细胞治疗致瘤性评估的全球监管考虑和实践。

IF 3 4区 医学 Q1 MEDICINE, LEGAL
Dehu Dou, Jing Lu, Jinhui Dou, Yan Huo, Xinjiang Gong, Xuefeng Zhang, Xijing Chen
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引用次数: 0

摘要

细胞治疗作为一种“活的药物”,具有固有的复杂性和异质性。致瘤性评价是细胞疗法安全性评价的一个重要方面。基于干细胞的治疗,如hESCs和hiPSCs,可能在最终产品中含有残留的未分化细胞,这些细胞具有很高的增殖和分化潜力,存在体内肿瘤形成的风险。此外,来源、表型、分化状态、增殖能力、体外培养条件、体外处理方法、注射部位和给药途径也会影响细胞的致瘤性风险。致瘤性评价需要考虑设计的复杂性和多因素影响。通过对部分现有已上市和开发不足产品的分析和总结,结合实践经验,发现全球在细胞致瘤性相关的要求和实践上存在许多差异。监管要求也各不相同,需要结合产品特性和监管考虑因素,考虑对不同地区申请人申报要求的指导和支持。本文综合总结了主要监管机构对致瘤性的要求。目前,全球在技术实施指南上没有统一的监管共识,评价体系也没有建立量化或标准化的措施。然而,在法规要求和行业实践总结的基础上,通过文献研究和代表性上市产品致瘤策略分析,初步明确了致瘤性评价的基本重点和评价策略,为各种细胞治疗产品的致瘤性设计提供参考。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Global regulatory considerations and practices for tumorigenicity evaluation of cell-based therapy.

Cell-based therapy, as a "living drug", possesses inherent complexity and heterogeneity. Tumorigenicity evaluation is a crucial aspect of safety assessment for cell-based therapies. Stem cell-based therapies such as hESCs and hiPSCs, may contain residual undifferentiated cells in final product, which have a high potential for proliferation and differentiation, posing a risk of tumor formation in vivo. Additionally, the source, phenotype, differentiation status, proliferative capacity, ex vivo culture conditions, ex vivo processing methods, injection site, and route of administration also influence the tumorigenicity risk of the cells. Tumorigenicity evaluation needs to consider the complexity of design and multifactorial influences. Through the analysis and summary of partial existing marketed and under-development products, combined with practical experience, it is found that there are many differences in requirements and practices related to cell tumorigenicity globally. Regulatory requirements also vary, and guidance and support for applicants' declaration requirements in different regions need to be considered in conjunction with product characteristics and regulatory considerations. This article comprehensively summarizes the requirements of tumorigenicity from main regulatory agencies. Currently, there is no unified global regulatory consensus on technical implementation guide, measures for quantitation or standardization have not been established for evaluation systems. However, based on regulatory requirements and industry practice summaries, through literature research and analysis of tumorigenicity strategy of representative marketed products, the basic focus, and evaluation strategies for tumorigenicity assessment have been preliminarily clarified, providing a reference for the tumorigenicity design of variety of cell-based therapy products.

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来源期刊
CiteScore
6.70
自引率
8.80%
发文量
147
审稿时长
58 days
期刊介绍: Regulatory Toxicology and Pharmacology publishes peer reviewed articles that involve the generation, evaluation, and interpretation of experimental animal and human data that are of direct importance and relevance for regulatory authorities with respect to toxicological and pharmacological regulations in society. All peer-reviewed articles that are published should be devoted to improve the protection of human health and environment. Reviews and discussions are welcomed that address legal and/or regulatory decisions with respect to risk assessment and management of toxicological and pharmacological compounds on a scientific basis. It addresses an international readership of scientists, risk assessors and managers, and other professionals active in the field of human and environmental health. Types of peer-reviewed articles published: -Original research articles of relevance for regulatory aspects covering aspects including, but not limited to: 1.Factors influencing human sensitivity 2.Exposure science related to risk assessment 3.Alternative toxicological test methods 4.Frameworks for evaluation and integration of data in regulatory evaluations 5.Harmonization across regulatory agencies 6.Read-across methods and evaluations -Contemporary Reviews on policy related Research issues -Letters to the Editor -Guest Editorials (by Invitation)
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