美国FDA《非临床毒理学研究病理学同行评议指南草案》关注点探讨

Interpretation of the FDA Draft Guidance on Pathology Peer Review in Nonclinical Toxicology Studies

目的:探讨美国食品药品监督管理局于2019年7月发布的《非临床毒理学研究病理学同行评议指南草案》内容,以期为我国药物非临床安全性评价更好地开展病理学同行评议提供借鉴。方法:对《非临床毒理学研究病理学同行评议指南草案》的制定背景、有关非临床毒理学研究的病理学同行评议的计划、管理、记录和报告的建议进行分析,并与经济合作与发展组织分别于2012年颁布的《长期毒性和致癌性实验的设计和实施》指导性文件第116号和2014年颁布的第16号文件《组织病理学同行评议GLP要求指导原则》进行比较。结果:从与病理学同行评议相关的8个方面内容对《非临床毒理学研究病理学同行评议指南草案》进行梳理,有关病理学同行评议的定义、同行评议病理学家的资质、病理学同行评议的时间及类型分别与OECD第16号文件中相应内容一致。而关于在非GLP机构进行GLP研究病理学同行评议的要求、病理学同行评议过程的记录、病理学同行评议声明的内容及签署、如何确保专题病理学家的解释结果不会受到过度影响,以及解决专题病理学家和同行评议病理学家分歧的程序与OECD第16号文件中相应内容存在差异。结论:《非临床毒理学研究病理学同行评议指南草案》的发布旨在给委托方、病理学家、机构负责人、专题负责人和质量保证人员提供指导,以使组织病理学同行评议的计划、管理、记录和报告符合GLP原则要求。本文将有助于我国药物非临床安全性评价建立一致的病理学同行评议的计划、管理、记录和报告程序。

Objective:To explore the contents of Draft Guidance on Pathology Peer Review in Nonclinical Toxicology Studies published by the Food and Drug Administration(FDA)in July 2019 in order to provide references for better performing pathology peer review in the field of nonclinical safety evaluation of drugs in China.Methods:Background of the Draft Guidance on Pathology Peer Review in Nonclinical Toxicology Studies and the recommendations for planning,management,documentation and reporting of pathology peer review were analyzed and compared with the guidance document No.116 the Conduct and Design of Chronic Toxicity and Carcinogenicity Studies and the guidance document No.16 the GLP Requirements for Peer Review of Histopathology issued by the Organisation for Economic Cooperation and Development(OECD)in 2012 and 2014 respectively.Results:The FDA Draft Guidance on Pathology Peer Review in Nonclinical Toxicology Studies was analyzed from eight aspects related to pathology peer review.Definition of pathology peer review,qualification of peer review pathologists,time and type of pathology peer review were consistent with the corresponding parts in OECD document No.16.However,there were many differences between them in the following aspects:requirements for conducting pathology peer review of a GLP compliant study in non-GLP compliant site,documentation of pathology peer review process,contents and signing of pathology peer review statement,the way to ensure that the interpretation of the study pathologist was not unduly influenced,and the procedure for resolving the differences between the study pathologist and peer review pathologists.Conclusion:The FDA Draft Guidance on Pathology Peer Review in Nonclinical Toxicology Studies was intended to provide a guidance for sponsors,pathologists,facility managers,study directors and quality assurance staff so as to make the planning,management,documentation and reporting of pathology peer review in accordance with GLP principles.The paper will help to establish a consistent procedure for planning,management,documentation and reporting pathology peer review in the field of nonclinical safety evaluation of drugs in China.