中英文版APIC原料药厂GMP审计表2010(详细)

2010版GMP附录原料药第一章范围第一条本附录适用于非无菌原料药生产及无菌原料药生产中非无菌生产工序的操作。

第二条原料药生产的起点及工序应当与注册批准的要求一致。

第二章厂房与设施第三条非无菌原料药精制、干燥、粉碎、包装等生产操作的暴露环境应当按照D级洁净区的要求设置。

第四条质量标准中有热原或细菌内毒素等检验项目的，厂房的设计应当特别注意防止微生物污染，根据产品的预定用途、工艺要求采取相应的控制措施。

第五条质量控制实验室通常应当与生产区分开。

当生产操作不影响检验结果的准确性，且检验操作对生产也无不利影响时，中间控制实验室可设在生产区内。

第三章设备第六条设备所需的润滑剂、加热或冷却介质等，应当避免与中间产品或原料药直接接触，以免影响中间产品或原料药的质量。

当任何偏离上述要求的情况发生时，应当进行评估和恰当处理，保证对产品的质量和用途无不良影响。

第七条生产宜使用密闭设备；密闭设备、管道可以安置于室外。

使用敞口设备或打开设备操作时，应当有避免污染的措施。

第八条使用同一设备生产多种中间体或原料药品种的，应当说明设备可以共用的合理性，并有防止交叉污染的措施。

第九条难以清洁的设备或部件应当专用。

第十条设备的清洁应当符合以下要求：（一）同一设备连续生产同一原料药或阶段性生产连续数个批次时，宜间隔适当的时间对设备进行清洁，防止污染物（如降解产物、微生物）的累积。

如有影响原料药质量的残留物，更换批次时，必须对设备进行彻底的清洁。

（二）非专用设备更换品种生产前，必须对设备（特别是从粗品精制开始的非专用设备）进行彻底的清洁，防止交叉污染。

（三）对残留物的可接受标准、清洁操作规程和清洁剂的选择，应当有明确规定并说明理由。

第十一条非无菌原料药精制工艺用水至少应当符合纯化水的质量标准。

第四章物料第十二条进厂物料应当有正确标识，经取样（或检验合格）后，可与现有的库存（如储槽中的溶剂或物料）混合，经放行后混合物料方可使用。

应当有防止将物料错放到现有库存中的操作规程。

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。

APIC原料药厂清洁验证指南（201405 中英文）ACTIVE PHARMACEUTICAL INGREDIENTS COMMITTEE (APIC)GUIDANCE ON ASPECTS OF CLEANING VALIDATIONIN ACTIVE PHARMACEUTICAL INGREDIENT PLANTSAPIC 原料药工厂中清洁验证指南May 2014Table of Contents1.0 FOREWORD 前言The original version of this guidance document has now been updated by the APIC Cleaning Validation Task Force on behalf of the Active Pharmaceutical Ingredient Committee (APIC) of CEFIC.本指南文件的原版本现已由APIC清洁验证工作组代表CEFIC的APIC委员会进行了更新。

The Task Force members are:- 以下是工作组的成员Annick Bonneure, APIC, BelgiumTom Buggy, DSM Sinochem Pharmaceuticals, The NetherlandsPaul Clingan, MacFarlan Smith, UKAnke Grootaert, Janssen Pharmaceutica, BelgiumPeter Mungenast, Merck KGaA, Germany.Luisa Paulo, Hovione FarmaCiencia SA, PortugalFilip Quintiens, Genzyme, BelgiumClaude Vandenbossche, Ajinomoto Omnichem, BelgiumJos van der Ven, Aspen Oss B.V., The NetherlandsStefan Wienken, BASF, Germany.With support and review from:- 以下为提供支持和进行审核的人员Pieter van der Hoeven, APIC, BelgiumAnthony Storey, Pfizer, U.K.Rainer Fendt, BASF, Germany.The subject of cleaning validation in active pharmaceutical ingredient manufacturing plants has continued to receive a large amount of attention from regulators, companies and customers alike.原料药生产工厂的清洁验证一直是法规人员、公司和客户等关注的问题。

