欧盟GMP附录15：确认与验证(修订版英文+中文)

2021年1月25日发(作者：第一课堂)
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
91/41 2/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
1 5
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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32
页

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
................ .................................................. ................................
1
0

6.

运输确认
.......................... .................................................. ......................
1
9

7.

包装验证
..................................... .................................................. ...........
2
0

8.

公用工程的确认
.................................. .................................................. ...
2
0

9.

检验方法验证

. .................................................. ........................................
2
1

10.

11.

12.

清洁验证

................................. .................................................. ............
2
1

变更控制

..... .................................................. ........................................
2
5

词汇表

.
.............. .................................................. ..................................
2
6



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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
、< br>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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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.
概述

质量风险管理的方法 应作为质量风险管理系统的一部分贯穿于药品的整个
生命周期，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决定确
认和验证的范围和程度。
回顾性验证不再被认为是可接受的方式。< br>如果方法经过
论证，
并且获取数据的整个过程中有足够的保证性控制措施，
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。

1. ORGANISING AND PLANNING FOR QUALIFICATION AND
VALIDATION

1.
确认和验证的组织和计划

qualification and validation activities should be planned and take the life
cycle of facilities, equipment, utilities, process and product into consideration.
1.1.
所有的确认和验证都 应当被计划，并考虑到设施、设备、公用系统、工艺和
产品的生命周期。

ication and validation activities should only be performed by suitably
trained personnel who follow approved procedures.
1.2.
确认和验证活动应只能由经过培训合格的人员严格按照批准的程序实施。

ication/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.
1.3.
确认或验证人员应按照药品质量体系中指定要求进行报告，
尽管并不一定是
报告给质量管理或质量保证部门。
然而，
对于整个验证生命周期来说，
应当有合
适的质量监督。

key elements of the site qualification and validation programme should
be clearly defined and documented in a validation master plan (VMP) or
equivalent document.
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1.4.
应当在验证主计划（
VMP
）或其等同文件 中，清晰地界定和记录现场确认与
验证程序的关键性要素。

1.5. The VMP or equivalent document should define the qualification/validation
system and include or reference information on at least the following:
1.5.
验证主计划或其等同文件中应定义确认
/
验证体系，至少包括如下信息：

i. Qualification and Validation policy;
i.
确认与验证的方针政策。

ii. The organisational structure including roles and responsibilities for
qualification and validation activities;
ii.
在确认和验证活动中的组织结构，包括分工和职责。

y of the facilities, equipment, systems, processes on site and the
qualification and validation status;
iii.
现场设施、设备、系统、工艺汇总表及其确认和验证状态。

control and deviation management for qualification and validation;
iv.
确认与验证活动的变更控制和偏差管理。

v. Guidance on developing acceptance criteria;
v.
开发可接受标准的指南。

nces to existing documents;
vi.
现有文件的参考资料。

qualification and validation strategy, including requalification, where
applicable.
vii.
确认与验证的策略，适当时应包括再确认。

large and complex projects, planning takes on added importance and
separate validation plans may enhance clarity
1.6.
对于大型和复杂的项目，
增加计划重点和独立的验证计划将有助于明晰要做
的工作。

1.7.A quality risk management approach should be used for qualification and
validation activities. In light of increased knowledge and understanding from
any changes during the project phase or during commercial production, the
risk assessments should be repeated, as required. The way in which risk
assessments are used to support qualification and validation activities should
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be clearly documented.
1.7.
在确认与验证活动中应使用质量风险管理的方法，
随着在项目开展或者商业
化生产的过程中的知识积累及理解加深，
应当根据需要对风险进行不 断地重复评
估，并清楚地记录确认与验证的风险评估所采用的方法。

1.8. Appropriate checks should be incorporated into qualification and validation
work to ensure the integrity of all data obtained.
1.8.
应将适当的检查加入到确认和验证工作中，以保证所获得的数据的完整性。

2. DOCUMENTATION, INCLUDING VMP

2.
文件，包括验证主计划

2.1. Good documentation practices are important to support knowledge
management throughout the product lifecycle.
2.1.
在产品的生命周期中，良好的文件管理对于知识管理而言是非常重要的。

2.2. All documents generated during qualification and validation should be
approved and authorised by appropriate personnel as defined in the
pharmaceutical quality system.
2.2.
确认与验证产生的所有文件都应当由药品质量管理体系规定的人批准和授
权。

2.3. The inter-relationship between documents in complex validation projects
should be clearly defined.
2.3.
在复杂的验证项目中，应清楚地说明文件之间的内在关系。

