Puig Montserrat, Shubow Sophie
Office of Pharmaceutical Quality Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, United States.
Office of Clinical Pharmacology, Office of Translational Sciences; Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, United States.
Front Immunol. 2025 Jun 18;16:1608401. doi: 10.3389/fimmu.2025.1608401. eCollection 2025.
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 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.
由于对这些产品的高需求，预计未来几年治疗性肽的全球市场将继续快速增长。化学和重组肽制造工艺日益复杂，可能会影响产品质量属性，包括与免疫原性风险相关的属性。虽然产品相关因素（包括杂质）会影响生物制品的免疫原性已得到充分证实，但评估特定产品质量属性对免疫原性的实际影响却很困难。尽管在复杂肽产品的分析表征方面取得了重大进展，但我们对杂质对整体肽免疫原性风险的重要性的理解仍存在差距，对于最适合的控制策略是什么也仍存在疑问。当没有临床数据来告知风险时，这些差距对后续治疗性肽产品免疫原性风险的评估影响最大。目前关于杂质鉴定阈值的监管指南很少，用于评估杂质免疫原性风险的计算机免疫原性评估方法存在技术和方法上的局限性。我们强调这些挑战，并提供应对这些挑战的考虑要点。
