SYSTEMATIC REVIEW article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1581153
This article is part of the Research TopicAdvances in Immunogenicity Risk Assessment, Monitoring and Mitigation of BiologicsView all 5 articles
Immunogenicity Risk Assessment for Tailored Mitigation and Monitoring of Biotherapeutics During Development: Recommendations from the European Immunogenicity Platform
Provisionally accepted
Joanna Grudzinska-Goebel1*
Karin Benstein2
Karien Bloem3
Kyra J. Cowan4
Boris Gorovits5
Maria Jadhav6Melody Janssen7
Vibha Jawa8Andrea Kiessling9
Daniel Kramer2
Arno J Kromminga10,11
Marcel van der Linden12
Susana Liu13
Gregor P Lotz14
Linlin Luo15Mantas Malisauskas16Celine Marban-Doran17
Daniel T Mytych18
Elisa Oquendo Cifuentes19
Susanne Pippig20
Sandra Ribes21Myrthe Rouwette22
Weiping Shao23
Sophie Tourdot24Karin Nana Weldingh25Veerle Snoeck26- 1Preclinical Development, Pharmaceuticals R&D, Bayer AG, Berlin, Germany
- 2Translational Medicine Unit, Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany
- 3R&D Antibodies and Immunogenicity, Pharma and Biotech Services, Sanquin Diagnostic Services, Amsterdam, Netherlands
- 4Drug Metabolism and Pharmacokinetics, New Biological Entities, Research and Development, Merck KGaA, Darmstadt, Hesse, Germany
- 5Bioanalytical Sciences, Regeneron Pharmaceuticals Inc, Tarrytown, NY, United States
- 6Pharmacokinetic Sciences - Drug Disposition, Biomedical Research, Novartis,, Cambridge, MA, United States
- 7SciPot Consultancy B.V, Amsterdam, Netherlands
- 8Translational Medicine, Bristol Myers Squibb, Lawrenceville, NJ, United States
- 9Precliclinical safety, Biomedical Research, Novartis, Basel, Switzerland
- 10Biolytics, BioNTech SE, Mainz, Germany
- 11Kromminga Consulting, Hamburg, Germany
- 12Bioanalytical Science, Genmab B.V., Utrecht, Netherlands
- 13Translational Clinical Sciences, Biologics & Immunogenicity, Clinical Bioanalytics, Pfizer, Vaughan, Ontario, Canada
- 14Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Munich, Penzberg, Germany
- 15Regulated Bioanalytics, Merck & Co., Inc., Rahway, NJ, United States
- 16Non-Clinical Safety Research, H. Lundbeck A/S, Valby, Denmark
- 17Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel,, Basel, Switzerland
- 18Clinical Immunology Department, Clinical Development, Amgen, Inc., Thousand Oaks, California, United States
- 19Drug Metabolism and Pharmacokinetics, Boehringer-Ingelheim Pharmaceuticals Inc, Ridgefield, United States
- 20Scientific Affairs, Formycon, Martinsried, Germany
- 21Global Clinical Development, Hexal AG (a Sandoz company), Holzkirchen, Germany
- 22Bioanalysis & Protein Interaction department, Byondis B.V., Nijmegen, Netherlands
- 23Integrated Bioanalysis, Clinical Pharmacology and Safety Sciences, AstraZeneca, Gaithersburg, MD, United States
- 24Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Andover MA, United States
- 25Non-Clinical and Clinical Assay Sciences, Novo Nordisk A/S, Måløv, Denmark
- 26Precision Medicine, Early Clinical Development & Translational Science, UCB, Braine-l’Alleud, Belgium
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Bringing safe and effective drugs to patients is of utmost importance for the pharmaceutical industry, with immunogenicity (IG) being a critical factor that influences both aspects. Biotherapeutics can elicit unwanted immune responses, potentially leading to (severe) safety implications, reduced patient benefits, and may result in termination of development. Therefore, understanding IG risks throughout drug development is essential for both drug developers and health agencies (HAs). The Immunogenicity Risk Assessment (IRA) facilitates the identification of IG risk factors and allows the establishment of effective mitigation and monitoring strategies. In this publication, the European Immunogenicity Platform (EIP) presents a comprehensive IRA framework aligned across pharmaceutical industry, emphasizing its significance in product development - from early de-risking to bioanalytical monitoring and mitigation measures during clinical trials. The EIP also provides an updated list of IG risks, offers distinct recommendations for assigning overall IG risk levels prior to the start of clinical development and highlights business considerations within this assessment.
Keywords: Immunogenicity1, immunogenicity risk assessment2, biotherapeutics3, immunogenicity mitigation4, bioanalyis5, anti-drug antibody6, immunogenicity de-risking7, immunogenicity monitoring8
Received: 21 Feb 2025; Accepted: 15 Apr 2025.
Copyright: © 2025 Grudzinska-Goebel, Benstein, Bloem, Cowan, Gorovits, Jadhav, Janssen, Jawa, Kiessling, Kramer, Kromminga, van der Linden, Liu, Lotz, Luo, Malisauskas, Marban-Doran, Mytych, Oquendo Cifuentes, Pippig, Ribes, Rouwette, Shao, Tourdot, Weldingh and Snoeck. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Joanna Grudzinska-Goebel, Preclinical Development, Pharmaceuticals R&D, Bayer AG, Berlin, Germany
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.