2.4. Validation protocols should be prepared which defines the critical systems,
attributes and parameters and the associated acceptance criteria.
2.4.
制定验证方案的时候，
应当定义关键系统、
属性、
参数及 相关的可接受标准。

2.5. Qualification documents may be combined together, where appropriate,
e.g. installation qualification (IQ) and operational qualification (OQ).
2.5.
确认文件适当的时候可以合并，例如< br>IQ
和
OQ
的文件可以合并在一起。

2.6. Where validation protocols and other documentation are supplied by a
third party providing validation services, appropriate personnel at the
manufacturing site should confirm suitability and compliance with internal
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procedures before approval. Vendor protocols may be supplemented by
additional documentation/test protocols before use.
2.6.
如果验证方案和其它文件记录由验证服务第三方提供，
应当由企 业内部的合
适人员确认其适用性，
满足内部规定后方可批准。
在使用之前，
可 由附加的文件
或测试对供应商提供的方案进行补充。

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.
2.7.
在执行期间，对已批准方案的任何重大变更，如可接受标准、操作参数等，
均需按照偏差记录在册，并进行科学合理的评判。

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 discussed in the report
。

2.8.
若验证结 果不符合预定的可接受标准需作为偏差处理，
并按照内部规程进行
全面调查。任何与偏差关联的 东西都应当在验证报告中进行讨论。

2.9. The review and conclusions of the validation should be reported and the
results obtained summarised against the acceptance criteria. Any subsequent
changes to acceptance criteria should be scientifically justified and a final
recommendation made as to the outcome of the validation.
2.9.
验证的评价和结论都应当被报告，且结果应与可接受标准 比对，对可接受标
准的任何后期变更都应当进行科学的评判，并在验证结果中做出最终建议。

2.10. A formal release for the next stage in the qualification and validation
process should be authorised by the relevant responsible personnel either as
part of the validation report approval or as a separate summary document.
Conditional approval to proceed to the next qualification stage can be given
where certain acceptance criteria or deviations have not been fully addressed
and there is a documented assessment that there is no significant impact on
the next activity.
2.10.
由相关的负责人对确认与验证 过程中的阶段性放行，既可以作为验证报
告批准的一部分，
也可以是单独的总结文件。
因某个可接受标准未达到或偏差未
关闭，
并通过评估确定对下一阶段活动无显著影响，
可以有条件的放行进入下一
阶段。

3. QUALIFICATION STAGES FOR EQUIPMENT, FACILITIES, UTILITIES
AND SYSTEMS.

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3.
设备、设施、公用工程和系统的确认阶段

3.1. Qualification activities should consider all stages from initial development
of the user requirements specification through to the end of use 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:
3.1.
设备、设施、公用工程或系统的确认活动应当贯穿其用户需求说明书 的制定
到使用的各个阶段，主要阶段及其要求如下：

User requirements specification (URS)

用户需求说明（
URS
）

3.2. The specification for equipment, facilities, utilities or systems should be
defined in a URS and/or a functional specification. The essential 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.
3.2.
设备、
设施、
公用工程或系统的说明应当在
URS
文件和
/
或功能说明中定义，
应考虑质量的关键性因素，并把
GMP
风险降低到可接受 水平。
URS
应该是整
个验证生命周期中的参照。

Design qualification (DQ)

设计确认

3.3. The next element in the qualification of equipment, facilities, utilities, or
systems is DQ where the compliance of the design with GMP should be
demonstrated and documented. The requirements of the user requirements
specification should be verified during the design qualification.
3.3.
确认活动的第二阶段就是设计确认，
这里应当用文件证明其符合
G MP
要求，
还应当对用户需求说明中的要求进行确认。

Factory acceptance testing (FAT) /Site acceptance testing (SAT)

工厂验收测试（
FAT
）
/
现场验收测试（
SAT
）

3.4. Equipment, especially if incorporating novel or complex technology, may
be evaluated, if applicable, at the vendor prior to delivery.
3.4.
如果需要的话，设备（尤其是新型或复杂 的设备）在供应商发货前应在其产
地被充分的评估。

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3.5. Prior to installation, equipment should be confirmed to comply with the
URS/functional specification at the vendor site, if applicable.
3.5.
如果 需要的话，在供应商的现场，设备应在安装之前被确认是否符合
URS
或功能说明的要求。
3.6. Where appropriate and justified, documentation review and some tests
could be performed at the FAT or other stages without the need to repeat on
site at IQ/OQ if it can be shown that the functionality is not affected by the
transport and installation.
3.6.
合 适的话，
经过评估，
文件审核和部分测试可以在
FAT
时或其他阶段进行，< br>如果能够证明其功能在运输和安装中未受影响，就不需要在
IQ/OQ
时重复进行
已经做过的审核和测试了。

