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EU GMP 附录 13 临床试验用人药 GMP 指南

Guidelines

指南（定稿）

Detailed Commission guidelines on good manufacturing practice for investigational medicinal products for human use,
pursuant to the second subparagraph of Article 63(1) of Regulation (EU) No 536/2014

依据法规 EU 536/2014 第 63（1）条第二段，对人用临床试验药品制订的 GMP 详细指南。

英文 PDF 官网下载链接：

https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-10/guideline_adopted_1_en_act_part1_v3.pdf

发布日期：2017 年 12 月 8 日

实施日期：临床试验法规 (EU) No 536/2014 生效日起

译文仅供参考

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INTRODUCTION 概述

These guidelines are based on the second subparagraph of Article 63(1) of Regulation (EU) No 536/2014.

本指南基于法规 EU 536/2014 第 63（1）条第二段。

These guidelines complement Commission Delegated Regulation (EU) 2017/1569 of 23 May 2017 supplementing
Regulation (EU) No 536/2014 on the good manufacturing practice for investigational medicinal products for human use and
arrangements for inspections that has as its legal basis the first subparagraph of Article 63(1) of Regulation (EU) No
536/2014.

本指南补充 2017 年 5 月 23 日的托管法案 EU 2017/1569，该法案是对 EU 536/2014 对人用临床试验药品的 GMP

方面以及检查安排方面的增补，其法律基础是法规 EU 536/2014 第 63（1）条。

These guidelines lay down appropriate tools to address specific issues concerning investigational medicinal products with
regard to good manufacturing practice. The tools are flexible to provide for changes as knowledge of the process increases
and appropriate to the stage of development of the product.

本指南提供适当的工具来解决关于临床试验药品在 GMP 方面的特定问题。这些工具随着工艺知识增长灵活可变，

并且适合于药品研发的不同阶段。

An investigational medicinal product is defined in Article 2(5) of Regulation (EU) No 536/2014 as a medicinal product which
is being tested or used as a reference, including as a placebo, in a clinical trial and manufacturing is defined as total and
partial manufacture, as well as the various processes of dividing up, packaging and labelling (including blinding) in Article
2(24) of that Regulation.

临床试验药品的定义在法规 EU 536/2014 中定义为临床试验中的试验用药或用作对比的药品，包括空白药；生产

则定义为法规第 2（24）条中的全部和部分生产，以及分割、包装和贴标（包括设盲）的不同工艺操作。

Article 63(1) of Regulation (EU) No 536/2014 provides that investigational medicinal products shall be manufactured by
applying manufacturing practice which ensures the quality of such medicinal products in order to safeguard the safety of the
subject and the reliability and robustness of clinical data generated in the clinical trial ("good manufacturing practice").

法规 EU 536/2014 第 63（1）条要求临床试验药品应在确保此药品质量的生产规范下生产，以保护试验对象的安
全，确保临床试验中产生的临床数据可靠性和稳健性（GMP）。

Good manufacturing practice for investigational medicinal products is set out in Commission Delegated Regulation (EU) No
2017/1569 and in these guidelines.

临床试验药品的优良生产规范在托管法规 EU2017/1569 中和本指南中规定。

Furthermore, where applicable, the manufacturers and the competent authorities should also take into account the detailed
guidelines referred to in the second paragraph of Article 47 of Directive 2001/83/EC , published by the Commission in the
"Guide to good manufacturing practice for medicinal products and for investigational medicinal products" (EudraLex,
Volume 4). Examples of applicable parts of EudraLex, Volume 4 to investigational medicinal products, not specifically
mentioned in these guidelines, are Part I, Chapters 2, and 6, and Part III.

