上海万逸医药科技有限公司刘伟强译
Ref. Ares(2015)1380025 - 30/03/2015
EUROPEAN COMMISSION
DIRECTORATE-GENERAL FOR HEALTH AND FOOD SAFETY
Medicinal Products – Quality, Safety and Efficacy
Brusls, 30 March 2015
EudraLex
Volume 4
EU Guidelines for
Good Manufacturing Practice for
Medicinal Products for Human and Veterinary U
欧盟人用及兽用药品GMP指导原则
Annex 15: Qualification and Validation
附件15：确认与验证
Legal basis for publishing the detailed guidelines: Article 47 of Directive 2001/83/EC
on the Community code relating to medicinal products for human u 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
宝宝找数字of good manufacturing practice (GMP) for medicinal products as laid down in Directive
2003/94/EC for medicinal products for human u and Directive 91/412/EEC for veterinary u.
Status of the document: Revision
老干妈回锅肉文件状态：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 ctions 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：附录15至2001年颁布以来，制造业和法规环境发生了显著变化，因此
需要更新附录以反应这些环境的变化，附录15的修订还考虑到了欧盟药品监管法
规（Eudralex）第四卷第一部分、第二部分有关内容、附录11、ICH Q8、Q9、Q19
和Q11、欧盟药品质量工作组（QWP）工艺验证指南的变更以及制造技术变化等因
素。
Deadline for coming into operation: 1 October 2015
实施日期：2015年10月1日
Principle原则
This Annex describes the principles of qualification and validation which are applicable to the facilities, equipment, utilities and process ud for the manufacture of medicinal products and may also be ud 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 process, which may affect the quality of the product, should be formally documented and the impact on the validated status or control strategy assd. Computerid systems ud for the manufacture of medicinal products should also be validated according to the requirements of Annex 11. The relevant concepts and guidance prented in ICH Q8, Q9, Q10 and Q11 should also be taken into account.
本附件描述的相关原则，既适用于用于生产医药产品的厂房、设施，设备以及工艺的确认与验证活动，也可用于在欧盟药品监管法规（Eudralex）第四卷第二部分没有导入附加要求的活性物质的补充
可选指南。GMP要求企业在贯穿产品和工艺的生产周期过程中通过确认与验证控制有关操作的关键要素。任何计划对厂房、设施、设备和工艺进行变更可能会影响产品质量时，应当采用正式记录的方式对验证状态和控制策略进行评估。用于医药产品生产的计算机化系统应按照附件11的要求进行验证。本文件也考虑了ICH Q8、Q9、Q10和Q11的相关的概念和指导。
General通用要求
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 bad on a justified and documented risk asssment of the facilities, equipment, utilities and process. 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 ud provided that this approach has been justified and that there is adequate assurance that controls were in place throughout the acquisition of such data.
质量风险管理方法应当贯穿于整个医药产品生命周期。作为质量风险管理系统的一部分，应对厂房、设施、设备工艺确认与验证的范围和程度进行风险评估。回顾性验证不再认为是可以接受的方式。用
于支持确认和或验证研究的数据是通过外部途径获取的，企业应当对获取数据对外部的途径进行评估，并充分保证在数据获取的整个过程中都处于控制状态。
1.ORGANISING AND PLANNING FOR QUALIFICATION AND
VALIDATION
确认与研制的组织和计划
1.1.All qualification and validation activities should be planned and take the life
cycle of facilities, equipment, utilities, process and product into consideration.
所有确认与验证活动应在设备、工艺、产品的生命周期中有计划地实施
1.2.Qualification and validation activities should only be performed by suitably trained
personnel who follow approved procedures.
确认与验证活动应由被进行适当培训的人员按照批准的程序实施
唐山钢厂1.3.Qualification/validation personnel should report as defined in the pharmaceutical
quality system although this may not necessarily be to a quality management or a quality assurance function. However, there should be appropriate quality oversight over the whole validation life cycle.
药品质量管理体系规定确认/验证人员应进行报告，不过在质量管理和质量保证的职责中可能不是必须的，但需要在整个验证生命周期中进行适当的质量监控。
1.4.The key elements of the site qualification and validation programme should be
clearly defined and documented in a validation master plan (VMP) or equivalent document.
工厂确认与验证程序的关键要素应当在验证总计划或等效文件中明确定义。
1.5.The VMP or equivalent document should define the qualification/validation
system and include or reference information on at least the following:
验证总计划或等效文件应定义确认/验证系统并至少包含或引用以下内容：
i.Qualification and Validation policy;
确认与验证方针
ii.The organisational structure including roles and responsibilities for qualification and validation activities;
进行确认与验证活动的组织机构包括职位和职责
iii.Summary of the facilities, equipment, systems, process on site and the qualification and validation status;
概述工厂的厂房、设备、系统、工艺及确认与验证状态
iv.Change control and deviation management for qualification and validation;
确认与验证的变更控制和偏差管理
v.Guidance on developing acceptance criteria;
开发可接受标准的指导
vi.References to existing documents;
相关程序文件
vii.The qualification and validation strategy, including requalification, where applicable.