3.7. FAT may be supplemented by the execution of a SAT following the receipt
of equipment at the manufacturing site.
3.7.
在药品生产场地收到设备后，可以紧接着做
SAT
作为
F AT
的补充。

Installation qualification (IQ)

安装确认（
IQ
）

3.8. IQ should be performed on equipment, facilities, utilities, or systems.
3.8.
设备、设施、公用工程或系统应进行安装确认。

3.9. IQ should include, but is not limited to the following:
3.9.
安装确认包括但不限于以下内容：

i. Verification of the correct installation of components, instrumentation,
equipment, pipe work and services against the engineering drawings and
specifications;
i.
对照设计图纸和说明书，对组件、仪表、设备、管道和服务的安装正确
性进行确认。

ii. Verification of the correct installation against pre-defined criteria;
ii.
按照预先设定的标准对安装正确性进行确认。

iii. Collection and collation of supplier operating and working instructions and
maintenance requirements;
iii.
收集并核对供应商操作、工作指令和维护要求。

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iv. Calibration of instrumentation;
iv.
仪表校准。

v. Verification of the materials of construction.
v.
核对部件的材质。

Operational qualification (OQ)

运行确认（
OQ
）

3.10. OQ normally follows IQ but depending on the complexity of the
equipment, it may be performed as a combined Installation/Operation
Qualification (IOQ).
3.10.
OQ
一般紧跟着
IQ
，但是根据设备的复杂情况，OQ
也可以合并在安装
/
运行方案中执行
(IOQ)
。

3.11. OQ should include but is not limited to the following:
3.11.
运行确认包括但不限于以下内容：

i. Tests that have been developed from the knowledge of processes, systems
and equipment to ensure the system is operating as designed;
i.
根据工艺、系统和设备的相关知识开展测试，以确保其可以像设计的那
样运行。

ii. Tests to confirm upper and lower operating
limits, and /or “worst case”
conditions.
ii.
对其上下操作线或最差工况进行测试。

3.12. The completion of a successful OQ should allow the finalisation of
standard operating and cleaning procedures, operator training and
preventative maintenance requirements.
3.12.
成功的完成
OQ
后，就可以进行标准操作规程、清洁规程、员工 培训、
预防性维护的最终定稿。

Performance qualification (PQ)

性能确认（
PQ
）

3.13. PQ should normally follow the successful completion of IQ and OQ.
However, it may in some cases be appropriate to perform it in conjunction with
OQ or Process Validation.
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3.13.
性能确认一般是在安装确认和运行确认成功完成之后。但是，在有些情
况 下，也可以将其与运行确认或工艺验证合并进行。

3.14. PQ should include, but is not limited to the following:
3.14.
性能确认包括但不限于以下内容：

i. Tests, using production materials, qualified substitutes or simulated product
proven to have equivalent behaviour under normal operating conditions with
worst case batch sizes. The frequency of sampling used to confirm process
control should be justified;
i.
设备使用生产物料、合格替代物或模拟产 品在最差批量工况的正常操作
条件下进行测试，被证明具有等同表现。工艺控制的取样频次应当经过充分
证明。

ii. Tests should cover the operating range of the intended process, unless
documented evidence from the development phases confirming the
operational ranges is available.
ii.
测试应覆盖预期工艺的操作范围，除非有文件证明在研发阶段确认过操
作范围。

4. RE-QUALIFICATION

4.
再确认

4.1. Equipment, facilities, utilities and systems should be evaluated at an
appropriate frequency to confirm that they remain in a state of control.
4.1.
应当对设备、设施、公用工程和系统保持合适的评估频率，以确保其依然在
受控状态。

4.2. Where re-qualification is necessary and performed at a specific time
period, the period should be justified and the criteria for evaluation defined.
Furthermore, the possibility of small changes over time should be assessed.
4.2.
如果需要在一个特定时间周期内进行再验证，则应对该时间周 期进行论证，
并确定评估的标准。此外，应评估随着时间推移产生小变更的可能性。

5. PROCESS VALIDATION

5.
工艺验证

General

通则

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5.1. The requirements and principles outlined in this section are applicable to
the manufacture of all pharmaceutical dosage forms. They cover the initial
validation of new processes, subsequent validation of modified processes, site
transfers and ongoing process verification. It is implicit in this annex that a
robust product development process is in place to enable successful process
validation.
5.1.
本节 提出的要求和原则适用于所有药品剂型，包括新工艺的初次验证、工艺
变更后的验证、
现场转移 及持续的工艺验证。
本附录认为一个成熟稳定的研发工
艺有助于确保工艺验证的成功。

