欧洲药典CEP证书修订更新规定指南中英对照版
欧盟GMP附录15确认和验证中英文新版
欧盟GMP附录15确认和验证欧盟GMP附录15确认和验证ANNEX 15 附件15Qualification and Validation确认和验证Table of Contents 目录1. Qualification and Validation 确认和验证2. Planning for Validation 验证计划3. Documentation 文件4. Qualification 确认5. Process Validation 工艺验证6. Cleaning Validation 清洁验证7. Change Control 变更控制8. Revalidation 再验证9. Glossary 术语表Qualification and Validation 确认和验证Principle 原理1.This Annex describes the principles of qualification and validation which are applicable to the manufacture of medicinal products. It is a requirement of GMP that manufacturers identify what validation work is needed to prove control of the critical aspects of their particular operations. Significant changes to the facilities, the equipment and the processes, which may affect the quality of the product, should be validated. A risk assessment approach should be used to determine the scope and extent of validation.1.本附件描述了确认和验证的原理，适用于医药产品的生产者。
20100731 欧盟API GMP 中英文对照 CX 20110112
EUROPEAN 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 Medicinal 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Table of Contents目录1 Introduction1简介1.1 Objective1.1目的1.2 Regulatory Applicability1.2法规适用性1.3 Scope1.3范围2 Quality Management2质量管理2.1 Principles2.1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 Activities 2.4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 Review2.6产品质量回顾3 Personnel3 人员3.1 Personnel Qualifications3.1 人员资质3.2 Personnel Hygiene3.2 人员卫生3.3 Consultants3.3 顾问4 Buildings and Facilities4 厂房设施4.1 Design and Construction4.1 设计和建造4.2 Utilities4.2 公用工程4.3 Water4.3 水4.4 Containment4.4 限制4.5 Lighting4.5 照明4.6 Sewage and Refuse4.6 废水废物4.7 Sanitation and Maintenance4.7 公共卫生及保养5 Process Equipment5 工艺设备5.1 Design and Construction5.1 设计和建造5.2 Equipment Maintenance and Cleaning5.2 设备的保养和清洁5.3 Calibration5.3 校验5.4 Computerized Systems5.4 计算机系统6 Documentation and Records6 文件和记录6.1 Documentation System and Specifications6.1 文件系统与规格标准6.2 Equipment Cleaning and Use Record6.2 设备清洁和使用记录6.3 Records of Raw Materials, Intermediates, API Labelling and Packaging Materials 6.3 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 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 Production 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 Intermediates 9 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 General 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 Validation12 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 Analytical 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 (including Laboratories)16 合同生产企业（包含实验室）17 Agents, Brokers, Traders, Distributors, Repackers, and Relabellers 17 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 and Holding of APIs and Intermediates 17.4 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/Fermentation 18 用于细胞培养/发酵而得原料药的特殊指南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19.2 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 Annex 18 to the GMP Guide reflecting the EU’s agreement to ICH Q7A and has been used by manufacturers and GMP inspectorates on a voluntary basis. Article 46 (f) of Directive 2001/83/EC and Article 50 (f) of Directive 2001/82/EC; as amended by Directives 2004/27/EC and 2004/28/EC respectively, place new obligations 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 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。
cep电子版纸版递交指南中英文cepguidanceforcepapplications
201306 PA/PH/CEP(09)108 2R CEP电子提交和纸质提交指南（中英文）官网原文下载：新版本生效日期：2013年8月1日Certification of Substances DivisionFK/CBPUBLIC DOCUMENT公开文件(LEVEL 1)第一层次English only/Anglais seulement仅英文版PA/PH/CEP(09)108, 2RStrasbourg, June 2013 Certification of suitability to Monographs of the European PharmacopoeiaGuidance for electronic and paper submissionsFor Certificates of Suitability (CEP) applicationsCEP电子和纸质申报指南Date of implementation: 1 August 2013Address: 7, sllee Kastner, CS 30026F-67081 Strasbourg (France)Telephone: 33(0)3 88 41 30 30 – Fax: 33 (0) 3 88 41 27 71 – e-mail:Internet:Table of content目录1Introduction介绍2Scope and general requirements范围和一般要求3Electronic submission formats电子申报格式eCTD submission format eCTD申报格式NeeS submission format NeeS申报格式PDF format PDF格式4Submission of paper dossiers纸质文件提交5Content and structure of an application申报的内容和结构6Lifecycle management of applications申报的生命周期管理Granularity and updated sections章节分类和更新部分When to submit a baseline Module 3什么时候提交基准模块37Validation by the EDQM EDQM验证8Routes (or pathways) of submission递交方式（途径）9Security安全性1Introduction介绍This document is guidance for electronic and paper submissions for Certificates of Suitability (CEPs) applications. Information and requirements described in this document are intended to facilitate the handling and assessment of submissions for certificates of suitability (CEPs) and to maintain their lifecycle even if the submission is not an eCTD.本文件意在指导CEP的电子和纸质申报。
