FDA-无菌药品生产指南(中英文版)介绍
FDA无菌生产cGMP指南(中文)[1]
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行业指南无菌制造工艺生产 无菌药品的cGMP美国FDA2004年9月目 录I.引言II.背景A.法规框架B.技术框架III.范围IV.厂房与设施A.关键区－100级（ISO 5）B.支持洁净区C.洁净区分隔D.空气过滤1.滤膜2.高效空气过滤（HEPA）E.设计V.人员培训、确认和监督A.人员B.实验室人员C.监督计划VI.组分和容器/胶塞A.组分B.容器/胶塞1.准备2.检查容器胶塞密封系统VII.内毒素控制VIII.时限IX.无菌工艺与灭菌的验证A.工艺模拟试验1.设计研究2.频率和试验次数3.试验时间4.试验批量5.灌装线运行速度6.环境条件7.培养基8.培养基灌装产品的培养和检查9.试验结果的解释B.过滤效率C.设备、容器和胶塞的灭菌1.确认和验证2.设备监控和仪表校验X.实验室管理A.环境监控1.总体书面计划2.确定限度和趋势分析计划3.消毒效率4.监控方法B.微生物培养基和鉴别C.过滤前产品微生物载量D.供替换的微生物试验方法E.尘粒监控XI.无菌检查A.微生物实验室管理B.取样和培养C.无菌检查阳性调查XII.批记录审核：生产工艺控制文件附录1:无菌作业隔离器附录2:吹－灌－封技术附录3:过滤前的作业和密封作业参考文献术语I.引言II.背景A.法规框架B.技术框架III.范围IV.厂房与设施A.关键洁净区－100级（ISO 5）B.支持性洁净区C.洁净区分隔D.空气过滤1.滤膜压缩气体应有适当的纯度（如不含油），且经过滤后微生物和微粒方面的质量应相当于或优于其导入环境的空气质量。
洁净间经常使用的压缩气体如压缩空气、氮气和二氧化碳，通常用于清洁和保护目的。
膜过滤器可用于过滤压缩气体以达到高质量标准。
进行无菌作业时，如处理无菌物料和操作无菌设备使用的无菌气体，通常由这类过滤器过滤后获取。
FDA建议在例如通往灭菌釜腔室的空气管道中、在消除冻干机内的真空时、及存有无菌物料的储罐上采用无菌膜过滤器。
FDA灭菌工艺验证申报资料指南(中英文)
Guidance for Industry for the Submission Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products人药和兽药无菌工艺验证申报资料的工业指南Center for Drug Evaluation and Research (CDER)Center for Veterinary Medicine (CVM)November 1994CMC 2FDA药品评价与研究中心（CDER）FDA兽药中心（CVM）1994年11月TABLE OF CONTENTSI. INTRODUCTION (1)A. Purpose (1)B. Documenting Sterilization Process Validation (2)C. Remarks (2)II. INFORMATION FOR TERMINAL MOIST HEAT STERILIZATIONPROCESSES (3)A. Description of the Process and Product ........................ .. (3)1. The Drug Product and Container-Closure System (3)2. The Sterilization Process (3)3. The Autoclave Process and Performance Specifications (4)4. Autoclave Loading Patterns (4)5. Methods and Controls to Monitor Production Cycles (4)6. Requalification of Production Autoclaves (4)7. Reprocessing (4)B. Thermal Qualification of the Cycle (4)1. Heat Distribution and Penetration Studies (4)2. Thermal Monitors (5)3. The Effects of Loading on Thermal Input (5)4. Information Included in the Batch Record ........................................... . 5C. Microbiological Efficacy of the Cycle (5)1. Identification and Characterization of Bioburden Organisms (6)2. Specifications for Bioburden (6)3. Identification, Resistance, and Stability of BiologicalIndicators (6)4. The Resistance of the Biological Indicator Relative to That ofBioburden (6)5. Microbiological Challenge Studies (7)D. Microbiological Monitoring of the Environment (7)E. Container-Closure and Package Integrity (7)1. Simulation of the Stresses From Processing (7)2. Demonstrate Integrity Following the Maximum Exposure (8)3. Multiple Barriers (8)4. The Sensitivity of the Test (8)5. Integrity Over the Product Shelf Life (8)F. Bacterial Endotoxins Test and Method (8)G. Sterility Testing Methods and Release Criteria (8)H. Evidence of Formal, Written Procedures (9)III. OTHER TERMINAL STERILIZATION PROCESSES (9)A. Ethylene Oxide (9)1. Description of the Sterilizer (9)2. Cycle Parameters (10)3. Microbiological Methods (10)4. Stability (10)B. Radiation (10)1. The Facility and the Process (10)2. The Packaging of the Product (10)3. Multiple-Dose Mapping Studies (10)4. Microbiological Methods and Controls (11)5. Monitoring Stability (11)IV. INFORMATION FOR ASEPTIC FILL MANUFACTURING PROCESSES WHICH SHOULD BE INCLUDED IN DRUG APPLICATIONS (11)A. Buildings and Facilities (11)1. Floor Plan (11)2. Location of equipment (11)B. Overall Manufacturing Operation (11)1. Drug Product Solution Filtration (12)2. Specifications Concerning Holding Periods (12)3. Critical Operations (12)C. Sterilization and Depyrogenation of Containers, Closures, Equipment, andComponents (12)1. Bulk Drug Solution Components That are SterilizedSeparately (13)2. Sterilization Information in the Batch Records (13)D. Procedures and Specifications for Media Fills (13)E. Actions Concerning Product When Media Fills Fail (14)F. Microbiological monitoring of the environment (15)1. Microbiological Methods (15)2. Yeasts, Molds, and Anaerobic Microorganisms (15)3. Exceeded Limits (15)G. Container-Closure and Package Integrity (15)H. Sterility Testing Methods and Release Criteria (16)I. Bacterial Endotoxins Test and Method (16)J. Evidence of Formal Written Procedures (16)V. MAINTENANCE OF MICROBIOLOGICAL CONTROL AND QUALITY: STABILITY CONSIDERATIONS (16)A. Container-Closure Integrity (16)B. Preservative Effectiveness (17)C. Pyrogen or Endotoxin Testing (17)VI. ADDITIONAL INFORMATION (17)GUIDANCE FOR INDUSTRY1FOR THE SUBMISSION OF DOCUMENTATION FOR STERILIZATION PROCESS VALIDATION IN APPLICATIONS FOR HUMAN AND VETERINARY DRUGPRODUCTS人药和兽药无菌工艺验证申报资料的工业指南I. INTRODUCTION1、概述A. PurposeThis document is intended to provide guidance for the submission of information and data in support of the efficacy of sterilization processes in drug applications for both human and veterinary drugs. The recommendations in the guidance apply to applications for sterile drug products (new drug applications, new animal drug applications, abbreviated new drug applications, abbreviated antibiotic applications, and abbreviated new animal drug applications). These recommendations also apply to previously approved applications when supplements associated with the sterile processing of approved drugs are submitted. Information and data in support of sterility assurance may also be necessary in investigational new drug and investigational new animal drug applications.A. 目的本文件旨在为证明人药和兽药无菌工艺有效性申请上报的信息和资料提供指南。