5.2. Section 5 should be used in conjunction with the current EMA guideline on
Process Validation.
5.2.
第五节应该和现行的欧洲药品局关于工艺验证的指南联合使用。

5.2.1. The guideline on Process Validation is intended to provide guidance on
the information and data to be provided in the regulatory submission only.
However GMP requirements for process validation continue throughout the
lifecycle of the process
5.2.1.
本工艺验证指南仅仅为提交给药政当局的相关 信息和数据提供指导。然
而，
GMP
对工艺验证的要求依然是贯穿于工艺的整个生命周 期。

5.2.2. This approach should be applied to link product and process
development. It will ensure validation of the commercial manufacturing
process and maintenance of the process in a state of control during routine
commercial production.
5.2.2.
本方法适用于关联 产品和工艺开发，它可以确保商业化的生产工艺和工
艺维护在商业化生产期间处于受控状态。

5.3. Manufacturing processes may be developed using a traditional approach
or a continuous verification approach. However, irrespective of the approach
used, processes must be shown to be robust and ensure consistent product
quality before any product is released to the market. Manufacturing processes
using the traditional approach should undergo a prospective validation
programme, wherever possible, prior to certification of the product.
Retrospective validation is no longer an acceptable approach.
5.3.
可以使用传统方法或持续改进的方法对生产工艺进行开发。但是，不管使用
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何种方法，工艺都必须是成熟稳 定的，并确保在产品上市之前其质量的一致性。
使用传统方法开发的生产工艺在产品放行前都应当经过前 验证。
回顾性验证不再
是可接受的方式。

5.4. Process validation of new products should cover all intended marketed
strengths and sites of manufacture. Bracketing could be justified for new
products based on extensive process knowledge from the development stage
in conjunction with an appropriate ongoing verification programme.
5.4.
新产品的工艺验证应当包括所有计划上市的规格和生产场所。
基于开发阶段
大量的工艺知识，
结合适当的正在进行中的验证程序，
新产品可以经过论证采用
界定法。

5.5. For process validation of products which are transferred from one site to
another or within the same site, the number of validation batches could be
reduced by the use of a bracketing approach. However, existing product
knowledge, including the content of the previous validation, should be
available. Different strengths, batch sizes and pack sizes/container types may
also use a bracketing approach, if justified.
5.5.
对于 同一地点内或者两个不同地点之间的场地转移的工艺验证，
可以使用界
定法减少验证批次。但是 ，必须保证现有的产品知识（包括上一次的验证内容）
可用。不同之处在于，可以使用界定法决定批量、 包装规格、包装容器类型。

5.6. For the site transfer of legacy products, the manufacturing process and
controls must comply with the marketing authorisation and meet current
standards for marketing authorisation for that product type. If necessary,
variations to the marketing authorisation should be submitted.
5.6.
对于 老产品的生产地址转移
,
生产工艺和控制应符合上市监督管理要求，
产品
类型 应符合相应的现行上市标准。必要的时候还应当提交上市许可的变更。

5.7. Process validation should establish whether all quality attributes and
process parameters, which are considered important for ensuring the validated
state and acceptable product quality, can be consistently met by the process.
The basis by which process parameters and quality attributes were identified
as being critical or non-critical should be clearly documented, taking into
account the results of any risk assessment activities.
5.7.
工艺验证应 当证明是否所有的质量属性和工艺参数
（被认为可以确保验证状
态和产品质量的重要项目）能够与工艺持续相符。
应当根据风险评估的结果，
在
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文件中明确哪些工艺参数和质量属性是关键的或者不关键的。

5.8. Normally batches manufactured for process validation should be the same
size as the intended commercial scale batches and the use of any other batch
sizes should be justified or specified in other sections of EudraLex, Volume 4.
5.8.
工艺验证批次与计划商业化生产的上市批次的批量应保持一致，
使用其他批
量应按照第四卷其他部分相关的要求进行评估和说明。

5.9. Equipment, facilities, utilities and systems used for process validation
should be qualified. Test methods should be validated for their intended use.
5.9.
设备、设施、公用工程和系统在工艺验证前应经过确 认，预定用途的检验方
法应经过验证。

5.10. For all products irrespective of the approach used, process knowledge
from development studies or other sources should be accessible to the
manufacturing site, unless otherwise justified, and be the basis for validation
activities.
5.10.
与所使用的方法无关，除非经过其他评估，所 有产品在研发阶段或者其
它来源的工艺知识应当被生产工厂做接收，并作为验证活动开展的基础。

