FDAGMP中英文对照标准版.docx

1、FDAGMP中英文对照标准版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.INTRODUCTION1.1Objective 目的1.2Regulatory Applicability 法规的适用性1.3Scope 范围2.QUALITY MANAGEMENT .质量管理2.1Principles 总则2.2Responsibilities of the Quality Unit(s) 质量部门的责任2.3Responsibili

2、ty for Production Activities 生产作业的职责2.4Internal Audits (Self Inspection) 内部审计(自检)2.5Product Quality Review 产品质量审核3.PERSONNEL 人员3.1Personnel Qualifications 人员的资质3.2Personnel Hygiene 人员卫生3.3Consultants 顾问4.BUILDINGS AND FACILITIES 建筑和设施4.1Design and Construction 设计和结构4.2Utilities 公用设施4.3Water 水4.4Cont

3、ainment 限制4.5Lighting 照明4.6Sewage and Refuse 排污和垃圾4.7Sanitation and Maintenance 卫生和保养5.PROCESS EQUIPMENT工艺设备5.1Design and Construction 设计和结构5.2Equipment Maintenance and Cleaning 设备保养和清洁5.3Calibration. 校验5.4Computerized Systems 计算机控制系统6.DOCUMENTATION AND RECORD文件 和记录6.1Documentation System and Specif

4、ications 文件系统和质量标 准6.2Equipment cleaning and Use Record 设备的清洁和使用记录6.3Records of Raw Materials, Intermediates, API Labeling and Packaging Materials1原料、中间体、原料药的标签和包装材料的记录6.4Master Production Instructions (Master Production and Control Records) 生产工艺规程(主生产和控制记录)6.5Batch Production Records (Batch Product

5、ion and Control Records) 批生产记录(批生产和控制记录)6.6Laboratory Control Records 实验室控制记录6.7Batch Production Record Review 批生产记录审核7.MATERIALS MANAGEMENT 物料管理7.1General Controls 控制通则7.2Receipt and Quarantine 接收和待验7.3Sampling and Testing of Incoming Production Materials 进厂物料的 取样与测试7.4Storage 储存7.5Re-evaluation 复验

6、8.PRODUCTION AND IN-PROCESS CONTROL 生产和过程控制8.1Production Operations 生产操作8.2Time Limits 时限8.3In-process Sampling and Controls 工序取样和控制8.4Blending Batches of Intermediates or APIs 中间体或原料药的混 批8.5Contamination Control 污染控制9.PACKAGING AND IDENTIFICATION LABELING OF APIs ANDINTERMEDIATES 原料药和中间体的包装和贴签9.1Ge

7、neral 总则9.2Packaging Materials 包装材料9.3Label Issuance and Control 标签发放与控制9.4Packaging and Labeling Operations 包装和贴签操作10.STORAGE AND DISTRIBUTION存和分发10.1Warehousing Procedures 入库程序10.2Distribution Procedures 分发程序11.LABORATORY CONTROLS 实验室控制11.1General Controls 控制通则11.2Testing of Intermediates and APIs

8、 中间体和原料药的测试11.3Validation of Analytical Procedures 分析方法的验证11.4Certificates of Analysis 分析报告单11.5Stability Monitoring of APIs 原料药的稳定性监测11.6Expiry and Retest Dating 有效期和复验期11.7Reserve/Retention Samples 留样12.VALIDATION .验证12.1Validation Policy 验证方针12.2Validation Documentation 验证文件12.3Qualification 确认12

9、.4Approaches to Process Validation 工艺验证的方法212.5Process Validation Program 工艺验证的程序12.6Periodic Review of Validated Systems 验证系统的定期审核12.7Cleaning Validation 清洗验证12.8Validation of Analytical Methods 分析方法的验证13.CHANGE CONTROL 变更的控制14.REJECTION AND RE-USE OF MATER 拒L收和物料的再利用14.1Rejection 拒收14.2Reprocessin

10、g 返工14.3Reworking 重新加工14.4Recovery of Materials and Solvents 物料与溶剂的回收14.5Returns 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弋理商、经纪人、贸易商、经销商、重新包装者和重新贴签者17.1Applicability 适用性17.2Tr