中英文对照FDA原料药GMP指南
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。
【医疗药品管理】美国FDA原料药生产质量管理规范(中英文)
DIRECTION OF GMP (GOOD MANUFACTURING PRACTICE )OFRAW MATERIALS BY FDA美国FDA原料药生产质量管理规范（中英文）Table of Contents 目录1. INTRODUCTION 简介1.1 Objective 目的1.2 Regulatory Applicability法规的适用性1.3 Scope 范围2. QUALITY MANAGEMENT .质量管理2.1 Principles 总则2.2 Responsibilities of the Quality Unit(s) 质量部门的责任2.3 Responsibility for Production Activities 生产作业的职责2.4 Internal Audits (Self Inspection) 内部审计（自检）2.5 Product Quality Review 产品质量审核3. PERSONNEL 人员3.1 Personnel Qualifications 人员的资质3.2 Personnel Hygiene 人员卫生3.3 Consultants 顾问4. BUILDINGS AND FACILITIES 建筑和设施4.1 Design and Construction 设计和结构4.2 Utilities 公用设施4.3 Water 水4.4 Containment 限制4.5 Lighting 照明4.6 Sewage and Refuse 排污和垃圾4.7 Sanitation and Maintenance 卫生和保养5. PROCESS EQUIPMENT 工艺设备5.1 Design and Construction 设计和结构5.2 Equipment Maintenance and Cleaning 设备保养和清洁5.3 Calibration. 校验5.4 Computerized Systems 计算机控制系统6. DOCUMENTATION AND RECORDS 文件和记录6.1 Documentation System and Specifications 文件系统和质量标准6.2 Equipment cleaning and Use Record 设备的清洁和使用记录6.3 Records of Raw Materials, Intermediates, API Labeling and Packaging Materials 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)生产工艺规程（主生产和控制记录）6.5 Batch Production Records (Batch Production and Control Records)批生产记录（批生产和控制记录）6.6 Laboratory Control Records 实验室控制记录6.7 Batch Production Record Review 批生产记录审核7. MATERIALS MANAGEMENT 物料管理7.1 General Controls 控制通则7.2 Receipt and Quarantine 接收和待验7.3 Sampling and Testing of Incoming Production Materials 进厂物料的取样与测试7.4 Storage 储存7.5 Re-evaluation 复验8. PRODUCTION AND IN-PROCESS CONTROLS 生产和过程控制8.1 Production Operations 生产操作8.2 Time Limits 时限8.3 In-process Sampling and Controls 工序取样和控制8.4 Blending Batches of Intermediates or APIs 中间体或原料药的混批8.5 Contamination Control 污染控制9. PACKAGING AND IDENTIFICATION LABELING OF APIs AND INTERMEDIATES原料药和中间体的包装和贴签9.1 General 总则9.2 Packaging Materials 包装材料9.3 Label Issuance and Control 标签发放与控制9.4 Packaging and Labeling Operations 包装和贴签操作10. STORAGE AND DISTRIBUTION.储存和分发10.1 Warehousing Procedures 入库程序10.2 Distribution Procedures 分发程序11. LABORATORY CONTROLS 实验室控制11.1 General Controls 控制通则11.2 Testing of Intermediates and APIs 中间体和原料药的测试11.3 Validation of Analytical Procedures 分析方法的验证11.4 Certificates of Analysis分析报告单11.5 Stability Monitoring of APIs 原料药的稳定性监测11.6 Expiry and Retest Dating 有效期和复验期11.7 Reserve/Retention Samples 留样12. VALIDATION .验证12.1 Validation Policy 验证方针12.2 Validation Documentation 验证文件12.3 Qualification 确认12.4 Approaches to Process Validation 工艺验证的方法12.5 Process Validation Program 工艺验证的程序12.6 Periodic Review of Validated Systems 验证系统的定期审核12.7 Cleaning Validation 清洗验证12.8 Validation of Analytical Methods 分析方法的验证13. CHANGE CONTROL 变更的控制14. REJECTION AND RE-USE OF MATERIALS.拒收和物料的再利用14.1 Rejection 拒收14.2 Reprocessing 返工14.3 Reworking 重新加工14.4 Recovery of Materials and Solvents 物料与溶剂的回收14.5 Returns 退货15. COMPLAINTS AND RECALLS 投诉与召回16. CONTRACT MANUFACTURERS (INCLUDING LABORATORIES)协议生产商（包括实验室）17. AGENTS, BROKERS, TRADERS, DISTRIBUTORS, REPACKERS, AND RELABELLERS 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 适用性17.2 Traceability of Distributed APIs and Intermediates已分发的原料药和中间体的可追溯性17.3 Quality Management 质量管理17.4 Repackaging, Relabeling, and Holding of APIs and Intermediates原料药和中间体的重新包装、重新贴签和待检17.5 Stability 稳定性17.6 Transfer of Information 信息的传达17.7 Handling of Complaints and Recalls 投诉和召回的处理17.8 Handling of Returns 退货的处理18. Specific Guidance for APIs Manufactured by Cell Culture/Fermentation用细胞繁殖/发酵生产的原料药的特殊指南18.1 General 总则18.2 Cell Bank Maintenance and Record Keeping 细胞库的维护和记录的保存18.3 Cell Culture/Fermentation 细胞繁殖/发酵18.4 Harvesting, Isolation and Purification 收取、分离和精制18.5 Viral Removal/Inactivation steps 病毒的去除/灭活步骤19. APIs for Use in Clinical Trials 用于临床研究的原料药19.1 General 总则19.2 Quality 质量19.3 Equipment and Facilities设备和设施19.4 Control of Raw Materials 原料的控制19.5 Production 生产19.6 Validation 验证19.7 Changes 变更19.8 Laboratory Controls 实验室控制19.9 Documentation 文件20. Glossary 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。
美国FDA原料药生产高质量管理系统要求规范(中英文)