实用文档Q7a（中英文对照）FDA原料药GMP指南Table of Contents 目录1. INTRODUCTION 1. 简介1.1 Objective 1.1目的1.2 Regulatory Applicability 1.2法规的适用性1.3 Scope 1.3范围2. QUALITY MANAGEMENT 2.质量管理2.1 Principles 2.1总则2.2 Responsibilities of the Quality2.2质量部门的责任Unit(s)2.3生产作业的职责2.3 Responsibility for ProductionActivities2.4 Internal Audits (Self Inspection) 2.4内部审计（自检）2.5 Product Quality Review 2.5产品质量审核3. PERSONNEL 3. 人员3.1 Personnel Qualifications 3.人员的资质3.2 Personnel Hygiene 3.2 人员卫生3.3 Consultants 3.3 顾问4. BUILDINGS AND FACILITIES 4. 建筑和设施4.1 Design and Construction 4.1 设计和结构4.2 Utilities 4.2 公用设施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 排污和垃圾4.7 Sanitation and Maintenance 4.7 卫生和保养5. PROCESS EQUIPMENT 5. 工艺设备5.1 Design and Construction 5.1 设计和结构5.2 Equipment Maintenance and Cleaning 5.2 设备保养和清洁5.3 Calibration 5.3 校验5.4 Computerized Systems 5.4 计算机控制系统6. DOCUMENTATION AND RECORDS 6. 文件和记录6.1 Documentation System andSpecifications6.1 文件系统和质量标准6.2 Equipment cleaning and Use Record 6.2 设备的清洁和使用记录6.3 Records of Raw Materials, Intermediates, API Labeling and Packaging Materials 6.3 原料、中间体、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 生产工艺规程（主生产和控制记录）6.5 Batch Production Records (BatchProduction and Control Records)6.5 批生产记录（批生产和控制记录）6.6 Laboratory Control Records 6.6 实验室控制记录6.7 Batch Production Record Review 6.7批生产记录审核7. MATERIALS MANAGEMENT 7. 物料管理7.1 General Controls 7.1 控制通则7.2 Receipt and Quarantine 7.2接收和待验7.3 Sampling and Testing of IncomingProduction Materials7.3 进厂物料的取样与测试7.4 Storage 7.4储存7.5 Re-evaluation 7.5复验8. PRODUCTION AND IN-PROCESS CONTROLS 8. 生产和过程控制8.1 Production Operations 8.1 生产操作8.2 Time Limits 8.2 时限8.3 In-process Sampling and Controls 8.3 工序取样和控制8.4 Blending Batches of Intermediates orAPIs8.4 中间体或原料药的混批8.5 Contamination Control 8.5 污染控制9. PACKAGING AND IDENTIFICATION LABELINGOF APIs AND INTERMEDIATES9. 原料药和中间体的包装和贴签9.1 General 9.1 总则9.2 Packaging Materials 9.2 包装材料9.3 Label Issuance and Control 9.3 标签发放与控制9.4 Packaging and Labeling Operations 9.4 包装和贴签操作10. STORAGE AND DISTRIBUTION 10.储存和分发10.1 Warehousing Procedures 10.1 入库程序10.2 Distribution Procedures 10.2 分发程序11. LABORATORY CONTROLS 11.实验室控制11.1 General Controls 11.1 控制通则11.2 Testing of Intermediates and APIs 11.2 中间体和原料药的测试11.3 Validation of Analytical Procedures 11.3 分析方法的验证11.4 Certificates of Analysis 11.4 分析报告单11.5 Stability Monitoring of APIs 11.5 原料药的稳定性监测11.6 Expiry and Retest Dating 11.6 有效期和复验期11.7 Reserve/Retention Samples 11.7 留样12. VALIDATION 12.验证12.1 Validation Policy 12.1 验证方针12.2 Validation Documentation 12.2 验证文件12.3 Qualification 12.3 确认12.4 Approaches to Process Validation 12.4 工艺验证的方法12.5 Process Validation Program 12.5 工艺验证的程序12.6 Periodic Review of ValidatedSystems12.6验证系统的定期审核12.7 Cleaning Validation 12.7 清洗验证12.8 Validation of Analytical Methods 12.8 分析方法的验证13. CHANGE CONTROL 13.变更的控制14. REJECTION AND RE-USE OF MATERIALS 14.拒收和物料的再利用14.1 Rejection 14.1 拒收14.2 Reprocessing 14.2 返工14.3 Reworking 14.3 重新加工14.4 Recovery of Materials and Solvents 14.4 物料与溶剂的回收14.5 Returns 14.5 退货15. COMPLAINTS AND RECALLS 15.投诉与召回16. CONTRACT MANUFACTURERS (INCLUDINGLABORATORIES)16.协议生产商（包括实验室）17. AGENTS, BROKERS, TRADERS, DISTRIBUTORS, REPACKERS, AND RELABELLERS 17.代理商、经纪人、贸易商、经销商、重新包装者和重新贴签者17.1 Applicability 17.1适用性17.2 Traceability of Distributed APIsand Intermediates17.2已分发的原料药和中间体的可追溯性17.3 Quality Management 17.3质量管理17.4 Repackaging, Relabeling, and Holding of APIs and Intermediates 17.4原料药和中间体的重新包装、重新贴签和待检17.5 Stability 17.5稳定性17.6 Transfer of Information 17.6 信息的传达17.7 Handling of Complaints and Recalls 17.7 投诉和召回的处理17.8 Handling of Returns 17.8 退货的处理18. Specific Guidance for APIs Manufactured by Cell Culture/Fermentation 18. 用细胞繁殖/发酵生产的原料药的特殊指南18.1 General 18.1 总则18.2 Cell Bank Maintenance and RecordKeeping18.2细胞库的维护和记录的保存18.3 Cell Culture/Fermentation 18.3细胞繁殖/发酵18.4 Harvesting, Isolation andPurification18.4收取、分离和精制18.5 Viral Removal/Inactivation steps 18.5 病毒的去除/灭活步骤19.APIs for Use in Clinical Trials 19.用于临床研究的原料药19.1 General 19.1 总则19.2 Quality 19.2 质量19.3 Equipment and Facilities 19.3 设备和设施19.4 Control of Raw Materials 19.4 原料的控制19.5 Production 19.5 生产19.6 Validation 19.6 验证19.7 Changes 19.7 变更19.8 Laboratory Controls 19.8 实验室控制19.9 Documentation 19.9 文件20. Glossary 20. 术语Q7a GMP Guidance for APIsQ7a原料药的GMP指南1. INTRODUCTION 1. 简介1.1 Objective 1.1目的This document is intended to provide guidance regarding good manufacturing practice (GMP) for the manufacturing of active pharmaceutical ingredients (APIs) under an appropriate system for managing quality. It is also intended to help ensure that APIs meet the quality and purity characteristics that they purport, or are represented, to possess. 本文件旨在为在合适的质量管理体系下制造活性药用成分（以下称原料药）提供有关优良药品生产管理规范（GMP）提供指南。

GMP相关的英文缩写1. AQAI(Automated Quality Assurance Inspection Equipment):在线自动质量保证检查设备.2. API(Active Pharmaceutical Ingredient):活性药物物质,即原料药.3. ANDA (Abbreviated New Drug Application):简化新药申请.4. ADR(Adverse Drug Reaction):不良反应.5. BSE(Bovine Spongiform Encephalopathy):疯牛病.6. BPCS(Business Planning and Control System):业务计划及控制系统.7. BIA(Business impact assessment): 商业影响评估.8. cGMP(current Good Manufacturing Practice):现行药品生产质量管理规范.9. CCCD(China Certification Committee for Drugs):中国药品认证委员会.10. CIP(Cleaning In Place):在线清洁. 11. CV(Concurrent Validation):同步验证.12. CDER( Center for Drug Evaluation and Research): 药品研究与评价中心.13. COA(Certificate Of Analysis):分析报告单.14. CFR(Code of Federal Regulation):(美国)联邦法规.15. CDC(Centers for Disease Control and Prevention):疾病预防控制中心.16. COS / CEP( Certificate of Suitability for European Pharmacopeia ):欧洲药典适用性证书.17. CCD (Certification Committee for Drugs):药品认证管理中心. 18. CPMP(Committee for Proprietary Medicinal Products): 欧洲专利药品委员会.19. CTD(Common Technical Document):通用技术文件.20. CDC( Centers for Disease Control and Prevention): 疾病预防控制中心.21. GMP(Good Manufacturing Practice):药品生产质量管理规范. 22. ICH(International Conference on Harmonization of Technical Requ irements for Registration of Pharmaceuticals for Human Use):人用药品注册技术要求国际协调会. 23. EU(European Union):欧洲联盟.24. EFPIA(European Federation of Pharmaceutical Industries Associations ):欧洲制药工业协会联合会.25. MHW(Ministry of Health and Welfare,Japan):日本厚生省. 26. JPMA(Japan Pharmaceutical Manufacturers Association):日本制药工业协会.27. FDA(US Food and Drug Adminiistration):美国食品与药品管理局.28. PRMA(Pharmaceutical Research and Manufacturers of America):美国药物研究和生产联合会.29. WHO(World Health Organization):世界卫生组织.30. IFPMA(International Federation of Pharmaceutical Manufacturers As sociations):国际制药工业协会联合会.31. TQC(Total Quality Control),TQM(Total Quality Management): 全面质量管理.32. PDCA(Plan,Do,Check,Action):计划,执行,检查,处理.33. QA(Quality Assurance):质量保证.34. QC (Quality Control):质量控制.35. QS(Quality System):质量体系.36. QM(Quality Management): 质量管理.37. SOP(Standard Operating Procedure): 标准操作规程.38. SMP(Standard Management Procedure):标准管理程序.39. SOR(Standard Operating Record): 标准操作记录.40. GEP(Good Engineering Practice):工程设计规范.41. HVAC(Heating Ventilation and Air Conditioning):空调净化系统.42. DQ(Design Qualification):设计确认.43. IQ(Installation Qualification):安装确认.44. OQ(Operational Qualification):运行确认.45. PQ(Performance Qualification):性能确认.46. OOS(Out-Of-Specification):检验不合格;超标.47. PFDS(Process Flow Diagrams):工艺流程图.48. MRA(cMutual Reognition Agreements): 现场检查多边认同协议.49. DMF( Drug Master File):药物主文件.50. EDMF(European Drug Master File)欧盟药物主文件.51. EDQM（European Directorate for Quality Medicines）: 欧洲药品质量管理局.52. ORA(Office of Regulatory Affairs):药政事务办公室.53. GGPs( Good Guidance Practices): 优良指南规范.54. MOA(Method Of Analysis):分析方法.55. VMP(Validation Master Plan):验证主计划.56. VP(Validation Protocol):验证方案.57. MSDS(Material Safety Data Sheet):物料安全技术说明书.58. NDA (New Drug Application):新药申请.59. OTC(Over-the-counter):非处方.60. INN(International Nonproprietary Name):国际非专有名称.61. USP(the united state pharmacopeia): 美国药典.62. NF(National Formulary):(美国)国家药品集.63. GAP(Good Agricultural Practice):中药材种植管理规范.64. GCP(Good Clinical Practice):药物临床试验质量管理规范.65. GLP(Good Laboratory Practice):药物实验室管理规范.66. GSP(Good Supply Practice):药品经营质量管理规范.67. GUP(Good Use Practice):药品使用质量管理规范.68. SM(Starting Material):起始物料.69. PMF(Plant Master File); SMF(Site Master File):工厂主文件.70. EDL(List of Essential Drugs ) : 基本药物目录.71. PI(Package Insert):说明书.72. PCT( Patent Cooperation Treaty): 专利合作条约.73. PPAC(Patent Protection Association of China):中国专利保护协会.74. PIC( Person In Charge) :负责人.75. PDS(Pharmaceutical Development Services): 整体新药研发机构.76. SPC(Summary of Product Characteristics):产品特性摘要.。