确认与研制策略，包括再确认，如适用
1.6.For large and complex projects, planning takes on added importance and parate
validation plans may enhance clarity
对于大型和复杂的项目，计划更加体现其重要性并且独立的验证计划可能更明确
1.7. A quality risk management approach should be ud for qualification and
validation activities. In light of incread knowledge and understanding from any changes during the project pha or during commercial production, the risk asssments should be repeated, as required. The way in which risk asssments
are ud to support qualification and validation activities should be clearly documented.
质量风险管理方法应在确认和验证活动中采用，鉴于在项目过程中或商业化生产过程中知识积累和认识的加深，质量风险管理的方法在验证活动过程中应该反复进行。用于支持确认与验证的活动的风险评估应明确记录。家风家规家训
1.8.Appropriate checks should be incorporated into qualification and validation work
to ensure the integrity of all data obtained.
适当的检查应纳入确认与验证工作中，以确保所有获取的数据完整性。
2.DOCUMENTATION, INCLUDING VMP
文件包括验证总计划
2.1.Good documentation practices are important to support knowledge management
throughout the product l ifecycle.
良好的文件管理规范对于支持产品生命周期知识管理是重要的。
2.2.All documents generated during qualification and validation should be approved
and authorid by appropriate personnel as defined in the pharmaceutical quality system.
确认与验证过程中有关的所有文件应由药品质量体系规定的相关责任人审核、批准。
2.3.The inter-relationship between documents in complex validation projects should
be clearly defined.
在进行复杂验证项目时，文件之间的相互关系应明确定义
2.4.Validation protocols should be prepared which defines the critical systems,
attributes and parameters and the associated acceptance criteria.
在验证方案应明确关键系统、关键属性、关键参数及有关的可接受标准。
担当的近义词
2.5.Qualification documents may be combined together, where appropriate, e.g.
installation qualification (IQ) and operational qualification (OQ).
确认文件可以合并，如适当时：安装确认（IQ）可以和运行确认（OQ）合并。
2.6.Where validation protocols and other documentation are supplied by a third party
providing validation rvices, appropriate personnel at the manufacturing site should confirm suitabili
ty and compliance with internal procedures before approval. Vendor protocols may be supplemented by additional documentation/test protocols before u.
当验证方案和其他文件由进行验证服务的第三方提供时，企业的相关人员在批准前应审核适用性以及与内部程序的符合性。供应商的方案可以作为额外的文件/测试方案使用前的补充
2.7.Any significant changes to the approved protocol during execution, e.g.
acceptance criteria, operating parameters etc., should be documented as a deviation and be scientifically justified.
已批准方案在实施过程中的任何重大变更，如：可接受标准、操作参数等，应作为偏差进行记录并进行科学的评价。
2.8.Results which fail to meet the pre-defined acceptance criteria should be recorded
as a deviation and be fully investigated according to local procedures. Any implications for the validation should be discusd in the report
不符合预定可接受标准的结果应作为偏差进行记录，并应按照企业程序进行彻底调查。对于验证的任何影响应在报告中进行论述。
2.9.The review and conclusions of the validation should be reported and the results
obtained summarid against the acceptance criteria. Any subquent changes to acceptance criteria should be scientifically justified and a final recommendation made as to the outcome of the validation.
唐代诗人王维验证结论和回顾的结果应当报告，当获得的结果汇总后不符合预先设定的可接受标准时。任何可接受标准的后续变更应进行科学评估和对验证结果的最终建议生搬硬套的意思
2.10. A formal relea for the next stage in the qualification and validation process
should be authorid by the relevant responsible personnel either as part of the validation report approval or as a parate summary document. Conditional approval to proceed to the next qualification stage can be given where certain acceptance criteria or deviations have not been fully addresd and there is a documented asssment that there is no significant impact on the next activity.最好的防晒霜
当确认或验证分阶段进行时，只有当上一阶段的确认或验证活动符合预定目标且经书面批准后，方可进行下一阶段的确认或验证活动。上一阶段的确认或验证活动中某项预先设定标准不能满足或偏差处
理未完成，经评估对下一阶段的确认或验证活动无重大影响，企业可对上一阶段的确认或验证活动进行有条件的批准
3.QUALIFICATION STAGES FOR EQUIPMENT, FACILITIES, UTILITIES
AND SYSTEMS.
设备、设施、公用设施和系统的确认阶段
3.1.Qualification activities should consider all stages from initial development of the
ur requirements specification through to the end of u of the equipment, facility, utility or system. The main stages and some suggested criteria (although this depends on individual project circumstances and may be different) which could be included in each stage are indicated below:
确认活动应该考虑从用户需求的开发或最初的工艺研发到所使用的设备、设施和工艺结束的所以阶段。主要的阶段和每个阶段一些建议的标准如下（尽管可能由于不同项目环境可能有所不同）
Ur requirements specification (URS)用户需求
3.2.The specification for equipment, facilities, utilities or systems should be defined
in a URS and/or a functional specification. The esntial elements of quality need to be built in at this stage and any GMP risks mitigated to an acceptable level.
The URS should be a point of reference throughout the validation life cycle.
设备、设施、公用设施和系统说明应在用户需求和或功能说明书中进行定义。质量的必须要素需在这一阶段建立并将任何GMP风险降低到可接受水平。用户需求应为贯穿验证生命周期的参考点。
Design qualification (DQ)设计确认