11、aceability of Distributed APIs and Intermediates 已分发的原料药 和中间体的可追溯性17.3Quality Management 质量管理17.4Repackaging, 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17.5Stability 稳定性17.6Transfer of Information 信息的传达17.7Handling of Complaints and Recalls 投诉和召回的处理18.Specific Guidance for

12、 APIs Manufactured by Cell Culture/Fermentation用细胞繁殖 / 发酵生产的原料药的特殊指南18.1General 总则18.2Cell Bank Maintenance and Record Keeping 细胞库的维护和记录的保存18.3Cell Culture/Fermentation 细胞繁殖 / 发酵18.4Harvesting, Isolation and Purification 收取、分离和精制18.5Viral Removal/Inactivation steps 病毒的去除 / 灭活步骤19.APIs for Use in Cli

13、nical Trials 用于临床研究的原料药19.1General 总则19.2Quality 质量19.3Equipment and Facilities 设备和设施19.4Control of Raw Materials 原料的控制19.5Production 生产19.6Validation 验证19.7Changes 变更319.8Laboratory Controls 实验室控制19.9Documentation 文件20.Glossary 术语1.1Objective 1.1 目的This document is intended to provide guidance rega

14、rding 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

15、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。它也着眼于帮 助确保原料药符合其旨在达到或表明拥有的质量与纯度要求。In this guidance, the term manufacturing is defined to include all operations of receipt of materials, production, packaging, repackaging, labeling, relabeling, quality control, release, storage and distribution

16、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 statues. For the purposes of this guidance, the ter

17、ms current good manufacturing practices and good manufacturing practices are equivalent.本指南中所指的“制造”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） 是等同的。The guidance as a whole does not cover

18、safety aspects for the personnel engaged in manufacturing, nor aspects related to protecting the 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，也是国家法律规定的。This guidance is not intended to

19、 define registration and/or filing requirements or modify pharmacopoeial requirements. This guidance 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

20、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。1.2Regulatory Applicability 1.2 法规的适用性Within the world community, materials may vary as to their legal classification as an

21、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。1.3Scope 1.3 范围This guidance applies to the manufacture of

22、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. 4The sterilization and aseptic processing of sterile APIs are not covered by this guidance, but should be performed in accordance

23、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 culture/fermentation, recovery fr

24、om 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, whole cells, whole

25、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

26、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 capsules in bulk containers), or radiopharmaceuticals.本指南不包括所有疫苗、完整细胞、全血和血浆、全血和血浆的衍生 物(血浆成

27、分)和基因治疗的原料药。但是却包括以血或血浆为原材料生 产的原料药。值得注意的是细胞培养基(哺乳动物、植物、昆虫或微生物 的细胞、组织或动物源包括转基因动物)和前期生产可能应遵循 GMP 规范，但不包括在本指南之内。另外，本指南不适用于医用气体、散装的制 剂药(例如，散装的片剂和胶囊)和放射性药物的生产。Section 19 contains guidance that only applies to the manufacture of APIs used in the production of drug (medicinal) products specifically for clin

28、ical trials (investigational medicinal products).第 19 章的指南只适用于用在药品 (医疗用品) 生产中的原料药制造， 特别是临床实验用药(研究用医疗产品)的原料药制造。An API starting material is a raw material, an intermediate, or an API that is used in the production of an API and that is incorporated as a significant structural fragment into the structu

29、re 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.“原料药的起始物料”是指一种原料、中间体或原料药，用来生产一 种原料药，或者以主

30、要结构单元的形式被结合进原料药结构中。原料药的 起始物料可能是在市场上有售、能够通过合同或商业协议从一个或多个供 应商处购得，或由生产厂家自制。原料药的起始物料一般来说有特定的化 学特性和结构。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 entere

31、d into the process. For other processes (e.g., fermentation, extraction, purification), 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.生产厂商要指定并用书面文件说明原料药的生产从何处开始的理论 依据。对于合成工艺

32、而言， 就是“原料药的起始物料” 进入工艺的那一点。 对其他工艺(如：发酵，提取，纯化等)可能需要具体问题具体对待。表 1 给出了原料药的起始物料从哪一点引入工艺过程的指导原则。5From this point on, appropriate GMP as defined in this guidance 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 val