{"title":"细胞治疗致瘤性评估的全球监管考虑和实践。","authors":"Dehu Dou, Jing Lu, Jinhui Dou, Yan Huo, Xinjiang Gong, Xuefeng Zhang, Xijing Chen","doi":"10.1016/j.yrtph.2024.105769","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":20852,"journal":{"name":"Regulatory Toxicology and Pharmacology","volume":" ","pages":"105769"},"PeriodicalIF":3.0000,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Global regulatory considerations and practices for tumorigenicity evaluation of cell-based therapy.\",\"authors\":\"Dehu Dou, Jing Lu, Jinhui Dou, Yan Huo, Xinjiang Gong, Xuefeng Zhang, Xijing Chen\",\"doi\":\"10.1016/j.yrtph.2024.105769\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":20852,\"journal\":{\"name\":\"Regulatory Toxicology and Pharmacology\",\"volume\":\" \",\"pages\":\"105769\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2024-12-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Regulatory Toxicology and Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.yrtph.2024.105769\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, LEGAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Regulatory Toxicology and Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.yrtph.2024.105769","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, LEGAL","Score":null,"Total":0}
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.
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)