世界卫生组织药品标准专家委员会第50次技术报告

金少鸿2019年3月世界卫生组织药品专家委员会日内瓦 2015年6月12-16日 专家委员会委员未能参加：Ms Nilka M Guerrero Rivas, Technical Director, Radiopharmacy, Radiofarmacia de Centroamérica, SA, Ciudad del Saber, Panama; Dr Toru Kawanishi, Director General, National Institute of Health Sciences, Tokyo, Japan; Dr Adriaan J van Zyl, Cape Town, South Africa Professor Saleh A Bawazir, Consultant, College of Pharmacy, King Saud Unit, Riyadh, Saudi Arabia(Rapporteur) Professor Theo G Dekker, Professor Emeritus, Research Institute for Industrial Pharmacy, North-West University, Potchefstroom, South Africa Professor Jos Hoogmartens, Leuven, Belgium (Co-chairperson) Professor Jin Shaohong, Chief Expert for Pharmaceutical Products, National Institutes for Food and Drug Control, Beijing, People’s Republic of China Professor Henning G Kristensen, Vedbaek, Denmark Ms Gugu N Mahlangu, Director-General, Medicines Control Authority of Zimbabwe, Harare, Zimbabwe (Chairperson) Dr Justina A Molzon, Bethesda, MD, USA Mrs Lynda Paleshnuik, Arnprior, Ontario, Canada Dr Jitka Sabartova, Prague, Czech Republic (Rapporteur) 临时顾问未能参加：Dr Jean-Louis Robert, Luxembourg; Dr Jan Welink, Medicines Evaluation Board, Utrecht, Netherlands Professor Erwin Adams, Laboratorium voor Farmaceutische Analyse, Leuven, Belgium Dr Marius Brits, Director,WHO Collaborating Centre for the Quality Assurance of Medicines, North-West University, Potchefstroom, South Africa Dr Monica da Luz Carvalho Soares, Expert Health Regulation, Brazilian Health Surveillance Agency (ANVISA), Brasilia, Brazil Mr David Churchward, Expert Good Manufacturing and Distribution Practice Inspector, Inspection, Enforcement and Standards, Medicines & Healthcare products Regulatory Agency (MHRA), London, England Dr Alfredo García Arieta, Head of Service on Pharmacokinetics and Generic Medicines, Division of Pharmacology and Clinical Evaluation, Department of Human Use Medicines, Agencia Espanola de Medicamentos y Productos Sanitarios (AEMPS), Madrid, Spain Dr John Gordon, Wolfville, Nova Scotia, Canada Dr Olivier Le Blaye, Inspector, Trials and Vigilance Inspection Department, Agence nationale de sécurité du médicament (ANSM) et des produits de santé, Saint-Denis, France Dr John Miller, Ayr, Scotland Professor Alain Nicolas, Radiopharmacist, Pharmacie, Hospital Brabois Adultes, Vandoeuvre, France Mr Salim Akbaralli Veljee, Director, Food and Drugs Administration, Directorate of Food and Drugs Administration, Goa, India Mr John Wilkinson, Director of Devices, Medicines & Healthcare products Regulatory Agency (MHRA), London, England Ms Caroline Munyimba-Yeta, Director, Operations (Plant), NRB Pharma Zambia Limited, Lusaka, Zambia 联合国办公室代表未能参加：United Nations Development Programme (UNDP), New York, NY, USA United Nations Children’s Fund (UNICEF) Dr Peter Svarrer Jakobsen, Quality Assurance Specialist, UNICEF Supply Division, Copenhagen, Denmark 特别组织及相关机构代表未能参加：United Nations Industrial Development Organization (UNIDO), Vienna, Austria; World Intellectual Property Organization (WIPO), Geneva, Switzerland; World Bank, Washington, DC, USA; International Atomic Energy Agency (IAEA), Vienna, Austria World Trade Organization (WTO) Ms Daria Novozhilkina, Research