Abstract
In September 2018, the American Association of Pharmaceutical Scientists (AAPS) conducted an Annual Guidance Forum on the considerations related to immunogenicity testing for therapeutic protein products. In addition to a broad representation by the pharmaceutical industry, the event included strong representation by leading scientists from the US Food and Drug Administration (FDA). The agency and industry perspectives and updates to the guidance were presented. Specific topics that were discussed included the strategies of anti-drug antibody (ADA) assay cut-point assessments, the selection of ADA-positive controls (PCs), and the evaluation of PC performance. Assessment strategies and relevance of ADA assay attributes were also discussed, including assay drug tolerance and ADA assay sensitivity. The following is a summary of the discussion.
This is a preview of subscription content, log in via an institution to check access.
References
Mire-Sluis AR, Barrett YC, Devanarayan V, Koren E, Liu H, Maia M, et al. Recommendations for the design and optimization of immunoassays used in the detection of host antibodies against biotechnology products. J Immunol Methods. 2004;289(1–2):1–16.
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. J Pharm Biomed Anal. 2008;48(5):1267–81. https://doi.org/10.1016/j.jpba.2008.09.020.
Koren E, Smith HW, Shores E, Shankar G, Finco-Kent D, Rup B, et al. Recommendations on risk-based strategies for detection and characterization of antibodies against biotechnology products. J Immunol Methods. 2008;333(1–2):1–9. https://doi.org/10.1016/j.jim.2008.01.001.
Committee for Medicinal Products for Human Use C. Guideline on immunogenicity assessment of therapeutic proteins 2017; Available from: https://www.ema.europa.eu/documents/scientific-guideline/guideline-immunogenicity-assessment-therapeutic-proteins-revision-1_en.pdf.
FDA. Immunogenicity testing of therapeutic protein products — developing and validating assays for anti-drug antibody detection. Guidance for industry. U.S. Department of Health and Human Services Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Center for Biologics Evaluation and Research (CBER) 2019 [cited 2019]; January 2019:[Available from: https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm629728.pdf.
Shen M, Dong X, Tsong Y. Statistical evaluation of several methods for cut-point determination of immunogenicity screening assay. J Biopharm Stat. 2015;25(2):269–79. https://doi.org/10.1080/10543406.2014.979196.
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(5):1487–98. https://doi.org/10.1208/s12248-017-0107-3.
Shankar G, Arkin S, Cocea L, Devanarayan V, Kirshner S, Kromminga A, et al. Assessment and reporting of the clinical immunogenicity of therapeutic proteins and peptides-harmonized terminology and tactical recommendations. AAPS J. 2014;16(4):658–73. https://doi.org/10.1208/s12248-014-9599-2.
U.S. Pharmacopeia and the National Formulary General Chapter <1106> Immunogenicity assays—design and validation of immunoassays to detect anti-drug antibodies. 2014.
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
Myler, H., Gorovits, B., Phillips, K. et al. Report on the AAPS Immunogenicity Guidance Forum. AAPS J 21, 55 (2019). https://doi.org/10.1208/s12248-019-0328-8
Received:
Accepted:
Published:
DOI: https://doi.org/10.1208/s12248-019-0328-8