0731 欧盟API GMP 中英文对照 CX 0112.docx

1、0731 欧盟API GMP 中英文对照 CX 0112EUROPEAN COMMISSION 欧盟委员会ENTERPRISE AND INDUSTRY DIRECTORATE-GENERAL 企业与工业管理局Consumer goods 消费品Pharmaceuticals 药品Brussels, 03 February 2010 布鲁塞尔 2010.02.03ENTR/F/2/AM/an D(2010) 3374EudraLex（European Union Law On drug regulatory affairs） 欧盟药品法规The Rules Governing Medicina

2、l Products in the European Union欧盟医药产品管理规则Volume 4卷4Good Manufacturing Practice良好生产规范Medicinal Products for Human and Veterinary Use人用和兽用医药产品Part II: Basic Requirements for Active Substances used as Starting Materials第二部分：作为起始物料的原料药的基本要求Document History 文件历史An amendment is made to Part II of the GMP

3、 Guide to incorporate对GMP指南第二部分的修订是为了纳入与ICH Q9关于质量风险principles of Quality Risk Management in line with the ICH Q9管理的指南一致的质量风险管理原则。guideline on Quality Risk Management. Amendments correspond to对指南第一部分第一章有过类似的修订并在2008年2月公布过。similar changes made to Part I Chapter 1 of the Guide and publishedin February

4、 2008. A new section on Quality Risk Management is本版本新增加了2.19节，一个关于质量风险管理的新章节。introduced as section 2.19. The remaining sections of chapter 2 are第二章节其余部分进行了重新编号。2.21节进行了一个微小的变更，renumbered. A minor change is made to section 2.21. No other除此以外，没有其它的变更。changes have been made.September 20072007年9月Public

5、 consultation 公开咨询 April 2008 until October 20082008年4月至2008年10月Adopted by the European Commission 欧盟委员会通过31 January 20102010年1月31日Deadline for coming into operation 生效日期31 July 20102010年7月31日Table of Contents 1 Introduction 1简介 1.1 Objective 1.1目的 1.2 Regulatory Applicability 1.2法规适用性1.3 Scope 1.3范

6、围2 Quality Management 2质量管理2.1 Principles 2.1原则 2.2 Quality Risk Management2.2质量风险管理2.3 Responsibilities of the Quality Unit(s)2.3质量部门的职责2.4 Responsibility for Production Activities2.4生产活动的职责2.5 Internal Audits (Self-Inspection)2.5内部审计（自检）2.6 Product Quality Review 2.6产品质量回顾3 Personnel 3 人员3.1 Perso

7、nnel Qualifications3.1 人员资质3.2 Personnel Hygiene3.2 人员卫生3.3 Consultants 3.3 顾问4 Buildings and Facilities 4 厂房设施4.1 Design and Construction 4.1 设计和建造4.2 Utilities 4.2 公用工程4.3 Water 4.3 水4.4 Containment 4.4 限制4.5 Lighting 4.5 照明4.6 Sewage and Refuse 4.6 废水废物4.7 Sanitation and Maintenance 4.7 公共卫生及保养 5

8、 Process Equipment 5 工艺设备5.1 Design and Construction 5.1 设计和建造5.2 Equipment Maintenance and Cleaning 5.2 设备的保养和清洁5.3 Calibration 5.3 校验5.4 Computerized Systems 5.4 计算机系统6 Documentation and Records 6 文件和记录6.1 Documentation System and Specifications 6.1 文件系统与规格标准6.2 Equipment Cleaning and Use Record 6

9、.2 设备清洁和使用记录6.3 Records of Raw Materials, Intermediates, API Labelling and Packaging Materials6.3 原料、中间产品、原料药的标签和包装材料的记录6.4 Master Production Instructions (Master Production and Control Records)6.4 生产指令（生产和控制记录）6.5 Batch Production Records (Batch Production and Control Records)6.5批生产记录（批生产和控制记录）6.6

10、Laboratory Control Records6.6 实验室控制记录（批检验记录）6.7 Batch Production Record Review6.7 批生产记录审核7 Materials Management7 物料管理7.1 General Controls7.1 控制通则7.2 Receipt and Quarantine7.2 接受和待检7.3 Sampling and Testing of Incoming Production Materials7.3 到货物料的取样和检测7.4 Storage7.4 贮存7.5 Re-evaluation7.5 再评估8 Produc