文件号：共13页之第1页文件名称：工艺规程修订号：XX 替代文件号：新文件(或版本号) 生效日期：审批Dept. 部门Occupation职务Name姓名Signature签名Date日期Issued by制定人XXXX XXXX XXXXReviewed by 审核人MD制造部经理或助理XXXXReviewed by 审核人RMD新药与市场部经理或助理XXXXReviewed by审核人工程部经理或助理XXXXReviewed by审核人物控部经理或助理Reviewed by 审核人QA质量管理部经理或助理XXXXApproved by 批准人GMO总经理室副总经理（生产副总）XXXX文件号： 共13页之第2页文件名称： 工艺规程 修订号：XX 替代文件号：新文件(或版本号) 生效日期：1 目的建立XXXX(产品名称)工艺规程，保证工艺控制和工艺步骤严格的按规定执行。

2 范围适用于XXXXX(产品名称)的生产过程和中间控制。

3 职责制造部、新药与市场部、质量管理部对本规程的实施负责。

4制定依据药品生产质量管理规范（XXXX 年修订）第XXXX 条、第XXXX 条~第XXXX 条 中国药典（XXXX 年修订）第XXXX 条、第XXXX 条~第XXXX 条 国家食品药品监督管理局标准YBH011420065 程序5.1 工艺流程及环境区域划分十万级洁净区非洁净区中间产品检验成品检验成品经检验合格入库生产车间 XXXX 车间生产操作间房间号洁净温湿度及压差设备名称固定资产编原辅料外包装外包装材料内包装材料文件号：共13页之第3页文件名称：工艺规程修订号：XX 替代文件号：新文件(或版本号) 生效日期：工序级别号辅料处理湿法制粒间XXXX 十万级温湿度：XX℃~XX℃相对压差：XX%~XX%热风循环烘箱HG081007称量配料称量配料间（1）XXXX 十万级温湿度：≤XX℃相对压差：≤XX%热风循环烘箱N/A外包外包装XXXX 三十万级5.2 产品名称、剂型、规格产品名称：盐酸贝那普利胶囊商品名：XXXX剂型：胶囊剂规格：XXXX性状：本品为硬胶囊，内容物为白色至类白色颗粒和粉末。

OPERATIONAL QUALIFICATION STERILE PROCESS VALIDATIONCLEANING VALIDATION (1/25)1. DOCUMENT HISTORYAdoption by PIC/S Committee 10 - 11 December 1998Entry into force of version PR 1/99-1 01 March 1999Entry into force of version PI 006-1 01 September 20012. INTRODUCTIONThe basic principles and application of qualification and validation are describedin Annex 15 to the PIC/S and EU Guide to GMP. This document comprises individual Recommendations on four topics relating to Equipment Qualification and Process Validation in pharmaceutical manufacture, as follows:Ø Validation Master PlanØ Installation and Operational QualificationØ Non-Sterile Process ValidationØ Cleaning ValidationThe four Recommendations comprising this document define general principles pertaining to each of the topics.2. 导言PIC/S和EU GMP指导原则的附录15中对确认(Qualification)和验证(Validation)的基本原则及应用进行了阐述。

公司（原辅料）
我公司是保健品GMP认证企业，要求对物料生产企业（供应商）进行质量审计，现将质量审计材料寄给贵公司（厂），请按要求认真填写后加盖红章，并请连同贵公司提供有效的、加盖贵公司（厂）红章的如下资料一同寄回我公司。

（1）《生产许可证》或《卫生许可证》的复印件；
（2）《企业法人营业执照》的复印件；
（3）所购品种的批准文件复印件；
（4）所购品种当批检验报告书；
（4）所购品种有关质量标准；
（5）药品GMP或相关证书复印件。

来函请寄：
邮政编码：电话：
敬请合作！
附：本公司向贵公司购进的产品名称：
原辅料供应商审计表
编号：SOR-ZL-0010-01
编号：SOR-ZL-0010-01。

我国gmp2010GMP是Good Manufacturing Practice的缩写，是指《药品生产质量管理规范》。

与国际上的GMP标准相比，我国GMP2010在一些方面做出了具体的规定，以保证药品的生产和质量管理符合国家的法律法规，并在一定程度上提升药品的生产质量。

我国GMP2010的相关内容在附录中有详细的英文版规定，以下是对我国GMP2010英文附录的解读。

一、 Scope and Application (范围与适用性)我国GMP2010的英文附录中指出了该规范的范围和适用性，适用于所有在我国境内生产药品的企业。

这一规定明确了GMP的适用范围，为国内药品生产企业提供了依据和指导。

二、 Terms and Definitions (术语和定义)对于一些专业术语以及相关的定义，我国GMP2010的英文附录进行了详细的说明。

在药品生产过程中，对术语和定义的清晰理解是非常重要的，可以帮助企业提高对GMP规范的理解和执行。

三、 Personnel (人员)我国GMP2010的英文附录对药品生产企业的人员管理提出了具体的要求，包括对人员的培训、工作记录、合格证书等方面进行了规定。

这些要求可以帮助企业建立健全的人员管理制度，确保生产过程中人员的素质和能力符合相关要求。

四、 Buildings and Facilities (建筑和设施)对于药品生产企业的厂房和设施，我国GMP2010的英文附录也进行了详细的规定。

这些规定涵盖了厂房的选择、设计、维护等方面，为企业提供了在建筑和设施方面遵循的具体标准。

五、 Equipment (设备)在药品生产过程中使用的设备也是关键的一环，我国GMP2010的英文附录对此进行了具体的要求，包括设备的选择、验证、维护等方面的规定。

这些要求有助于确保生产设备的有效性和可靠性，保证药品生产质量的稳定性和可靠性。

六、 Materials (原辅料)对于药品生产中使用的原辅料，我国GMP2010的英文附录也包含了相关的要求。

1.实质性原那么2.客瞧性原那么3.相关性原那么4.可比性原那么5.一贯性原那么6.及时性原那么7.明晰性原那么8.权责发生制原那么9.配比性原那么10.慎重性原那么11.实际本钞票核算原那么12.划分收益性支出与资本性支出的原那么13.重要性原那么模版1：质量治理部门审计全然信息审计对象：审计日期：审计小组人员组成：姓名：部门审计要紧内容清单：1.人员和培训2.文件3.物料监控4.生产过程监控5.批记录审核和成品放行6.产品质量回忆7.验证8.用户投诉及不良反响9.退货10.自检11.质控设施12.检验操作13.检验仪器、设备及玻璃量器14.样品的取样、接收、贮存和检验15.检验试剂、试液和标准品、标准溶液的治理16.留样及稳定性实验17.微生物实验室治理其他：____________________________审计结论：经对上述内容进行审查，质量治理部门在人员方面…培训方面…，文件方面…，履行职责方面…。