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另外，在适用时，生产商和官方药监机构还应考虑指令 2001/83/EC 第 47 条第二段的详细指南，该指南是由 EC

在“药品和临床试验药品优良生产规范指南”（欧盟药事法第 4 卷）中发布的。欧盟药事法第 4 卷中对临床试验
药品的适用部分例子有第一部分第 2 章和第 6 章以及第三部分，这些内容在本指南中不再特别提及。

With regard to EudraLex, Volume 4, Part II, it should be noted that Regulation (EU) No 536/2014 does not lay down
requirements for good manufacturing practice for active substances of investigational medicinal products. However, if a
clinical trial is to be used to support the application for a marketing authorisation, Part II of EudraLex, Volume 4 would need
to be considered.

关于欧盟药事法第 4 卷第二部分，要注意的是法规 EU 536、2014 并不规定临床试验药品中活性物质的 GMP 要求。

但是，如果一个临床试验用以支持一份上市许可申报，则需要考虑欧盟药事法第 4 卷第二部分。

Procedures need to be flexible to provide for changes as knowledge of the process increases and appropriate to the stage
of development of the products.

程序需要具有灵活性，在工艺知识增长时可以进行变更，使其适合于药品的不同研发阶段。

In clinical trials there may be added risk to the subjects compared to patients treated with authorised medicinal products.
The application of good manufacturing practice for the manufacture and import of investigational medicinal products is
intended to ensure that subjects are not placed at undue risk, and that the results of clinical trials are unaffected by
inadequate quality, safety or efficacy arising from unsatisfactory manufacture or import. Equally, it is intended to ensure that
there is consistency between batches of the same investigational medicinal product used in the same or different clinical
trials and that changes during the development of an investigational medicinal product are adequately documented and
justified.

在临床试验中，相比于采用经批准的药品治疗的患者，受试对象可能会承担更多的风险。临床试验药品的生产和
进口所用 GMP 申报意在确保受试对象不会受到不恰当的风险危害，临床试验的结果不会受到由于生产或进口操
作不当而导致的质量、安全或有效性不充分而产生的影响。同样，还为了确保相同或不同的临床试验所用临床试
验药品不同批次之间的一致性，在临床试验药品研发期间的任何变更都要有充分的文件记录和论证。

The production of investigational medicinal products involves added complexity in comparison with authorised medicinal
products by virtue of lack of fixed routines, variety of clinical trial designs and consequent packaging designs.
Randomisation and blinding add to that complexity an increased risk of product cross-contamination and mix-up.
Furthermore, there may be incomplete knowledge of the potency and toxicity of the product and a lack of full process
validation. Moreover, authorised products may be used which have been re-packaged or modified in some way. These
challenges require personnel with a thorough understanding of and training in the application of good manufacturing
practice to investigational medicinal products. The increased complexity in manufacturing operations requires a highly
effective quality system.

相比于经过批准的药品，由于缺乏固定的常规管理，临床试验设计有差异，以及之后的包装设计有差异，临床试
验药品的生产有更高复杂性。随机抽取和设盲也对其复杂性增加了产品的交叉污染和混淆风险。另外，可能对于
药品的效价和毒性知识还不完整，缺乏全面工艺验证。还有，经批准的药品在重新包装或某种方式修改后可能仍
能使用。这些挑战需要人员对临床试验药品中 GMP 适用性具备有全面的理解和培训。生产操作的额外复杂性要
求更高效的质量体系。

For manufacturers to be able to apply and comply with good manufacturing practice for investigational medicinal products,
co-operation between manufacturers and sponsors of clinical trials is required. This co-operation should be described in a

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technical agreement between the sponsor and manufacturer, as referred to in recital 4 of Delegated Regulation 62 (EU) No
2017/1569.

对于有能力实施和符合临床试验药品 GMP 的生产商，生产商和临床试验申办人之间需要合作。此合作应在申办

人与生产商的技术协议中依托管法规 62 (EU) No 2017/1569 进行描述。

1 SCOPE 范围

These guidelines apply to manufacture or import of investigational medicinal products for human use.