DIRECTION OF GMP (GOOD MANUFACTURING PRACTICE )OF RAWMATERIALS BY FDA美国FDA原料药生产质量管理规范（中英文）Table of Contents 目录1. INTRODUCTION 简介1.1 Objective 目的1.2 Regulatory Applicability法规的适用性1.3 Scope 范围2. QUALITY MANAGEMENT .质量管理2.1 Principles 总则2.2 Responsibilities of the Quality Unit(s) 质量部门的责任2.3 Responsibility for Production Activities 生产作业的职责2.4 Internal Audits (Self Inspection) 内部审计（自检）2.5 Product Quality Review 产品质量审核3. PERSONNEL 人员3.1 Personnel Qualifications 人员的资质3.2 Personnel Hygiene 人员卫生3.3 Consultants 顾问4. BUILDINGS AND FACILITIES 建筑和设施4.1 Design and Construction 设计和结构4.2 Utilities 公用设施4.3 Water 水4.4 Containment 限制4.5 Lighting 照明4.6 Sewage and Refuse 排污和垃圾4.7 Sanitation and Maintenance 卫生和保养5. PROCESS EQUIPMENT 工艺设备5.1 Design and Construction 设计和结构5.2 Equipment Maintenance and Cleaning 设备保养和清洁5.3 Calibration. 校验5.4 Computerized Systems 计算机控制系统6. DOCUMENTATION AND RECORDS 文件和记录6.1 Documentation System and Specifications 文件系统和质量标准6.2 Equipment cleaning and Use Record 设备的清洁和使用记录6.3 Records of Raw Materials, Intermediates, API Labeling and Packaging Materials 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)生产工艺规程（主生产和控制记录）6.5 Batch Production Records (Batch Production and Control Records)批生产记录（批生产和控制记录）6.6 Laboratory Control Records 实验室控制记录6.7 Batch Production Record Review 批生产记录审核7. MATERIALS MANAGEMENT 物料管理7.1 General Controls 控制通则7.2 Receipt and Quarantine 接收和待验7.3 Sampling and Testing of Incoming Production Materials 进厂物料的取样与测试7.4 Storage 储存7.5 Re-evaluation 复验8. PRODUCTION AND IN-PROCESS CONTROLS 生产和过程控制8.1 Production Operations 生产操作8.2 Time Limits 时限8.3 In-process Sampling and Controls 工序取样和控制8.4 Blending Batches of Intermediates or APIs 中间体或原料药的混批8.5 Contamination Control 污染控制9. PACKAGING AND IDENTIFICATION LABELING OF APIs AND INTERMEDIATES原料药和中间体的包装和贴签9.1 General 总则9.2 Packaging Materials 包装材料9.3 Label Issuance and Control 标签发放与控制9.4 Packaging and Labeling Operations 包装和贴签操作10. STORAGE AND DISTRIBUTION.储存和分发10.1 Warehousing Procedures 入库程序10.2 Distribution Procedures 分发程序11. LABORATORY CONTROLS 实验室控制11.1 General Controls 控制通则11.2 Testing of Intermediates and APIs 中间体和原料药的测试11.3 Validation of Analytical Procedures 分析方法的验证11.4 Certificates of Analysis分析报告单11.5 Stability Monitoring of APIs 原料药的稳定性监测11.6 Expiry and Retest Dating 有效期和复验期11.7 Reserve/Retention Samples 留样12. VALIDATION .验证12.1 Validation Policy 验证方针12.2 Validation Documentation 验证文件12.3 Qualification 确认12.4 Approaches to Process Validation 工艺验证的方法12.5 Process Validation Program 工艺验证的程序12.6 Periodic Review of Validated Systems 验证系统的定期审核12.7 Cleaning Validation 清洗验证12.8 Validation of Analytical Methods 分析方法的验证13. CHANGE CONTROL 变更的控制14. REJECTION AND RE-USE OF MATERIALS.拒收和物料的再利用14.1 Rejection 拒收14.2 Reprocessing 返工14.3 Reworking 重新加工14.4 Recovery of Materials and Solvents 物料与溶剂的回收14.5 Returns 退货15. COMPLAINTS AND RECALLS 投诉与召回16. CONTRACT MANUFACTURERS (INCLUDING LABORATORIES)协议生产商（包括实验室）17. AGENTS, BROKERS, TRADERS, DISTRIBUTORS, REPACKERS, AND RELABELLERS 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 适用性17.2 Traceability of Distributed APIs and Intermediates已分发的原料药和中间体的可追溯性17.3 Quality Management 质量管理17.4 Repackaging, Relabeling, and Holding of APIs and Intermediates原料药和中间体的重新包装、重新贴签和待检17.5 Stability 稳定性17.6 Transfer of Information 信息的传达17.7 Handling of Complaints and Recalls 投诉和召回的处理17.8 Handling of Returns 退货的处理18. Specific Guidance for APIs Manufactured by Cell Culture/Fermentation用细胞繁殖/发酵生产的原料药的特殊指南18.1 General 总则18.2 Cell Bank Maintenance and Record Keeping 细胞库的维护和记录的保存18.3 Cell Culture/Fermentation 细胞繁殖/发酵18.4 Harvesting, Isolation and Purification 收取、分离和精制18.5 Viral Removal/Inactivation steps 病毒的去除/灭活步骤19. APIs for Use in Clinical Trials 用于临床研究的原料药19.1 General 总则19.2 Quality 质量19.3 Equipment and Facilities设备和设施19.4 Control of Raw Materials 原料的控制19.5 Production 生产19.6 Validation 验证19.7 Changes 变更19.8 Laboratory Controls 实验室控制19.9 Documentation 文件20. Glossary 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。
fda无菌工艺生产指南
fda无菌工艺生产指南1. 引言1.1 概述在生物制药和医疗器械行业，为了确保产品的质量和安全性，无菌工艺生产是至关重要的环节。
无菌工艺生产是指通过采取适当措施以防止细菌和其他微生物的污染，从而达到无菌状态的生产过程。
美国食品药品监督管理局（FDA）作为全球权威的监管机构，对无菌工艺生产提供了一套完整的指南。
1.2 文章结构本文将首先介绍FDA无菌工艺生产指南的背景和重要性，然后详细介绍该指南所包含的各项要求和实施措施。
在此基础上，还将讨论无菌工艺生产的重要性，并说明遵循国际标准与规定的必要性。
最后，总结已有研究成果及观点，并对未来发展进行展望。
1.3 目的本文旨在全面介绍FDA无菌工艺生产指南并分析其对于保障产品质量、安全性以及遵循国际标准与规定的重要性。
通过深入理解这些指导原则，生物制药和医疗器械行业的从业人员将能够更好地掌握无菌工艺生产的要求和措施，进而提升产品质量和安全性，满足监管机构的要求。
2. FDA无菌工艺生产指南2.1 简介无菌工艺生产指南是美国食品药品监督管理局（FDA）为了确保医疗产品和制药过程的安全性和质量而制定的准则。
无菌工艺生产是一种在没有任何微生物污染的条件下进行产品加工和包装的方法。
该指南旨在提供针对无菌环境和设备要求、操作程序以及清洁消毒控制方面的详细指导。
2.2 标准要求FDA对无菌工艺生产提出了一系列严格的标准要求，以确保产品在整个制造过程中都处于无菌状态。
这些标准要求包括但不限于：- 清洁消毒程序：必须制定有效的清洁消毒程序，确保所有接触于产品、容器、设备和环境表面的杂质被充分去除或灭活。
- 设备验证：所有用于无菌工艺生产的设备都需要经过验证，以确认它们能够提供足够的杀灭微生物的能力，并且不会引入新的污染源。
- 环境控制：必须建立合适的环境控制系统，包括空气过滤和压力控制，以防止非无菌物质进入生产区域。
- 包装材料检测：所有用于包装的材料都需要经过严格的检测，以确保其没有微生物污染或释放出可能引起污染的物质。
FDA无菌加工生产的无菌药品指南中英文对照版
监控程序
VI. COMPONENTS AND CONTAINER/CLOSURES .................................................... 27
药品成分和容器 /密封 A. Components..................................................................................................................................27
法规架构 B. Technical Framework .......................................................................................................iologics Evaluation and Research Food and Drug Administration