WHO GMP补充指南验证(中英对照)
Annex 4附件4Supplementary guidelines on good manufacturing practices: validation 药品生产质量管理规范补充指南：验证1Introduction简介2Scope范围3Glossary术语4Relationship between validation and qualification验证和确认之间的联系5. Validation5.1. Approaches to validation验证方法5.2. Scope of validation验证范围5Qualification确认6Calibration and verification校准和核实7Validation master plan验证主计划8Qualification and validation protocols确认和验证方案9Qualification and validation reports确认和验证报告10Qualification stages确认程序11Change control变更控制12Personnel人员References参考文献Appendix 1附录1Validation of heating, ventilation and air-conditioning systems采暖、通风和空气净化系统的验证Appendix 2附录2Validation of water systems for pharmaceutical use制药用水系统的验证Appendix 3附录3Cleaning validation清洁验证Appendix 4附录4Analytical method validation分析方法验证Appendix 5附录5Validation of computerized systems计算机系统的验证Appendix 6附录6Qualification of systems and equipment系统和设备的确认Appendix 7附录7Non-sterile process validation非灭菌工艺的验证1. Introduction简介Validation is an essential part of good manufacturing practices (GMP). It is, therefore, an element of the quality assurance programme associated with a particular product or process. The basic principles of quality assurance have as their goal the production of products that are fit for their intended use. These principles are as follows:验证是药品生产管理规范（GMP）的一个重要组成部分；也正因如此，所以它同时也是产品或工艺的质量保证计划的一个不可或缺的要素。
EDQM guidance_on_frequent_changes_to_applications关于“CEP常见变更申请指南”中英对照 2013.07.13
Certification of Substances DivisionFS/CBPUBLIC DOCUMENT(Level 1)English only/Anglais seulementPA/PH/CEP (11) 76Strasbourg, July 2012斯特拉斯堡，2012年7月Certification of Suitability toMonographs of the European PharmacopoeiaGuidance on frequent changes to applicationsfor Certificates of Suitability (CEPs)欧洲药典适用性证书常见CEP变更申请指南Address: 7 allée Kastner CS 30026 - F 67081 StrasbourgTelephone: 33 (0) 3 88 41 30 30 - E-mail:cep@edqm.eu - Fax: 33 (0) 3 88 41 27 71Internet : http://www.edqm.euThis document should be considered as an explicative note and should be read jointly with the EDQM Guideline on Revision/Renewal of Certificates of Suitability to the Monographs of the European Pharmacopoeia (PA/PH/CEP (04) 2).This document is intended as a guide to applicants when compiling their documentation fornotification/revision/renewal of their applications for certificates of suitability (CEPs). It has arisen from frequent issues occurring in submissions of notifications and revisions of dossiers for chemical purity, and it describes the key points to be considered.By improving the quality of the data submitted, the time for the evaluation of the dossiers will be reduced and requests for additional information will be limited. 本文件应被当作是解释性的文字，应与EDQM关于CEP修订/更新指南(PA/PH/CEP (04) 2)一起解读。
EDQM关于CEP证书申请相关程序(09) 109, 1R的修订中文译稿
PA/PH/CEP (09) 109, 1R EDQM关于CEP证书申请相关程序的修订"中文译稿Certification of Substance DivisionHB/CBPUBLICEnglish only/Anglais seulementPA/PH/CEP(09)109,1R斯特拉斯堡, 2010年3月欧洲药典适用性证书说明：EDQM关于CEP证书书面及电子递交程序的更新Address: 7 allée Kastner CS 30026 – F 67081 StrasbourgTelephone: 33 (0) 3 88 41 30 30 – Email:cep@edqm.eu – Fax: 33 (0) 3 88 41 27 71Internet: http://www.edqm.eu说明：EDQM关于CEP证书书面及电子递交程序的更新为了完全按照ICH M2 EWG 和EMA 的要求推进CEP证书的电子申请，CEP证书处修订了电子申报的要求。
电子申报被认为可通过提升工作流程和申请的生命周期管理从而更好地处理申报文件。
强烈建议申报人进行电子申报，不再同时上报打印版资料。
申请人必须选择是进行电子申报还是打印版申报；并在申报申请表格中注明选择。
该修订的指南已经出版，立即生效。
电子申报：电子申报可以是eCTD格式（优先考虑），NeeS 格式或模块3的单独PDF。
适用于新的或已存在的文件和各类申报。
关于电子申报的EDQM指导原则已经被修订，以符合ICH M2EWG（电子通用技术文件规格）的要求，同时根据申报格式给出了详细指导。
除了申请结构，还有一些关于电子申报的关键方面需要高度重视：-QOS必须使用EDQM的模板并提供PDF格式，不再接受word版。
-当模块3的章节受到影响时（例如缺陷信的回复，修订申请等），每次都要申报更新过的章节。
-e CTD，应描述CEP申请的信封的内容此新要求适用于任何新申请，通知，修订或者更新申请。
欧盟GMP附录15：确认与验证(修订版英文+中文)
EUROPEAN COMMISSIONENTERPRISE DIRECTORATE-GENERALSingle market, regulatory environment, industries under vertical legislationPharmaceuticals and cosmeticsBrussels,30 March 2015EudraLex欧盟药品管理法Volume 4EU Guidelines forGood Manufacturing Practice forMedicinal Products for Human and Veterinary Use第四卷欧盟人用和兽用药品GMP指南Annex 15: Qualification and Validation附录15:确认和验证Legal basis for publishing the detailed guidelines:Article 47 of Directive 2001/83/EC on the Community code relating to medicinal products for human use and Article 51 of Directive 2001/82/EC on the Community code relating to veterinary medicinal products. This document provides guidance for the interpretation of the principles and guidelines of good manufacturing practice (GMP) for medicinal products as laid down in Directive 2003/94/EC for medicinal products for human use and Directive 91/412/EEC for veterinary use.发布该细化指南的法律依据:人用药物欧共体法案指令2001/83/EC第47章和兽用药物欧共体法案指令2001/82/EC第51章。