11、tion and In-Process Controls8 生产和过程控制8.1 Production Operations8.1 生产操作8.2 Time Limits8.2 时间限制8.3 In-process Sampling and Controls8.3 中控取样和控制8.4 Blending Batches of Intermediates or APIs8.4 中间产品和原料药的混批8.5 Contamination Control8.5 污染控制9 Packaging and Identification Labelling of APIs and Intermediates9

12、 中间产品和原料药的包装和贴签9.1 General9.1 总则9.2 Packaging Materials9.2 包装材料9.3 Label Issuance and Control9.3 标签放行和控制9.4 Packaging and Labelling Operations9.4 包装和贴签操作10 Storage and Distribution10 贮存和销售10.1 Warehousing Procedures10.1 入库程序10.2 Distribution Procedures10.2 销售程序11 Laboratory Controls11 实验室控制11.1 Gene

13、ral Controls11.1 控制通则11.2 Testing of Intermediates and APIs11.2 中间产品和原料药的检测11.3 Validation of Analytical Procedures11.3 分析方法的验证11.4 Certificates of Analysis11.4 分析报告11.5 Stability Monitoring of APIs11.5 原料药的稳定性监测11.6 Expiry and Retest Dating11.6 失效和复检日期11.7 Reserve/Retention Samples11.7 留样12 Validat

14、ion12 验证12.1 Validation Policy12.1 验证方针12.2 Validation Documentation12.2 验证文件12.3 Qualification12.3 确认12.4 Approaches to Process Validation12.4 工艺验证方法12.5 Process Validation Program12.5 工艺验证计划12.6 Periodic Review of Validated Systems12.6 验证系统的定期审核12.7 Cleaning Validation12.7 清洁验证12.8 Validation of A

15、nalytical Methods12.8 分析方法验证13 Change Control13 变更控制14 Rejection and Reuse of Materials14 物料的拒收和再利用14.1 Rejection14.1 拒收14.2 Reprocessing14.2 返工14.3 Reworking14.3 重新加工14.4 Recovery of Materials and Solvents14.4 物料和溶剂的回收利用14.5 Returns14.5 退回15 Complaints and Recalls15 投诉和召回16 Contract Manufacturers (

16、including Laboratories)16 合同生产企业（包含实验室）17 Agents, Brokers, Traders, Distributors, Repackers, and Relabellers17 代理商、经纪商、贸易商、经销商、重新包装商和重新贴签商17.1 Applicability17.1 适用性17.2 Traceability of Distributed APIs and Intermediates17.2 已销售中间产品和原料药的追踪17.3 Quality Management17.3 质量管理17.4 Repackaging, Relabelling

17、and Holding of APIs and Intermediates17.4 中间产品和原料药的重新包装、重新贴签和处理17.5 Stability17.5 稳定性17.6 Transfer of Information17.6 信息的传输17.7 Handling of Complaints and Recalls17.7 投诉和召回的处理17.8 Handling of Returns17.8 退货的处理18 Specific Guidance for APIs Manufactured by Cell Culture/Fermentation18 用于细胞培养/发酵而得原料药的特殊

18、指南18.1 General18.1 总则18.2 Cell Bank Maintenance and Recordkeeping18.2 细胞库的维护和记录保存18.3 Cell Culture/Fermentation18.3 细胞培养/发酵18.4 Harvesting, Isolation, and Purification18.4 收获、分离和精制18.5 Viral Removal/Inactivation Steps18.5 病毒除去/灭火步骤19 APIs for Use in Clinical Trials19 用于临床试验的原料药19.1 General19.1 总则19.

