(中英文)-WHO药品GMP指南

Comment 微微微微1: 新增Comment 微微微微2: 修改Annex 2WHO good manufacturing practices for pharmaceutical products: main principles附录2WHO药品GMP：主要原则Introduction引言General considerations总则Glossary术语Quality management in the medicines industry: philosophy and essential elements制药企业的质量管理：GMP 理念和基本元素1. Pharmaceutical quality system 制药质量体系Quality risk management 质量风险管理Product quality review 产品质量回顾2. Good manufacturing practices for pharmaceutical products 药品GMP3. Sanitation and hygiene 清洁和卫生4. Qualification and validation 确认和验证5. Complaints 投诉6. Product recalls 产品召回7. Contract production, analysis and other activities 委托生产、检验和其他活动General 概述The contract giver 委托方The contract accepter 被委托方The contract 合同8. Self-inspection, quality audits and suppliers audits and approval 自检、质量审计、供应商审计和批准Items for self-inspection 自检项目Self-inspection team 自检团队Frequency of self-inspection 自检频率Self-inspection report 自检报告Follow-up action 后续措施Quality audit 质量审计Suppliers audits and approval 供应商审计和批准9. Personnel 人员General 概述Key personnel 关键人员10. Training 培训11. Personal hygiene 人员卫生12. Premises 厂房General 概述Ancillary areas 辅助区域Storage areas 仓储区域Weighing areas 称量区域Production areas 生产区域Quality control areas QC区域13. Equipment 设备14. Materials 物料General 概述Starting materials 起始物料Packaging materials 包装材料Intermediate and bulk products 中间体和成品Finished products 制剂Rejected, recovered, reprocessed and reworked materials 不合格、回收、返工和重加工物料Recalled products 召回产品Returned goods 退货Reagents and culture media 试剂和培养基Reference standards 标准品Waste materials 废弃物料Miscellaneous 其他15. Documentation 文件General 概述Documents required 需要的文件16. Good practices in production 生产良好规范General 概述Prevention of cross-contamination and bacterial contamination during production生产过程中交叉污染和额细菌污染的预防Processing operations 生产操作Packaging operations 包装操作17. Good practices in quality control QC良好规范Control of starting materials and intermediate, bulk and finished products 原材料、关键中间体、原料药和制剂的控制Test requirements 检测要求Batch record review 批记录审核Stability studies 稳定性研究References 参考文献Introduction引言The first WHO draft text on good manufacturing practices (GMP) was prepared in 1967 by a group of consultants at the request of the Twentieth World Health Assembly (resolution WHA20.34). It was subsequently submitted to the Twenty-first World Health Assembly under the title “Draft requirements for good manufacturing practice in the manufacture and quality control of medicines and pharmaceutical specialities” and was accepted.应第二十届世界卫生大会（大会决议WHA20.34）的要求， 1967年由一顾问小组起草了WHO 首版GMP草案。随后，以“药品和药学类的生产和质量控制的GMP草案要求”为题提交到第二十一届世界卫生大会并通过。The revised text was discussed by the WHO Expert Committee on Specifications for Pharmaceutical Preparations in 1968 and published as an annex to its twenty-second report. The text was then reproduced (with some revisions) in 1971 in the Supplement to the second edition of “The International Pharmacopoeia”.1968年，WHO 药品规范专家委员对修订的版本进行了讨论，并将其作为该委员会第22次报告附录出版。1971年，文档被复制后（有一些修订）作为国际药典第二版的补充内容出现。In 1969, when the World Health Assembly recommended the first version of the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce in resolution WHA22.50, it accepted at the same time the GMP text as an integral part of the Scheme. Revised versions of both the Certification Scheme and the GMP text were adopted in 1975 by resolution WHA28.65. Since then, the Certification Scheme has been extended to include the certification of: veterinary products administered to food-producing animals; starting materials for use in dosage forms, when they are subject to control by legislation in both the exporting Member State and the importing Member State; information on safety and efficacy (resolution WHA41.18, 1988).1969年，世界卫生大会在大会决议（WHA22.50）中形成第一版国际贸易的WHO药品质量认证计划，并在当时接受GMP文档作为计划的一部分。在1975年，决议WHA28.65 采用了修订后的认证体制和 GMP文档。从那时起，认证计划已扩展到包括以下内容的认证：可食用动物所用兽药进出口成员国有关法规控制的药品所用的起始物料。证明药品安全性和有效性的资料（决议WHA41.18，1998）In 1992, the revised draft requirements for GMP were presented in three parts, of which only Parts One and Two are reproduced in this document (1).1992年，修订后的GMP草案要求分为三个部分，其中只有1和2部分引入此文档中。“Quality management in the medicines industry: philosophy and essential elements”, outlines the general concepts of quality assurance (QA) as well as the principal components or subsystems of GMP, which are joint responsibilities of top management and of production and quality control management. These include hygiene, validation, self-inspection, personnel, premises, equipment, materials and documentation.“制药企业的质量管理： GMP理念和基本要素”概述了质量保证和GMP主要要素或体系的基本概念，这是企业最高管理层以及生产和质量控制部门的共同职责。包括卫生、验证、自检、人员、厂房、设备、物料和文件等内容。“Good practices in production and quality control”, provides guidance on actions to be taken separately by production and by quality control personnel for the implementation of the general principles of QA.“生产和质量良好规范 ”分别为生产和质量控制人员的具体操作提供了指南，以实现质量保证的基本总则。These two parts were subsequently supplemented by further guidelines which are integral parts of these GMP for pharmaceutical products. All these texts are available on the Medicines web page (/medicines/organization/qsm/activities/qualityassurance/gmp/gmpcover.html).