1401 Rockville Pike, Rockville, MD 20852-1448 /cber/guidelines.htm.
辅助洁净区域 C. Clean Area Separation ................................................................................................................ 11
净化区的隔离 D. Air Filtration ................................................................................................................................ 12
无菌药品和无菌工艺行业指南翻译
无菌药品和无菌工艺行业指南——无菌药品生产质量管理规范（cGMP指南）药物评价研究中心与生物制品评价研究中心共同成立的协调办公室和法规事务办公室一同对改指南做出修订。
引言该指南描述了美国食品药品监督管理局现行的一些设想，这些设想在上述题目中有所体现，该规范没有臆造任何权利，或将之授予任何组织或个人，其执行并不使FDA或公众社会承担义务。
如果有一种途径能够很好的满足当前所采用的法令和规章制度的要求，那就可以应用该途径。
假如你对所采用的途径有任何问题，都可以和负责该指南实施的FDA人员联系，如果不能确定相应的FDA人员，也可以电话联系，其联系电话已经在该指南扉页中列出。
Ⅰ简介：本指南旨在协助厂商满足FDA的cGMP规章的要求，特别是针对无菌药品和生物制品的无菌生产过程，该指南可以代替1987年制定的无菌药物生产企业无菌生产指南（无菌生产工艺指南），该修订版是1987年指南的修订和进一步说明。
为了使无菌药物建立一种简便的药物申请和生物制品许可申请，该指南文件应该与无菌药品提交指南互作补充（标题为：人用和兽用药物的无菌生产工艺验证文件申请的提交指南）。
在药物申请中的一些信息和数据类型在提交指南中有所描述，这主要是为了说明制造商的无菌工艺的有效性。
该指南通过对程序和法规的解释来帮助确保无菌生产厂商的设施满足相关CGMP要求，例如满足厂房设计、设备适用性、工艺验证和质量控制的要求。
包括该指南的FDA指南文件并非要求强制执行。
另外，指南是FDA现在一些构想的体现，它应当被视作一种建议性的文字，除非在个例中提到特殊的法律法规要求时，可以另当别论。
代理机构指南中所用语言都只是给我们的一种建议或者忠告，而非是要求。
在该指南出现的文字内容中包括了CFR（Code of Federal Regulation：美国联邦法规）的210和211章节中的部分内容，在药品cGMP中有所体现。
引用的文字内容主要是想通过本指南提供的一部分条款来帮助读者加深理解，这些在表格中的例子只是摘引，并不详尽，读者可以参阅CFR的全文，以便彻底了解相关章节的条款。
FDA 行业指南 中英对照 待完成
Guidance for IndustryContainer Closure Systems for Packaging Human Drugs and Biologics Chemistry, Manufacturing and Controls Documentation行业指南人用药品及生物制品的包装容器和封装系统：化学，生产和控制文件指南发布者：美国FDA下属的CDER及CBER发布日期：May 1999TABLE OF CONTENTS目录I. INTRODUCTION介绍II. BACKGROUND 背景A. Definitions 定义B. CGMP, CPSC and USP Requirements on Containers and Closures。
CGMP，CPSC和USP对容器和密封的要求C. Additional Considerations 其他需要考虑的事项III. QUALIFICATION AND QUALITY CONTROL OF PACKAGING COMPONENTS包装组件的合格要求以及质量控制A. Introduction 介绍B. General Considerations 通常要求C. Information That Should Be Submitted in Support of an Original Application for AnyDrug Product 为支持任何药品的原始申请所必须提供的信息D. Inhalation Drug Products 吸入性药品E. Drug Products for Injection and Ophthalmic Drug Products 注射剂和眼科用药F. Liquid-Based Oral and Topical Drug Products and Topical Delivery Systems 液体口服和外用药品和外用给药系统G. Solid Oral Dosage Forms and Powders for Reconstitution 口服固体剂型和待重新溶解的粉末H. Other Dosage Forms 其他剂型IV. POSTAPPROVAL PACKAGING CHANGES 批准后的包装变更V. TYPE III DRUG MASTER FILES 药品主文件第III类A. General Comments 总体评述B. Information in a Type III DMF 第III类DMF中包括的信息VI. BULK CONTAINERS 大包装容器A. Containers for Bulk Drug Substances 用于原料药的容器B. Containers for Bulk Drug Products 用于散装药品的容器ATTACHMENT A 附件AREGULATORY REQUIREMENTS 药政要求ATTACHMENT B 附件BCOMPLIANCE POLICY GUIDES THAT CONCERN PACKAGING 关于包装，所适用的政策指南ATTACHMENT C 附件CEXTRACTION STUDIES “提取性"研究ATTACHMENT D 附件DABBREVIATIONS 缩略语ATTACHMENT E 附件EREFERENCES 参考文献GUIDANCE FOR INDUSTRY1Container Closure Systems for Packaging Human Drugs and Biologics Chemistry, Manufacturing and Controls DocumentationI．INTRODUCTION介绍This document is intended to provide guidance on general principles2 for submitting information on packaging materials used for human drugs and biologics。
FDA 行业指南 中英对照 待完成
Guidance for IndustryContainer Closure Systems for Packaging Human Drugs and Biologics Chemistry, Manufacturing and Controls Documentation行业指南人用药品及生物制品的包装容器和封装系统：化学，生产和控制文件指南发布者：美国FDA下属的CDER及CBER发布日期：May 1999TABLE OF CONTENTS目录I.INTRODUCTION介绍II.BACKGROUND 背景A.Definitions 定义B.CGMP, CPSC and USP Requirements on Containers and Closures. CGMP, CPSC和USP对容器和密封的要求C.Additional Considerations 其他需要考虑的事项III.QUALIFICATION AND QUALITY CONTROL OF PACKAGING COMPONENTS包装组件的合格要求以及质量控制A.Introduction 介绍B.General Considerations 通常要求rmation That Should Be Submitted in Support of an Original Application for Any DrugProduct 为支持任何药品的原始申请所必须提供的信息D.Inhalation Drug Products 吸入性药品E.Drug Products for Injection and Ophthalmic Drug Products 注射剂和眼科用药F.Liquid-Based Oral and Topical Drug Products and Topical Delivery Systems 液体口服和外用药品和外用给药系统G.Solid Oral Dosage Forms and Powders for Reconstitution 口服固体剂型和待重新溶解的粉末H.Other Dosage Forms 其他剂型IV.POSTAPPROVAL PACKAGING CHANGES 批准后的包装变更V.TYPE III DRUG MASTER FILES 药品主文件第III类A.General Comments 总体评述rmation in a Type III DMF 第III类DMF中包括的信息VI.BULK CONTAINERS 大包装容器A.Containers for Bulk Drug Substances 用于原料药的容器B.Containers for Bulk Drug Products 用于散装药品的容器ATTACHMENT A 附件AREGULATORY REQUIREMENTS 药政要求ATTACHMENT B 附件BCOMPLIANCE POLICY GUIDES THAT CONCERN PACKAGING 关于包装，所适用的政策指南ATTACHMENT C 附件CEXTRACTION STUDIES “提取性”研究ATTACHMENT D 附件DABBREVIATIONS 缩略语ATTACHMENT E 附件EREFERENCES 参考文献GUIDANCE FOR INDUSTRY1Container Closure Systems for Packaging Human Drugs and BiologicsChemistry, Manufacturing and Controls DocumentationI．INTRODUCTION介绍This document is intended to provide guidance on general principles2 for submitting information on packaging materials used for human drugs and biologics.3 This guidance supersedes the FDA Guideline for Submitting Documentation for Packaging for Human Drugs and Biologics , issued in February 1987 and the packaging policy statement issued in a letter to industry dated June 30, 1995 from the Office of Generic Drugs.4 This guidance is not intended to describe the information that should be providedabout packaging operations associated with drug product manufacture. 本文件目的是为递交人用药品和生物制品的包装信息提供总体原则指南。