欧洲药典适用性证书的变更更新的管理程序 中英对照 2013.07.13
Procedures for management of revisions/renewals of certificates of suitability to the European Pharmacopoeia monographs Certification of suitability to Monographs of the European Pharmacopoeia欧洲药典适用性证书PROCEDURES FOR MANAGEMENT OF REVISIONS/RENEWALS OF CERTIFICATES OF SUITABILITY TO THE EUROPEAN PHARMACOPOEIAMONOGRAPHS欧洲药典适用性证书的变更/更新的管理程序Introduction:介绍This document should be read in conjunction with the EDQM “Guideline on Requirements on Revision/Renewal of Certificates of Suitability to the European Pharmacopoeia monographs”(PA/PH/CEP (04) 2, as amended), which describes the conditions to be fulfilled as well as the documentation to be submitted for each request for revision.此文件应该与EDQM的“欧洲药典适用性证书修订与更新规定指南” (PA/PH/CEP (04) 2)联合起来阅读，后者描述了每个变更所要求满足的条件，以及要提供的文件资料。
The procedures for the management of revisions of certificates of suitability (CEPs) are described below and have been revised according to the revised European Regulation for Variations to Marketing Authorisation Applications.对于CEP证书变更管理的程序，在下面进行了描述，并且按照新修订的欧洲市场授权申请的有关法规进行了修订。
EDQM guidance_on_frequent_changes_to_applications关于“CEP常见变更申请指南”中英对照 2013.07.13
Certification of Substances DivisionFS/CBPUBLIC DOCUMENT(Level 1)English only/Anglais seulementPA/PH/CEP (11) 76Strasbourg, July 2012斯特拉斯堡，2012年7月Certification of Suitability toMonographs of the European PharmacopoeiaGuidance on frequent changes to applicationsfor Certificates of Suitability (CEPs)欧洲药典适用性证书常见CEP变更申请指南Address: 7 allée Kastner CS 30026 - F 67081 StrasbourgTelephone: 33 (0) 3 88 41 30 30 - E-mail:cep@edqm.eu - Fax: 33 (0) 3 88 41 27 71Internet : http://www.edqm.euThis document should be considered as an explicative note and should be read jointly with the EDQM Guideline on Revision/Renewal of Certificates of Suitability to the Monographs of the European Pharmacopoeia (PA/PH/CEP (04) 2).This document is intended as a guide to applicants when compiling their documentation fornotification/revision/renewal of their applications for certificates of suitability (CEPs). It has arisen from frequent issues occurring in submissions of notifications and revisions of dossiers for chemical purity, and it describes the key points to be considered.By improving the quality of the data submitted, the time for the evaluation of the dossiers will be reduced and requests for additional information will be limited. 本文件应被当作是解释性的文字，应与EDQM关于CEP修订/更新指南(PA/PH/CEP (04) 2)一起解读。
欧洲药典-凡例(中英文对照)
欧洲药典-凡例1.1. GENERAL STATEMENTSThe General Notices apply to all monographs and other texts of the European Pharmacopoeia.总论的内容适用于各论和欧洲药典中的其它章节。
The official texts of the European Pharmacopoeia are published in English and French. Translations in other languages may be prepared by the signatory States of the European Pharmacopoeia Convention. In case of doubt or dispute, the English and French versions are alone authoritative.欧洲药典以英语和法语形式发行,欧洲药典委员会的签署国可将药典内容译成其它语言,但若发生争议,应以英语和法语版为权威。
In the texts of the European Pharmacopoeia, the word "Pharmacopoeia" without qualification means the European Pharmacopoeia. The official abbreviation Ph. Eur. may be used to indicate the European Pharmacopoeia.在欧洲药典中,如无特殊规定,“药典”是指欧洲药典,缩写Ph. Eur.也指欧洲药典。
The use of the title or the subtitle of a monograph implies that the article complies with the requirements of the relevant monograph. Such references to monographs in the texts of the Pharmacopoeia are shown using the monograph title and reference number in italics.文章中如果引用了各论中的标题和副标题意味着文章内容符合相关各论的要求。
CEP申请程序 中英文对照 来自于EDQM网站
COUNCIL OF EUROPEPUBLIC HEALTH COMMITTEE(Partial Agreement)RESOLUTION AP-CSP (07) 1(adopted by the Public Health Committee (Partial Agreement) (CD-P-SP)on 21/02/2007Certification of suitability to the monographs of the European Pharmacopoeia(revised version)欧洲议会公共卫生委员会（局部协定）决议AP-CSP (07) 1号2007年2月21日欧洲议会公共卫生委员会（局部协定）（CD-P-SP）通过欧洲药典适用性证书（修订版）The public Health Committee (Partial Agreement) (CD-P-SP) consisting, for the purposes of the Convention on the Elaboration of a European Pharmacopoeia, of delegations appointed by the Parities to the said Convention, namely the delegations of Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Croatia, Cyprus, the Czech Republic, Denmark, Estonia, Finland, "the Former Yugoslav Republic of Macedonia", France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxemburg, Malta, Montenegro, the Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovak Republic, Slovenia, Spain, Sweden, Switzerland, Turkey, United Kingdom and the European Union.Considering the implementation of the Procedure for the certification of suitability of monograph of the European Pharmacopoeia adopted on 1 July 1993 by the Public Health Committee (Partial Agreement) (CD-P-SP) in its resolution AP-(CSP (93) 5 and revised on:- 4 October 1996 Resolution AP-CSP (96) 5- 8 May 1998 Resolution AP-CSP (98) 2- 22 December 1999 Resolution AP-CSP (99) 4Having regard to the decision by the European Pharmacopoeia Commission at its session of November 2006 to update and complete the resolution AP-CSP (99) 4.Has therefore decided to amend the resolution AP-CSP (99) 4 and to replace it by the text attached.根据建立欧洲药典协定公约，公共卫生委员会（局部协定）(CD-P-SP)由以下公约成员国指定代表组成，即以下国家代表：奥地利、比利时、波斯尼亚和黑塞哥维那、保加利亚、克罗地亚、塞浦路斯、捷克共和国、丹麦、艾沙尼亚、芬兰、“前南斯拉夫的马其顿共和国”、法国、德国、希腊、匈牙利、冰岛、爱尔兰、意大利、拉脱维亚、利陶宛、卢森堡、马耳他、门的内哥罗、荷兰、挪威、波兰、葡萄牙、罗马尼亚、塞尔维亚、斯洛伐克共和国、斯洛文尼亚、西班牙、瑞典、瑞士、土耳其、英国和欧盟。
