正版 世界卫生组织药品标准专家委员会第47次技术报告 金少鸿,宁

1 前言

2 一般政策

2.1 药品质量保证中的重要问题

2.2 国际合作

2.2.1 与国际组织和机构的合作

2.2.2 药典协调组织

2.2.3 国际协调组织

2.2.4 国际药品管理机构会议

2.2.5 世界卫生大会关于建立打击假冒伪劣药品新机制的决议

3 质量控制——质量标准与检验方法

3.1 《国际药典》

3.1.1 第四版更新

3.1.2 附说明的工作计划

3.2 药品质量标准(含儿童用药)

3.2.1 免疫缺陷病毒(HIV)及相关病症治疗用药物

3.2.2 抗结核药

3.2.3 抗疟药

3.2.4 抗感染药

3.2.5 其他药物

3.3 协调后的文本

3.3.1 通则“5.5口服固体制剂溶出度检查”的修订

3.4 《国际药典》的前言、凡例和补充信息部分

3.4.1 胶囊通则的修订建议

3.4.2 制剂通则的修订建议：注射剂

3.4.3 “5.1单剂量制剂含量均匀度”的修订建议

3.4.4 高效液相色谱法的修订建议

3.4.5 第四版《国际药典》补充信息项下的通用检测方法：片剂硬度(抗破碎力)

3.4.6 第四版《国际药典》补充信息项下的通用检测方法：锥人度测定法

3.4.7 第四版《国际药典》补充信息项下的通用检测方法：脂溶性栓剂融变时限测定法

3.4.8 细菌内毒素

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 国际化学对照品动态

4.1.1 概述

4.1.2 国际化学对照品组织机构的行动报告

4.1.3 批准的国际化学对照品

4.1.4 《国际药典》补充信息：对照品和对照图谱

4.1.5 发放国际化学对照品的新程序

4.1.6 《国际药典》中国际化学对照品的命名原则

4.1.7 减少高纯度候选物质检测量的建议

5 质量控制——国家实验室

5.1 外部质量保证评估计划

5.1.1 回顾

5.1.2 程序4的最终报告

5.1.3 程序5的初步报告及可能的误差来源

5.1.4 第6期的建议

6 质量保证——药品生产质量管理规范(GMP)