原料药GMP指南中英文对照
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 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API Labeling and Packaging Materials 的记录6.4 生产工艺规程（主生产和控制记录）6.4 Master Production Instructions (MasterProduction and Control Records)6.5 批生产记录（批生产和控制记录）6.5 Batch Production Records (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 控制通则7.2 Receipt and Quarantine 7.2接收和待验7.3 进厂物料的取样与测试7.3 Sampling and Testing of IncomingProduction Materials7.4 Storage 7.4储存7.5 Re-evaluation 7.5复验8. 生产和过程控制8. PRODUCTION AND IN-PROCESSCONTROLS8.1 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 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. 原料药和中间体的包装和贴签9. PACKAGING AND IDENTIFICATIONLABELING OF APIs ANDINTERMEDIATES9.1 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 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 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。
美国fda用无菌工艺生产灭菌药品的指南1 9 8 7
美国FDA用无菌工艺生产灭菌药品的指南1 9 8 7年I．目的 (4)Ⅱ．导言 (4)III．厂房和设施 (6)Ⅳ．组分 (9)V，容器／密封件 (10)Ⅵ．时限 (11)Ⅶ．生产和工艺控制验证 (11)Ⅷ．试验室控制 (16)Ⅸ. 无菌检验 (17)X．参考资料 (20)I．目的本指南为有关人员提供用无菌工艺生产灭菌药品的—些操作和规程．这些操作和规程是由符合现行药品生产质量管理规范有关部分的合格方法所组成(21CFR210和211部分)。
应该注意，对21CFR600-680部分中规定的生物制品而言，210.2(a)和211.1（b)部分规定，同时遵守600-800部分和分篇210与211的适当规定是不可能的，对于这些生物制品将制订特殊的规定。
因此，生物制品的无菌检验和用于这样检验的培养基必须符合610.12部分的要求。
Ⅱ．导言本指南依据2lCFRl0.90而发布，它所叙述的通用原则和方法不是法定的，但是为FDA所认可。
厂家可依据本指南确保FDA的认可，或者遵循其他不同的规程。
厂家采用不同规程时，可事先同FDA商讨但并非必须这样)，以免日后为FDA所否定而浪费人力和财力。
如果当局认为需要，可以通过它在法规上的努力和有关人员提出的意见与建议，不时地修订本指南。
用无菌工艺和用最后灭菌方法生产灭菌药品有不同之处。
最后灭菌方法通常包括在高质量环境条件下产品容器的灌装和密封；产品、容器和密封件通常具有高度的微生物学的质量要求，但不是无菌的。
为降低产品的微生物含量并确保随后的灭菌处理成功，重要的是灌装和密封在高质量的环境中进行。
然后对在其最终容器中的产品进行灭菌处理----通常用加热法或辐射法。
在无菌工艺中，产品、容器和密封件都分别经过灭菌处理，然后放到—起。
因产品装入其最终容器后不再进行灭菌处理，所以为保持产品的无菌性，在极高质量的环境下进行产品灌装和容器封闭至关重要。
此外，无菌工艺比最终灭菌法通常有更多的变量，这—因素使得确保最终产品无菌更为困难，例如在无菌灌装前，最终产品的不同部分经过不同的灭菌处理----如玻璃器皿的干燥加热、胶塞经高压蒸汽处理、液体剂型的过滤，每—处理都需要完全有效并处于控制之下。
FDA-GMP中英文对照标准手册
FDA-GMP中英文对照标准手册
简介
本手册介绍了美国食品和药物管理局(cFDA)制定的GMP （Good Manufacturing Practice，良好生产规范）相关标准要求，包
括对药品、保健品、化妆品等品种的生产及质量控制方面的要求。
主要内容
本手册主要包括以下内容：
- GMP的概念及适用范围；
- GMP规范要求：包括生产区域、工艺流程、设备、人力资源
管理、记录和报告等各个方面的要求；
- 质量管理体系要求：包括质量管理手册、质量控制和检测、
审核和审批等各个方面的要求。
目的
本手册旨在帮助企业了解美国cFDA对药品、保健品和化妆品
等品种的GMP相关规定，引导企业建立健全的GMP质量管理体系，增强企业产品的质量稳定性和产品竞争力，提高顾客满意度。
结论
GMP是一项重要的质量管理制度，关系到药品、保健品和化
妆品等产品的制造和市场竞争力。
本手册提供了详细的GMP相关
规定，梳理了药品、保健品和化妆品等品种的生产和质量控制过程，可以帮助企业更好地了解并遵循GMP标准要求，从而提高产品的
质量稳定性和市场竞争力。
美国FDA用无菌工艺生产灭菌药品的指南1 9 8 7年
除这些生产区外，对有些设备也应提供高质量的过滤空气。设备中的空气与已灭菌的物料，或微生物和微粒含量均低的物料相接触处尤为重要。例如，除菌过滤器应用于冷冻干燥器真空间歇和热空气灭菌器的通风口处，以确保与已灭菌产品接触的空气是无菌的。同样，进入盛装已灭菌液体的常压容器中的空气也应是经过过滤的。用于盛装具有高度的微生物学的质量要求的物料贮罐内的空气也应是经过过滤的，并且过滤器应是干燥的，以防止随后堵塞凝聚，或微生物生长而弄湿(有两种方法可以达到这些要求，给过滤器供热和使用疏水性过滤器)。对这些空气过滤器定期进行完整性检测是重要的。
在灌装／封闭操作附近，空气不是需要具有高的微粒和微生物质量的唯—气体。接触产品、容器／密封件或产品接触的表面的其他气体，如N2和CO2(例如冲洗或复盖)也应经过无菌过滤。此外，压缩空气应无可检测到的油蒸汽。
关键区域相对于邻近的洁净要求较低的区域，应有正压差。可接受的压差为0.05inH2O。
控制区
控制区是准备未灭菌产品、加工过程中的物料和容器／密封件的区域，是第二类重要的环境控制区。它包括组件混合区和组件、加工过程中的物料、药品和经最后冲洗的与药品接触的设备、容器／密封件的表面暴露在工厂环境中的区域。为了降低最终产品中微粒污染物的水平和控制随后进行灭菌的物品及组件的微生物含量(生物负荷)，这—环境应具有高的微生物和微粒质量要求。
在无菌工艺中，可以每—组分单独灭菌或几种组分合并成混合物后灭菌。组分灭菌有几种方法，如经过严格的验证，每一种方法均可被接受。一种广泛采用的方法是将组分溶解于—种溶剂(如美国药典注射用水)中形成溶液，过滤该溶液。过滤用无菌膜或筒形过滤器。在组分受热可能有不利影响的情况下可以用这种方法。该方法的另—种情况是使过滤后的溶液进行组分的无菌结晶和沉淀，成为无菌粉末。然而这种方法比其他方法涉及更多的处理和操作，因此在操作中污染的可能性更大。
FDA 行业指南 中英对照 待完成
Container Closure Systems for Packaging Human Drugs and Biologics Chemistry, Manufacturing and Controls Documentation行业指南人用药品及生物制品的包装容器和封装系统：化学，生产和控制文件指南发布者：美国FDA下属的CDER及CBER发布日期：May 1999TABLE OF CONTENTS目录I.INTRODUCTION介绍II.BACKGROUND 背景A.Definitions 定义B.CGMP, CPSC and USP Requirements on Containers and Closures. CGMP, CPSC和USP对容器和密封的要求C.Additional Considerations 其他需要考虑的事项III.QUALIFICATION AND QUALITY CONTROL OF PACKAGING COMPONENTS包装组件的合格要求以及质量控制A.Introduction 介绍B.General Considerations 通常要求rmation That Should Be Submitted in Support of an Original Application forAny Drug Product 为支持任何药品的原始申请所必须提供的信息D.Inhalation Drug Products 吸入性药品E.Drug Products for Injection and Ophthalmic Drug Products 注射剂和眼科用药F.Liquid-Based Oral and Topical Drug Products and Topical Delivery Systems 液体口服和外用药品和外用给药系统G.Solid Oral Dosage Forms and Powders for Reconstitution 口服固体剂型和待重新溶解的粉末H.Other Dosage Forms 其他剂型IV.POSTAPPROVAL PACKAGING CHANGES 批准后的包装变更V.TYPE III DRUG MASTER FILES 药品主文件第III类A.General Comments 总体评述rmation in a Type III DMF 第III类DMF中包括的信息VI.BULK CONTAINERS 大包装容器A.Containers for Bulk Drug Substances 用于原料药的容器B.Containers for Bulk Drug Products 用于散装药品的容器ATTACHMENT A 附件AREGULATORY REQUIREMENTS 药政要求ATTACHMENT B 附件BCOMPLIANCE POLICY GUIDES THAT CONCERN PACKAGING 关于包装，所适用的政策指南ATTACHMENT C 附件CEXTRACTION STUDIES “提取性”研究ATTACHMENT D 附件DABBREVIATIONS 缩略语ATTACHMENT E 附件EREFERENCES 参考文献GUIDANCE FOR INDUSTRY1Container Closure Systems for Packaging Human Drugs and Biologics Chemistry, Manufacturing and Controls DocumentationI．