ICH-Q7(中英文对照)

人用药物注册技术要求国际协调会议( I C H ：International Conference on Harmonization of Technical Requirements for Registration ofPharmaceuticals for Human Use)ICH三方协调指南原料药的优良制造规范（GMP）指南ICH指导委员会2000年11月10日按ICH规程第4步建议采用本指南根据ICH规程由合适的ICH专家工作组起草并经向法规部门咨询。

在规程的第4步，建议欧洲共同体、日本和美国的药政部门采用其最终的草案。

原料药的优良制造规范（GMP）指南ICH三方协调指南ICH指导委员会2000年11月10日的会议按ICH规程第4步建议ICH的三个药政部门采用本指南目录1 引言INTRODUCTION (6)1.1 目的Objective (6)1.2 法规的适用性Regulatory Applicability (7)1.3 范围Range (7)2 质量管理QUALITY MANAGEMENT (9)2.1 原则Principles (9)2.2 质量部门的职责Responsibilities of the Quality Unit(s) (10)2.3 生产作业的职责Responsibility for Production Activities (12)2.4 内部审计（自检）Internal Audits (Self Inspection) (13)2.5 产品质量审核Product Quality Review (13)3 人员PERSONNEL (14)3.1 员工的资质Personnel qualifications (14)3.2 员工的卫生Personnel Hygiene (14)3.3 顾问Consultants (15)4 建筑和设施BUILDINGS AND FACILITIES (15)4.1 设计和结构Design and Construction (15)4.2 公用设施Utilities (16)4.3 水Water (17)4.4 限制Containment (18)4.5 照明Lighting (18)4.6 排污和垃圾Sewage and Refuse (18)4.7 清洁和保养Sanitation and Maintenance (19)5 工艺设备PROCESS EQUIPMENT (19)5.1 设计和结构Design and Construction (19)5.2 设备保养和清洁Equipment Maintenance and Cleaning (20)5.3 校验Calibration (21)5.4 计算机控制系统Computerized Systems (22)6 文件和记录DOCUMENTATION AND RECORDS (23)6.1 文件系统和规格Documentation System and Specifications (23)6.2 设备的清洁和使用记录Equipment Cleaning and Use Record (24)6.3 原料、中间体、原料药的标签和包装材料的记录Records of Materials , Intermediates, API Labelingand Packaging Materials (25)6.4 生产工艺规程Master Production Instructions (25)6.5 批生产记录Batch Production Records (26)6.6 实验室控制记录Laboratory Control Records (27)6.7 批生产记录审核Batch Production Record Review (28)7 物料管理MATERIALS MANAGEMENT (29)7.1 控制通则General Controls (29)7.2 接收和待验Receipt and Quarantine (30)7.3 进厂物料的取样和测试Sampling and Testing of Incoming Production Materials (30)7.4 储存Storage (32)7.5 重新评估Re-evaluation (32)8 生产和中间控制PRODUCTION AND IN-PROCESS CONTROLS (32)8.1 生产操作Production Operations (32)8.2 时间限制Time Limits (33)8.3 工序间的取样和控制In-process Sampling and Controls (34)8.4 中间体或原料药的混合Blending Batches of Intermediates or APIs (35)8.5 污染的控制Contamination Control (36)9 原料药和中间体的包装和贴签PACKAGING AND IDENTIFICATION LABELING OF APIs AND INTERMEDIATES (36)9.1 总则General (36)9.2 包装材料Packaging Materials (37)9.3 标签的发放和控制Labeling Issuance and Control (37)9.4 包装和贴签操作Packaging and Labeling Operations (38)10 储存和分发STORAGE AND DISTRIBUTION (39)10.1 入库程序Warehousing Procedures (39)10.2 分发程序Distribution Procedures (39)11 实验室控制LABORATORY CONTROLS (40)11.1 控制通则General Controls (40)11.2 中间体和原料药的测试Testing of Intermediates and APIs (41)11.3 分析程序的验证－参见12章Validation of Analytical Procedures - See Section 12. (11.3) (42)11.4 分析报告单Certificates of Analysis (42)11.5 原料药的稳定性监测Stability Monitorint of APIs (43)11.6 有效期和复验日期Expiry and Retest Dating (44)11.7 留样Reserve/Retention Samples (45)12 验证VALIDATION (45)12.1 验证方针Validation Policy (45)12.2 验证文件Validation Documentation (46)12.3 确认Qualification (46)12.4 工艺验证的方法Approaches to Process Validation (47)12.5 工艺验证的程序Process Validation Program (48)12.7 清洗验证Cleaning Validation (49)12.8 分析方法的验证Validation of Analytical Methods (51)13 变更的控制CHANGE CONTROL (51)14 物料的拒收和再用REJECTION AND RE-USE OF MATERIALS (52)14.1 拒收Rejection (52)14.2 返工Reprocessing (53)14.3 重新加工Reworking (53)14.4 物料和溶剂的回收Recovery of Materials and Solvents (54)14.5 退货Returns (54)15 投诉和召回COMPLAINTS AND RECALLS (55)16 协议制造商(包括实验室) CONTRACT MANUFACTURES (INCLUDING LABORATORIES) (56)17 代理商、经纪人、贸易商、经销商、重新包装者和重新贴签者 (57)AGENTS,BROKERS, TRADERS,DISTRIBUTORS,REPACKERS ,AND RELABELLERS (57)17.1 适用性Applicability (57)17.2 已分发原料药的可追溯性Traceability of Distributed APIs and Intermediates (57)17.3 质量管理Quality Management (57)17.4 原料药和中间体的重新包装、重新贴签和待检Repackaging,Relabeling,and Holding of APIs andIntermediates. (58)17.5 稳定性Stability (58)17.6 信息的传达Transfer of Information (58)17.7 投诉和召回的处理Handing of Complaints and Recalls (59)17.8 退货的处理Handing of Returns (59)18 用细胞繁殖/发酵生产的原料药的特殊指南 (59)SPECIFIC GUIDANCE FOR APIs MANUFACTURED BY CELL CULTURE/FERMENTATION (59)18.1 总则General (59)18.2 细胞库的维护和记录的保存Cell Bank Maintenance and Record Keeping (62)18.3 细胞繁殖/发酵Cell Culture/Fermentation (62)18.4 收取、分离和精制Harvesting, Isolation and Purifation (63)18.5 病毒的去除/灭活步骤Viral Removal/Inactivation Steps (64)19 用于临床研究的原料药(APIS FOR USE IN CLINICAL TRIALS) (65)19.1 总则General (65)19.2 质量quality (65)19.3 设备和设施Equipment and Facilities (66)19.4 原料的控制Control of Raw Materials (66)19.5 生产Production (66)19.6 验证Validation (67)19.7 变更Changes (67)19.8 实验室控制Laboratory Controls (67)19.9 文件Documentation (67)20. 术语表（GLOOSSARY） (68)原料药的优良制造规范(GMP) 指南Guidance for IndustryQ7A Good Manufacturing Practice Guidancefor Active Pharmaceutical IngredientsThis guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statutes and regulations.1 引言INTRODUCTION1.1 目的Objective本文件(指南)旨在为在合适的质量管理体系下制造活性药用成分(原料药以下称原料药)提供有关优良药品生产管理规范（GMP）提供指南。

201506 ICH Q7官方问答Q7 Implementation Working GroupICH Q7 Guideline: Good Manufacturing Practice Guide for Active PharmaceuticalIngredientsQuestions and AnswersCurrent versiondated 10 June 2015In order to facilitate the implementation of the Q7 Guidelines,the ICH Experts have developed a series of Q&As:Q7 Q&AsDocument HistoryICH Q7指南：原料药GMP指南问答2015-6-10Code History DateQ7 Q&As Approval by the ICH Steering Committee10 June 2015under Step 4ReferencesThese documents are published at .ICH E2E Pharmacovigilance Planning November 2004ICH Q1A(R2) Stability testing of new drug substance and products February 2003ICH Q5A Quality of Biotechnological Products: Viral Safety Evaluation of Biotechnology Products Derivedfrom Cell Lines of Human or Animal Origin September 1999ICH Q5B Quality of biotechnological products: Analysis of the construct in cells used for the productionof r-DNA derived protein products November 2005ICH Q5D Quality of Biotechnological Products: Derivation and Characterisation of Cell Substrates Used for Production of Biotechnological/Biological Products July 1997ICH Q6B Specifications: Test