本指南适用于人用临床试验用药品的生产和进口。

For advanced therapy investigational medicinal products, Article 16 of Commission Delegated Regulation (EU) No
2017/1569 states that the requirements of good manufacturing practice shall be adapted to the specific characteristic of
such products in accordance with a risk-based approach and consistent with good manufacturing requirements applicable
to authorised advanced therapy medicinal products. Those adaptations are addressed in the Guidelines on good
manufacturing practice for advanced therapy medicinal products. Therefore, these detailed guidelines on good
manufacturing practice for investigational medicinal products for human use do not apply to manufacture or import of
advanced therapy investigational medicinal products.

对于先进治疗临床试验药品，托管法案 EU 2017/1569 第 16 条声明 GMP 对该类药品的适用性应基于风险的方法，

并与批准的先进治疗药品的适用 GMP 要求相一致。这些 GMP 要求适用情况在先进治疗药品 GMP 指南中说明。
因此，本指南中人药临床试验药品 GMP 指南不适用于先进治疗临床药品的生产和进口。

Reconstitution of investigational medicinal products is not considered manufacturing, and therefore is not covered by this
guideline.

临床试验药品的重新调配不认为是生产，因此，不包括在本指南范围中。

The reconstitution is understood as the simple process of dissolving or dispersing the investigational medicinal product for
administration of the product to a trial subject, or diluting or mixing the investigation medicinal product with some other
substance(s) used as a vehicle for the purpose of administering it to a trial subject.

重新调配被理解为对临床试验药品在给试验对象使用时简单的溶解或分散过程，或者是采用一些其它物质稀释或
混合作为载体，其目的是为了给试验对象摄入临床试验药品。

Reconstitution is not mixing several ingredients, including the active substance, together to produce the investigational
medicinal product. An investigational medicinal product must exist before a process can be defined as reconstitution.

重新调配并不是混合几种成分，包括活性成分，一起生成临床试验药品。一个临床试验药品必须是在此之前就已
存在，之后的过程才能定义为重新调配。

The process of reconstitution has to be undertaken as close in time as possible to administration and has to be defined in
the clinical trial application dossier and document available at the clinical trial site.

重新调配的过程必须尽可能在接近使用时间时操作，必须在临床试验申报资料中指定，在临床试验场所必须可以
获得该文件。

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These guidelines do not apply to the processes referred to in Article 61(5) of Regulation (EU) No 536/2014. Member States
should make those processes subject to appropriate and proportionate requirements to ensure subject safety and reliability
and robustness of the data generated in the clinical trial.

本指南不适用于法规 EU 536/2014 第 61（5）条中所指的过程。成员国应对这些过程制订适当的要求，以确保试

验对象的安全性，以及在临床试验中所生成数据的可靠性和稳健性。

2 PHARMACEUTICAL QUALITY SYSTEM 药物质量体系

The pharmaceutical quality system required of the manufacturer according to Article 5 of Commission Delegated
Regulation (EU) No 2017/1569 and designed, set-up and verified by the manufacturer should be described in written
procedures taking into account EudraLex, Volume 4, Part I, Chapter 1, as applicable, to investigational medicinal products.

临床试验药品生产商应依据托管法案 EU 2017/1569 第 5 条的要求，同时考虑欧盟药事法第 4 卷第 1 部分第 1 章的

要求，在书面程序中设计、设置和核对其所需的药物质量体系。

The product specifications and manufacturing instructions may be changed during development but full control and
traceability of the changes should be documented and maintained. Deviations from any predefined specifications and
instructions should be registered, investigated and corrective and preventive action measures initiated as appropriate.

在研发期间，可以变更产品标准和生产指令，但变更的全面控制及可追溯性应有文件记录并保存。所有偏离既定
标准和指令的偏差均应登记、调查，适当时启动纠正和预防措施。

The selection, qualification, approval and maintenance of suppliers of starting materials, together with their purchase and
acceptance, should be documented as part of the pharmaceutical quality system to ensure the integrity of the supply chain
and protect against falsified products. The level of supervision should be proportionate to the risks posed by the individual
materials, taking into account their source, manufacturing process, supply chain complexity and the final use to which the
material is put in the investigational medicinal product. The supporting evidence for each supplier approval and material
approval should be documented and maintained.