Associate, Intellectual Property Division, Geneva, Switzerland 政府间组织代表未能参加：World Customs Organization (WCO), Brussels, Belgium; European Commission (EC), Directorate-General for Health and Consumer Protection, Brussels, Belgium Council of Europe Dr Stefan Almeling, Deputy Head, Laboratory Department, European Directorate for the Quality of Medicines & HealthCare (EDQM), Strasbourg, France European Medicines Agency (EMA) Mr Andrei Spinei, London, England 非政府组织代表未能参加：Commonwealth Pharmacists Association (CPA), London, England; Global Fund to Fight AIDS, Tuberculosis and Malaria, Geneva, Switzerland; International Society for Pharmaceutical Engineering (ISPE), Tampa, FL, USA; World Self-Medication Industry (WSMI), Ferney-Voltaire, France Active Pharmaceutical Ingredients Committee (APIC) Dr Landry Le Chevanton, Team Leader, Global Regulatory Affairs and Quality Management, DSM Nutritional Products Ltd, Switzerland The Stop TB Partnership Dr Nigorsulton Muzafarova, Product Quality Officer, Global Drug Facility (GDF), Geneva, Switzerland Dr Kaspars Lunte, Team Leader, Sourcing and Special Project, GDF, Geneva International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) Dr Betsy Fritschel, Director, Quality & Compliance, Johnson & Johnson, New Brunswick, NJ, USA Ms Valérie Faillat-Proux, Regulatory Affairs Senior Director, Access to Medicines & Malaria Programme, Sanofi, Gentilly, France International Generic Pharmaceutical Alliance (IGPA) Dr Koen Nauwelaerts, Quality and Regulatory Affairs Manager, EGA-European Generic and Biosimilar Medicines Association, Brussels, Belgium International Pharmaceutical Excipients Council (IPEC) Dr EckartKramer , SE Tylose GmbH & Co, Cologne, Germany International Pharmaceutical Federation (FIP) Ms Zuzana Kusynová, Policy Analyst and Project Coordinator, The Hague, Netherlands 观察员未能参加：Pharmaceutical Inspection Co-operation Scheme (PIC/S), Geneva, Switzerland Dr C Michelle Limoli, Senior International Health Advisor, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA Ms Wei Ningyi, Associate Researcher, Division of Chemical Drugs, National Institutes for Food and Drug Control, Beijing, People’s Republic of China Dr Gabriela Zenhausern, Senior Case Manager, Sector Authorisation, Swissmedic, Berne, Switzerland Professor Zhang Mei, Deputy Director and Vice Chairman, Institutesfor Food and Drug Control, Jiangsu, People’s Republic of China/Antibiotic Subcommittee, Chinese Pharmacopoeia Commission, People’s Republic of China 药典委员会未能参加：Farmacopea Argentina; Indian Pharmacopoeia Commission; Indonesian Pharmacopoeia Commission; Pharmacopoeia of Ukraine Farmacopéia Brasileira Mr Varley Dias Sousa, Coordinator, Coordination of Brazilian Pharmacopoeia, Brazilian Health Surveillance Agency (ANVISA), Brasilia, Brazil British Pharmacopoeia Ms Helen Corns, British Pharmacopoeia and Laboratory Services, Medicines & Healthcare products Regulatory Agency (MHRA), London, England Pharmacopoeia of the People’s Republic of China Dr Wang Fei, Beijing, People’s Republic of China European Pharmacopoeia9See underCouncil of Europe Council of Europe, Strasbourg, France Japanese Pharmacopoeia Dr Yoshihiro Matsuda, Deputy Director, Pharmaceutical and