Procedures and Acceptance Criteria forBiotechnological/Biological Products March 1999ICH Q7 Good Manufacturing Practice of APIs November 2000ICH Q8(R2) Pharmaceutical Development August 2009Part I: ‘Pharmaceutical Development’ November 2006Part II: ‘Annex to Pharmaceutical Development’, November 2008ICH Q9 Quality Risk Management and the ICH Q9 Briefing pack November 2005ICH Q10 Pharmaceutical Quality Systems June 2008ICH Q-IWG Training Programme for ICH Q8/Q9/Q10 November 2010ICH Q11 Development and Manufacturing of Active Pharmaceutical Ingredients May 2012 Legal Notice:This document is protected by copyright and may be used, reproduced, incorporated into other works, adapted, modified, translated or distributed under a public license provided that ICH's copyright in the document is acknowledged at all times. In caseof any adaption, modification or translation of the document, reasonable steps must be taken to clearly label, demarcate or otherwise identify that changes were made to or based on the original document. Any impression that the adaption, modification or translation of the original document is endorsed or sponsored by the ICH must be avoided.The document is provided "as is" without warranty of any kind. In no event shall the ICH or the authors of the original document be liable for any claim, damages or other liability arising from the use of the document.The above-mentioned permissions do not apply to content supplied by third parties. Therefore, for documents where the copyright vests in a third party, permission for reproduction must be obtained from this copyright holder.Table of ContentsPREFACE .............................................................................................................................. .. (1)1. INTRODUCTION -SCOPE (2)2. QUALITYMANAGEMENT (2)3.PERSONNEL ......................................................................................................................... . (3)4. BUILDINGS AND FACILITIES – CONTAINMENT (4)5. PROCESS EQUIPMENT –CLEANING (5)6. DOCUMENTATION ANDRECORDS (6)7. MATERIALSMANAGEMENT (7)8. PRODUCTION AND IN-PROCESSCONTROLS (8)9. PACKAGING AND IDENTIFICATION LABELLING OF APIS ANDINTERMEDIATES .................................................................................................................. .. (8)10. STORAGE ANDDISTRIBUTION (8)11. LABORATORYCONTROLS (9)12.VALIDATION (11)13. CHANGECONTROL (11)14. REJECTION AND REUSE OF MATERIALS (12)15. COMPLAINTS AND RECALLS (12)16. CONTRACT MANUFACTURERS (INCLUDINGLABORATORIES) .................................................................................................................. . (13)17. AGENTS, BROKERS, TRADERS, DISTRIBUTORS, REPACKERS, AND RELABELLERS ..................................................................................................................... .. (14)18. SPECIFIC GUIDANCE FOR APIS MANUFACTURED BY CELLCULTURE/FERMENTATION ................................................................................................ (15)19. APIS FOR USE IN CLINICAL TRIALS (15)20.GLOSSARY (16)21. ANNEX: Q&AS LINKED TO THE RESPECTIVE SECTIONS OF ICH Q7 (17)。

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 Systems5.4 计算机控制系统6. DOCUMENTATION AND RECORDS6. 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 Record6.2 设备的清洁和使用记录 6.3 Records of Raw Materials,Intermediates, API Labeling and Packaging Materials6.3 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 (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 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接收和待验 7.3 Sampling and Testing of Incoming Production Materials7.3 进厂物料的取样与测试 7.4 Storage7.4储存 7.5 Re-evaluation7.5复验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 时限 8.3 In-process Sampling and Controls8.3 工序取样和控制 8.4 Blending Batches of Intermediates or APIs8.4 中间体或原料药的混批 8.5 Contamination Control8.5 污染控制9. PACKAGING AND IDENTIFICATION LABELING OF APIs AND INTERMEDIATES9. 原料药和中间体的包装和贴签 9.1 General9.1 总则 9.2 Packaging Materials9.2 包装材料 9.3 Label Issuance and Control9.3 标签发放与控制 9.4 Packaging and Labeling Operations9.4 包装和贴签操作10. STORAGE AND DISTRIBUTION10.储存和分发 10.1 Warehousing Procedures10.1 入库程序 10.2 Distribution Procedures10.2 分发程序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 中间体和原料药的测试 11.3 Validation of Analytical Procedures11.3 分析方法的验证 11.4 Certificates of Analysis11.4 分析报告单 11.5 Stability Monitoring of APIs11.5 原料药的稳定性监测 11.6 Expiry and Retest Dating11.6 有效期和复验期 11.7 Reserve/Retention Samples11.7 留样12. V ALIDATION12.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 工艺验证的方法 12.5 Process Validation Program12.5 工艺验证的程序 12.6 Periodic Review of Validated Systems12.6验证系统的定期审核 12.7 Cleaning Validation12.7 清洗验证 12.8 Validation of Analytical Methods12.8 分析方法的验证13. CHANGE CONTROL13.变更的控制14. REJECTION AND RE-USE OFMATERIALS14.拒收和物料的再利用 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 物料与溶剂的回收 14.5 Returns14.5 退货15. COMPLAINTS AND RECALLS15.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, ANDRELABELLERS17.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 Applicability17.1适用性 17.2 Traceability of Distributed APIs and Intermediates17.2已分发的原料药和中间体的可追溯性 17.3 Quality Management17.3质量管理 17.4 Repackaging, Relabeling, and Holding of APIs and Intermediates17.4原料药和中间体的重新包装、重新贴签和待检17.5 Stability17.5稳定性 17.6 Transfer of Information17.6 信息的传达 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 APIsManufactured 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 General18.1 总则 18.2 Cell Bank Maintenance and Record Keeping18.2细胞库的维护和记录的保存 18.3 Cell Culture/Fermentation18.3细胞繁殖/发酵 18.4 Harvesting, Isolation and Purification18.4收取、分离和精制 18.5 Viral Removal/Inactivation steps18.5 病毒的去除/灭活步骤19. APIs for Use in Clinical Trials19. 用于临床研究的原料药 19.1 General19.1 总则 19.2 Quality19.2 质量 19.3 Equipment and Facilities19.3 设备和设施 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. 术语Q7a GMP Guidance for APIsQ7a 原料药的GMP 指南1. INTRODUCTION1. 简介 1.1 Objective1.1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。

