PERSPECTIVE article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1608401
This article is part of the Research TopicAdvances in Immunogenicity Risk Assessment, Monitoring and Mitigation of BiologicsView all 6 articles
Immunogenicity of Therapeutic Peptide Products: Bridging the Gaps Regarding the Role of Product-Related Risk Factors
Provisionally accepted
Montserrat Puig*
Sophie Shubow*- United States Food and Drug Administration, Silver Spring, United States
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The global market for therapeutic peptides is projected to continue to grow at a fast pace in the coming years in response to high demand for these products. The increasing complexity of chemical and recombinant peptide manufacturing processes may impact product quality attributes, including as related to immunogenicity risk. While it is well established that product-related factors, including impurities, can impact the immunogenicity of a biologic product, assessing the actual impact of a specific product quality attribute on immunogenicity is difficult. Despite significant advances in the analytical characterization of complex peptide products, gaps still exist in our understanding of the significance of impurities to the overall peptide immunogenicity risk, and questions remain about what the best-suited control strategies are. These gaps have the largest impact on the assessment of immunogenicity risk of follow-on therapeutic peptide products, when clinical data are not available to inform that risk. Current regulatory guidance on impurity qualification thresholds is sparse, and in vitro and in silico immunogenicity assessment methods for evaluating the immunogenicity risk of impurities present technical and methodological limitations. We highlight these challenges and offer points to consider for handling them.
Keywords: Immunogenicity, Therapeutic peptides, Risk Assessment, impurities, Qualification threshold
Received: 08 Apr 2025; Accepted: 23 May 2025.
Copyright: © 2025 Puig and Shubow. 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:
Montserrat Puig, United States Food and Drug Administration, Silver Spring, United States
Sophie Shubow, United States Food and Drug Administration, Silver Spring, United States
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.