6.1 世界卫生组织药品生产质量管理规范的更新

6.2 培训材料

7 质量保证——新思路

7.1 质量风险管理

7.2 药典协调

7.3 快检技术

7.4 关于实验室检测报告的调查

8质量保证——药物的分销与贸易

8.1 采购机构质量保证系统文件范本的修订

8.2 基于质量保证系统文件范本的评估工具

8.3 各国供应链的监管

8.4 药品贸易与分销规范的修订建议

9 优先需要的基本药物(包括活性药物成分)的认证

9.1 世界卫生组织药品认证项目的进展

10 活性药物成分的认证

10.1 活性药物成分认证进展

11 质量控制实验室的认证

11.1 质量控制实验室认证项目进展

11.2 世界卫生组织质量监督项目进展

12 监管指南

12.1 儿童药物的临时调配与使用

12.2 认证产品变更指导原则

12.3 世界卫生组织药品认证项目与各国药品管理机构在认证药品的评估与快速注册方面的合作

12.4 对抽样与市场监督的建议

12.5 对照药品

12.6 豁免体内生物等效研究

13 命名、术语与数据库

13.1 质量保证术语

13.2 药物的国际非专利名称

14 综合信息

14.1 药物质量保证：指导原则及相关文件的汇编

14.2 策略

世界卫生组织（WHO），创建于1948年，作为联合国的一个专门机构，是指导和协调国际卫生事务及公共健康的权威机构。世界卫生组织宪章的宗旨之一就是提供人类健康领域客观、可靠的信息和建议，并通过范围广泛的出版计划履行其部分职责。 本组织寻求通过出版物支持各会员国的卫生战略，提出对全球人口最迫切关注的公共健康问题。根据发展水平不同的会员国的需要，世界卫生组织出版了实用手册、指南和针对特殊领域卫生工作人员的培训资料；国际适用的指导原则和标准；卫生政策、卫生计划和健康研究的综述与分析；为决策者提供技术指导和建议的近期新共识报告。这些出版物与疾病的预防与控制、建立以初级卫生保健为基础的公平卫生体系、促进个人与社区的健康水平等世界卫生组织的优先行动紧密联系。为提高所有人群的健康水平，需要在全球范围内传播和交流来自世界卫生组织各会员国的知识和经验，还需要公共卫生和生物医学科学的权威人士之间的合作。 为保证尽优选可能地利用卫生事务方面的权威信息和指导意见，世界卫生组织在全球广泛发行其出版物，并鼓励对世界卫生组织出版物进行翻译和采用。通过在全球范围内促进和保护健康、预防和控制疾病，世界卫生组织的出版物致力于实现本机构的主要目标——人人拥有尽可能高水平的健康。 世界卫生组织技术报告丛书利用不同国际专家组的研究成果，向WHO提供范围广泛的医学和公共卫生方面的近期新科学和技术指导建议，上述专家组的成员以个人名义而不是政府或其他机构的代表身份为WHO服务，专家组成员没有报酬，他们的观点不反映WHO的决定或主张的政策。

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。 下列新指导原则已经被批准并推荐使用：国际化学对照品的审批程序；WHO质量风险管理指导原则；WHO认证产品的变更指导原则；WHO药品认证程序与国家药品监管机构在WHO认证药品的评估和加快国家注册之间的合作程序。