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USEICH H ARMONISED T RIPARTITE G UIDELINEG OOD M ANUFACTURING P RACTICE G UIDE FOR A CTIVE P HARMACEUTICAL I NGREDIENTSQ7Current Step 4 versiondated 10 November 2000This Guideline has been developed by the appropriate ICH Expert Working Group and has been subject to consultation by the regulatory parties, in accordance with the ICH Process. At Step 4 of the Process the final draft is recommended for adoption to the regulatory bodies of the European Union, Japan and USA.中英文对照Q7Current Step 4 versionG OOD M ANUFACTURING P RACTICE G UIDE FOR A CTIVE P HARMACEUTICAL I NGREDIENTSICH Harmonised Tripartite GuidelineHaving reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 10 November 2000, this guideline is recommended for adoption to the three regulatory parties to ICHTable of Contents 目录1. INTRODUCTION 1. 前言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 产品质量回顾3. PERSONNEL 3. 人员3.1 Personnel Qualifications 3.1人员资格3.2 Personnel Hygiene 3.2 个人卫生3.3 Consultants 3.3 顾问4. BUILDINGS AND FACILITIES 4. 建筑和设施4.1 Design and Construction 4.1 设计和建造4.2 Utilities 4.2 公用设施4.3 Water 4.3 水4.4 Containment 4.4 特殊限制4.5 Lighting 4.5 照明4.6 Sewage and Refuse 4.6 污物和废弃物4.7 Sanitation and Maintenance 4.7 卫生和维护5. PROCESS EQUIPMENT 5. 工艺设备5.1 Design and Construction 5.1 设计和建造5.2 Equipment Maintenance and Cleaning 5.2 设备维护和清洁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 and Specifications 6.1 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, 6.3 原料、中间体、原料药的标签和包装材料的记录API Labeling and Packaging Materials6.4 Master Production Instructions 6.4 主生产指令（主生产和控制记录）(Master Production and Control Records)6.5 Batch Production Records 6.5 批生产记录（批生产和控制记录）(BatchProduction and Control Records)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 一般要求7.2 Receipt and Quarantine 7.2 接收和待验7.3 Sampling and Testing of Incoming Production Materials 7.3 来料的取样与检测7.4 Storage 7.4 储存7.5 Re-evaluation 7.5 再评价8. PRODUCTION AND IN-PROCESS CONTROLS 8. 生产管理和生产过程控制8.1 Production Operations 8.1 生产管理8.2 Time Limits 8.2 时限8.3 In-process Sampling and Controls 8.3 生产过程中的取样和控制8.4 Blending Batches of Intermediates or APIs 8.4 中间体或原料药的混批8.5 Contamination Control 8.5 污染控制9. PACKAGING AND IDENTIFICATION 9. 原料药和中间体的包装和贴签LABELING OF APIs AND INTERMEDIATES9.1 General 9.1 通则9.2 Packaging Materials 9.2 包装材料9.3 Label Issuance and Control 9.3 标签发放与管理9.4 Packaging and Labeling Operations 9.4 包装和贴签管理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.实验室管理11.1 General Controls 11.1通则11.2 Testing of Intermediates and APIs 11.2 中间体和原料药的检测11.3 Validation of Analytical Procedures 11.3 分析方法的验证11.4 Certificates of Analysis 11.4 检验报告11.5 Stability Monitoring of APIs 11.5 原料药的稳定性考察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 Validated Systems 12.6 对已验证的系统的定期回顾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.变更控制14. REJECTION AND RE-USE OF MATERIALS 14.物料的拒收和再利用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 16.协议生产商（包括实验室）(INCLUDING LABORATORIES)17. AGENTS, BROKERS, TRADERS, DISTRIBUTORS, 17.代理商、经纪人、贸易商、经销商、重新包装者REPACKERS, AND RELABELLERS 和重新贴签者17.1 Applicability 17.1 适用性17.2 Traceability of Distributed APIs and Intermediates 17.2 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 18. 用细胞繁殖/发酵生产的原料药的特殊指南Culture/Fermentation18.1 General 18.1 总则18.2 Cell Bank Maintenance and Record Keeping 18.2 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.本文件旨在提供在适当的体系下为了控制生产原料药的质量而实施的药品生产质量管理规范（GMP）的指南。

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE ICH H ARMONISED T RIPARTITE G UIDELINEG OOD M ANUFACTURING P RACTICE G UIDE FORA CTIVE P HARMACEUTICAL I NGREDIENTSRecommended for Adoptionat Step 4 of the ICH Processon 10 November 2000by the ICH Steering CommitteeThis Guideline has been developed by the appropriate ICH Expert Working Group and has been subject to consultation by the regulatory parties, in accordance with the ICH Process. At Step 4 of the Process the final draft is recommended for adoption to the regulatory bodies of the European Union, Japan and USA.G OOD M ANUFACTURING P RACTICE G UIDE FORA CTIVE P HARMACEUTICAL I NGREDIENTSICH Harmonised Tripartite GuidelineHaving reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 10 November 2000, this guideline is recommended foradoption to the three regulatory parties to ICHTABLE OF CONTENTS1. INTRODUCTION (1)1.1 Objective (1)1.2 Regulatory Applicability (1)1.3 Scope (1)2. QUALITY MANAGEMENT (4)2.1 Principles (4)2.2 Responsibilities of the Quality Unit(s) (4)2.3 Responsibility for Production Activities (5)2.4 Internal Audits (Self Inspection) (5)2.5 Product Quality Review (6)3. PERSONNEL (6)3.1 Personnel Qualifications (6)3.2 Personnel Hygiene (6)3.3 Consultants (7)4. BUILDINGS AND FACILITIES (7)4.1 Design and Construction (7)4.2 Utilities (8)4.3 Water (8)4.4 Containment (9)4.5 Lighting (9)4.6 Sewage and Refuse (9)4.7 Sanitation and Maintenance (9)5. PROCESS EQUIPMENT (9)5.1 Design and Construction (9)5.2 Equipment Maintenance and Cleaning (10)5.3 Calibration (11)5.4 Computerized Systems (11)Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients6. DOCUMENTATION AND RECORDS (12)6.1 Documentation System and Specifications (12)6.2 Equipment Cleaning and Use Record (13)6.3 Records of Raw Materials, Intermediates, API Labelling andPackaging Materials (13)6.4 Master Production Instructions(Master Production and Control Records) (13)6.5 Batch Production Records (Batch Production and Control Records).. 