INTRODUCTION介绍This document is intended to provide guidance on general principles2 for submitting information on packaging materials used for human drugs and biologics.3 This guidance supersedes the FDA Guideline for Submitting Documentation for Packaging for Human Drugs and Biologics , issued in February 1987 and the packaging policy statement issued in a letter to industry dated June 30, 1995 from the Office of Generic Drugs.4 This guidance is not intended to describe the information that should be provided about packaging operations associated with drug product manufacture. 本文件目的是为递交人用药品和生物制品的包装信息提供总体原则指南。
FDA无菌生产指南-中英文对照版.doc
FDA无菌生产指南-中英文对照版Translated from / 译自：Guidance for IndustrySterile Drug Products Produced by Aseptic Processing —Current Good Manufacturing Practice行业指南无菌加工生产的无菌药品—现行的生产质量管理规范(cGMP）U.S. Department of Health and Human ServicesFood and Drug AdministrationCenter for Drug Evaluation and Research (CDER)Center for Biologics Evaluation and Research (CBER)Office of Regulatory Affairs (ORA)September 2004Pharmaceutical CGMPsCopyright SCI Version 1Copyright SCI Version 1Copyright SCI Version 1TABLE OF CONTENTSI. INTRODUCTION (1)简介II. BACKGROUND (2)背景A.Regulatory Framework (3)法规架构B.Technical Framework (3)技术架构III. SCOPE (5)适用范围IV. BUILDINGS AND FACILITIES (6)厂房和建筑A.Critical Area – Class 100 (ISO 5) (8)关键区域– 100级(ISO 5)B. Supporting Clean Areas (11)辅助洁净区域C. Clean Area Separation (11)净化区的隔离D.Air Filtration (13)空气过滤1.Membrane (13)膜过滤2.High-Efficiency Particulate Air (HEPA) (14)高效颗粒空气过滤器(HEPA)E.Design (17)设计V. PERSONNEL TRAINING, QUALIFICATION, & MONITORING (21)人员的培训，资格认定和监控A.Personnel (22)人员boratory Personnel (26)实验室人员C.Monitoring Program (26)监控程序VI. COMPONENTS AND CONTAINER/CLOSURES (28)药品成分和容器/密封A. Components (28)Copyright SCI Version 1药品成分B. Containers/Closures (31)容器/密封1.Preparation (31)准备2. .................................................................................. Inspection of Container Closure System33容器密封系统的检查VII. ENDOTOXIN CONTROL (35)内毒素控制VIII. TIME LIMITATIONS (37)时间限制IX. VALIDATION OF ASEPTIC PROCESSING AND STERILIZATION (38)无菌加工和灭菌的验证A. Process Simulations (38)工艺模拟1.Study Design (39)研究设计2.Frequency and Number of Runs (41)运行频率和次数3.Duration of Runs (42)运行时间4.Size of Runs (43)批量5.Line Speed (44)运行速度6.Environmental Conditions (44)环境质量7.Media (45)培养基8.Incubation and Examination of Media-Filled Units (46)培养基灌装单位的培养和检查9.Interpretation of Test Results (48)试验结果解释B. Filtration Efficacy (50)过滤功效C. Sterilization of Equipment, Containers, and Closures (53)设备、容器和密封的灭菌1.Qualification and Validation (54)确认和验证2.Equipment Controls and Instrument Calibration (56)设备控制和仪器校准X. LABORATORY CONTROLS (59)实验室控制Copyright SCI Version 1A. Environmental Monitoring (61)环境监测1. ...................................................................................................... General Written Program61书面程序2.Establishing Levels and a Trending Program (63)建立监测标准和趋势分析程序3.Disinfection Efficacy (64)消毒功效4.Monitoring Methods (64)监测方法B. Microbiological Media and Identification (66)微生物培养基及微生物的鉴定C. Prefiltration Bioburden (67)过滤前的生物负荷D. Alternate Microbiological Test Methods (68)可替代的微生物测试方法E. Particle Monitoring (68)颗粒监测XI. STERILITY TESTING (69)无菌试验A. Microbiological Laboratory Controls (71)微生物实验室控制B. Sampling and Incubation (71)取样和培养C. Investigation of Sterility Positives (72)无菌试验阳性结果的调查XII. BATCH RECORD REVIEW: PROCESS CONTROL DOCUMENTATION (77)批生产纪录审核：工艺控制文件化APPENDIX 1: ASEPTIC PROCESSING ISOLATORS (79)附录1: 无菌隔离装置APPENDIX 2: BLOW-FILL- SEAL TECHNOLOGY (87)附录2：吹-灌-封技术APPENDIX 3: PROCESSING PRIOR TO FILLING AND SEALING OPERATIONS (91)附录3：灌装和密封前的工艺REFERENCES (94)参考文献RELEVANT GUIDANCE DOCUMENTS (95)相关指南文件GLOSSARY (96)Copyright SCI Version 1术语表Copyright SCI Version 1Guidance for Industry1Sterile Drug Products Produced byAseptic Processing — Current Good Manufacturing PracticeI.INTRODUCTION简介This guidance is intended to help manufacturers meet the requirements in the Agency's current good manufacturing practice (CGMP) regulations (2l CFR parts 210 and 211) when manufacturing sterile drug and biological products using aseptic processing. This guidance replaces the 1987 Industry Guideline on Sterile Drug Products Produced by Aseptic Processing (Aseptic Processing Guideline). This revision updates and clarifies the 1987 guidance.本指南旨在帮助生产商在应用无菌工艺制造无菌药品和生物制剂时，达到FDA cGMP规章(美国联邦法规的第210及第211节)要求。
FDA英文药品说明书规定项目中英对照
FDA英文药品说明书规定项目中英对照--------------------------------------------------------------------------------药品说明书旧称description,instruction,direction.今称insert,package insert美国FDA规定其应包括十项。