Medical Devices Agency, Division of Pharmacopoeia and Standards for Drugs, Office of Standards and Guidelines Development, Pharmaceuticals and Medical Devices Agency, Tokyo, Japan Pharmacopoeia of the Republic of Korea Dr Kwangmoon Lee, Deputy Director, Drug Research Division, Pharmaceutical Standardization Research and Drug Research Division, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Chungcheongbuk-do, Republic of Korea State Pharmacopoeia of the Russian Federation Dr Elena Sakanyan, Director, Centre of Pharmacopoeia and International Collaboration, Scientific Centre for Expert Evaluation of Medicinal Products of the Ministry of Health of the Russian Federation, Moscow, Russian Federation Ms Olga Gubareva, Head, International Cooperation Department, Moscow, Russian Federation United States Pharmacopeia Dr Kevin Moore, Manager, Pharmacopeial Harmonization, Rockville, MD, USA Dr Kelly S Willis, Senior Vice President, Global Public Health, Rockville, MD, USA 来自WHO大区办公室的代表未能参加：Regional Office for Africa; Regional Office for the Americas; Regional Office for the Eastern Mediterranean; Regional Office for Europe; Regional Office for South-East Asia Regional Office for the Western Pacific Ms Uhjin Kim, Essential Medicines and Health Technology, Division of Health Systems, WHO Regional Office for the Western Pacific, Manila, Philippines WHO秘书处未能参加：Traditional and Complementary Medicine (HIS/Service Delivery and Safety (SDS)/TCM) Health Systems and Innovation (HIS) Dr M-P Kieny, Assistant Director-General Essential Medicines and Health Products (HIS/EMP) Mr C de Joncheere, Director, Essential Medicines and Health Products (EMP) Regulation of Medicines and other Health Technologies (EMP/RHT) Dr L Rago, Head Technologies, Standards and Norms (EMP/RHT/TSN) Dr DJ Wood, Coordinator Medicines Quality Assurance (EMP/RHT/TSN) Dr S Kopp, Group Lead, Medicines Quality Assurance (Secretary) Dr H Schmidt, TSN Dr H Chen, TSN (volunteer) International Nonproprietary Name (INN/RHT/TSN) Dr RG Balocco, Group Lead Policy, Access and Use (EMP/PAU) Ms Bernadette Cappello Prequalification Team (EMP/RHT/PQT) Mr M McDonald, Coordinator Mr JRH Kuwana Mr D Mubangizi, Group Lead, Inspections Ms T Muvirimi Regulatory Systems Strengthening (RSS/RHT/RHT) Dr M Ward, Coordinator Safety and Vigilance Team (EMP/RHT/SAV) Miss P Bourdillon-Esteve, Analyst Global TB Programme (GTB) Dr C Gilpin, Laboratories, Diagnostics and Drug-Resistance (LDR) Dr L Nguyen, LDR Prevention of Noncommunicable Diseases (PND) Dr Dongbo Fu, Technical Officer, National Capacity Ms M Zweygarth (report writer) 利益申明 Members of the WHO Expert Committee on Specifications for Pharmaceutical Preparations and temporary advisers reported the following: Dr E Adams, Dr M Brits, Mr D Churchward, Dr T Dekker, Dr A Garcia Arieta, Dr J Gordon, Professor J Hoogmartens, Professor Jin S, Dr O Le Blaye, Dr J Molzon, Dr A Nicolas, Ms L Paleshnuik, Dr J Sabartova, Dr M Da Luz Carvalho Soares and Mr S Akbaralli Veljee reported no conflict of interest Professor S Bawazir reported that he is in the process of establishing a new consultancy Professor HG Kristensen reported that he has provided testimonies as an independent expert in