146.6 Laboratory Control Records (15)6.7 Batch Production Record Review (15)7. MATERIALS MANAGEMENT (16)7.1 General Controls (16)7.2 Receipt and Quarantine (16)7.3 Sampling and Testing of Incoming Production Materials (17)7.4 Storage (17)7.5 Re-evaluation (18)8. PRODUCTION AND IN-PROCESS CONTROLS (18)8.1 Production Operations (18)8.2 Time Limits (19)8.3 In-process Sampling and Controls (19)8.4 Blending Batches of Intermediates or APIs (19)8.5 Contamination Control (20)9. PACKAGING AND IDENTIFICATION LABELLING OF APIsAND INTERMEDIATES (20)9.1 General (20)9.2 Packaging Materials (21)9.3 Label Issuance and Control (21)9.4 Packaging and Labelling Operations (21)10. STORAGE AND DISTRIBUTION (22)10.1 Warehousing Procedures (22)10.2 Distribution Procedures (22)11. LABORATORY CONTROLS (23)11.1 General Controls (23)11.2 Testing of Intermediates and APIs (24)11.3 Validation of Analytical Procedures (24)11.4 Certificates of Analysis (24)Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients11.5 Stability Monitoring of APIs (25)11.6 Expiry and Retest Dating (25)11.7 Reserve/Retention Samples (25)12. VALIDATION (26)12.1 Validation Policy (26)12.2 Validation Documentation (26)12.3 Qualification (27)12.4 Approaches to Process Validation (27)12.5 Process Validation Program (28)12.6 Periodic Review of Validated Systems (28)12.7 Cleaning Validation (28)12.8 Validation of Analytical Methods (29)13. CHANGE CONTROL (29)14. REJECTION AND RE-USE OF MATERIALS (30)14.1 Rejection (30)14.2 Reprocessing (30)14.3 Reworking (31)14.4 Recovery of Materials and Solvents (31)14.5 Returns (31)15. COMPLAINTS AND RECALLS (32)16. CONTRACT MANUFACTURERS (INCLUDING LABORATORIES). 3217. AGENTS, BROKERS, TRADERS, DISTRIBUTORS, REPACKERS,AND RELABELLERS (33)17.1 Applicability (33)17.2 Traceability of Distributed APIs and Intermediates (33)17.3 Quality Management (33)17.4 Repackaging, Relabelling and Holding of APIs and Intermediates (33)17.5 Stability (34)17.6 Transfer of Information (34)17.7 Handling of Complaints and Recalls (34)17.8 Handling of Returns (34)18. SPECIFIC GUIDANCE FOR APIs MANUFACTURED BY CELLCULTURE/FERMENTATION (35)18.1 General (35)18.2 Cell Bank Maintenance and Recordkeeping (36)18.3 Cell Culture/Fermentation (36)Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients18.4 Harvesting, Isolation, and Purification (37)18.5 Viral Removal/Inactivation Steps (37)19. APIs FOR USE IN CLINICAL TRIALS (38)19.1 General (38)19.2 Quality (38)19.3 Equipment and Facilities (38)19.4 Control of Raw Materials (39)19.5 Production (39)19.6 Validation (39)19.7 Changes (39)19.8 Laboratory Controls (39)19.9 Documentation (39)20. GLOSSARY (40)G OOD M ANUFACTURING P RACTICE G UIDE FORA CTIVE P HARMACEUTICAL I NGREDIENTS1. INTRODUCTION1.1 ObjectiveThis document (Guide) 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 requirements for quality and purity that they purport or are represented to possess.In this Guide “manufacturing” is defined to include all operations of receipt of materials, production, packaging, repackaging, labelling, relabelling, quality control, release, storage and distribution of APIs and the related controls. In this Guide the term “should” indicates recommendations that are expected to apply unless shown to be inapplicable or replaced by an alternative demonstrated to provide at least an equivalent level of quality assurance. For the purposes of this Guide, the terms “current good manufacturing practices” and “good manufacturing practices” are equivalent.The Guide as a whole does not cover safety aspects for the personnel engaged in the manufacture, nor aspects of protection of the environment. These controls are inherent responsibilities of the manufacturer and are governed by national laws.This Guide is not intended to define registration/filing requirements or modify pharmacopoeial requirements. This Guide does not affect the ability of the responsible regulatory agency to establish specific registration/filing requirements regarding APIs within the context of marketing/manufacturing authorizations or drug applications. All commitments in registration/filing documents must be met.1.2 Regulatory ApplicabilityWithin the world community, materials may vary as to the legal classification as an API. When a material is classified as an API in the region or country in which it is manufactured or used in a drug product, it should be manufactured according to this Guide.1.3 ScopeThis Guide applies to the manufacture of APIs for use in human drug (medicinal) products. It applies to the manufacture of sterile APIs only up to the point immediately prior to the APIs being rendered sterile. The sterilization and aseptic processing of sterile APIs are not covered by this guidance, but should be performed in accordance with GMP guidelines for drug (medicinal) products as defined by local authorities.This Guide covers APIs that are manufactured by chemical synthesis, extraction, cell culture/fermentation, by recovery from natural sources, or by any combination of these processes. Specific guidance for APIs manufactured by cell culture/fermentation is described in Section 18.Good Manufacturing Practice Guide for Active Pharmaceutical IngredientsThis Guide excludes all vaccines, whole cells, whole blood and plasma, blood and plasma derivatives (plasma fractionation), and gene therapy APIs. However, it does include APIs that are produced using blood or plasma as raw materials. Note that cell substrates (mammalian, plant, insect or microbial cells, tissue or animal sources including transgenic animals) and early process steps may be subject to GMP but are not covered by this Guide. In addition, the Guide does not apply to medical gases, bulk-packaged drug (medicinal) products, and manufacturing/control aspects specific to radiopharmaceuticals.Section 19 contains guidance that only applies to the manufacture of APIs used in the production of drug (medicinal) products specifically for clinical trials (investigational medicinal products).An “API Starting Material” is a raw material, intermediate, or an API that is used in the production of an API and that is incorporated as a significant structural fragment into the structure of the API. An API Starting Material