一.drug names(药物名称)1.通常每种药物有三个名字(1)proprietary name（商品名称）(2)popular name（俗名）(3)chemical name（化学名）2.说明书标题多用商品名其右上角标有R者，表示registered trademark（注册商标）二.description（性状）(常用description,introduction,composition)包括药品的chemical structure（化学结构）、chemical composition（化学成分）、physical and chemical properties（物理和化学性质）三.clinical pharmacology（临床药理学）常用的还有：clinical data（临床数据）、clinical experience（临床经验）、clinical use（临床应用）、clinical observation（临床观察）、clinical effect（临床疗效）、clinical discussion（临床讨论）、mode of mechanism of action（临床机理及途径）、pharmacological actions（药理作用）、therapeutical actions（治疗作用）、bacteriology（细菌学）、microbiology（微生物学）、physiology（生理学）、toxicology（毒理学）四.indications and usage（适应证和用法）常用标题：indications,major indications,clinical indications,principal indications,condications,uses,treatment五.contraindications（禁忌证）1.常用标题contraindications,restriction on use(限制使用)2.常用词（组）pregnant women孕妇women of childbeating age育龄妇女be hypersensitive to 对......过敏者allergic reaction变态反应lactation,early infancy乳期heart,cardiac,myocardial心脏，心脏的，心肌的kidney,renal肾，肾脏的liver,hepatic肝，肝脏的insufficiency,impairment机能不全damage,danger,failure损伤，危险，衰?BR>六.precautions（注意事项）常用标题:causions,remark,note,notice,attention,awakening, N.B.七.warnings（警告）常用标题：additional warnings(告戒事项)八.adverse reactions（不良反应）常用标题：side reaction（副反应）、untoward reaction（不良反应）、toxicity reaction（毒性反应）、anaphylactic reaction（过敏反应）、side effects,by-effects,after effects,undesirable effects（副作用）、double infection（双重感染）九.overdosage（用药过量）常用标题：treatment of overdosage(用药过量的治疗)十.dosage and administration（剂量用法）1.常用标题：administration procedure,method for administration,method of use,direction for use,how to use,recommendation,reconstitution（用法）posology,dosage（剂量）application and dosage,usage and dosage（用法与剂量）clinical application（临床应用）2.mode of administration(给药方式)intramuscularly肌肉注射intragluteally臀肌注射intraarterially动脉注射intravenously静脉注射intrathecally鞘内注射intracerebeospinally脑脊髓腔注射orally口服parentarally肠道外给药locally局部给药subconjunctivally结膜下给药sublingually舌下给药submucously黏膜下给药现各大药厂的说明书，项目远远超过十项，如：1.animal pharmacology and animal toxicology（动物药理学和动物毒理学）2.absorption and excretion（吸收和排泄）3.tolerance（耐受性）4.drug interactions（药物相互作用）5.storage and duration of efficacy（贮藏与失效期）6.packages（包装）7.advantages（优点）8.references（参考文献）9.further information（补充说明）10.manufacturer（生产者）。
FDA无菌原料药检查指南-中英文版
GUIDE TO INSPECTIONS OF STERILE DRUG SUBSTANCE MANUFACTURERSFDA无菌原料药检查指南Note: This document is reference material for investigators and other FDA personnel. The document does not bind FDA, and does no confer any rights, privileges, benefits, or immunities for or on any person(s).注：本文件是FDA现场检查官和其他FDA人员的参考资料。
本文件并不束缚FDA，也不赋予任何人任何权利、特权、好处以便获得赦免。
One of the more difficult processes to inspect and one which has presented considerable problems over the years is that of the manufacture of sterile bulk drug substances. Within the past several years, there have been a number of batches of sterile bulk drug substances from different manufacturers which exhibited microbiological contamination. One manufacturer had approximately 100 batches contaminated in a 6 month time period. Another had approximately 25 batches contaminated in a similar period. Other manufacturers have had recalls due to the lack of assurance of sterility. Although the Inspection Guide for Bulk Drug Substances provides some direction for the inspection of the sterile bulk drug substance, it does not provide the detailed direction needed.在过去多年中，现场检查最难的，也是出现问题最多的领域就是无菌原料药的制造。
FDA-GMP中英文对照标准版
DIRECTION OF GMP (GOOD MANUFACTURING PRACTICE )OF RAW MATERIALS BY FDATable of Contents 目录1. INTRODUCTION1.1 Objective 目的1.2 Regulatory Applicability法规的适用性1.3 Scope 范围2. QUALITY MANAGEMENT .质量管理2.1 Principles 总则2.2 Responsibilities of the Quality Unit(s) 质量部门的责任2.3 Responsibility for Production Activities 生产作业的职责2.4 Internal Audits (Self Inspection) 内部审计（自检）2.5 Product Quality Review 产品质量审核3. PERSONNEL 人员3.1 Personnel Qualifications 人员的资质3.2 Personnel Hygiene 人员卫生3.3 Consultants 顾问4. BUILDINGS AND FACILITIES 建筑和设施4.1 Design and Construction 设计和结构4.2 Utilities 公用设施4.3 Water 水4.4 Containment 限制4.5 Lighting 照明4.6 Sewage and Refuse 排污和垃圾4.7 Sanitation and Maintenance 卫生和保养5. PROCESS EQUIPMENT 工艺设备5.1 Design and Construction 设计和结构5.2 Equipment Maintenance and Cleaning 设备保养和清洁5.3 Calibration. 校验5.4 Computerized Systems 计算机控制系统6. DOCUMENTATION AND RECORDS 文件和记录6.1 Documentation System and Specifications 文件系统和质量标准6.2 Equipment cleaning and Use Record 设备的清洁和使用记录6.3 Records of Raw Materials, Intermediates, API Labeling and Packaging Materials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)生产工艺规程（主生产和控制记录）6.5 Batch Production Records (Batch Production and Control Records)批生产记录（批生产和控制记录）6.6 Laboratory Control Records 实验室控制记录6.7 Batch Production Record Review 批生产记录审核7. MATERIALS MANAGEMENT 物料管理7.1 General Controls 控制通则7.2 Receipt and Quarantine 接收和待验7.3 Sampling and Testing of Incoming Production Materials 进厂物料的取样与测试7.4 Storage 储存7.5 Re-evaluation 复验8. PRODUCTION AND IN-PROCESS CONTROLS 生产和过程控制8.1 Production Operations 生产操作8.2 Time Limits 时限8.3 In-process Sampling and Controls 工序取样和控制8.4 Blending Batches of Intermediates or APIs 中间体或原料药的混批8.5 Contamination Control 污染控制9. PACKAGING AND IDENTIFICATION LABELING OF APIs AND INTERMEDIATES原料药和中间体的包装和贴签9.1 General 总则9.2 Packaging Materials 包装材料9.3 Label Issuance and Control 标签发放与控制9.4 Packaging and Labeling Operations 包装和贴签操作10. STORAGE AND DISTRIBUTION.