EU GMP 指南附件15 - 确认和验证 2015年最新版

EudraLex Volume 4

EU Guidelines for

GOOD MANUFACTURING PRACTICE FOR

MEDICINAL PRODUCTS

欧盟药品GMP指南

ANNEX 15 QUALIFICATION AND VALIDATION

附件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.

公布详细指南的法律依据：指令2001/83/EC第47款关于人药共同体代码，和2001/82/EC第51款关于兽药共同体代码的要求。本文件为指令2003/94/EC中制订的人药GMP以及指令91/412/EEC兽药GMP原则和指南提供诠释。

Status of the document: Revision

文件状态：修订

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.

变更理由：自从附录15在2001年公布以来，生产和法规环境已发生了重大变化，有必要对此附录进行更新以反映环境的变化。本次对附录15的修订考虑了欧洲药事法卷4第一部分其它部分的变化，与第二部分、附录11、ICH Q8 Q9 Q10以及Q11、QWP的工艺验证指南的关系，以及生产技术的变化。

Deadline for coming into operation: 1 October 2015

最后实施时间：2015年10月1日

Content

目录

PRINCIPLE 原则 (4)

GENERAL 通则 (4)

1ORGANISING AND PLANNING FOR QUALIFICATION AND VALIDATION确认和验证的组织和计划 (4)

2DOCUMENTATION,INCLUDING VMP文件记录，包括VMP (6)

3QUALIFICATION STAGES FOR EQUIPMENT,FACILITIES,UTILITIES AND SYSTEMS.设备、设施、公用系统和系统的确认阶段 (7)

4RE-QUALIFICATION再确认 (10)

5PROCESS VALIDATION工艺验证 (10)

6VERIFICATION OF TRANSPORTATION运输确认 (16)

7VALIDATION OF PACKAGING包装验证 (17)

8QUALIFICATION OF UTILITIES公用系统确认 (17)

9VALIDATION OF TEST METHODS检验方法验证 (18)

10CLEANING VALIDATION清洁验证 (18)

11CHANGE CONTROL变更控制 (21)

12GLOSSARY术语 (22)

PRINCIPLE 原则

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.

本附录描述了确认和验证的原则，该原则适用于药品生产用设施、设备、公用系统和工艺，也可用作活性物质的可选补充指南，但并不对欧盟药事法第4卷第二部分引入附加要求。GMP要求生产商通过在产品和工艺的整个生命周期中进行确认和验证，对其操作关键方面进行控制。所有可能影响产品质量的设施、设备、公用系统和工艺计划变更均应进行正式记录，并评估其对验证状态和控制策略的影响。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。同时还应考虑ICH Q8 Q9 Q10和Q11是的相关概念和指南要求。

General 通则

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 validation studies which were obtained from sources outside of the manufacturers own programmes may be used provided that this approach has been justified and that there is adequate assurance that controls were in place throughout the acquisition of such data.

质量风险管理的方法应贯穿药品的整个生命周期。作为质量风险管理系统的一部分，决定确认和验证的范围和程度时应基于对设施、设备、公用系统和工艺的论证和书面风险评估。回顾性验证不再被认为是可以接受的方法。如果经过论证，并且获得数据的整个过程有足够控制保证，也可以使用从生产商自身程序以外获得的用于支持确认和/或验证研究的数据。

1ORGANISING AND PLANNING FOR QUALIFICATION AND VALIDATION 确认和验证的组织和计划

1.1All qualification and validation activities should be planned and take the life cycle of facilities, equipment,

utilities, process and product into consideration.

所有确认和验证活动应进行计划，并考虑设施、设备、公用系统、工艺和产品的生命周期

1.2Qualification and validation activities should only be performed by suitably trained personnel who

follow approved procedures.

确认和验证活动应由经过适当培训的人员实施，并遵守已批准的程序