can be an article of commerce, a material purchased from one or more suppliers under contract or commercial agreement, or produced in-house. API Starting Materials normally have defined chemical properties and structure.The company should designate and document the rationale for the point at which production of the API begins. For synthetic processes, this is known as the point at which "API Starting Materials" are entered into the process. For other processes (e.g. fermentation, extraction, purification, etc), this rationale should be established on a case-by-case basis. Table 1 gives guidance on the point at which the API Starting Material is normally introduced into the process.From this point on, appropriate GMP as defined in this Guide should be applied to these intermediate and/or API manufacturing steps. This would include the validation of critical process steps determined to impact the quality of the API. However, it should be noted that the fact that a company chooses to validate a process step does not necessarily define that step as critical.The guidance in this document would normally be applied to the steps shown in gray in Table 1. It does not imply that all steps shown should be completed. The stringency of GMP in API manufacturing should increase as the process proceeds from early API steps to final steps, purification, and packaging. Physical processing of APIs, such as granulation, coating or physical manipulation of particle size (e.g. milling, micronizing), should be conducted at least to the standards of this Guide.This GMP Guide does not apply to steps prior to the introduction of the defined "API Starting Material".Good Manufacturing Practice Guide for Active Pharmaceutical IngredientsTable 1: Application of this Guide to API ManufacturingType ofManufacturingApplication of this Guide to steps (shown in grey) used in this type ofmanufacturing ChemicalManufacturing Production of the APIStartingMaterialIntroduction of the API Starting Material into process Production of Intermediate(s) Isolation and purification Physical processing, and packaging API derived from animal sources Collection oforgan, fluid, ortissue Cutting, mixing, and/or initialprocessingIntroduction of the API Starting Material into process Isolation and purification Physical processing, and packaging API extracted from plant sources Collection of plants Cutting andinitialextraction(s) Introduction of the API StartingMaterial intoprocessIsolation and purification Physical processing, and packaging Herbal extracts used as API Collection of plants Cutting and initial extraction Further extraction Physicalprocessing,andpackagingAPI consisting of comminuted or powdered herbs Collection of plants and/or cultivation and harvesting Cutting/ comminuting Physicalprocessing,andpackagingBiotechnology: fermentation/ cell culture Establishment of master cell bank and working cell bank Maintenance of working cell bank Cell culture and/or fermentation Isolation and purification Physicalprocessing,andpackaging“Classical” Fermentation to produce an API Establishment of cell bank Maintenance of the cell bank Introduction of the cells into fermentation Isolation and purificationPhysicalprocessing,andpackagingGood Manufacturing Practice Guide for Active Pharmaceutical Ingredients2. QUALITY MANAGEMENT2.1 Principles2.10 Quality should be the responsibility of all persons involved in manufacturing.2.11 Each manufacturer should establish, document, and implement an effectivesystem for managing quality that involves the active participation of management and appropriate manufacturing personnel.2.12 The system for managing quality should encompass the organisational structure,procedures, processes and resources, as well as activities necessary to ensure confidence that the API will meet its intended specifications for quality and purity. All quality related activities should be defined and documented.2.13 There should be a quality unit(s) that is independent of production and thatfulfills both quality assurance (QA) and quality control (QC) responsibilities. This can be in the form of separate QA and QC units or a single individual or group, depending upon the size and structure of the organization.2.14 The persons authorised to release intermediates and APIs should be specified. 2.15 All quality related activities should be recorded at the time they are performed.2.16 Any deviation from established procedures should be documented and explained.Critical deviations should be investigated, and the investigation and its conclusions should be documented.2.17 No materials should be released or used before the satisfactory completion ofevaluation by the quality unit(s) unless there are appropriate systems in place to allow for such use (e.g. release under quarantine as described in Section 10.20 or the use of raw materials or intermediates pending completion of evaluation).2.18 Procedures should exist for notifying responsible management in a timely mannerof regulatory inspections, serious GMP deficiencies, product defects and related actions (e.g. quality related complaints, recalls, regulatory actions, etc.).2.2 Responsibilities of the Quality Unit(s)2.20 The quality unit(s) should be involved in all quality-related matters.2.21 The quality unit(s) should review and approve all appropriate quality-relateddocuments.2.22 The main responsibilities of the independent quality unit(s) should not bedelegated. These responsibilities should be described in writing and should include but not necessarily be limited to:1. Releasing or rejecting all APIs. Releasing or rejecting intermediates for useoutside the control of the manufacturing company;2. Establishing a system to release or reject raw materials, intermediates,packaging and labelling materials;3. Reviewing completed batch production and laboratory control records ofcritical process steps before release