这两部分随后通过药品GMP指南不可缺少的一部分内容进一步补充，这些内容可在药品网站上查到：(/medicines/organization/qsm/activities/qualityassurance/gmp/gmpcover.html).Considerable developments in GMP have taken place in the intervening years, and important national and international documents, including new revisions, have appeared (2-5). Thus there is a necessity to revise the main principles and incorporate the concept of validation.这些年来，GMP领域取得很大的发展，重要的国家和国际文件已经出现，包括新修订的（2-5）。因此有必要修订主要原则和合并验证概念。Among other items of feedback discussed during the consultation on WHO guidelines for medicines quality assurance, quality control (QC) laboratories and transfer of technology on 2731 July 2009, the need was identified to incorporate a new section on “Product quality review” under Chapter 1: “Quality assurance”.在2009年7月27-31日，协商WHO有关药品质量保证、质量控制实验室和技术转移指南期间，对反馈进行了讨论，认为有必要在第一章“质量保证” 加入一个新的章节“产品质量回顾 ”（ 1.6）。In addition, several updates were suggested to further enhance the guidelines. These included the concept of risk management, replacing “drugs” by the term “medicines” and introducing the concept of a “quality unit”.另外，指南中加入了几个更新，包括风险管理的关键，用术语“药品drugs”取代了“药medicines”并新引入 “质量部门”的概念。During 2012 the Secretariat was made aware that the current Goodmanufacturing practices (GMP) for pharmaceutical products: main principles,published as Annex 3 in the WHO Technical Report Series, No. 961, 2011,would need updating (/medicines/areas/quality_safety/quality_assurance/production/en/index.html Quality assurance of pharmaceuticals:a compendium of guidelines and related materials).2012年，秘书处意识到当前的“附件3：WHO药品 GMP：主要原则” ，WHO 技术报告系列，编号：961, 2011需要更新。（/medicines/areas/quality_safety/quality_assurance/production/en/index.html Quality assurance of pharmaceuticals:a compendium of guidelines and related material） Comment 微微微微3: 修改The WHO Expert Committee on Specifications for Pharmaceutical Preparations discussed the need for an update during its forty-seventh meeting and agreed to pursue the matter accordingly.WHO药品规范专家委员会在第47次会议中讨论并同意进行文件更新工作。The following sections were updated in the newly revised version and, after the usual consultation process, were presented to the forty-eighth Expert Committee for adoption:Section: Pharmaceutical quality systemSection 2: 2. Good manufacturing practices for pharmaceutical productsSection 7: Contract production, analysis and other activitiesSection 17: 17. Good practices in quality control 通过常规磋商流程，在新修订版本中对以下部分进行了更新，并提交给第48次专家委员会进行采纳：章节1：药品质量体系章节2: 2、药品生产管理规范章节7：委托生产、检验和其他活动章节17： 17、QC良好规范General considerations总则Licensed pharmaceutical products (marketing authorization) should be manufactured only by licensed manufacturers (holders of a manufacturing authorization) whose activities are regularly inspected by competent national authorities. This guide to GMP shall be used as a standard to justify GMP status, which constitutes one of the elements of the WHO Certification Scheme on the quality of pharmaceutical products moving in international commerce, through the assessment of applications for manufacturing authorizations and as a basis for the inspection of manufacturing facilities. It may also be used as training material for government medicines inspectors, as well as for production, QC and QA personnel in the industry. 许可的药品（销售许可）只能由经许可的定期由国家药品主管机构检查的生产商（生产许可的持有人）生产。本指南被用作标准来验证GMP状态，通过对生产许可申请的评估和对生产设施检查的依据，构成国际贸易药品质量WHO认证计划的一部分。此外，本指南也可用作政府药品检查员以及制药企业的生产、质量控制和质量保证人员的培训材料。The guide is applicable to operations for the manufacture of medicines in their finished dosage forms, including large-scale processes in hospitals and the preparation of supplies for use in clinical trials.该指南适用于药品生产的成品剂型的操作，包括在医院的大规模处理以及供给临床试验用药的制备。The good practices outlined below are to be considered general guides1, and they may be adapted to meet individual needs. The equivalence of alternative approaches to QA, however, should be validated. The guide as a whole does not cover safety aspects for the personnel engaged in manufacture or environmental protection: these are normally governed by national legislation. A new concept of hazard analysis related to the risks in production and personnel safety has also newly recommended (WHO Technical Report Series, No. 961, Annex 7). The manufacturer should assure the safety of workers and take the necessary measures to prevent pollution of the external environment.下述规范被视为基本指导原则 1，也可能适用于个体需求。然而对于质量保证，应验证两种方法的等同性。该指南没有覆盖从事生产或环境保护人员的安全方面：这些通常由国家法律来管理。生产和人员安全性相关的危险分析的新概念也引入了（WHO 技术报告系列，编号： 961，附录 7）。生产商应当保证工人的安全并采取必要的措施防止外部环境的污染。International Nonproprietary Names (INN) for pharmaceutical substances designated by WHO should be used when available, together with other designated names.如适用，应当使用WHO 指定的国际非专利药品名称或其他指定的名称。Glossary术语The definitions given below apply to the terms used in this guide. They may have different meanings in other contexts.下述定义适用于本指南使用的术语。在其他文章中这些术语可能有其他的意思。active pharmaceutical ingredient (API)Any substance or mixture of substances in