起始物料供应商的选择、确认、批准和维护，以及起始物料的采购和接收均应有文件记录作为药物质量体系的一
部分，以确保供应链的完整性，保护不受假药危害。监管的水平应与各物料所具有的风险水平相当，同时考虑其
来源、生产工艺、供应链复杂性和物料在临床试验用药品生产中的最终用途。每个供应商批准和物料批准的支持
性证据应有书面记录并保存记录。

2.1 Product specification file 产品标准文件

Products specification file, in light of Article 2(3) of Commission Delegated Regulation (EU) No 2017/1569, brings
together and contains all of the essential reference documents to ensure that investigational medicinal products are
manufactured according to good manufacturing practice for investigational medicinal products and the clinical trial
authorisation. The products specification files is one of the essential elements of pharmaceutical quality system.

产品标准文件，依据托管法案 2017/1569 第 2（3）条，是将所需的参考文件放在一起整合，以确保临床试验药品

的生产符合临床试验药品的 GMP 要求，以及临床试验批件要求。产品标准文件是药物质量体系的基本要素之一。

Applicable sections of the product specification file should be available at the start of manufacturing of the first batch of
investigational medicinal product for a clinical trial.

产品标准文件的适应部分应在第一批临床试验药品生产开始时就能获得。

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The product specification file should be continually updated as development of the product proceeds, ensuring appropriate
traceability to the previous versions. It should include or refer to at least the following documents:

当药品研发向前推进时，产品标准文件应持续更新，同时确保对历史版本的适当可追溯性。文件应包括或引用至
少以下文件：

i. Specifications and analytical methods for starting materials, packaging materials, intermediate product, bulk product
and finished product;

起始物料、包装材料、中间产品、散装产品和成品的质量标准和分析方法

ii. Manufacturing methods;

生产方法

iii. In-process testing and methods;

中控检测和方法

iv. Approved label copy;

批准过的标签副本

v. Relevant clinical trial authorisations and amendments thereof, clinical trial protocol and randomisation codes, as
appropriate;

相关临床试验批件及其补充件、临床试验方案和随机代码（适当时）

vi. Relevant technical agreements with contract givers and acceptors, as appropriate;

适当时，与委托方或受托方之间的相关技术协议

vii. Stability plan and reports;

稳定性计划和报告

viii. Details of plans and arrangements for reference and retention samples;

对照品和留样的详细计划和安排

ix. Storage and transport conditions;

运输和存贮条件

x. Details of the supply chain including manufacturing, packaging, labelling and testing sites for the investigational
medicinal products, preferably in the format of a comprehensive diagram.

供应链的详细信息，包括临床试验药品的生产、包装、标签和检测场所，最好是以综合图形的格式呈现

This list of documents is neither exhaustive nor exclusive.

上述文件清单并不是完全的。

The contents of the product specification file will vary depending on the product and the stage of development.

产品标准文件的内容依据产品及开发所处的阶段不同而不同。
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Where different manufacturing steps are carried out at different locations under the responsibility of different qualified
persons, it is acceptable to maintain separate files limited to information of relevance to the activities at the respective
locations. The manufacturing site should have access to the necessary documentation of the product specification file,
including changes, to enable the relevant activities to be performed.

如果不同的生产步骤在不同的地方执行，由不同的 QP 管理，则可以接受在相对应的地方只保存与该处所执行活
动有关的有限文件。生产场所应可以获得必要的生产标准文件，包括变更，以保证能够实施相关活动。

3 PERSONNEL 人员

The requirements as regards the personnel are defined in Article 6 of Commission Delegated Regulation (EU) No
2017/1569. The EudraLex, Volume 4, Part I, Chapter 2 should also be taken into account as appropriate.

人员的要求在托管法案 EU 2017/1569 第 6 条中已有规定。同时还要考虑欧盟药事法第 4 卷第一部分第 2 章中适用

的要求。

All personnel involved with the manufacture, import, storage or handling of investigational medicinal products should be
appropriately trained in the requirements specific to these types of product.