of the API for distribution;4. Making sure that critical deviations are investigated and resolved;5. Approving all specifications and master production instructions;6. Approving all procedures impacting the quality of intermediates or APIs;Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients7. Making sure that internal audits (self-inspections) are performed;8. Approving intermediate and API contract manufacturers;9. Approving changes that potentially impact intermediate or API quality;10. Reviewing and approving validation protocols and reports;11. Making sure that quality related complaints are investigated and resolved;12. Making sure that effective systems are used for maintaining and calibratingcritical equipment;13. Making sure that materials are appropriately tested and the results arereported;14. Making sure that there is stability data to support retest or expiry dates andstorage conditions on APIs and/or intermediates where appropriate; and15. Performing product quality reviews (as defined in Section 2.5).2.3 Responsibility for Production ActivitiesThe responsibility for production activities should be described in writing, and should include but not necessarily be limited to:1. Preparing, reviewing, approving and distributing the instructions for theproduction of intermediates or APIs according to written procedures;2. Producing APIs and, when appropriate, intermediates according to pre-approved instructions;3. Reviewing all production batch records and ensuring that these arecompleted and signed;4. Making sure that all production deviations are reported and evaluated andthat critical deviations are investigated and the conclusions are recorded;5. Making sure that production facilities are clean and when appropriatedisinfected;6. Making sure that the necessary calibrations are performed and recordskept;7. Making sure that the premises and equipment are maintained and recordskept;8. Making sure that validation protocols and reports are reviewed andapproved;9. Evaluating proposed changes in product, process or equipment; and10. Making sure that new and, when appropriate, modified facilities andequipment are qualified.2.4 Internal Audits (Self Inspection)2.40 In order to verify compliance with the principles of GMP for APIs, regularinternal audits should be performed in accordance with an approved schedule. 2.41 Audit findings and corrective actions should be documented and brought to theattention of responsible management of the firm. Agreed corrective actions should be completed in a timely and effective manner.2.5 Product Quality Review2.50 Regular quality reviews of APIs should be conducted with the objective ofverifying the consistency of the process. Such reviews should normally be conducted and documented annually and should include at least:− A review of critical in-process control and critical API test results;− A review of all batches that failed to meet established specification(s);− A review of all critical deviations or non-conformances and related investigations;− A review of any changes carried out to the processes or analytical methods;− A review of results of the stability monitoring program;− A review of all quality-related returns, complaints and recalls; and− A review of adequacy of corrective actions.2.51 The results of this review should be evaluated and an assessment made ofwhether corrective action or any revalidation should be undertaken. Reasons for such corrective action should be documented. Agreed corrective actions should be completed in a timely and effective manner.3. PERSONNEL3.1 Personnel Qualifications3.10 There should be an adequate number of personnel qualified by appropriateeducation, training and/or experience to perform and supervise the manufacture of intermediates and APIs.3.11 The responsibilities of all personnel engaged in the manufacture of intermediatesand APIs should be specified in writing.3.12 Training should be regularly conducted by qualified individuals and should cover,at a minimum, the particular operations that the employee performs and GMP as it relates to the employee's functions. Records of training should be maintained.Training should be periodically assessed.3.2 Personnel Hygiene3.20 Personnel should practice good sanitation and health habits.3.21 Personnel should wear clean clothing suitable for the manufacturing activity withwhich they are involved and this clothing should be changed when appropriate.Additional protective apparel, such as head, face, hand, and arm coverings, should be worn when necessary, to protect intermediates and APIs from contamination.3.22 Personnel should avoid direct contact with intermediates or APIs.3.23 Smoking, eating, drinking, chewing and the storage of food should be restricted tocertain designated areas separate from the manufacturing areas.3.24 Personnel suffering from an infectious disease or having open lesions on theexposed surface of the body should not engage in activities that could result in compromising the quality of APIs. Any person shown at any time (either by medical examination or supervisory observation) to have an apparent illness or open lesions should be excluded from activities where the health condition could adversely affect the quality of the APIs until the condition is corrected orqualified medical personnel determine that the person's inclusion would not jeopardize the safety or quality of the APIs.3.3 Consultants3.30 Consultants advising on the manufacture and control of intermediates or APIsshould have sufficient education, training, and experience, or any combination thereof, to advise on the subject for which they are retained.3.31 Records should be maintained stating the name, address, qualifications, and typeof service provided by these consultants.4. BUILDINGS AND FACILITIES4.1 Design and Construction4.10 Buildings and facilities used in the manufacture of intermediates