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Survey Outcome on Immunogenicity Risk Assessment Tools for Biotherapeutics: an Insight into Consensus on Methods, Application, and Utility in Drug Development

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Abstract

A survey conducted by the Therapeutic Product Immunogenicity (TPI) community within the American Association of Pharmaceutical Scientists (AAPS) posed questions to the participants on their immunogenicity risk assessment strategies prior to clinical development. The survey was conducted in 2 phases spanning 5 years, and queried information about in silico algorithms and in vitro assay formats for immunogenicity risk assessments and how the data were used to inform early developability effort in discovery, chemistry, manufacturing and control (CMC), and non-clinical stages of development. The key findings representing the trends from a majority of the participants included the use of high throughput in silico algorithms, human immune cell-based assays, and proteomics based outputs, as well as specialized assays when therapeutic mechanism of action could impact risk assessment. Additional insights into the CMC-related risks could also be gathered with the same tools to inform future process development and de-risk critical quality attributes with uncertain and unknown risks. The use of the outputs beyond supporting early development activities was also noted with participants utilizing the risk assessments to drive their clinical strategy and streamline bioanalysis.

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Author information

Author notes

  1. Jochem Gokemeijer, Yi Wen, and Vibha Jawa contributed equally.

Authors and Affiliations

  1. Bristol Myers Squibb, 100 Binney Street, Cambridge, Massachusetts, 02143, USA

    Jochem Gokemeijer

  2. Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, 46285, USA

    Yi Wen, Robin Walsh & Laurent Malherbe

  3. Bristol Myers Squibb, Lawrenceville, New Jersey, 08540, USA

    Vibha Jawa

  4. Takeda Pharmaceuticals, 300 Massachusetts Ave, Cambridge, Massachusetts, 02139, USA

    Shibani Mitra-Kaushik

  5. Genentech Inc., South San Francisco, California, 94080, USA

    Shan Chung, Jennie Lill & Qui Phung

  6. Merck & Co., Inc., South San Francisco, California, 94080, USA

    Alan Goggins

  7. EMD Serono Research & Development Institute, (A Business of Merck KGaA, Darmstadt, Germany), Billerica, Massachusetts, 01826, USA

    Seema Kumar

  8. Novo Nordisk A/S, Maaloev, Denmark

    Kasper Lamberth

  9. Merck & Co., Inc., West Point, Pennsylvania, 19486, USA

    Karen Liao

  10. EpiVax, Providence, Rhode Island, 02909, USA

    Brian J. Roberts

  11. Janssen R&D LLC., 1400 McKean Road, Spring House, Pennsylvania, 19477, USA

    Michael Swanson

  12. Spark Therapeutics, Philadelphia, Pennsylvania, USA

    Inderpal Singh

  13. BioMedicine Design, Pfizer Inc., Andover, Massachusetts, 01810, USA

    Sophie Tourdot

  14. Clinical Immunology, Amgen, Thousand Oaks, California, 91320, USA

    Mark A. Kroenke

  15. Bonnie Rup Consulting, LLC, 42 Commonwealth Ave, Boston, Massachusetts, 02116, USA

    Bonita Rup

  16. GlaxoSmithKline, Rockville, Maryland, 20850, USA

    Theresa J. Goletz

  17. AbbVie, Irvine, California, 92612, USA

    Swati Gupta

  18. ImmunXperts, 6041, Charleroi, Belgium

    Sofie Pattijn

Authors
  1. Jochem Gokemeijer
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Contributions

Jochem G. and Shibani M–K. conceived the project and performed the survey. Jochem G., Yi W., and Vibha J. analyzed the data and wrote the manuscript. Jochem G., Shibani M–K., Theresa G., Swati G., Shan C., Alan G., Seema K., Kasper L., Karen L., Jennie L., Qui P., Robin W., Brian R., Michael S., Inderpal S., Sophie T., Mark K., Laurent M., and Sofie P. responded to the survey and provided data. All authors reviewed and approved the manuscript.

Corresponding author

Correspondence to Jochem Gokemeijer.

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Conflict of Interest

Jochem G. and Vibha J. are employees of Bristol Myers Squibb, Yi W., Robin W., and Laurent M. are employees of Eli Lilly and Company. Shibani Mitra-Kaushik is an employee of Takeda Pharmaceuticals. Theresa Goletz is an employee of GSK. Bonita Rup works as an independent consultant. Swati Gupta is employee of AbbVie. Jennie Lill and Qui Phung are employees of Genentech. Mark Kroenke is an employee of Amgen. Seema Kumar is an employee of EMD Serono. Alan Goggins is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Karen Liao is an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA currently, and was employed by GSK at survey participation.

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Gokemeijer, J., Wen, Y., Jawa, V. et al. Survey Outcome on Immunogenicity Risk Assessment Tools for Biotherapeutics: an Insight into Consensus on Methods, Application, and Utility in Drug Development. AAPS J 25, 55 (2023). https://doi.org/10.1208/s12248-023-00820-7

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