目的: 2025年版《中华人民共和国药典》即将收录人用抗体偶联药物（Human Antibody-Drug Conjugates,ADC）制品总论,针对其制造和检定部分进行阐述和讨论,为行业具体实施提供指导。方法: 参考WHO、ICH、国家药典委员会和国家药品监督管理局药品审评中心的相关法规和指南,提出制定关于ADC总论的讨论和思考。结果与结论: 欧美和其他国家药典中尚未对抗体偶联药物的生产和质量控制进行总体要求,目前国家药品监督管理局药品审评中心发布的《抗体偶联药物药学研究与评价技术指导原则》是首个已出台的相关药品规范生产和质量控制的指南。本文在参考相关法规的基础上,在建立国际化水平的标准编制指导思想下,主要讨论ADC总论中涉及的相关药物产品在研发、制备过程和质量控制中需遵循的一般原则和基本要求,为相关产业提供参考。
Objective: The 2025 edition of the Pharmacopoeia of the People's Republic of China is about to include a general principles of Human Antibody-Drug Conjugates (ADC) for human use. This section will elaborate and discuss the manufacturing and testing of ADC products, providing guidance for specific implementation in the industry. Methods: Based on the relevant regulations and guidelines of WHO, ICH, the National Pharmacopoeia Commission, and the Center for Drug Evaluation of the National Medical Products Administration, the discussion and consideration on the general principles of ADC were put forward. Results and Conclusion: In the pharmacopoeias of Europe, America, and other countries, there are currently no overall requirements for the production and quality control of Antibody-Drug Conjugates (ADC). The “Guiding Principles for Pharmaceutical Research and Evaluation Techniques of Antibody-Drug Conjugates” issued by the Center for Drug Evaluation of the National Medical Products Administration is the first guideline that has been introduced for the standardized production and quality control of such drugs. Based on the reference to relevant regulations and the guidance of establishing international standards, this article mainly discusses the general principles and basic requirements that need to be followed in the research and development, preparation process, and quality control of relevant drug products involved in the general principles of ADC. This aims to provide a reference for the relevant industries.
[1] 王兰,郭莎,于传飞,等. 抗体偶联药物质量控制和临床前评价专家共识[J].中国药事,2018,32(7):993-1004.
[2] 国家药品监督管理局药品审评中心. 抗体偶联药物药学研究与评价技术指导原则[EB/OL].(2024-02-07)[2024-09-08].https://www.cde.org.cn/main/fullsearch/fullsearchpage.
[3] ICH. Pharmaceutical Development Q8[EB/OL].(2009-08)[2024-09-08]. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q8_R1/Step4/Q8_R2_Guideline.pdf.
[4] ICH. Quality Tisk Management Q9[EB/OL].(2023-01-18)[2024-09-08]. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q9/Step4/Q9_Guideline.pdf.
[5] ICH. Pharmaceutical Quality System Q10[EB/OL].(2008-06-04)[2024-09-08]. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q10/Step4/Q10_Guideline.pdf.
[6] ICH. Quality Guidelines. Quality of Biotechnological Products Q5E. Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process[EB/OL].(2004-11-18)[2024-09-21]. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q5E/Step4/Q5E_Guideline.pdf.
[7] ICH. Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/Biological Entities) Q11[EB/OL]. (2012-05-01)[2024-09-21]. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q11/Step4/Q11_Guideline.pdf.
[8] 国家药品监督管理局药品审评中心.化学药物原料药制备和结构确证研究的技术指导原则[EB/OL].(2005-03)[2024-09-21].https://www.doc88.com/p-1877568563072.html.
[9] 王军志. 生物技术药物研究开发和质量控制[M].第三版.北京:科学出版社,2018.
[10] 武刚,付志浩,徐刚领,等.抗体偶联药物研发进展[J].生物医学转化,2021,2(4):1-11.
[11] ICH. Quality Guidelines. Quality of Biotechnological Products Q5A, Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin [EB/OL].(2023-11-01)[2024-10-03].http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Gui-delines/Quality/Q5A_R1/Step4/Q5A_R1_Guideline.pdf.
[12] ICH. Quality Guidelines. Quality of Biotechnological Products Q5B, Quality of Biothechnological Products: Analysis of the Expression Construct in Cells Used for Production of r-DNA Derived Protein Products[EB/OL]. (1995-11-30)[2024-09-25]. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q5B/Step4/Q5B_Guideline.pdf.
[13] ICH. Quality Guidelines. Specifications Q6B, Specification: Test Procedures and Acceptance Criteria for Biothechnological/Biological Products[EB/OL].(1999-03-10)[2024-09-26]. http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q6B/Step4/Q6B_Guideline.pdf.
[14] WHO. WHO Guidelines on the Quality, Safety, and Efficacy of Biotherapeutic Products Prepared by Recombinant DNA Technology[EB/OL].(2013-06-28)[2024-09-26].http://www.who.int/biologicals/WHO_rDNA_2nd_public_consultation_28_June_2013.pdf.
[15] WHO. Guidelines for Assuring the Quality of Pharmaceutical Andbiological Products Prepared by Recombinant DNA Technology.No.814[EB/OL].(1991)[2024-09-29]. http://www.who.int/bloodproducts/publications/WHO_TRS_814_A3.pdf.
[16] USP. General Chapters:<1045>Biotechnology-derived articles. [EB/OL].(2022)[2024-09-29]. http://www.doc88.com/p-0864873291166.html.
[17] FDA. Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product [EB/OL]. (2012)[2024-09-29].http://www.fda.gov/downloads/Drugs/GuidanceComplianceReg-ulatoryInformation/Guidances/UCM291134.pdf.
[18] 国家药品监督管理局食品药品审核查验中心. 抗体类药品现场检查指南(征求意见稿)[EB/OL].(2022-05-27)[2024-10-03].https://www.cfdi.org.cn/resource/news/14650.html.
[19] 齐连权,韦薇,常翠云,等.抗体偶联药物及其质量研究与质量控制[J].中国新药杂志,2019,28(12):1428-1432.
[20] FDA. Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009 [EB/OL]. (2012)[2024-10-03].http://www.fda.gov/downloads/Drugs/Guidances/UCM273001.pdf.
