neutralizing. The first two phases are designed to rule out any false-positives; then when a positive is detected the following phases are utilized to determine the amount of ADA and to characterize the ADA’s ability to interfere (neutralize) the therapeutic .

Our Approach: At Xeno Diagnostics, ADA assays are tailored for each different therapeutic. We leverage our assay development expertise to ensure that every condition from buffers, blockers, and more are tailored to maximize binding kinetics for your product while minimizing errant noise.

ADA assays are validated to GLP regulations, and clients are informed at each stage of the process: from assay development and validation through statistical analysis and cut-point determination. Our Assay Development and Validation services are designed to match the regulatory requirement, scientific goal, and budget of each client. 

References:

1. Wang, Y.-M. C. et al. Evaluating and Reporting the Immunogenicity Impacts for Biological Products–a Clinical Pharmacology Perspective. AAPS J. 18, 395–403 (2016).
2. Center for Drug Evaluation and Research. Immunogenicity Assessment for Therapeutic Protein Products. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/immunogenicity-assessment-therapeutic-protein-products (2020).
3. Center for Drug Evaluation and Research. Immunogenicity Testing of Therapeutic Protein Products —Developing and Validating Assays for Anti-Drug Antibody Detection. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/immunogenicity-testing-therapeutic-protein-products-developing-and-validating-assays-anti-drug (2020).
4. Center for Drug Evaluation and Research. Immunogenicity Information in Human Prescription Therapeutic Protein and Select Drug Product Labeling–Content and Format. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/immunogenicity-information-human-prescription-therapeutic-protein-and-select-drug-product-labeling (2025).
5. Gupta, S. et al. Recommendations for the validation of cell-based assays used for the detection of neutralizing antibody immune responses elicited against biological therapeutics. J. Pharm. Biomed. Anal. 55, 878–888 (2011).
6. Shankar, G. et al. Assessment and Reporting of the Clinical Immunogenicity of Therapeutic Proteins and Peptides—Harmonized Terminology and Tactical Recommendations. AAPS J. 16, 658–673 (2014).
7. Shankar, G. et al. Recommendations for the validation of immunoassays used for detection of host antibodies against biotechnology products. J. Pharm. Biomed. Anal. 48, 1267–1281 (2008).
8. Shen, M., Dong, X. & Tsong, Y. Statistical evaluation of several methods for cut-point determination of immunogenicity screening assay. J. Biopharm. Stat. 25, 269–279 (2015).

Related Topics and Assays:

• Immunoassays
• Immunogenicity
• Mixed Lymphocyte Reactions
• IgG and IgM quantification
• Alpha-Gal Assays