储存和分发10.1 Warehousing Procedures 入库程序10.2 Distribution Procedures 分发程序11. LABORATORY CONTROLS 实验室控制11.1 General Controls 控制通则11.2 Testing of Intermediates and APIs 中间体和原料药的测试11.3 Validation of Analytical Procedures 分析方法的验证11.4 Certificates of Analysis分析报告单11.5 Stability Monitoring of APIs 原料药的稳定性监测11.6 Expiry and Retest Dating 有效期和复验期11.7 Reserve/Retention Samples 留样12. VALIDATION .验证12.1 Validation Policy 验证方针12.2 Validation Documentation 验证文件12.3 Qualification 确认12.4 Approaches to Process Validation 工艺验证的方法12.5 Process Validation Program 工艺验证的程序12.6 Periodic Review of Validated Systems 验证系统的定期审核12.7 Cleaning Validation 清洗验证12.8 Validation of Analytical Methods 分析方法的验证13. CHANGE CONTROL 变更的控制14. REJECTION AND RE-USE OF MATERIALS.拒收和物料的再利用14.1 Rejection 拒收14.2 Reprocessing 返工14.3 Reworking 重新加工14.4 Recovery of Materials and Solvents 物料与溶剂的回收14.5 Returns 退货15. COMPLAINTS AND RECALLS 投诉与召回16. CONTRACT MANUFACTURERS (INCLUDING LABORATORIES)协议生产商（包括实验室）17. AGENTS, BROKERS, TRADERS, DISTRIBUTORS, REPACKERS, AND RELABELLERS 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 适用性17.2 Traceability of Distributed APIs and Intermediates已分发的原料药和中间体的可追溯性17.3 Quality Management 质量管理17.4 Repackaging, Relabeling, and Holding of APIs and Intermediates原料药和中间体的重新包装、重新贴签和待检17.5 Stability 稳定性17.6 Transfer of Information 信息的传达17.7 Handling of Complaints and Recalls 投诉和召回的处理17.8 Handling of Returns 退货的处理18. Specific Guidance for APIs Manufactured by Cell Culture/Fermentation用细胞繁殖/发酵生产的原料药的特殊指南18.1 General 总则18.2 Cell Bank Maintenance and Record Keeping 细胞库的维护和记录的保存18.3 Cell Culture/Fermentation 细胞繁殖/发酵18.4 Harvesting, Isolation and Purification 收取、分离和精制18.5 Viral Removal/Inactivation steps 病毒的去除/灭活步骤19. APIs for Use in Clinical Trials 用于临床研究的原料药19.1 General 总则19.2 Quality 质量19.3 Equipment and Facilities设备和设施19.4 Control of Raw Materials 原料的控制19.5 Production 生产19.6 Validation 验证19.7 Changes 变更19.8 Laboratory Controls 实验室控制19.9 Documentation 文件20. Glossary 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。
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U.S. Department of Health and Human Services Food and Drug Administration
Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER)
B. Technical Framework.................................................................................................................... 3 技术架构
III. SCOPE ............................................................................................................................... 4 适用范围
Translated from / 译自：
Guidance for Industry
Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice
行业指南 无菌加工生产的无菌药品 —现行的生产质量管理规范(cGMP）
II. BACKGROUND ............................................................................................................... 2 背景
A. Regulatory Framework ................................................................................................................. 2 法规架构
Food and Drug Administration 5600 Fishers Lane
Rockville, MD 20857 (Tel) 301-827-4573 /cder/guidance/index.htm
or
Office of Communication, Training and Manufacturers Assistance, HFM-40
U.S. Department of Health and Human Services Food and Drug Administration
Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER)
Additional copies are available from: Office of Training and Communication Division of Drug Information, HFD-240 Center for Drug Evaluation and Research
IV. AND FACILITIES .................................................................................... 6 厂房和建筑
A. Critical Area – Class 100 (ISO 5) ................................................................................................. 8 关键区域– 100 级 (ISO 5)
Center for Biologics Evaluation and Research Food and Drug Administration
1401 Rockville Pike, Rockville, MD 20852-1448 /cber/guidelines.htm.
B. Supporting Clean Areas .............................................................................................................. 11 辅助洁净区域
Office of Regulatory affairs (ORA)
September 2004 Pharmaceutical CGMPs
Copyright SCI Version 1
Contains Nonbinding Recommendations
TABLE OF CONTENTS
I. INTRODUCTION............................................................................................................. 1 简介
Office of Regulatory Affairs (ORA) September 2004
Pharmaceutical CGMPs
Copyright SCI Version 1
Guidance for Industry
Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice