EUROPEAN COMMISSION
ENTERPRISE DIRECTORATE-GENERAL
Single market, regulatory environment, industries under vertical legislation
Pharmaceuticals and cosmetics
Brussels,30 March 2015
EudraLex
欧盟药品管理法 Volume 4 EU Guidelines for
Good Manufacturing Practice for
Medicinal Products for Human and Veterinary Use
第四卷欧盟人用和兽用药品GMP指南 Annex 15: Qualification and Validation 附录15:确认和验证 Legal basis for publishing the detailed guidelines:Article 47 of Directive 2001/83/EC on the Community code relating to medicinal products for human use and Article 51 of Directive 2001/82/EC on the Community code relating to veterinary medicinal products. This document provides guidance for the interpretation of the principles and guidelines of good manufacturing practice (GMP) for medicinal products as laid down in Directive 2003/94/EC for medicinal products for human use and Directive 91/412/EEC for veterinary use.
发布该细化指南的法律依据:人用药物欧共体法案指令2001/83/EC第47章和兽用药物欧共体法案指令2001/82/EC第51章。本文件为人药GMP指令2003/94/EC以及兽药GMP
指令91/412/EEC的原则和指南提供诠释。
Status of the document: Revision
文件状态：修订版
Reasons for changes: Since Annex 15 was published in 2001 the manufacturing and regulatory environment has changed significantly and an update is required to this Annex to reflect this changed environment. This revision to Annex 15 takes into account changes to other sections of the EudraLex, Volume 4, Part I, relationship to Part II, Annex 11, ICH Q8, Q9, Q10 and Q11, QWP guidance on process validation, and changes in manufacturing technology.
变更原因：从2001年附录15发布以后，制药生产和法规环境都有了显著变化，需要相应的更新来反映变化的环境。本文对附录15所做的修订考虑了欧盟法规第四卷第一部分质量管理和第二部分活性物质作起始物料以及附录11计算机化系统的验证、ICH Q8药物研发、ICH Q9质量风向管理、ICH Q11药物研发和生产、质量工作组的工艺验证指南和生产技术的变化。
Deadline for coming into operation:1 October 2015
最终实施日期：2015年10月1日
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目录
原则 .................................................................................................................. 2 概述 .................................................................................................................. 3 1. 确认和验证的组织和计划 ........................................................................... 3 2. 文件，包括验证主计划 ............................................................................... 5 3. 设备、设施、公用工程和系统的确认阶段 .................................................. 7 5. 工艺验证 .................................................................................................. 10 6. 运输确认 .................................................................................................. 19 7. 包装验证 .................................................................................................. 20 8. 公用工程的确认 ....................................................................................... 20 9. 检验方法验证 ........................................................................................... 21 10. 11. 12.
清洁验证 ............................................................................................... 21 变更控制 ............................................................................................... 25 词汇表 ................................................................................................... 26
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Principle
This Annex describes the principles of qualification and validation which are applicable to the facilities, equipment, utilities and processes used for the manufacture of medicinal products and may also be used as supplementary optional guidance for active substances without introduction of additional requirements to EudraLex, Volume 4, Part II. It is a GMP requirement that manufacturers control the critical aspects of their particular operations through qualification and validation over the life cycle of the product and process. Any planned changes to the facilities, equipment, utilities and processes, which may affect the quality of the product, should be formally documented and the impact on the validated status or control strategy assessed. Computerised systems used for the manufacture of medicinal products should also be validated according to the requirements of Annex 11. The relevant concepts and guidance presented in ICH Q8, Q9, Q10 and Q11 should also be taken into account. 原则
本附录描述了确认与验证的基本原则，适用于药品生产中的设施、设备、公用系统及工艺,也可以用于第四卷第二部分《活性物质作起始物料》的附加要求中没有介绍部分的补充性、选择性指南。GMP要求生产商应通过确认和验证对整个生命周期内的产品和工艺涉及的关键操作中的关键因素来进行控制。所有影响产品质量的计划性变更（含设施、设备、工艺系统和工艺），都应当有正式文件或记录，并评估其对验证状态或是控制策略的影响。用于药品生产的计算机化系统也应根据附录11的要求进行验证。同时，应当考虑现行的ICH Q8、Q9、Q10、Q11中的相关理念和指南要求。 General
A quality risk management approach should be applied throughout the lifecycle of a medicinal product. As part of a quality risk management system, decisions on the scope and extent of qualification and validation should be based on a justified and documented risk assessment of the facilities, equipment, utilities and processes. Retrospective validation is no longer considered an acceptable approach. Data supporting qualification and/or
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