and APIs shouldbe located, designed, and constructed to facilitate cleaning, maintenance, and operations as appropriate to the type and stage of manufacture. Facilities should also be designed to minimize potential contamination. Where microbiological specifications have been established for the intermediate or API, facilities should also be designed to limit exposure to objectionable microbiological contaminants as appropriate.4.11 Buildings and facilities should have adequate space for the orderly placement ofequipment and materials to prevent mix-ups and contamination.4.12 Where the equipment itself (e.g., closed or contained systems) provides adequateprotection of the material, such equipment can be located outdoors.4.13 The flow of materials and personnel through the building or facilities should bedesigned to prevent mix-ups or contamination.4.14 There should be defined areas or other control systems for the followingactivities:− Receipt, identification, sampling, and quarantine of incoming materials, pending release or rejection;− Quarantine before release or rejection of intermediates and APIs;− Sampling of intermediates and APIs;− Holding rejected materials before further disposition (e.g., return, reprocessing or destruction);− Storage of released materials;− Production operations;− Packaging and labelling operations; and− Laboratory operations.4.15 Adequate, clean washing and toilet facilities should be provided for personnel.These washing facilities should be equipped with hot and cold water as appropriate, soap or detergent, air driers or single service towels. The washing and toilet facilities should be separate from, but easily accessible to, manufacturing areas. Adequate facilities for showering and/or changing clothes should be provided, when appropriate.4.16 Laboratory areas/operations should normally be separated from production areas.Some laboratory areas, in particular those used for in-process controls, can be located in production areas, provided the operations of the production process do not adversely affect the accuracy of the laboratory measurements, and the laboratory and its operations do not adversely affect the production process or intermediate or API.4.2 Utilities4.20 All utilities that could impact on product quality (e.g. steam, gases, compressedair, and heating, ventilation and air conditioning) should be qualified and appropriately monitored and action should be taken when limits are exceeded.Drawings for these utility systems should be available.4.21 Adequate ventilation, air filtration and exhaust systems should be provided,where appropriate. These systems should be designed and constructed to minimise risks of contamination and cross-contamination and should include equipment for control of air pressure, microorganisms (if appropriate), dust, humidity, and temperature, as appropriate to the stage of manufacture.Particular attention should be given to areas where APIs are exposed to the environment.4.22 If air is recirculated to production areas, appropriate measures should be takento control risks of contamination and cross-contamination.4.23 Permanently installed pipework should be appropriately identified. This can beaccomplished by identifying individual lines, documentation, computer control systems, or alternative means. Pipework should be located to avoid risks of contamination of the intermediate or API.4.24 Drains should be of adequate size and should be provided with an air break or asuitable device to prevent back-siphonage, when appropriate.4.3 Water4.30 Water used in the manufacture of APIs should be demonstrated to be suitable forits intended use.4.31 Unless otherwise justified, process water should, at a minimum, meet WorldHealth Organization (WHO) guidelines for drinking (potable) water quality.4.32 If drinking (potable) water is insufficient to assure API quality, and tighterchemical and/or microbiological water quality specifications are called for, appropriate specifications for physical/chemical attributes, total microbial counts, objectionable organisms and/or endotoxins should be established.4.33 Where water used in the process is treated by the manufacturer to achieve adefined quality, the treatment process should be validated and monitored with appropriate action limits.4.34 Where the manufacturer of a non-sterile API either intends or claims that it issuitable for use in further processing to produce a sterile drug (medicinal) product, water used in the final isolation and purification steps should be monitored and controlled for total microbial counts, objectionable organisms, and endotoxins.4.4 Containment4.40 Dedicated production areas, which can include facilities, air handling equipmentand/or process equipment, should be employed in the production of highly sensitizing materials, such as penicillins or cephalosporins.4.41 Dedicated production areas should also be considered when material of aninfectious nature or high pharmacological activity or toxicity is involved (e.g., certain steroids or cytotoxic anti-cancer agents) unless validated inactivation and/or cleaning procedures are established and maintained.4.42 Appropriate measures should be established and implemented to prevent cross-contamination from personnel, materials, etc. moving from one dedicated area to another.4.43 Any production activities (including weighing, milling, or packaging) of highlytoxic non-pharmaceutical materials such as herbicides and pesticides should not be conducted using the buildings and/or equipment being used for the production of APIs. Handling and storage of these highly toxic non-pharmaceutical materials should be separate from APIs.4.5 Lighting4.50 Adequate lighting should be provided in all areas to facilitate cleaning,maintenance, and proper operations.4.6 Sewage and Refuse4.60 Sewage, refuse, and other waste (e.g., solids, liquids, or gaseous