David Cockburn-欧盟药品流通管理规范中文翻译
质量体系的维护
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批发商的新义务-2
如接收到或供货疑似伪劣产品，应向主管部门通报 确认供货批发商符合GDP 确保任何代理商符合法规要求
13
药品流通
目的：加强GDP条款
比如：当接收到/供货确认或疑似伪劣产品时，批发商有义务通知监管机构
将代理商列入药品立法管理的范围
•
• •
批发商必须持有批发经销许可证
• 由所在成员国国家的主管机构颁发
2
进口欧盟
欧盟以外国家/地区的药品进入欧盟，须持生产许可证
3
批发商的责任
合适的厂房设施和设备
• 随时都可接受检查
合适的人员
• 包括一个“负责人员”，此人需达到国家法规所规定的最低要求
•
•
只能从经过批准的供货商采购药品
只能向经批准的代理商供货
6
更新版的欧盟GDP指南
修订稿公开征求意见的截日期：2011年12月31日 主要变化：
• 文件结构类似于欧盟GMP指南
质量管理 人员 厂房设施与设备 文件 投诉、退货、伪劣药品与召回 委托贮运 自检 运输
贮运操作
代理商
7
检查
批发商许可证持有者需接受国家监管机构的检查
• 批准前进行
•
•
定期检查
飞行检查（因某种原因而作的检查）
欧盟药品流通管理规范
生产和质量符合处处长 David Cockburn
中国医药设备工程协会 会议， 北京， 2012年3月
An agency of the European Union
内容
• 批发分销授权 • 药品流通管理规范
• 药品防伪指令的影响
1
欧洲药典CEP证书修订更新规定指南中英对照版
欧洲药典CEP证书修订更新规定指南中英对照版Date of implementation: 1 March 2010Introduction:The holder of a Certificate of suitability shall inform the EDQM of any change to the information in the certification dossier by sending an application form and all necessary documents demonstrating that the conditions laid down in the present guideline are met.Classification of changesThe changes have been classified in three categories (notification/minor/major) depending on the potential impact of the change on the quality of the final substance. These three categories are based on those (IA-IAIN/IB/II) of the Commission Regulation (EC) No 1234/2008 concerning the examination of variations to the terms of marketing authorisation for medicinal products for human use and veterinary medicinal products.Any change not classified as a notification or a major change should be classified as a minor change except in the following cases where a new application should be submitted:- addition of a new route of synthesis and/or a new manufacturing site where the specifications of the final substance are different from the one already approved- transfer to a new holder that is not the same legal entity as the approved one, where the transfer does not occur because of a merger or because the company is sold, and where the manufacturer does not take out the Certificate of suitability in their own name.The changes related to Ph. Eur. monograph revisions or any other regulatory requirements are treated separately andgenerally initiated by the EDQM.执行日期：2010年3月1日介绍：欧洲药典适用性证书持有人必须向EDQM报告所有与申报文件有关的变更，申报时应填写申请表格和所有必要的资料，证明变更符合现行指南的规定。
欧盟GMP中英文对照.docx
European Union药品生产质量管理规范GUIDE TO GOOD MANUFACTURING PRACTICE FOR MEDICINAL PRODUCTSThe rules governing medicinal products in the European Union药品生产质量管理规范目录第一章质量管理CHAPTER 1: QUALITY MANAGEMENT原则 (5)Principle (5)质量保证 (5)Quality Assurance (5)药品生产质量管理规范(GMP) (7)Good Manufacturing Practice for Medicinal Products (7)质量控制 (QC) (9)Quality Control (9)产品质量回顾 (10)第二章人员CHAPTER 2: PERSONNEL (11)原则 (11)Principle (11)通则 (12)General (12)关键人员 (12)Key Personnel (12)培训 (12)Training (15)人员卫生 (16)Personnel Hygiene (16)第三章厂房和设备CHAPTER 3: PREMISES AND EQUIPMENT (18)原则 (18)Principle (18)厂房 (18)Premises (18)通则 (18)General (18)生产区 (19)The rules governing medicinal products in the European Union药品生产质量管理规范Production Area........................................................................................................................19贮存区21....................................................................................................................................Storage Area21............................................................................................................................. 