5.11. For process validation batches, production, development, or other site
transfer personnel may be involved. Batches should only be manufactured by
trained personnel in accordance with GMP using approved documentation. It
is expected that production personnel are involved in the manufacture of
validation batches to facilitate product understanding.
5.11.
对于工艺验证批而言，
生产、
研发或者其他现场转移的人员均需要参加。
验证批次必须由按照
GMP
文件规定培训合 格的人员进行生产，
这样有助于生产
人员通过工艺验证批次生产加深对工艺的理解。

5.12. The suppliers of critical starting and packaging materials should be
qualified prior to the manufacture of validation batches; otherwise a
justification based on the application of quality risk management principles
should be documented.
5.12.
在工艺验证开始之前， 应审核起始物料、包装材料的供应商，以确定其
资质。否则，应当根据风险管理的原则来证明不这样做的 理由。

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5.13. It is especially important that the underlying process knowledge for the
design space justification (if used) and for development of any mathematical
models (if used) to confirm a process control strategy should be available.
5.13.
需要特别强调的是，
基于设计空间
（如有使用）
和工艺开发数学模型
（如
有使用）的基础知识确定的工艺控制策略是可 接受的。

5.14. Where validation batches are released to the market, this should be
pre- defined. The conditions under which they are produced should fully comply
with GMP, with the validation acceptance criteria, with any continuous process
verification criteria (if used) and with the marketing authorisation or clinical trial
authorisation.
5.14.
验证 批上市之前，
应确定产品的生产环境应完全符合
GMP
、
验证可接受
标准、持续工艺确认标准（如有使用），并获得上市许可或临床许可。

5.15. For the process validation of investigational medicinal products (IMP),
please refer to Annex 13.
5.15.
临床试验用药品（
IMP
）的工艺验证，参见附录
13
。

Concurrent validation

同步验证

5.16. In exceptional circumstances, where there is a strong benefit-risk ratio for
the patient, it may be acceptable not to complete a validation programme
before routine production starts and concurrent validation could be used.
However, the decision to carry out concurrent validation must be justified,
documented in the VMP for visibility and approved by authorised personnel.
5.16.
在特殊情况下，如果对患者利益明显大于风险，允许在常 规商业化生产
前没有完成验证程序而使用同步验证。
然而，
进行同步验证的决定必须进 行论证，
并在验证主计划中明确，且经被授权的人批准。

5.17. Where a concurrent validation approach has been adopted, there should
be sufficient data to support a conclusion that any given batch of product is
uniform and meets the defined acceptance criteria. The results and conclusion
should be formally documented and available to the Qualified Person prior to
certification of the batch.
5.17.
当采用同步验证的时候，
应有足够数据支持做出
“
批次 间产品是均一的且
符合预定可接受标准
”
的结论。结果和结论应进行正式记录，并在批 放行前通过
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质量授权人审核。

Traditional process validation

传统工艺验证

5.18. In the traditional approach, a number of batches of the finished product
are manufactured under routine conditions to confirm reproducibility.
5.18.
在传统方式中，
需要在正常条件下生产出很多批成品才能确认其重现性。

5.19. The number of batches manufactured and the number of samples taken
should be based on quality risk management principles, allow the normal
range of variation and trends to be established and provide sufficient data for
evaluation. Each manufacturer must determine and justify the number of
batches necessary to demonstrate a high level of assurance that the process
is capable of consistently delivering quality product.
5.19.
生产批次数和取样样品数量都应基于质量风 险管理的原则，如果能够提
供足够的数据进行评估，
允许规定变动和趋势的范围。
生产 商需要确定和交代必
须生产多少批次才可以表明工艺能够持续生产出优质产品的高水平保证度。

5.20. Without prejudice to 5.19, it is generally considered acceptable that a
minimum of three consecutive batches manufactured under routine conditions
could constitute a validation of the process. An alternative number of batches
may be justified taking into account whether standard methods of manufacture
are used and whether similar products or processes are already used at the
site. An initial validation exercise with three batches may need to be
supplemented with further data obtained from subsequent batches as part of
an on-going process verification exercise.
5.20.
一般来说，
在不违背
5.19
的情况下，
正常生产条件下至少连续生 产三个
批次可被认为满足工艺验证要求。
若使用其他批次数，
需从该场地是否使用标准
操作方法、
是否有类似产品或工艺进行评估。
初次的三批验证可能需要后续足够
批次生产数据来补充，并作为连续工艺确认的一部分。

5.21. A process validation protocol should be prepared which defines the
critical process parameters (CPP), critical quality attributes (CQA) and the
associated acceptance criteria which should be based on development data or
documented process knowledge.
5.21.
应准备工艺验证方案，根据研发数据或工艺知识明确关键工艺参数、关
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