综上认为，是否能保障质量治理体系的有效运行。

审计报告一、全然情况简介二、要紧咨询题及其风险评估要紧咨询题：经对上述咨询题的综合评估，本企业质量治理部门在履行保证产品的质量和平安方面存在风险如下：三、整改建议和跟踪检查结果包括对存在咨询题的整改建议、整改时限建议，跟踪检查等内容。

四、审计小组成员签字审计记录13.11所有的培养箱、冰箱是否有经校验的温度计？13.12是否按规定记录温度及湿度？14.样品的取样、接收、贮存和检验YES NO14.1样品的请验、取样、接收和发放是否有文件规定？并有记录？14.2取样是否符合要求？-现场抽查：品名：-进货件数：件；取样件数：件-取样封口情况：；标识情况：-取样场所及操作过程：-取样工具：_________-取样量：___________-样品的分装是否符合要求，样品的标签是否符合要求？14.3样品的存放是否符合规定？14.4样品的接收、分发是否有记录？14.5样品发放后是否规定检验时刻？14.6检验记录是否及时填写，无转抄或打草稿现象？文字修改是否符合规定？14.7检验记录是否包括以下内容：-产品及物料的名称、剂型及规格-批号及来源-检验依据-仪器及设备的型号和编号-检验记录是否能追溯到操作的每个过程，包括配制、各项具体操作、计算的过程及偏差处理的过程等？-检验结果，包括瞧瞧情况、计算过程、原始图谱或曲曲折折曲曲折折折折曲曲折折曲曲折折折折折折线图-检验日期-是否按企业规定的质量标准做出的明确结论-检验人员及复核人的签字14.8核查检验记录是否按检验操作规程进行了全项的检验？14.9检验记录和报告书是否按规定维持？14.10是否对空白的检验记录进行了操纵治理？14.11检验记录和报告是否由负责人审核？并在报告上签字？14.12OOS的处理是否符合要求？15.检验试剂、试液和标准品、标准溶液的治理YES NO15.1是否购置有检验所需的所有试剂、试液？15.2试剂、试液及标准品是否有接收的记录？15.3检验用的试剂试液、标准品、比立品及标准溶液的治理是否有文件规定？15.4试剂、试液、标准品的贮存是否适当？15.5试剂、试液的日常治理是否整洁有序？是否有标识能寻到相应试剂、试液？15.6试液的配制是否有配制记录？15.7每一个试液是否有标签讲明该试液的名称、浓度、配制日期、有效期及配制人？并能与配制记录相对应？15.8标准溶液的标定是否是在符合要求的环境下进行？15.9标准溶液的贮存是否符合要求？标准溶液的发放是否有记录？15.10标准溶液是否有标签标明：名称、浓度、〔校正因子〕和最后一次的标定浓度、配制人、配制日期、标定人及标定日期？15.11标准溶液是否按期复标？15.12标准溶液的配制记录是否全面？配制记录是否包括恒重、配制、标定、复标的全过程及偏差处理的过程？15.13毒性药品的治理是否符合文件规定？15.14标准品、比立品的治理15.14.1检验用的标准品、比立品是否齐全？依据质量标准抽查15.14.2是否优先使用法定的标准品？15.14.3企业的二级标准品是否有以下规程和记录-精制-鉴不、及相关必要的检测及质量标准-每批工作标准品是否认期用法定标准品进行标化-批准-贮存-标识是否包括了名称、批号、制备日期、有效期及贮存条件15.15配制试液或检验用的水是否符合相应要求？16.留样及稳定性实验YES NO16.1是否有留样及稳定性实验的文件规定？16.2留样室的温湿度是否与贮存要求相符合？16.3留样室的治理是否清洁、整洁？16.4所有留样的药品和批次是否有具体的记录？16.5所有生产的批次是否均已留样？抽查。

国食药监注[2010]387号附件国食药监注〔2010〕387 号附件：化学药品CTD格式申报资料撰写要求CTD格式申报主要研究信息汇总表（原料药）2.3.S.1 基本信息2.3.S.1.1 药品名称原料药的中英文通用名、化学名2.3.S.1.2 结构原料药的结构式、分子式、分子量2.3.S.1.3 理化性质原料药的主要物理和化学性质：性状(如外观，颜色，物理状态)；熔点或沸点；比旋度，溶解性，溶液pH, 分配系数，解离常数，将用于制剂生产的物理形态（如多晶型、溶剂化物、或水合物），生物学活性等。

2.3.S.2 生产信息2.3.S.2.1 生产商生产商的名称（一定要写全称）、地址以及生产场所的地址。

2.3.S.2.2 生产工艺和过程控制（1）工艺流程图：参见申报资料3.2.S.2.2（注明页码）。

（2）工艺描述：按反应路线简述各步反应的反应类型（氧化、还原、取代、缩合、烃化、酰化等），各步反应的原料、试剂、溶剂和产物的名称，终产物的精制方法和粒度控制等；特殊的反应条件（如高温、高压、深冷等）应说明。

详细内容参见申报资料3.2.S.2.2（注明页码）。

（3）生产设备：参见申报资料3.2.S.2.2（注明页码）。

（4）大生产的拟定批量：kg（g）/批。

— 1 —2.3.S.2.3 物料控制生产用物料（如起始物料、反应试剂、溶剂、催化剂等）的质量控制信息（包括来源、质量标准等），参见申报资料3.2.S.2.3（注明页码）。

2.3.S.2.4 关键步骤和中间体的控制列出所有关键步骤及其工艺参数控制范围。

关键步骤确定依据参见申报资料3.2.S.2.4或3.2.S.2.6（注明页码）。

中间体的质量控制参见申报资料3.2.S.2.4（注明页码）。

2.3.S.2.5 工艺验证和评价无菌原料药：工艺验证方案（编号：--，版本号：--）和验证报告（编号：--，版本号：--）参见申报资料3.2.S.2.5（注明页码）。