22 质量控制区....................................................................................................................... Quality Control Area2222 附助区................................................................................................................................. Ancillary Areas2223 设备...................................................................................................................................... Equipment23第四章文件24CHAPTER 4: DOCUMENTATION24原则...................................................................................................................................... Principle2425 通则...................................................................................................................................... General2527 文件要求............................................................................................................................. Documents Required2727 SpecificationsSpecifications for starting and packaging27materialsSpecifications for Intermediate and Bulk 27ProductsSpecifications for FinishedProducts......................................................................................28Manufacturing Formulae and ProcessingInstructions (28)Packaging Instructions............................................................................................................30Batch ProcessingRecords.......................................................................................................31 Batch Packaging32Records. ...................................................................................................... Procedures and33 Records......................................................................................................... Receipt34Sampling.............................................................................................................................................................................................................................................................................34 35 Testing35OtherThe rules governing medicinal products in the European Union药品生产质量管理规范第五章生产CHAPTER 5: PRODUCTION36................................................. .............................................原则36......................................................................................................................................Principle (36)36通则......................................................................................................................................General (36)39生产过程中对交叉污染的预防.................................................................................... Prevention of Cross-contamination in Production (39)验证 (40)Validation (40)原料 (41)Starting Materials (41)..............................................................................................生产操作：中间产品和待包装产品42.......................................................................... Processing Operations:Intermediate and Bulk Products.. (42)包装材料 (43)Packaging Materials (43)包装操作44............................................................................................................................. Packaging Operations (44).....................................................................................成品46...................................................................................................................................... Finished Products. (46)46不合格、回收料和退货物料 ........................................................................................Rejected, Recovered and Returned Materials (46)第六章质量控制CHAPTER 6: QUALITY CONTROL (48)原则 (48)Principle (48)The rules governing medicinal products in the European Union药品生产质量管理规范通则 ........................................ . (48)48General... ................................................................................................................................质量控制实验室规范49......................................................................................................Good Quality Control LaboratoryPractice.....................................................................................................................................................................................................4949Documentation50Sampling................................................................................................................................52Testing... ................................................................................................................................销售产品的稳定性考察54.................................................................................................第七章 委托生产与委托检验CHAPTER 7: CONTRACT MANUFACTURE AND ANALYSIS (55)原则55........................................ ..............................................................................................Principle...................................55..............................................................................................通则56........................................ ..............................................................................................General (56).............................................................................................. 委托方56.................................... ..............................................................................................The Contract Giver (56)............................................................................................ 受托方57.................................... .............................................................................................The Contract Acceptor57.............................................................................................合同58........................................ ..............................................................................................The Contract.............................58.............................................................................................第八章 投诉与召回CHAPTER 8: COMPLAINTS AND PRODUCT RECALL (59)原则 ........................................ . (59)Principle.................................... ..............................................................................................59 投诉 ........................................ ..............................................................................................59 Complaints................................ . (59)召回 ........................................................................................................................................60 Recalls......................................................................................................................................60第九章自查CHAPTER 9: SELF INSPECTION (61)原则 ......................................................................................................................................................................................................................................................... 61 Principle (61)附件 8 原辅料和包装材料的取样4ANNEX8 SAMPLING OF STARTING AND PACKAGING MATERIALS (63)原则 (63)Principle (63)人员 (63)Personnel (63)原辅料 (63)Starting materials (64)包装材料 (65)Packaging material (65)第一章质量管理CHAPTER 1 QUALITY MANAGEMENTPrinciple原则生产许可证持有厂家只能生产医药产品，以确保药品符合其预期的使用目的，符合销售许可证的要求，并不因药品安全性、质量或药效方面的问题而给患者带来风险。
IPEC全文译稿中英文对照
FOREWORD 前言The quality of excipients is critical to assure the safety, quality and efficacy of medicines. Excipients have a wide range of applications and are essential components of the drug product formulation. Characteristics that excipients impart to formulated drug products include cosmetic appearance, stability and delivery of the active ingredient. Therefore, applying appropriate Good Manufacturing Practice (GMP) principles to excipients is essential. 辅料的质量对保证药品的安全、质量和功效是至关重要的。
辅料的应用范围广泛，是药品生产配方的基本成分。
辅料的特性直接影响药品的配方，包括化妆品的外观、稳定性和活性成分的输送。
因此，应用适当的GMP 规则是辅料的基础。
In contrast to finished dosage forms and Active Pharmaceutical Ingredients (APIs), there are no specific GMP regulations for excipients. In addition, there are a large number of applications of this diverse range of materials which makes the development of excipient GMP guidelines challenging. However, there is a general expectation that excipients are manufactured to recognised GMP principles.与制剂和原料药相比，没有明确的针对辅料的GMP的规则。
欧洲药品GMP检查指南及附件(中英文)
GUIDE TO GOOD MANUFACTURINGPRACTICE FOR MEDICINAL PRODUCTS药品GMP检查指南.PIC/S July 2004Reproduction prohibited for commercial purposes.Reproduction for internal use is authorised,provided that the source is acknowledged.Editor: PIC/S SecretariatP.O. Box 5695CH-1211 Geneva 11e-mail: daniel.brunner@web site: :// 1 July 2004 PE 009-2TABLE OF CONTENT目录INTRODUCTION介绍 (1)CHAPTER 1 QUALITY MANAGEMENT 质量管理 (4)PRINCIPLE 原则 (4)QUALITY ASSURANCE 质量保证 (4)GOOD MANUFACTURING PRACTICE FOR MEDICINAL PRODUCTS (GMP) 药品GMP (6)QUALITY CONTROL 质量控制 (7)CHAPTER 2 PERSONNEL 人员 (10)PRINCIPLE 原则 (10)GENERAL 通则 (10)KEY PERSONNEL 关键人员 (10)TRAINING 培训 (13)PERSONAL HYGIENE 个人卫生 (14)CHAPTER 3 PREMISES AND EQUIPMENT 厂房和设备 (16)PRINCIPLE 原则 (16)PREMISES General总则 (16)Production Area 生产区域 (17)Storage Areas 储存区域 (19)Quality Control Areas 质量控制区域 (20)Ancillary Areas 辅助区域 (20)EQUIPMENT 设备 (21)CHAPTER 4 DOCUMENTATION 文件 (23)PRINCIPLE 原则 (23)GENERAL 总则 (23)DOCUMENTS REQUIRED 必需的文件 (25)MANUFACTURING FORMULA AND PROCESSING INSTRUCTIONS 生产方法和加工指示 (27)PACKAGING INSTRUCTIONS 包装指示 (28)BA TCH PROCESSING RECORDS 批加工记录 (29)BA TCH PACKAGING RECORDS 批包装记录 (30)PROCEDURES AND RECORDS 程序和记录 (32)CHAPTER 5 PRODUCTION 生产 (36)PRINCIPLE 原则 (36)GENERAL 通则 (36)PREVENTION OF CROSS-CONTAMINATION IN PRODUCTION 生产过程中防止交叉污染 (38)V ALIDATION 验证 (39)STARTING MA TERIALS 起始物料 (40)PROCESSING OPERA TIONS - INTERMEDIATE AND BULK PRODUCTS 加工操作：中间体和散装产品 (42)PACKAGING MATERIALS 包装材料 (42)PACKAGING OPERATIONS 包装操作 (43)FINISHED PRODUCTS 最终成品 (45)REJECTED, RECOVERED AND RETURNED MATERIALS 拒绝的，回收的和退回的物料46CHAPTER 6 QUALITY CONTROL 质量控制 (48)PRINCIPLE 原则 (48)GENERAL 通则 (48)GOOD QUALITY CONTROL LABORATORY PRACTICE 优良质量控制实验室实践 (49)DOCUMENTATION 文件 (49)SAMPLING 取样 (50)TESTING 检测 (52)CHAPTER 7 CONTRACT MANUFACTURE AND ANAL YSIS 合同加工和分析 (55)PRINCIPLE 原则 (55)GENERAL 通则 (55)THE CONTRACT GIVER 合同提供人 (55)THE CONTRACT ACCEPTOR 合同接受人 (56)THE CONTRACT 合同 (57)CHAPTER 8 COMPLAINTS AND PRODUCT RECALL 抱怨和产品召回 (59)PRINCIPLE 原则 (59)COMPLAINTS 抱怨 (59)RECALLS 召回 (60)CHAPTER 9 SELF INSPECTION 自检 (61)PRINCIPLE 原则 (61)ANNEX 1 MANUFACTURE OF STERILE MEDICINAL PRODUCTS无菌药品的生产 (63)PRINCIPLE (63)GENERAL (63)BLOW/FILL/SEAL TECHNOLOGY (67)TERMINALL Y STERILISED PRODUCTS (67)ASEPTIC PREPARA TION (68)PERSONNEL (68)PREMISES (70)EQUIPMENT (71)SANITATION (71)PROCESSING (71)STERILISATION (73)STERILISATION BY HEA T (74)MOIST HEAT (75)DRY HEAT (75)STERILISATION BY RADIATION (75)STERILISATION WITH ETHYLENE OXIDE (76)FILTRATION OF MEDICINAL PRODUCTS WHICH CANNOT BE STERILISED IN THEIR FINAL CONTAINER (77)FINISHING OF STERILE PRODUCTS (77)QUALITY CONTROL (78)ANNEX 2 MANUFACTURE OF BIOLOGICAL MEDICINAL PRODUCTS FOR HUMAN USE人用生物药品的生产 (79)SCOPE (79)PRINCIPLE (79)PERSONNEL (80)PREMISES AND EQUIPMENT (81)ANIMAL QUARTERS AND CARE (82)DOCUMENTATION (82)PRODUCTION (83)QUALITY CONTROL (84)ANNEX 3 MANUFACTURE OF RADIOPHARMACEUTICALS 放射性药品的生产 (85)PRINCIPLE (85)PERSONNEL (85)PREMISES AND EQUIPMENT (85)PRODUCTION (86)QUALITY CONTROL (86)DISTRIBUTION AND RECALLS (86)ANNEX 4 MANUFACTURE OF VETERINARY MEDICINAL PRODUCTS OTHER THAN IMMUNOLOGICALS MANUFACTURE OF PREMIXES FOR MEDICATED FEEDING STUFFS 除为预混合加药饲料原料生产的免疫产品以外的，兽药产品的生产 (87)THE MANUFACTURE OF ECTOPARASITICIDES (88)THE MANUFACTURE OF VETERINARY MEDICINAL PRODUCTS CONTAINING PENICILLINS (88)RETENTION OF SAMPLES (point 1.4. viii and point 6.14.) (88)STERILE VETERINARY MEDICINAL PRODUCTS (88)ANNEX 5 MANUFACTURE OF IMMUNOLOGICAL VETERINARY MEDICAL PRODUCTS免疫兽药产品的生产 (89)PRINCIPLE (89)PERSONNEL (89)PREMISES (90)EQUIPMENT (93)ANIMALS AND ANIMAL HOUSES (94)DISINFECTION - WASTE DISPOSAL (94)PRODUCTION (95)STARTING MA TERIALS (95)QUALITY CONTROL (98)ANNEX 6 MANUFACTURE OF MEDICINAL GASES药用气体的生产 (99)1. PRINCIPLE (99)2. PERSONNEL (99)3. PREMISES AND EQUIPMENT (99)4. DOCUMENTA TION (100)5. PRODUCTION (101)6. QUALITY CONTROL (104)7. STORAGE AND RELEASE (105)ANNEX 7 MANUFACTURE OF HERBAL MEDICINAL PRODUCTS草药产品的生产 (108)PRINCIPLE (108)PREMISES (108)DOCUMENTATION (108)SAMPLING (109)QUALITY CONTROL (110)ANNEX 8 SAMPLING OF STARTING AND PACKAGING MA TERIALS起始物料和包装材料的取样 (111)PRINCIPLE (111)PERSONNEL (111)STARTING MA TERIALS (111)PACKAGING MATERIAL (112)ANNEX 9 MANUFACTURE OF LIQUIDS, CREAMS AND OINTMENTS流体，霜体和膏体药品的生产 (113)PRINCIPLE (113)PRODUCTION (113)ANNEX 10 MANUFACTURE OF PRESSURISED METERED DOSE AEROSOL PREPARATIONS FOR INHALATION吸入式剂量仪的气雾剂的生产 (115)PRINCIPLE (115)GENERAL (115)PREMISES AND EQUIPMENT (115)PRODUCTION AND QUALITY CONTROL (116)ANNEX 11 COMPUTERISED SYSTEMS 计算机化系统 (117)PRINCIPLE (117)PERSONNEL (117)V ALIDATION (117)ANNEX 12 USE OF IONISING RADIATION IN THE MANUFACTURE OF MEDICINAL PRODUCTS使用离子放射生产药品 (120)INTRODUCTION (120)RESPONSIBILITIES (120)DOSIMETRY (121)V ALIDATION OF THE PROCESS (121)COMMISSIONING OF THE PLANT (122)PREMISES (124)PROCESSING (124)DOCUMENTATION (126)MICROBIOLOGICAL MONITORING (126)ANNEX 13 MANUFACTURE OF INVESTIGA TIONAL MEDICINAL PRODUCTS观察期药品的生产 (127)PRINCIPLE (127)GLOSSARY (128)QUALITY MANAGEMENT (130)PERSONNEL (130)PREMISES AND EQUIPMENT (130)DOCUMENT A TION (131)PRODUCTION (132)QUALITY CONTROL (136)RELEASE OF BATCHES (137)SHIPPING (139)COMPLAINTS (139)RECALLS AND RETURNS (139)DESTRUCTION (140)ANNEX 14 MANUFACTURE OF PRODUCTS DERIVED FROM HUMAN BLOOD OR HUMAN PLASMA生产自人类血液或人体组织分离的产品 (143)PRINCIPLE (143)GLOSSARY (144)QUALITY MANAGEMENT (144)PREMISES AND EQUIPMENT (145)BLOOD AND PLASMA COLLECTION (145)TRACEABILITY AND POST COLLECTION MEASURES (146)PRODUCTION AND QUALITY CONTROL (147)RETENTION OF SAMPLES (148)DISPOSAL OF REJECTED BLOOD, PLASMA OR INTERMEDIATES (148)ANNEX 15 QUALIFICATION AND V ALIDATION 确认和验证 (149)PRINCIPLE (149)PLANNING FOR V ALIDATION (149)DOCUMENTATION (150)QUALIFICATION (150)PROCESS V ALIDATION (151)CLEANING VALIDATION (153)CHANGE CONTROL (154)REV ALIDATION (154)GLOSSARY (154)[ANNEX 16] [QUALIFIED PERSON AND BA TCH RELEASE]*经授权的人员和批放行 (157)ANNEX 17 PARAMETRIC RELEASE参数放行 (158)1. PRINCIPLE (158)2. PARAMETRIC RELEASE (158)3. PARAMETRIC RELEASE FOR STERILE PRODUCTS (158)4. GLOSSARY (160)[ANNEX 18] [GMP GUIDE FOR ACTIVE PHARMACEUTICAL INGREDIENTS] 17原料药GMP 指南 (161)GLOSSARY术语表 (162)GUIDE TO GOOD MANUFACTURING PRACTICE FOR MEDICINAL PRODUCTS药品GMP指南INTRODUCTION介绍为进一步消除药品贸易壁垒，促进许可证的一致性，以及确保整个欧洲在研发，生产和控制药品中保持高标准的质量保证，根据药品检查协会（PIC）同意，药品检查使用一致的GMP原则，和药品检查合作计划表中的欧洲药品GMP及其附录。