questions on validity and for infringement of patents at courts in Denmark, Norway and Sweden In all cases testimony related to drug formulations No items conflict with the subjects of the meeting Ms GN Mahlangu reported that she would receive an out-of-pocket allowance from her current employer, the Medicines Control Authority of Zimbabwe, in accordance with the travel allowances schedule for sponsored travel Dr J Miller reported that he has acted as a consultant for national authorities Ms C Munyiamba-Yeta reported that she was employed by the Zambian Regulatory Authority for seven years until 2014 For the moment she works as an independent consultant Mr J Wilkinson reported that he was employed with the European Medical Devices Industry Association until December 2012 The interests summarized above do not give rise to a conflict of interest such that the expert concerned should be partially or totally excluded from participation in the Expert Committee on Specifications for Pharmaceutical Preparations However, following WHO’s policy, they were disclosed within the Committee so that other members were aware of them All other members of the Expert Committee declared no relevant interests Many of the Expert Committee Members have extensive governmental experience and expertise – including consulting with WHO – in the areas that are the subject of the Expert Committee agenda, and which were considered very relevant and important for the challenging tasks faced by the Committee It was suggested that the Secretariat should provide more detail on the type of conflict to be reported in the declarations of interest for regulatory authorities The Secretariat agreed to follow up this suggestion with the WHO Office of the Legal Counsel

药品标准专家委员会目标是为药品质量保证工作建立明确、独立并适用的标准和指导原则。通过全球范围内的协商以及建立国际共识的程序建立标准。 《世界卫生组织药品标准专家委员会（第50次技术报告）》是“世界卫生组织技术报告丛书”之一，具体包含了质量保证——合作倡议、监管指南等部分。 本报告供国内药品研发、质量控制和质量保证、药品检验、药品注册和监督人员参考。

1 前言
2 一般政策
2.1 重大药品质量的保证
2.2 国际合作
3 质量控制——质量标准和检验方法
3.1 《国际药典》
3.1.1 增修订情况
3.1.2 2015-2016年工作计划
3.2 包括儿童用药和放射药品的质量标准
3.2.1 孕产妇、新生儿、儿童和青少年用药物
3.2.2 抗疟药
3.2.3 抗结核药物
3.2.4 热带病药物
3.2.5 慢性病药物和精神类药物
3.2.6 其他抗感染药物
3.2.7 其他药物
3.2.8 放射药品
3.3 通则
4 质量控制——国际标准物质(国际化学对照品和红外对照图谱)
4.1 国际化学对照品(ICRS)进展与ICRS委员会报告
4.2 通则
4.2.1 标准物质与对照图谱
5 质量控制——国家实验室
5.1 外部质量保证评估计划
5.2 疑似假冒伪劣药品的检测指南
6 质量控制实验室的认证
6.1 质量控制实验室认证的更新
6.2 WHO质量监测项目的更新
7 质量保证——合作倡议
7.1 世界药典国际会议
7.2 药典标准质量管理规范
7.3 FIP-WHO技术指导原则：缺乏儿童专用药品时健康护理专业人员的考虑要点
8 质量保证——药品生产质量管理规范(GMP)
8.1 WHO生物制品GMP的更新
8.2 WHO原料药GMP问题和答案的更新
8.3 WHO关于GMP-验证的更新
8.4 检查报告模板的更新
8.5 检查员会议的更新和建议
8.5.1 关于非无菌药物制剂GMP的加热、通风和空调系统补充指导原则
8.5.2 药品检查中风险分类
8.6 关于数据与记录管理规范的指导
9 质量保证——药品分销与贸易
9.1 起始物料的贸易与分销质量管理规范
9.2 WHO关于国际贸易中药品质量的认证计划一问答
9.3 药品质量监测的指南
9.4 监测和监督项目的进展
10 优先需要的基本药物和原料药的认证
10.1 WH0认证项目的进展
10.2 WHO认证小组与国家监管机构关于加快WHO预认证药物和疫苗审批和注册的合作程序
11 监管指南
11.1 关于开展体内生物等效性研究机构的指南
11.2 WHO多来源药品变更的一般指导原则
11.3 豁免多来源(仿制药)药品体内研究的评估原则修订进展
11.4 可豁免体内研究的WH0基本药物品种目录更新
11.5 多来源(仿制药)药品等效性评价用国际对照药品目录的更新
11.6 药品监管质量管理规范
12 命名、术语和数据库
13 总结和建议
附录
附录1 药典质量管理规范
附录2 FIP-WH0技术指导原则：缺乏儿童专用药品时健康护理专业人员的考虑要点
附录3 世界卫生组织生物制品生产质量管理规范
附录4 GMP指南：现场检查报告
附录5 数据和记录管理规范指南
附录6 药品起始物料的贸易和分销管理规范
附录7 药品质量监测指导原则
附录8 世界卫生组织(WHO)认证工作组与国家监管机构在WHO认证药品和疫苗的评估和加快国家注册之间的合作程序
附录9 实施体内生物等效性研究机构指南
附录10 WH0多来源药品变更指导原则