ICHQ7中英文Word文档格式.docx

1、Approval by the Steering Committee under Step 2 and release for public consultation. 19 July 2000 Approval by the Steering Committee under Step 4 and recommendation for adoption to the three ICH regulatory bodies. 10 November 2000 ICH Harmonised Tripartite Guideline Having reached Step 4 of the ICH

2、Process at the ICH Steering Committee meeting on 10 November 2000, this guideline is recommended for adoption to the three regulatory parties to ICH Table 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 Pri

3、nciples 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 Co

4、nsultants 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

5、 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,Intermediat

6、es, 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 Materials 6.4 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 Pro

7、duction 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 Pr

8、oduction 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

9、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 Test

10、ing 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

11、 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 M

12、ethods 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

13、 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, Rela

14、beling, 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Cult

15、ure/Fermentation 18.1 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

16、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 Object

17、ive 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 characteris

18、tics 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。它也有助于帮助确保活性药物成分（APIs）符合其应有的质量和纯度要求。In this guidance, the term manufacturing is defined to include all operations of receipt of materials, production, packaging, repackaging,labeling, relabeling, q

19、uality control, release,storage and distribution of APIs and the related controls. In this guidance, the term should identifies recommendations that, when followed, will ensure compliance with CGMPs. An alternative approach may be used if such approach satisfies the requirements of the applicable st

20、atues. For the purposes of this guidance, the terms current good manufacturing practices and good manufacturing practices are equivalent.本指南中的“生产”定义为包括物料接收、生产、包装、重新包装、贴签、重新贴签、质量控制、放行、原料药的储存和分发及其相关控制的所有操作。本指南中，“应当”一词表示希望采用的建议，除非证明其不适用或者可用一种已证明有同等或更高质量保证水平的供选物来替代。本指南中的“现行优良生产管理规范（cGMP）”和“优良生产管理规范（GMP）

21、”是等同的。The guidance as a whole does not cover safety aspects for the personnel engaged in manufacturing, nor aspects related to protectingthe environment. These controls are inherent responsibilities of the manufacturer and are governed by national laws.本指南在总体上未涉及生产人员的安全问题，亦不包括环保方面的内容。这方面的管理是生产者固有的责任

22、，也是国家法律规定的。This guidance is not intended to define registration and/or filing requirements or modify pharmacopoeial requirements. Thisguidance does not affect the ability of the responsible regulatory agency to establish specific registration/filing requirementsregarding APIs within the context of m

23、arketing/manufacturing authorizations or drug applications. All commitments in registration/filing documents should be met.本指南未规定注册/归档的要求、或修改药典的要求。本指南不影响负责药政审理部门在原料药上市/制造授权或药品申请方面建立特定注册/归档要求的能力。注册/归档的所有承诺必须做到。1.2 Regulatory Applicability 1.2 法规的适用性Within the world community, materials may vary as to

24、 their 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 guidance.在世界范围内对原料药的法定定义是各不相同的。当某种物料在其制造或用于药品的地区或国家被称为原料药，就应该按照本指南进行生产。1.3 Scope 1.3 范围This guidan

25、ce 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 sho

26、uld be performed in accordance with GMP guidances for drug （medicinal） products as defined by local authorities.本文件适用于人用药品（医疗用品）所含原料药的生产。它适用于无菌原料药在灭菌前的步骤。本指南不包括无菌原料药的消毒和灭菌工艺，但是，应当符合地方当局所规定的药品（医疗用品）生产的GMP 指南。This guidance covers APIs that are manufactured by chemical synthesis,extraction, cell cultur

27、e/fermentation, recovery from natural sources, or any combination of these processes. Specific guidance for APIs manufactured by cell culture/fermentation is described in Section 18.本文件适用于通过化学合成、提取、细胞培养/发酵，通过从自然资源回收，或通过这些工艺的结合而得到的原料药。通过细胞培养/发酵生产的原料药的特殊指南则在第18 章论述。This guidance excludes all vaccines,

28、 whole cells, whole blood and plasma, blood and plasma derivatives （plasma fractionation）, andgene 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 guidance. In addition, the guidance does not apply to medical gases, bulk-packaged drug （medicinal） products （e.g., tablets or capsul