Professor SABawazir, Head of Drug Sector and Vice-President, Saudi Food and Drug Authority, Riyadh, Saudi Arabia (Chairperson) Professor TG Dekker, Research Institute for Industrial Pharmacy, North-West University, Potchefstroom, South AfricaMs Ms NM Guerrero Rivas, Quality Assurance, Laboratory,Instituto Especializado de Análisis, Ciudad Universitaria Octavio Méndez Pereira, Panamá, Republic of Panama(Co-Chairperson) Professor JHoogmartens, Leuven, Belgium Professor S Jin, Chief Expert for Pharmaceutical Products, National Institutes for Food and Drug Control, Beijing, People’s Republic of China (Rapporteur) Professor HGKristensen, Vedbaek, Denmark Ms GNMahlangu, Director-General, Medicines Control Authority of Zimbabwe, Harare, Zimbabwe Ms CMunyimba-Yeta, Director, Inspectorate and Licensing, Pharmaceutical Regulatory Authority, Lusaka, Zambia (Rapporteur) Ms LSlamet, Deputy for Therapeutic Products, Narcotics, Psychotropic and Addictive Substance Control, National Agency of Drug and Food Control, Jakarta Pusat, Indonesia1 临时顾问 Professor JBDressman, Director, Institute of Pharmaceutical Technology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany缺席会议。 Ms MY Low, Director, Pharmaceutical Division, Applied Sciences Group, Health Sciences Authority, Singapore Professor AJ Nunn, Formby, Liverpool, England Mrs L Paleshnuik, Arnprior, Ontario, Canada Dr S Parra, Manager, Generic Drug Quality Division缺席会议。, Bureau of Pharmaceutical Sciences,Therapeutic Products Directorate, Health Canada, Ottawa, Ontario, Canada Ms M-LRabouhans, Chiswick, London, England Dr J-L Robert, Head of Department, Service duContrle des Médicaments, Laboratoire National de Santé, Luxembourg Dr AJ van Zyl, Sea Point, South Africa 来自联合国机构的代表缺席会议: United Nations Development Programme, New York, NY, USA。 United Nations Children’s Fund (UNICEF) Dr PSJakobsen, Quality Assurance Specialist, UNICEF Supply Division, Copenhagen, Denmark 来自专门机构和有关组织的代表缺席会议: International Atomic Energy Agency, Vienna, Austria; United Nations Industrial。 The Global Fund to Fight AIDS, Tuberculosis and Malaria Ms JDaviaud, Quality Assurance Specialist, Grant Management Support, Geneva, Switzerland 来自政府间组织的代表缺席会议: European Commission, Brussels, Belgium; European Medicines Agency, London, England。 Council of Europe Dr A Lodi, Head of Laboratory Department, European Directorate for the Quality of Medicines & HealthCare, Strasbourg, France 来自非政府组织的代表缺席会议: Commonwealth Pharmacists Association, London, England; European Chemical Industry Council, Brussels, Belgium。 International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) Dr GL France, Vice Chair, Regulatory Policy and Technical Standards (RPTS), IFPMA, and Region Head, Quality Europe, Novartis Consumer Health Services SA, Novartis Group:Quality Systems & Standards, Switzerland Dr RHorder, Abbott, England International Generic Pharmaceutical Alliance (IGPA) Dr N Cappuccino, Chief Executive Officer, Pharmaceutical Intellectual Resource Services LLC, Lambertville, NJ, USA International Pharmaceutical Excipients Council (IPEC) Dr EKrmer, Good distribution practices (GDP) Committee Chair, IPEC Europe, Brussels, Belgium International Pharmaceutical Federation (FIP) Dr LBesancon, The Hague, Netherlands International Society for Pharmaceutical Engineering (ISPE) Dr GL France, Region Head, Quality Europe, Novartis Consumer Health Services SA, Novartis Group: Quality Systems & Standards, Switzerland World Self-Medication Industry (WSMI) Dr RTorano, Quality Executive, Pharmacopoeial Intelligence and Advocacy, GlaxoSmithKline, England 观察员 Pharmaceutical Inspection Co-operation Scheme (PIC/S) Dr A Hayes, Geneva, Switzerland 药典委员会缺席会议: Farmacopea Argentina, Buenos Aires, Argentina; Farmacopéia Brasileria, Santa Maria RS, Brazil。 British Pharmacopoeia Commission Mrs M Vallender, Editor-in-Chief, BP and Laboratory Services, London, England Pharmacopoeia of the People’s Republic of ChinaDr P Wang, Deputy Secretary-General, Beijing, People’s Republic of China Indonesian Pharmacopoeia Commission Dr AZaini, Director for Standardization of Drug and Food Control, National Agency of Therapeutic Products and Household Healthcare,Percetakan, Indonesia Committee of the Japanese Pharmacopoeia Dr TKawanishi, Deputy Director General, National Institute of Health Sciences, Tokyo, Japan Pharmacopoeia of the Republic of Korea Dr I Kim, Director, Pharmaceutical Standardization and Research Division, National Institute of Food and Drug Safety Evaluation(NIFDS),Korea Food and Drug Administration(KFDA),Chungbuk, Republic of Korea;Dr H-S Kim, Deputy Director, Pharmaceutical Standardization Division, National Institute of Food and Drug Safety Evaluation (NIFDS), Korea Food and Drug Administration (KFDA),Chungbuk, Republic of Korea State Pharmacopoeia of the Russian Federation Dr AMironov, General Director, Federal State Budgetary Institution Scientific Centre for Expert Evaluation of Medicinal Products (FSBI SCEMP); Dr IV Sakaeva, Deputy General Director, FSBI SCEMP; Dr EI Sakanjan, Director, Centre of Pharmacopoeia and International