19、2 Quality19.2 质量19.3 Equipment and Facilities19.3 设备设施19.4 Control of Raw Materials19.4 原料的控制19.5 Production19.5 生产19.6 Validation19.6 验证19.7 Changes19.7 变更19.8 Laboratory Controls19.8 实验室控制19.9 Documentation19.9 文件20 Glossary20 词汇表1 Introduction1 介绍This guideline was published in November 2000 as A

20、nnex 18 to the GMP Guidereflecting the EUs agreement to ICH Q7A and has been used by manufacturers andGMP inspectorates on a voluntary basis. Article 46 (f) of Directive 2001/83/EC andArticle 50 (f) of Directive 2001/82/EC; as amended by Directives 2004/27/EC and2004/28/EC respectively, place new ob

21、ligations on manufacturing authorisation holders to use only active substances that have been manufactured in accordance with Good Manufacturing Practice for starting materials. The directives go on to say that the principles of Good Manufacturing Practice for active substances are to be adopted as

22、detailed guidelines. Member States have agreed that the text of former Annex 18 should form the basis of the detailed guidelines to create Part II of the GMP Guide.本指南已经在2000年11月以GMP指南附录18的形式公布过，它反应了欧盟对ICH Q7A的认可以，该指南已经被生产商和GMP检查员在自愿的原则下所使用。法令2001/83/EC的第46条和法令2001/82/EC的第50条分别修订为法令2004/27/EC和2004/2

23、8/EC，赋予了生产许可证持有人新的责任，即药品生产企业只能使用按照GMP要求生产的原料药作为起始物料。这些法令还指出将制定GMP的细则。会员国认为原来的附录18已构成详细指南的基础，可以作为GMP指南的第二部分。1.1Objective1.1 目的These guidelines are intended to provide guidance regarding Good ManufacturingPractice (GMP) for the manufacture of active substances under an appropriate system for managing

24、quality. It is also intended to help ensure that active substances meet therequirements for quality and purity that they purport or are represented to possess.In these guidelines “manufacturing” includes all operations of receipt of materials,production, packaging, repackaging, labeling, relabelling

25、, quality control, release,storage and distribution of active substances and the related controls. The term “should” indicates recommendations that are expected to apply unless shown to beinapplicable, modified in any relevant annexes to the GMP Guide, or replaced by analternative demonstrated to pr

26、ovide at least an equivalent level of quality assurance.The GMP Guide as a whole does not cover safety aspects for the personnel engaged in manufacture, nor aspects of protection of the environment. These controls are inherent responsibilities of the manufacturer and are governed by other parts of t

27、he legislation .These guidelines are not intended to define registration requirements or modify pharmacopoeial requirements and do not affect the ability of the responsiblecompetent authority to establish specific registration requirements regarding activesubstances within the context of marketing/m

28、anufacturing authorisations. Allcommitments in registration documents must be met.这些指南准备在适当的质量管理体系下为原料药生产提供关于药品生产质量管理规范的指导。这也是为了帮助确保原料药符合他们所声称和拥有的质量和纯度的要求。在这些指南中“生产”包含所有关于原料药的物料的接受、生产、包装、重新包装、贴签、重新贴签、质量控制、放行、贮存和销售的操作以及相关的控制。 “should”一词表示对预期应用的建议，除非表明不适用，或者是可以由提供同等质量水平的其它方法所替代。GMP指南整体上不涉及生产人员安全方面的内容，

29、也不设计环境保护方面。这些是生产者固有的责任，并由其它法规管理。这些指南没有定义注册方面的要求或修订药典的要求，本指南不影响主管机关在原料药销售/生产范围内制定特殊注册要求。所有在注册文件中的承诺必须得到满足。1.2Scope1.2 范围These guidelines apply to the manufacture of active substances for medicinal productsfor both human and veterinary use. They apply to the manufacture of sterile activesubstances onl

30、y up to the point immediately prior to the active substance being rendered sterile. The sterilisation and aseptic processing of sterile active substances are not covered, but should be performed in accordance with the principles and guidelines of GMP as laid down in Directive 2003/94/EC and interpre

31、ted in the GMP Guide including its Annex 1.这些指南适用于人用和兽用药品中使用到的原料药的生产。也适用于无菌API的生产，仅到API刚刚被灭菌前的那个时间点上为止。原料药的灭菌和无菌处理不包含在本指南中，但是应该按照法令2003/94/EC和GMP指南附件1的方针和指导执行。In the case of ectoparasiticides for veterinary use, other standards than theseguidelines, that ensure that the material is of appropriate quality, may be used.对于兽用外用杀虫剂，除