by-products frommanufacturing) in and from buildings and the immediate surrounding area should be disposed of in a safe, timely, and sanitary manner. Containers and/or pipes for waste material should be clearly identified.4.7 Sanitation and Maintenance4.70 Buildings used in the manufacture of intermediates and APIs should be properlymaintained and repaired and kept in a clean condition.4.71 Written procedures should be established assigning responsibility for sanitationand describing the cleaning schedules, methods, equipment, and materials to be used in cleaning buildings and facilities.4.72 When necessary, written procedures should also be established for the use ofsuitable rodenticides, insecticides, fungicides, fumigating agents, and cleaning and sanitizing agents to prevent the contamination of equipment, raw materials, packaging/labelling materials, intermediates, and APIs.5. PROCESS EQUIPMENT5.1 Design and Construction5.10 Equipment used in the manufacture of intermediates and APIs should be ofappropriate design and adequate size, and suitably located for its intended use, cleaning, sanitization (where appropriate), and maintenance.5.11 Equipment should be constructed so that surfaces that contact raw materials,intermediates, or APIs do not alter the quality of the intermediates and APIs beyond the official or other established specifications.5.12 Production equipment should only be used within its qualified operating range.。

国际人用药品注册技术协调会ICH 三方协调指导原则原料药的药品生产质量管理规范指南Q7（ICH 第四阶段版本）2000 年 11 月10日根据ICH进程，本指南由ICH专家工作组制定，并征求了监管机构的建议。

在进程的第四阶段，最终草案推荐给欧盟、日本和美国的监管机构采用。

Q7现行第四阶段版本原料药的药品生产质量管理规范指南ICH 指导委员会在2000年11月10日完成了ICH进程的第四阶段，该指南推荐给ICH三方的监管机构采用。

目录1总则 (6)1.1目的 (6)1.2法规适用性 (6)1.3范围 (6)2质量管理 (9)2.1原则 (9)2.2质量管理部门的职责 (10)2.3生产部门的职责 (11)2.4内部审计（自检） (12)2.5产品质量回顾 (12)3人员 (13)3.1人员资质 (13)3.2人员卫生 (13)3.3顾问 (14)4厂房和设施 (14)4.1设计和建造 (14)4.2公用设施 (15)4.3水 (16)4.4控制 (17)4.5照明 (17)4.6污水和污物 (17)4.7卫生和维护 (17)5工艺设备 (18)5.1设计和构造 (18)5.2设备的维护和清洁 (19)5.3校准 (20)5.4计算机化系统 (20)6文件和记录 (21)6.1文件系统和质量标准 (21)6.2设备的清洁和使用记录 (22)6.3原料、中间体、原料药标签和包装材料的记录 (23)6.4工艺规程（主生产和检验记录） (23)6.5批生产记录（批生产和检验记录） (24)6.6检验记录 (26)6.7批生产记录审核 (27)7物料管理 (27)7.1原则 (27)7.2接收和待验 (28)7.3进厂物料的取样和检验 (29)7.4贮存 (30)7.5再评估 (30)8生产和过程控制 (30)8.1生产操作 (30)8.2时限 (32)8.3中间控制和取样 (32)8.4中间体或原料药的混合 (33)8.5污染的控制 (34)9原料药和中间体的包装和贴签 (34)9.1原则 (34)9.2包装材料 (35)9.3标签的发放和控制 (35)9.4包装和贴签操作 (36)10贮存和发运 (36)10.1入库规程 (36)10.2发运规程 (37)11实验室管理 (37)11.1基本原则 (37)11.2中间体和原料药的检测 (39)11.3分析方法的验证—参见第12节 (39)11.4检验报告 (39)11.5原料药稳定性考察 (40)11.6有效期和复验期 (41)11.7留样 (42)12验证 (42)12.1验证方针 (42)12.2验证文件 (43)12.3确认 (43)12.4工艺验证的方式 (44)12.5工艺验证程序 (45)12.6已验证系统的定期审核 (45)12.7清洁验证 (46)12.8分析方法的验证 (47)13.变更控制 (48)14物料的拒绝放行和再使用 (49)14.1拒绝放行 (49)14.2返工 (49)14.3重新加工 (49)14.4物料和溶剂的回收 (50)14.5退货 (50)15投诉和召回 (51)16受托生产商（包括实验室） (52)17.代理商、中间商、贸易商、经销商、分包装商和重新贴签方 (53)17.1适用性 (53)17.2已发运的原料药和中间体的可追溯性 (53)17.3质量管理 (54)17.4中间体和原料药的分包装、重新贴签和存放 (54)17.5稳定性 (54)17.6信息传递 (54)17.7投诉和召回的处理 (55)17.8退货处理 (55)18细胞培养/发酵生产原料药专用指南 (55)18.1通则 (55)18.2细胞库的维护和记录保存 (57)18.3细胞培养/发酵 (58)18.4收获、分离和纯化 (59)18.5病毒去除/灭活步骤 (60)19临床试验用原料药 (60)19.1通则 (60)19.2质量 (61)19.3设备和设施 (61)19.4原料的控制 (62)19.5生产 (62)19.6验证 (62)19.7变更 (63)19.8实验室控制 (63)19.9文件 (63)20.术语 (64)原料药的药品生产质量管理规范指南1总则1.1目的本指南旨在适宜的质量管理体系下为原料药（英文简称APIs）的生产提供药品生产质量管理规范(GMP)指导。

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文档下载后可定制修改，请根据实际需要进行调整和使用，谢谢！本店铺为大家提供各种类型的实用资料，如教育随笔、日记赏析、句子摘抄、古诗大全、经典美文、话题作文、工作总结、词语解析、文案摘录、其他资料等等，想了解不同资料格式和写法，敬请关注！Download tips: This document is carefully compiled by this editor. I hope that after you download it, it can help you solve practical problems. The document can be customized and modified after downloading, please adjust and use it according to actual needs, thank you! In addition, this shop provides you with various types of practical materials, such as educational essays, diary appreciation, sentence excerpts, ancient poems, classic articles, topic composition, work summary, word parsing, copy excerpts, other materials and so on, want to know different data formats and writing methods, please pay attention!《ICH Q7 样原料药的药品生产质量管理指南》概述1. 引言在药品生产中，原料药的质量是确保最终产品安全有效性的关键因素之一。

精心整理INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USEICH H ARMONISED T RIPARTITE G UIDELINEG OOD M ANUFACTURING P RACTICE G UIDE FOR A CTIVE P HARMACEUTICAL I NGREDIENTSQ7Having reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 10 November 2000, this guideline is recommended for adoption to the three regulatory parties to ICHTable of Contents 目录1. INTRODUCTION 1. 前言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 质量部门的责任精心整理2.3 Responsibility for Production Activities 2.3 生产的职责2.4 Internal Audits (Self Inspection) 2.4 内部审计（自检）2.5 Product Quality Review 2.5 产品质量回顾3. PERSONNEL 3. 人员3.1 Personnel Qualifications 3.1人员资格3.2 Personnel Hygiene 3.2 个人卫生3.3 Consultants 3.3 顾问4. BUILDINGS AND FACILITIES 4. 建筑和设施4.1 Design and Construction 4.1 设计和建造4.2 Utilities 4.2 公用设施4.3 Water 4.3 水4.4 Containment 4.4 特殊限制4.5 Lighting 4.5 照明5.3 Calibration7.4 Storage8.2 Time Limits9.1 General9.3 Label Issuance and Control 9.3 标签发放与管理9.4 Packaging and Labeling Operations 9.4 包装和贴签管理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.实验室管理11.1 General Controls 11.1通则11.2 Testing of Intermediates and APIs 11.2 中间体和原料药的检测11.3 Validation of Analytical Procedures 11.3 分析方法的验证11.4 Certificates of Analysis 11.4 检验报告11.5 Stability Monitoring of APIs 11.5 原料药的稳定性考察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.验证精心整理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 对已验证的系统的定期回顾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.变更控制14. REJECTION AND RE-USE OF MATERIALS 14.物料的拒收和再利用14.1 Rejection 14.1 拒收14.2 Reprocessing 14.2 返工14.3 Reworking 14.3 重新加工14.5 Returns17.5 Stability18.1 General19.1 General19.2 Quality19.5 Production19.6 Validation19.7 Changes20. Glossary1. 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.本文件旨在提供在适当的体系下为了控制生产原料药的质量而实施的药品生产质量管理规范（GMP）的指南。