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Date of implementation: 1 March 2010Introduction:The holder of a Certificate of suitability shall inform the EDQM of any change to the information in the certification dossier by sending an application form and all necessary documents demonstrating that the conditions laid down in the present guideline are met.Classification of changesThe changes have been classified in three categories (notification/minor/major) depending on the potential impact of the change on the quality of the final substance. These three categories are based on those (IA-IAIN/IB/II) of the Commission Regulation (EC) No 1234/2008 concerning the examination of variations to the terms of marketing authorisation for medicinal products for human use and veterinary medicinal products.Any change not classified as a notification or a major change should be classified as a minor change except in the following cases where a new application should be submitted:- addition of a new route of synthesis and/or a new manufacturing site where the specifications of the final substance are different from the one already approved- transfer to a new holder that is not the same legal entity as the approved one, where the transfer does not occur because of a merger or because the company is sold, and where the manufacturer does not take out the Certificate of suitability in their own name.The changes related to Ph. Eur. monograph revisions or any other regulatory requirements are treated separately and generally initiated by the EDQM.执行日期：2010年3月1日介绍：欧洲药典适用性证书持有人必须向EDQM报告所有与申报文件有关的变更，申报时应填写申请表格和所有必要的资料，证明变更符合现行指南的规定。
变更分类根据变更对最终产品可能产生的影响程度，变更分为三类（通知/微小/重大）。
分类原则是根据EC法规1234/2008 (IA-IAIN/IB/II)：EC成员国审核人用和兽用制剂销售许可证变更规定所有未划为通知或者重大变更的变更都是微小变更，但以下情形必须按新证书申请办理：- 增加新合成途径或新生产场地，而且成品质量标准发生变化。
- 持有人转让，新持有人与现行法人不同，这种转让不是公司合并、出售的结果，生产厂也没有以自己名义获取原有证书。
欧洲药典修订或其它法规要求而产生的变更另论，通常由EDQM发起。
Documentation to be providedFor any revision the documentation should consist of:- a cover letter- the application form, duly filled and listing all the changes applied for- a description of each change together with a justification- data showing, when applicable, that the conditions have been met- update of the relevant section(s) of the dossier (presented in EU-CTD format).- the specific documents described below for each change and supporting the change- supportive information, including comparative data with the previous version of the dossier (in tabular format), showing the approved and the proposed section and highlighting the changesConsequential changes should be identified and the relation between the changes should be described.Each time batch data are needed:- they should be in accordance with the specifications of the current Ph. Eur. monograph and when relevant with the additional requirements included in the Certificate of suitability- the manufacturing site, the manufacturing date and the size of the batches should be specified.- quan titative results should be presented numerically (i.e. not in general terms such as “complies”) and with the appropriate number of decimal places.需要申报的文件所有变更的申报文件必须包括以下内容：- 附函- 申请表，列出申请的变更- 变更内容并说明变更的合理性- 若适用的的话，表明符合条件的数据- 更新申报文件相关的章节（按EU-CTD格式）- 下述各种变动所要求的具体文件- 支持性信息，包括与原版本的对比数据（以表格格式），表明原内容及现内容，强调变更应该识别间接的变更，并描述变更之间的关系。
所有变更都需要申报批分析数据：- 而且必须现行欧洲药典标准、以及CEP证书附加的有关要求。
- 必须说明生产场地、生产日期和生产批量。
- 应以数字形式表示定量结果（即：不得笼统表达为“合格”等），数位应合理。
The changes are presented in five sections:- Notifications (N and T)- Typical minor revisions for Certificates of suitability for chemical purity and microbiological quality or for TSE Certificates of suitability- Major revisions (MAJ)- Renewal- Transfer of holdershipEditorial changes should not be submitted as separate variations but should be reported at the same time as changes concerning the respective part of the dossier. In any case, a declaration should be provided that the content of the concerned part of the dossier has not been changed by the editorial changes (except for the change itself).以下分五节讨论各种变更情况：通知（N和T）化学纯度和微生物质量的CEP证书或TSE证书的典型微小变更重大变更（MAJ）更新证书持有人转让文字性变更不应作为单独的变更提交，但当文件相关部分变更时应当同时报告。
不管怎么样，应该申明：除了变更本身之外，文件相关部分的内容没有因文字性的变更而发生变更。
NOTIFICATIONS (IN/AN)Notifications are split into immediate notifications and notifications with annual reporting.1. Immediate notifications (IN):IN1) Change in the name and/or address of the certificate holder of the final substance (former N1) Conditions:- the certificate holder shall remain the same legal entity (except where the company is sold or in case of a merger).Specific Documentation:- a formal document from a relevant official body (e.g. Chamber of Commerce) in which the new name or the new address is mentioned- all updated declarations (annexes to the application form).通知（（IN/AN）通知分为立即通知和年度报告的通知1. 立即通知ININ1 原料药证书持有人名称或地址变更（以前的N1）条件：- 证书持有人法人地位不变（公司出让或被兼并除外）。