Q7a（中英文对照）FDA原料药GMP指南Table of Contents 目录1. INTRODUCTION 1. 简介1.1 Objective 1.1目的1.2 Regulatory Applicability 1.2法规的适用性1.3 Scope 1.3范围2. QUALITY MANAGEMENT 2.质量管理2.1 Principles 2.1总则2.2 Responsibilities of the Quality Unit(s) 2.2质量部门的责任2.3 Responsibility for Production Activities 2.3生产作业的职责2.4 Internal Audits (Self Inspection) 2.4内部审计（自检）2.5 Product Quality Review 2.5产品质量审核3. PERSONNEL 3. 人员3.1 Personnel Qualifications 3.人员的资质3.2 Personnel Hygiene 3.2 人员卫生3.3 Consultants 3.3 顾问4. BUILDINGS AND FACILITIES 4. 建筑和设施4.1 Design and Construction 4.1 设计和结构4.2 Utilities 4.2 公用设施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 排污和垃圾4.7 Sanitation and Maintenance 4.7 卫生和保养5. PROCESS EQUIPMENT 5. 工艺设备5.1 Design and Construction 5.1 设计和结构5.2 Equipment Maintenance and Cleaning 5.2 设备保养和清洁5.3 Calibration 5.3 校验5.4 Computerized Systems 5.4 计算机控制系统6. DOCUMENTATION AND RECORDS 6. 文件和记录6.1 Documentation System andSpecifications6.1 文件系统和质量标准6.2 Equipment cleaning and Use Record 6.2 设备的清洁和使用记录6.3 Records of Raw Materials, Intermediates, API Labeling and Packaging Materials 6.3 原料、中间体、原料药的标签和包装材料的记录6.4 Master Production Instructions (MasterProduction and Control Records)6.4 生产工艺规程（主生产和控制记录）6.5 Batch Production Records (BatchProduction and Control Records)6.5 批生产记录（批生产和控制记录）6.6 Laboratory Control Records 6.6 实验室控制记录6.7 Batch Production Record Review 6.7批生产记录审核7. MATERIALS MANAGEMENT 7. 物料管理7.1 General Controls 7.1 控制通则7.2 Receipt and Quarantine 7.2接收和待验7.3 Sampling and Testing of IncomingProduction Materials7.3 进厂物料的取样与测试7.4 Storage 7.4储存7.5 Re-evaluation 7.5复验8. PRODUCTION AND IN-PROCESSCONTROLS8. 生产和过程控制8.1 Production Operations 8.1 生产操作8.2 Time Limits 8.2 时限8.3 In-process Sampling and Controls 8.3 工序取样和控制8.4 Blending Batches of Intermediates orAPIs8.4 中间体或原料药的混批8.5 Contamination Control 8.5 污染控制9. PACKAGING AND IDENTIFICATIONLABELING OF APIs ANDINTERMEDIATES9. 原料药和中间体的包装和贴签9.1 General 9.1 总则9.2 Packaging Materials 9.2 包装材料9.3 Label Issuance and Control 9.3 标签发放与控制9.4 Packaging and Labeling Operations 9.4 包装和贴签操作10. STORAGE AND DISTRIBUTION 10.储存和分发10.1 Warehousing Procedures 10.1 入库程序10.2 Distribution Procedures 10.2 分发程序11. LABORATORY CONTROLS 11.实验室控制11.1 General Controls 11.1 控制通则11.2 Testing of Intermediates and APIs 11.2 中间体和原料药的测试11.3 Validation of Analytical Procedures 11.3 分析方法的验证11.4 Certificates of Analysis 11.4 分析报告单11.5 Stability Monitoring of APIs 11.5 原料药的稳定性监测11.6 Expiry and Retest Dating 11.6 有效期和复验期11.7 Reserve/Retention Samples 11.7 留样12. V ALIDATION 12.验证12.1 Validation Policy 12.1 验证方针12.2 Validation Documentation 12.2 验证文件12.3 Qualification 12.3 确认12.4 Approaches to Process Validation 12.4 工艺验证的方法12.5 Process Validation Program 12.5 工艺验证的程序12.6 Periodic Review of Validated Systems 12.6验证系统的定期审核12.7 Cleaning Validation 12.7 清洗验证12.8 Validation of Analytical Methods 12.8 分析方法的验证13. CHANGE CONTROL 13.变更的控制14. REJECTION AND RE-USE OFMATERIALS14.拒收和物料的再利用14.1 Rejection 14.1 拒收14.2 Reprocessing 14.2 返工14.3 Reworking 14.3 重新加工14.4 Recovery of Materials and Solvents 14.4 物料与溶剂的回收14.5 Returns 14.5 退货15. COMPLAINTS AND RECALLS 15.投诉与召回16. CONTRACT MANUFACTURERS(INCLUDING LABORATORIES)16.协议生产商（包括实验室）17. AGENTS, BROKERS, TRADERS, DISTRIBUTORS, REPACKERS, AND RELABELLERS 17.代理商、经纪人、贸易商、经销商、重新包装者和重新贴签者17.1 Applicability 17.1适用性17.2 Traceability of Distributed APIs andIntermediates17.2已分发的原料药和中间体的可追溯性17.3 Quality Management 17.3质量管理17.4 Repackaging, Relabeling, and Holding of APIs and Intermediates 17.4原料药和中间体的重新包装、重新贴签和待检17.5 Stability 17.5稳定性17.6 Transfer of Information 17.6 信息的传达17.7 Handling of Complaints and Recalls 17.7 投诉和召回的处理17.8 Handling of Returns 17.8 退货的处理18. Specific Guidance for APIs Manufactured by Cell Culture/Fermentation 18. 用细胞繁殖/发酵生产的原料药的特殊指南18.1 General 18.1 总则18.2 Cell Bank Maintenance and RecordKeeping18.2细胞库的维护和记录的保存18.3 Cell Culture/Fermentation 18.3细胞繁殖/发酵18.4 Harvesting, Isolation and Purification 18.4收取、分离和精制18.5 Viral Removal/Inactivation steps 18.5 病毒的去除/灭活步骤19.APIs for Use in Clinical Trials 19.用于临床研究的原料药19.1 General 19.1 总则19.2 Quality 19.2 质量19.3 Equipment and Facilities 19.3 设备和设施19.4 Control of Raw Materials 19.4 原料的控制19.5 Production 19.5 生产19.6 Validation 19.6 验证19.7 Changes 19.7 变更19.8 Laboratory Controls 19.8 实验室控制19.9 Documentation 19.9 文件20. Glossary 20. 术语Q7a GMP Guidance for APIs Q7a原料药的GMP指南1. INTRODUCTION 1. 简介1.1 Objective 1.1目的This document is intended to provide guidance regarding good manufacturing practice (GMP) for the manufacturing of active pharmaceutical ingredients (APIs) under an appropriate system for managing quality. It is also intended to help ensure that APIs meet the quality and purity characteristics that they purport, or are represented, to possess. 本文件旨在为在合适的质量管理体系下制造活性药用成分（以下称原料药）提供有关优良药品生产管理规范（GMP）提供指南。

模版3：产品工艺验证审计
编写说明：
1.本模板适用于药品生产企业工艺验证的审计。

2.建议企业每年对每个剂型至少抽取1－2个风险性较高的品种按照本模板进
行工艺验证审计。

3.一份记录表格仅适用于一个产品的审计。

4.所有品种的审计出具一份审计报告。

5.审计结论应能够反映出企业工艺验证的整体状况，并给予明确的结论。

基本信息
审计对象：
剂型名称规格
审计日期：
审计小组人员组成：
姓名：部门
审计主要内容清单：
1、产品情况
2、质量标准情况
3、验证方案和报告
4、验证记录
5、检验结果
6、再验证
其它：_____________
审计结论：
经对上述内容进行审查，该产品工艺验证………。

一、基本情况简介
二、主要问题及其风险评估
主要问题：
经过对上述问题的综合评估，本企业的质量部门在质量管理体系以及对产品的质量和安全方面存在风险如下：
三、整改建议和跟踪检查结果
包括对存在问题的整改建议、整改时限建议，跟踪检查等内容。

四、审计小组成员签字。

模版：委托生产审计
根本信息
审计对象：
生产地址：
受托方产品情况描述：
审计日期：
审计小组人员组成：
姓名：部门
审计主要内容活单：
1、合同
2、委托方
3、受托方
4、现场审计工程
审计结论:
经对上述内容进行审查,该产品 .
一、根本情况简介
二、主要问题及其风险评估
主要问题：
经过对上述问题的综合评估,本企业的质量部门在质量治理体系以及对产品的质量和平安方面存在风险如下：
三、整改建议和跟踪检查结果
包括对存在问题的整改建议、整改时限建议,跟踪检查等内容.
四、审计小组成员签字
附件:
委托生产现场审计工程。

T D V N O N O F F I C I A L T R A N S L A T I O NGMP(Revised in 2010)Order from Ministry of Public Health, PR. ChinaNo. 79"Good Manufacturing Practice (revised in 2010)" was approved by the Ministry of Health on October 19, 2010. It will come into force from 1st, March of 2011.Minister: Chen Zhu17th, Jan, 2011T D V N O N O F F I C I A L T R A N S L A T I O NContents1. General Provisions (4)2. Quality Management (5)2.1 General rules (5)2.2 Quality assurance (5)2.3 Quality control (6)2.4 Quality Risk Management (7)3. Organization and personnel (8)3.1 General rules (8)3.2 Key personnel (8)3.3 Training (11)3.4 Personnel hygiene (11)4. Facility and utilities (13)4.1 General provisions (13)4.2 Production area (13)4.3 Warehousing area (15)4.4 Quality Control Area (16)4.5 Auxiliary area (17)5. Equipment (18)5.1 General rules (18)5.2 Design and installation (18)5.3 Maintenance and repair (18)5.4 Use and cleaning (19)5.5 Calibrations (20)5.6 Water for drug manufacturing (20)6. Materials and products (22)6.1 General rules (22)6.2 Raw materials and excipients (23)6.3 Intermediate products and bulk products (24)6.4 Packaging materials (24)6.5 Final products (25)6.6 Materials and products which need special management (25)6.7 Other (25)7. Validation and qualification (27)T D V N O N O F F I C I A L T R A N S L A T I O N8. Document management (28)8.1 Principles (28)8.2 Quality Standards (30)8.3 Process procedure (31)8.4 Batch production records (32)8.5 Batch Packaging Records (33)8.6 Operating procedures and records (33)9. Production Management (35)9.1 Principle (35)9.2 Prevent contamination and cross contamination in process of production (36)9.3 Production operations (37)9.4 Packaging operations (37)10. Quality control and quality assurance (40)10.1 Quality Control Laboratory Management Section (40)10.2 Release of materials and products (44)10.3 Continued stability study (45)10.4 Change Control (46)10.5 Deviation treatment (47)10.6 Corrective and preventive measures (48)10.7 Evaluation and approval of suppliers (49)10.8 Product quality review and analysis (50)10.9 Complaints and adverse reaction reports (51)11. Contractual production and analysis (53)11.1 Principle (53)11.2 The Company (53)11.3 The Contractor (53)11.4 Contract (54)12. Chapter12 Product shipment and recall (55)12.1 Principle (55)12.2 Delivery and transportation (55)12.3 Recall (55)13. Self-check (57)13.1 Principle (57)13.2 Self-analysis (57)14. Supplementary Provisions (57)T D V N O N O F F I C I A L T R A N S L A T I O N1. General ProvisionsArticle 1 This practice is established according to "Drug Administration Law of PRC" and "Implementation Regulations of the PRC Drug Administration Law" in order to regulate drug production quality control.Article 2 Pharmaceutical companies should establish a drug quality management system. The system should cover all factors that affect drug quality, including all of organized and planned activities that ensure the quality of medicines meet its intended use.Article 3 This practice, as a part of quality management system, acts as the basic requirements for drug production management and quality control with the aim of minimizing contamination, cross-contamination and confusion, error and other risks in the process of drug production to ensure Pharmaceutical companies can constantly produce drugs meeting its intended use and registration requirements.Article 4 Enterprises should strictly enforce the practice; adhere to the honest and trustworthy, and to prohibit any false, deceptive behavior.T D V N O N O F F I C I A L T R A N S L A T I O N2. Quality Management2.1 General rulesArticle 5 Enterprises should establish a quality target that meets pharmaceutical quality management requirements, applying all of requirements on safety, efficacy and quality control related with drug registration to whole process of drug production, control and product release, storage and shipment to ensure that production of pharmaceuticals meet their intended use and registration requirements.Article 6 Top management personnel should ensure implementation of established quality objectives; staff of different levels, suppliers and distributors should work together and assume their responsibilities.Article 7 Enterprises should be equipped with adequate, qualified staff, facilities, facilities and equipment to provide necessary conditions for achievement of quality objectives.2.2 Quality assuranceArticle 8 Quality assurance is part of the quality management system. Enterprises must establish a quality assurance system, while building a complete documentation system to ensure effective operation of the system.Article 9 Quality assurance system should ensure that:1. design and development of drugs reflects requirements of this practice;2. production management and quality control activities are consistent withrequirements of this Code;3. management responsibilities are clearly defined;4. raw materials and packaging materials purchased and used are correct;5. effective control of intermediate products;6. implementation of validation and verification;7. perform production, analysis, analyze and review strictly in accordance withprocedures;8. each batch can only be released with approval of qualified person;9. appropriate measures for drug quality assurance are available in process of storage,shipment and subsequent operation ;10. periodic analysis and evaluation of validity and applicability of quality assurancesystem in accordance with self-analysis operating proceduresArticle 10: The basic requirements for Pharmaceutical production and quality management:T D V N O N O F F I C I A L T R A N S L A T I O N(a) To develop production process, and perform systematic review to certify it can sustainably and stably manufacture qualified products(b) Production technology and major changes need to be validated;(c) Equipped with necessary resources, including at least the following:1. Personnel with appropriate qualifications and qualified by training;2. Adequate premises and facility;3. Proper equipment and maintenance support;4. Right raw materials, packaging materials and labels;5. Approved procedures and operation procedures;6. Appropriate storage conditions.(d) Accurate and understandable language should be used to develop operation procedures;(e) The operators are trained to operate in accordance with proper operating procedures;(f) Production process should be documented; deviations should be investigated and recorded;(g) Batch records and shipping records should allow traceability of complete history of batch products, and should be kept properly for easy reference;(h) Reduce quality risk in process of drug shipment;(i) Establishment of drug recall system should ensure any batch can be recalled after distribution;(j) Investigate complaints and quality defects and take measures to prevent recurrence of similar quality defects.2.3 Quality controlArticle11: Quality control, including related organization, documentation system, and sampling, and analysis to ensure materials or products complete their necessary analysis prior to release and to confirm quality meet requirements.Article 12: The basic requirements of quality control:(a) QC shall be equipped with appropriate facilities, equipment, instruments and trained personnel for effective and reliable completion of all related quality control activities; (b) Operating procedures should be available for sampling, analysis, test of raw materials, packaging materials, intermediate products, packaging and finished products as well as stability analysis of the product, and if necessary, carry out environmental monitoring to ensure compliance with the requirements of this practice;(c) Authorized personnel should sample raw materials, packaging materials, intermediate products, packaging and finished products in accordance with required method;(d) Analysis methods should be validated or confirmed;(e) Sampling, analysis, and check should be recorded, and deviations should be investigated and recorded(f) Materials, intermediate products, packaging and finished products must be checked and analyzed according to quality standards and should be recorded;T D V N O N O F F I C I A L T R A N S L A T I O N(g) Packaging materials and final product should have sufficient retained samples for necessary analysis or check except the final finished packaging container that is too large, retained samples for finished product should be packaged the same as final packaging.2.4 Quality Risk ManagementArticle 13 Quality risk management, a kind of prospective and retrospective method, is a systematic process to evaluate, control, communication, review the quality risk.Article 14 Quality risks should be evaluated on basis of scientific knowledge and experience to ensure product quality.Article 15: The methods, measures, forms and documents formed in the process of quality risk management process should be appropriate to the level of existing risk.T D V N O N O F F I C I A L T R A N S L A T I O N3. Organization and personnel3.1 General rulesArticle 16 Enterprises should establish a management structure appropriate to drug manufacturing and organizational structure chart.Enterprises should establish an independent quality control department to perform quality assurance and quality control responsibilities. Quality assurance department and quality control departments can be established separately within quality management department.Article 17 Quality control department should be involved in all quality related activities, and responsible for reviewing all documents relevant to this practice. Quality management personnel shall not delegate responsibilities to other departments.Article 18 Enterprises should be equipped with adequate and suitably qualified (including education, training and practical experience) management and operations staff; responsibilities of each department and each position should be clearly defined. Responsibilities cannot be missed, and overlapped responsibilities should be clarified. Responsibilities of each person should not be overburden.All personnel should be clear about and understand their responsibilities, familiar with requirements related to their duties and receive proper traiing, including pre-service training and continuing training.Article 19: Normally responsibilities should not be delegated to others. The responsibilities which are in definite need of delegation can be delegated to the qualified and designated personnel.3.2 Key personnelArticle 20 Key personnel should be full-time staff in the enterprise, at least including responsible person, person in charge of production management, quality management and qualified person.Person responsible for quality control and production management shall not serve each other. Person responsible for quality management and quality qualified can serve each other. Operating procedures should be developed to ensure qualified personnel perform their duties independently, free from interference from business leaders and other personnel.Article 21 Owners of enterprisesThe responsible person for enterprise, as the primary responsible person for the enterprise, should cover overall responsibility for daily management of enterprises. TheT D V N O N O F F I C I A L T R A N S L A T I O Nresponsible persons shall be responsible for providing necessary resources, rational planning, organization and coordination to ensure independent performance of responsibilities of quality management department in order to ensure realization of business objectives and production of pharmaceuticals in accordance with the regulatory requirements.Article 22 Person in charge of production managementQualifications:Person in charge of production management should at least have a degree in pharmacy (or intermediate professional titles or Licensed Pharmacist) with at least three years’ engagement in drug production and quality management experience, including at least one year of medicine production management experience, and have been trained on professional knowledge relating to manufactured product.Main responsibilities:1. To ensure drugs are manufactured and stored in accordance with approved process procedures to ensure drug quality;2. To ensure strict implementation of all operation procedures related to the operation and production;3. To ensure batch production and packaging records have been reviewed and sent to quality management department;4. To ensure implementation of facilities and equipment maintenance for good running condition;5. To ensure completion of all necessary validation;6. To ensure personnel related to production receive necessary pre-service training and continuing training, and adjust training contents basing on actual needs.Article 23 Personal in charge of quality managementQualifications: person in charge of quality management should have at least a degree in pharmacy or related (or intermediate professional titles or Licensed Pharmacist) with at least five years’ experience in pharmaceutical production and quality management, including at least one year in medicine Quality management, and have received professional knowledge training relating to manufactured products.Main responsibilities1. To ensure raw materials, packaging materials, intermediate products, packaging and finished products meet requirements and quality standards approval in registration;2. To ensure completion of batch record review before product release;3. To ensure completion of all necessary analysis;4. Approve operation procedures about quality standards, sampling methods, analysis methods and other quality management;5. Review and approve all quality-related changes;6. To ensure all significant deviations and OOS of analysis results have been timely investigated and handled;7. Approve and monitor contractual(entrusted) analysis;T D V N O N O F F I C I A L T R A N S L A T I O N 8. Supervision of facilities and equipment maintenance to ensure it keeps in good running condition;9. To ensure completion of necessary qualification or validation, review and approval of qualification or validation protocols and reports;10. To ensure complete self-analysis;11. Assessment and approval of materials suppliers;12. Ensure all quality-related complaints have been investigated, and timely and correctly treated;13. To ensure completion of quality continual stability study, and provide stability study data;14. To ensure completion of quality review;15. To ensure quality control and quality assurance personnel have received necessary pre-service training and continuing training, and training need to be adjusted according to actual needs.Article 24 Person in charge of production management and quality management normally share following responsibilities:(a) Review and approve products process procedures, operation procedures and other documents;(b) To supervise facilities hygiene status;(c) Ensure key equipment has been qualified;(d) Ensure completion of production process validation;(e) Ensure all related employees have received necessary pre-service training and continuing training, and training need to be adjusted basing on actual need;(f) Approve and supervise contractual production;(g) Identify and monitor the storage conditions of materials and products;(h) Record-keeping;(i)Monitoring implementation of the practice;(j) Monitoring factors that affect product quality.Article 25 Qualified peopleQualifications:The qualified person should have at least bachelor degree in pharmacy or related (or intermediate professional titles or Licensed Pharmacist) with at least five years’ practices in pharmaceutical production and quality management, and have engaged in pharmaceutical production process control and quality analysis.The qualified person shall have necessary professional knowledge, and shall only perform responsibilities after receive training related to product release.(B) Main responsibilities:1. Involving in establishment of the enterprise quality system, internal self-check and external quality audit, validation, and reports of adverse drug reaction, product recalls and other quality management activities;T D V N O N O F F I C I A L T R A N S L A T I O N2. Assume responsibilities of product release to ensure production and analysis for each batch released are in line with relevant laws and regulations, drug registration requirements and quality standards;3. The qualified person should present product release review record in accordance with the second article mentioned above before product release and should incorporate it in the batch record.3.3 TrainingArticle 26 Enterprise shall designate specific department or person responsible for training management; training or plan reviewed or approved by person in charge of production management and quality management should be available. Training records should be preserved.Article 27: All personnel related with pharmaceutical production and quality should be trained, and training should be appropriate to the requirements for corresponding position. In addition to theory and practice training of this practice, responsibilities and skills training about related positions and laws and regulation should be available. And actual result of training should be evaluated.Article 28 Operator engaged in high-risk operation areas (such as: production area for high activity, highly toxic, infectious, and sensitizing materials) should receive specialized training.3.4 Personnel hygieneArticle 29 All personnel should receive training on hygiene requirements; enterprises should establish personal hygiene rules to minimize risk of contamination caused by person.Article 30 Personal hygiene practice should include health, hygiene habits and dressing. Person in production areas and quality control should have proper understanding of personal hygiene practice. Enterprises should take measures to ensure implementation of personnel Hygienic Practice.Article 31 Enterprises should manage personnel health and establish health files. Production personnel in direct contact with drugs shall receive health checks before induction and later health check should be performed at least once a year.Article 32 Enterprises should take appropriate measures to keep person wound surface, infectious diseases or other diseases that may contaminate drug from being engaged in drug production.T D V N O N O F F I C I A L T R A N S L A T I O NArticle 33 Visitors and untrained personnel shall not have access to production and quality control areas. When there is need for access, instruction on personal hygiene, dressing and other matters should be given.Article 34: Any person entering the production area shall change clothes in accordance with provisions. Materials, style and dressing way of clothes should be appropriate to work engaged and air cleanliness level.Article 35 Personnel entering the clean production areas shall not wear make-up accessories.Article 36 There should be no smoking and eating, storage of food, beverages, cigarettes and drugs for personal use and other non-production items in production and storage area.Article 37 Operators should not directly touch drugs, and packaging materials and equipment surface that will be contact with drug with bare hands.T D V N O N O F F I C I A L T R A N S L A T I O N4. Facility and utilities4.1 General provisionsArticle 38 Facilities sites, design, layout, construction, renovation and maintenance must comply with requirements of pharmaceutical production to minimize contamination, cross contamination, confusion and errors and to facilitate cleaning, operation and maintenance.Article 39: The sites for facilities should be selected by taking protective measures for facilities and production into consideration. Facilities should be located in an environment able to minimize risk of contamination on materials and product.Article 40 Enterprises should have a clean production environment; factory floors, roads and transportation should not cause contamination to production of drugs; overall layout of production, administrative, living and support areas should be reasonable and not impede each other; facilities, personnel and materials flow within the facilities should be reasonable.Article 41 Facilities should be properly maintained and maintenance activities will not adversely affect drug quality. Facilities should be cleaned and sanitized according to detailed written operating procedures.Article 42 Facilities should be equipped with proper lighting, temperature, humidity and ventilation to ensure quality of product produced and stored as well as performance of related equipment will not be directly or indirectly affected.Article 43 Facilities and utilities should be designed and installed to prevent entrance of insects or other animals. Necessary measures should be taken to prevent use of rodenticides, pesticides and smoke agent will not cause contamination on equipment, materials, and products.Article 44 Appropriate measures should be taken to prevent access of unauthorized personnel. Production, storage and quality control areas should not be used as access for staff that not belongs to this area.Article 45 Facilities, utilities, fixed pipeline as-built drawings after completion of construction or reconstruction should be reserved.4.2 Production areaT D V N O N O F F I C I A L T R A N S L A T I O NArticle 46 Facilities, production utilities and equipment should be designed and used as required for drug properties, process flow and level of cleanliness in order to reduce risk of contamination and cross-contamination and also meet following requirements :(a) Feasibility of multi-drug facilities, production utilities and equipment should beevaluated by taking drug properties, process and intended use into consideration, and related evaluation report should be available.(b) Drugs with special properties, such as highly sensitizing drugs (e.g. penicillin) or biological products (such as BCG or other use of medicines prepared from microbial activity), must be produced with dedicated and independent facilities, production utilities and equipment. Operation area of penicillin with a large amount of dust should maintain a relatively negative pressure. The exhaust discharged into outdoors should be purified to meet requirements and air vents should be away from other air purification system inlet;(c) Production of β-lactam structure and sex hormone contraceptive drugs must use dedicated utilities (such as a independent air purification systems) and equipment and should be strictly separated from production areas for other drugs;(d) Certain hormones, cytotoxic class, highly active chemicals should be produced with dedicated utilities (such as a separate air purification systems) and equipment; special protective measures, if needed, should be validated. Drugs mentioned above can share same utilities and equipment through divided production.(e) The exhaust fan of air purification system mentioned in above b, c, and d should be purified.(f) Drug production facilities should not be used to produce non-medicinal products that may adversely affect drug quality.Article 47 Production areas and storage areas should be equipped with sufficient space to ensure orderly storage of equipment, materials, intermediate products, packaging and finished products and to avoid confusion of different products or materials, cross contamination, and omission and error caused by production or quality control operations.Article 48 Air purification systems should be installed according to drug variety, operation requirement as well as external environment in order that production area can be ventilated properly, temperature and humidity are controlled, and air is purified and filtered to ensure production environment for drug meet requirement.Pressures difference between clean areas and non-clean areas clean areas, among clean areas of different levels should not be less than 10 psi. When necessary, pressure difference should be maintained among areas with the same level of cleanliness but different functions (operating room).Areas where liquid and solid preparations, cavity medication (including rectal application), topical pharmaceutical skin preparations and other non-sterileT D V N O N O F F I C I A L T R A N S L A T I O Npreparations as well as final processing of packaging materials with direct contact with drug are exposed should be designed in accordance with requirements for D-level in Annex. Company can establish control on microorganism according to product specification and properties.Article 49 Inner surfaces of clean area (walls, floors, ceiling) should be smooth, with tight interface, free from cracks and fall-off particles to avoid dust and permit effective cleaning and if necessary, sanitization.Article 50 Various channels, lighting, air outlets and inlets and other public utilities should be designed and installed to facilitate cleaning. And maintenance should be performed from outside.Article 51 Drainage facilities should be appropriate to installation installed to avoid back-flow. Open drain should be avoided, and be as shallow as possible to facilitate cleaning and sanitization.Article 52 Raw materials and excipients for preparation should be weighed in preparation room specially designed.Article 53: Operation rooms that generate dust (operation rooms such as sampling, weighing, mixing, and packaging of dried material or product) should maintain relatively negative pressure or take special measures to prevent spread of dust, cross-contamination and to facilitate cleaning.Article 54 Facilities or areas used for dug packaging should be properly designed to avoid confusion or cross-contamination. Isolation measures should be taken when there are several packaging lines in the same area.Article 55 Production areas should be equipped with appropriate lighting; lighting in visual check area shall meet requirements.Article 56: In-process control can be located within production area when in-process control operation will not adversely affect product quality.4.3 Warehousing areaArticle 57 Storage areas should be equipped with sufficient space to ensure orderly storage of quarantined, accepted, rejected, return or recalled raw materials and excipients, packaging materials, intermediate products, packaging and finished products and other materials and products.Article 58 Storage areas should be designed and constructed to ensure good storage conditions and equipped with ventilation and lighting utilities. Storage area should be able to meet storage conditions for materials or products (such as temperature andT D V N O N O F F I C I A L T R A N S L A T I O Nhumidity, protection from light) and requirements for safe storage. The storage area needs to be analyzed and monitored.Article 59 Highly reactive materials or products and printed packaging materials should be stored in a secure area.Article 60 Reception, distribution and shipping areas should be able to protect materials, products from being impacted by outside weather (such as rain, snow). Layout and utilities of receiving area should be able to ensure outer packages for materials and product can be cleaned before warehousing.Article 61: If an independent area is used to store quarantine materials, this area should be labeled clearly and only restricted to authorized personnel.Rejected, returned or recalled materials or products should be quarantined.If other means are adopted to replace physical separation, this method should be of equivalent security.Article 62: Usually there should be separate material sampling area. Air cleanliness level in sampling area should be consistent with production requirements. If sampling is performed in other area or by other means, contamination or cross contamination should be avoided.4.4 Quality Control AreaArticle 63 Quality control laboratory should normally be separated from production areas. Biological analysis, microbiological and radioisotope laboratory should also be separated from each other.Article 64 Laboratory should be designed to meet its intended use and to avoid confusion and cross-contamination. And there should be enough area for sample disposal, storage of retained samples and samples for stability study as well as record keeping.Article 65: When necessary, specialized equipment room should be set to keep sensitive equipment from static electricity, vibration, humidity or other external disturbances.Article 66 Laboratory used to treat biological or radioactive samples and other special items should be consistent with relevant national requirements.Article 67 Experimental animal rooms should be strictly separated from other areas; its design and construction shall comply with relevant regulations and equipped with separate air-handling facilities and dedicated channels for animals.。