所有参与生产、进口、存贮和处置临床试验药品的人员均应接受过与这些产品类型有关的特定要求的适当培训。

Even where the number of staff involved in the manufacturing or import of investigational medicinal products is small, there
should be, for each batch, separate people responsible for production and quality control.

即使参与生产或进口临床试验药品的员工人数非常少，对于每个批次，仍应有单独的人员负责其生产和质量控
制。

The qualified person has to fulfil the conditions of qualification set out in Article 49(2) and (3) of Directive 2001/83/EC, as
per Article 61(2)(b) of Regulation (EU) No 536/2014.

QP 必须满足指令 2001/83/EC 第 49（2）和（3）条以及法规 536/2014 第 61（2）（b）中设定的资质条件。

The responsibilities of the qualified person are set out in Article 62 of Regulation (EU) No 536/2015 and further elaborated
in Article 12 of Commission Delegated Regulation (EU) No 2017/1569.

QP 的职责在法规 EU 536/2015 第 62 条中已经设定，并在托管法案 EU 2017/1569 第 12 条中有进一步说明。

The qualified person that certifies the finished batch of investigational medicinal products for use in the clinical trial should
ensure that there are systems in place that meet the requirements of good manufacturing practice and should have a broad
knowledge of pharmaceutical development, clinical trial processes and supply chain of the batch concerned.

认证临床使用药品制剂批次的 QP 应确保具备有符合 GMP 要求的系统，并应具备药物开发、临床试验流程和相

关批次供应链的广泛知识。

4 PREMISES AND EQUIPMENT 设施和设备

The toxicity, potency or sensitising potential may not be fully understood for investigational medicinal products and this
reinforces the need to minimise all risks of cross-contamination. The design of equipment and premises, inspection/test
methods and acceptance limits to be used after cleaning should reflect the nature of these risks and take account of the
quality risk management principles detailed in EudraLex, Volume 4, Part I, Chapters 3 and 5.

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对于临床试验药品来说，其毒性、效价和潜在过敏情况可能并不完全了解，这就增加了尽可能减少所有交叉污染
风险的需求。设备和设施的设计、准备在清洁之后使用的检查/测试方法和可接受限度均应反映出这些风险的属
性，并考虑欧盟药事法第 4 卷第一部分第 3 章和第 5 章中的质量风险管理原则。

Consideration should be given to campaign manufacturing, where appropriate. Account should be taken of the solubility of
the product in decisions about the choice of cleaning solvent.

适当时应考虑周期生产。在确定清洁剂选择时应考虑产品的可溶性。

A quality risk management process, which includes a potency and toxicological evaluation, should be used to assess and
control the cross-contamination risks presented by the investigational medicinal products manufactured. Factors that
should be taken into account include:

质量风险管理流程，包括效价和毒性评估，均应用于评估和控制临床药品生产中呈现的交叉污染风险。应包括的
因素包括：

i. facility/equipment design and use;

设备/设备设计和使用

ii. personnel and material flow;

人流和物流

iii. microbiological controls;

微生物控制

iv. physio-chemical characteristics of the active substance;

活性物质的理化特性

v. process characteristics;

工艺特性

vi. cleaning processes;

清洁工艺

vii. analytical capabilities relative to the relevant limits established from the evaluation of the
investigational medicinal products.

分析能力相对于临床药品评估中所建立的相关限度

Premises and equipment are expected to be qualified in accordance with EudraLex, Volume 4, Annex 15.

设施和设备应依据欧盟药事法第 4 卷附录 15 进行确认。

5 DOCUMENTATION 文件记录

Documentation should be generated and controlled in line with the principles detailed in EudraLex, Volume 4, Part I,
Chapter 4. The retention period for instructions and records required to demonstrate compliance with good manufacturing
practice should be defined according to the type of document while complying with the requirement of Article 8 of

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Commission Delegated Regulation (EU) No 2017/1569, where relevant. In line with Article 8(1) of the above mentioned
Delegated Regulation the documentation shall be consisted with the Product Specification File. Documents which are part
of the Products Specification File shall be retained for the period of at least 5 years as required by Article 8(3) of the
Delegated Regulation.

