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Clinical Immunogenicity Risk Assessment Strategy for a Low Risk Monoclonal Antibody

  • Review Article
  • Theme: Compendium of Immunogenicity Risk Assessments: an Industry Guidance Built on Experience and Published Work
  • Published:
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Abstract

This article provides a theoretical case-study risk assessment report for a low-risk monoclonal antibody (mAb) therapeutic. In terms of risk, there are considerations around risks to safety, but also risks regarding effects on pharmacokinetics (PK), pharmacodynamics (PD), and efficacy. Much of the discussion in this document is around the risk of immunogenicity incidence. A higher incidence of immunogenicity would necessitate a detailed review of the PK, efficacy and safety in anti-drug antibody (ADA) positive and ADA negative subjects, in order to evaluate potential effects. The publication is intended to provide a framework of some the current thought processes around assessing immunogenicity risk and for building strategies to mitigate those risks. For this example, we have created a hypothetical antibody, ABC-123, targeting a membrane protein on antigen presenting cells, for the treatment of rheumatoid arthritis (RA). This hypothetical antibody therapeutic is provided as an example for the purposes of risk assessment for a low risk molecule, although any application of similar approach would be case by case.

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Author information

Author notes

  1. Robert Kernstock and Gizette Sperinde contributed equally to this work.

Authors and Affiliations

  1. Immunochemistry Department, PPD Laboratories, Richmond, VA, USA

    Robert Kernstock

  2. BioAnalytical Sciences, Genentech, Inc., South San Francisco, CA, USA

    Gizette Sperinde

  3. Deborah Finco Consulting, LLC, Groton, CT, USA

    Deborah Finco

  4. CSL Innovation Pty. Ltd., Melbourne, Australia

    Roslyn Davis

  5. Predictive and Clinical Immunogenicity, Merck & Co., Inc., West Point, PA, USA

    Diana Montgomery

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  1. Robert Kernstock
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  2. Gizette Sperinde
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  3. Deborah Finco
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  4. Roslyn Davis
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  5. Diana Montgomery
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Correspondence to Diana Montgomery.

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Kernstock, R., Sperinde, G., Finco, D. et al. Clinical Immunogenicity Risk Assessment Strategy for a Low Risk Monoclonal Antibody. AAPS J 22, 60 (2020). https://doi.org/10.1208/s12248-020-00440-5

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