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关于当前行业实践的智商调查结果 - 第1部分:免疫原性风险评估。

IQ Survey Results on Current Industry Practices-Part 1: Immunogenicity Risk Assessment.

作者信息

Grimaldi Christine, Richards Susan, Baltrukonis Daniel, Sims Belouski Shelley, Coble Kelly, Dholakiya Sanjay L, Grudzinska-Goebel Joanna, Kolaitis Gerry, Leu Jocelyn H, Luo Linlin, Lowe Stephen, Niu Tao, Toft-Hansen Henrik, Yang Jianning, Wu Benjamin

机构信息

Bioanlytical Sciences, Regeneron, Inc, Tarrytown, New York, USA.

Translational Medicine and Early Development, Sanofi R&D, Cambridge, Massachusetts, USA.

出版信息

Clin Pharmacol Ther. 2025 Jun;117(6):1596-1604. doi: 10.1002/cpt.3568. Epub 2025 Jan 28.

Abstract

An immunogenicity risk assessment (IRA) is a relatively new expectation of health authorities that is increasingly incorporated into the drug development process across the pharmaceutical/biotech industry. The guiding principle for an IRA includes a comprehensive evaluation of product- and patient-related factors that may influence the immunogenic potential of a biotherapeutic drug and a potential action plan. The Immunogenicity Working Group from the IQ Consortium (Clinical Pharmacology Leadership Group) has conducted a survey to understand the current practices for conducting IRAs and relevant aspects of bioanalysis. Survey results were provided by 19 IQ member companies participating in the Clinical Pharmacology Leadership Group (CPLG) and the Translational and ADME Sciences Leadership Group (TALG). Nearly all the respondents reported experience with monoclonal antibodies (mAb), with 10 other drug modalities including bioengineered protein therapeutics such as fusion and multi-domain proteins, peptides, oligonucleotides as well as gene and cell therapies. The survey results demonstrate that most companies have a defined IRA process, and there was a common understanding that the IRA may need to be revised as more information becomes available or the drug development strategy changes. Some differences found across the respondents are related to the time frame for implementation of IRA document, the types of preclinical data and computational methods used to assess risk, and how the IRA informs clinical plans and documentation practices. These results highlight that while there have been widespread insights gained with performing IRA for mAbs, more experience is needed to perform IRAs for the novel modalities.

摘要

免疫原性风险评估(IRA)是卫生当局提出的一项相对较新的要求,越来越多地被纳入整个制药/生物技术行业的药物开发过程中。IRA的指导原则包括对可能影响生物治疗药物免疫原性潜力的产品和患者相关因素进行全面评估以及制定潜在的行动计划。IQ协会(临床药理学领导小组)的免疫原性工作组进行了一项调查,以了解进行IRA的当前做法和生物分析的相关方面。参与临床药理学领导小组(CPLG)和转化与药物代谢动力学科学领导小组(TALG)的19家IQ成员公司提供了调查结果。几乎所有受访者都报告了单克隆抗体(mAb)方面的经验,还涉及其他10种药物类型,包括生物工程蛋白疗法,如融合蛋白和多结构域蛋白、肽、寡核苷酸以及基因和细胞疗法。调查结果表明,大多数公司都有明确的IRA流程,并且大家普遍认为,随着更多信息的获得或药物开发策略的改变,可能需要对IRA进行修订。受访者之间发现的一些差异与IRA文件的实施时间框架、用于评估风险的临床前数据类型和计算方法,以及IRA如何为临床计划和文件记录实践提供信息有关。这些结果突出表明,虽然在对单克隆抗体进行IRA方面已经获得了广泛的见解,但对新型药物类型进行IRA还需要更多经验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d50/12087687/da0c97fc06d0/CPT-117-1596-g003.jpg

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