Cooperation, FSBI SCEMP; Dr ON Gubareva, Deputy Head, Department of International Cooperation, FSBI SCEMP; Dr RA Lavrenchuk, Research Fellow, Department of State Pharmacopoeia and Pharmacopoeia Analysis, FSBI SCEMP, Pharmacopoeia Committee, Ministry of Health, Moscow, Russian Federation Pharmacopoeia of Ukraine Professor OGryzodub, Director, Ukrainian Scientific Pharmacopoeial Centre for Quality of Medicines, Pharmacopoeia of Ukraine, Kharkov, Ukraine; Dr MDmitriieva, Senior Research Officer, Head of the PTS Group, Ukrainian Scientific Pharmacopoeial Centre for Quality of Medicines, Pharmacopoeia of Ukraine, Kharkov, Ukraine United States Pharmacopeia Dr Karen Russo, Vice President, Small Molecules, Documentary Standards Division, Rockville, MD, USA 来自WHO大区办公室的代表缺席会议: Regional Office for Africa, Brazzaville, Congo; Regional Office for the Americas, Pan American Health Organization, Washington, DC, USA; Regional Office for the Eastern Mediterranean, Cairo, Egypt; Regional Office for Europe, Copenhagen, Denmark; Regional Office for South-East Asia, New Delhi, India; Regional Office for the Western Pacific, Manila, Philippines。 WHO Secretariat Health Systems and Services (HSS)缺席会议。 Dr CF Etienne, Assistant Director-General Essential Medicines and Health Products (HSS/EMP) Mr C de Joncheere, Director, Essential Medicines and Health Products (EMP) Quality Assurance and Safety: Medicines (EMP/QSM) Dr LRgo,Coordinator, Quality Assurance and Safety: Medicines (QSM) Dr S Kopp, Manager, Medicines Quality AssuranceProgramme, QSM (Secretary) Dr H Schmidt, QSM Blood Products and RelatedBiologicals, QSM8 Medicines Regulatory SupportProgramme (MRS), QSM Dr APrat International Nonproprietary NamesProgramme (INN), QSM Dr RGBalocco, Manager PrequalificationProgramme, QSM Dr JSabartova Dr MSmid Medicines Access and Rational Use (EMP/MAR)缺席会议。 Traditional Medicine (Health Policy, Development and Services (HDS)/TRM)9 Quality, Safety and Standards (Immunization, Vaccines and Biologicals(IVB)/QSS)9 Mr David Bramley (report writer) Special acknowledgement and appreciation is given to Dr JAMolzon, Associate Director for International Programs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA, who attended as observer in her function as member of the WHO Expert Advisory Panel on the International Pharmacopoeia and Pharmaceutical Preparations 利益声明 Members of the WHO Expert Committee on Specifications for Pharmaceutical Preparations and temporary advisers reported the following: Professor SBawazir, Professor T Dekker, Ms N Guerrero Rivas,Professor J Hoogmartens, Professor S Jin, Ms MY Low, Ms CMunyimba-Yeta, Dr L Paleshnuik, Ms M-L Rabouhans and Dr J-L Robert reported no conflicts of interest Professor HGKristensen reported that he and his wife, a former employee of Novo Nordisk, hold investment interests in the company Professor Kristensen has provided an expert opinion and testimony as an independent expert in patent cases regarding the formulation and processing of medicines The declaration did not conflict with the subjects of the meeting Ms GNMahlangu reported that she would receive an out-of-pocket allowance from the Medicines Control Authority of Zimbabwe in accordance with the travel allowances schedule for sponsored travel Dr S Parra reported that she is a full-time employee of a governmental organization (Canadian Ministry of Health) and, as such, is a civil servant receiving remuneration from a regulatory agency Dr Parra works for the department that approves new medicines for the Canadian market As an employee of Health Canada she represents her organization in international forums and was present in sessions on topics relevant to her work (ie evaluation of the quality part of drug applications) as a stakeholder Professor AJ Nunn reported that he took part in discussions of thepaediatric hospital pharmacy practice for Rosemont Pharmaceuticals, for which he personally received payment in 2012 His research unit received a research grant in 2011 of ￡250 000 from the United Kingdom National Institute for Health Research; a research grant “GRIP” WP5 from EU FP7 for the current year of 6 million (part-consortium); and personal conference costs in 2011 from the European Paediatric Formulations Initiative He is a member of the European Medicines Agency (EMA) Paediatric Committee (PDCO) and PDCO Formulation Working Party, considering formulation development for paediatric investigation parties and for guidelines (2010~2014) Professor Nunn was not present in any Expert Committee session during which individual products were discussed Dr AJ van Zyl reported that he received the fees for the current year for consulting for the United States Pharmacopeia (USP), the Global Fund, and pharmaceutical companies He has provided an expert opinion on good manufacturing practices (GMP) in an arbitration case for Norton Rose, Cape Town, South Africa, from August 2011 to date The declarations of interest were presented to the Expert Committee for information There were no comments from Committee members or temporaryadvisers