文件记录应按欧盟药事法第 4 卷第一部分第 4 章中详细说明的原则制订和受控。指令和记录的保存期限应依据文

件类型确定，如有关，同时还应符合托管法案 EU 2017/1569 第 8 条的要求。依据上述托管法规第 8（1）条规定，
文件应与产品标准文件保持一致。依托管法案第 8（3）的要求，作为产品标准文件的一部分的文件应保存至少 5
年。

The sponsor has specific responsibilities for document retention of the clinical trial master file according to Article 58 of
Regulation (EU) No 536/2014 and is required to retain such documentation for at least 25 years after the end of the trial. If
the sponsor and the manufacturer are not the same entity, the sponsor has to make appropriate arrangements with the
manufacturer to fulfil the sponsor’s requirement to retain the clinical trial master file. Arrangement for retention of such
documents and the type of documents to be retained should be defined in an agreement between the sponsor and
manufacturer.

依据法规 EU 536/2014 第 58 条，申办人对于临床试验主文件的文件保存负有特定的责任，其应保存此文件至试验

结束后至少 25 年。如果申办人和生产商不是同一实体，则申办人必须与生产商做出适当安排来满足申办人保存
临床试验主文件的要求。此类文件保存的安排及需要保存的文件类型应在申办人和生产商之间的协议中规定。

5.1 Specification and instructions 标准和指令

Specifications for starting materials, immediate packaging materials, intermediate products, bulk products and finished
products, manufacturing formulae and processing and packing instructions should be as comprehensive as possible given
the current state of knowledge. They should be re-assessed during development and updated as necessary. Each new
version should take into account the latest data, current technology used, regulatory and pharmacopoeial developments
and should allow traceability to the previous document. Any changes should be carried out according to a written procedure
which should address any implications for product quality such as stability and bioequivalence. The approval process for
instructions and changes thereof shall include responsible personnel at the manufacturing site.

起始物料、内包材、中间体、散装成品和包装完的成品的标准、生产处方和工艺以及包装指令均应依据当前知识
状态尽可能全面。必要时，在药品研发期间应进行评估和更新。每个新版本均应考虑最新数据、当前所用技术、
法规和药典发展，应保持对历史文件的可追溯性。所有变更均应按照书面程序实施，其中应说明所有对药品质量
的可能影响，如稳定性和生物等效性。指令和变更的批准流程应包括生产场所的负责人。

Rationales for changes should be recorded and the consequences of a change on product quality and on any on-going
clinical trials should be investigated and fully documented.

变更的合理性应记录，变更对于产品质量和任何正在进行中的临床试验所产生的后果应进行调查并全面记录。

5.2 Order 订单

The manufacturer should retain the order for investigational medicinal products as part of the batch documentation. The
order should request the processing and/or packaging of a certain number of units and/or their distribution and be given by
or on behalf of the sponsor to the manufacturer. The order should be in writing, though it may be transmitted by electronic
means, and be precise enough to avoid any ambiguity. It should be formally authorised by the sponsor or his representative
and refer to the product specification file and the relevant clinical trial protocol as appropriate.

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生产商应保存临床试验药品的订单作为批文件的一部分。订单中应要求生产和/或包装指定数量单位和/或其销售，
由生产商的申办人或其代表发出。订单应为书面方式，可以采用电子方式传送，必须足够明确以避免模糊。应由
申办人或其代表正式批准，并引用产品标准文件和相关的临床试验方案（适当时）。

5.3 Manufacturing formulae and processing instructions 生产处方和加工指令

For every manufacturing operation or supply there should be clear and adequate written instructions and written records
which are prepared using the specific clinical study information detailed in the product specification file. Records are
particularly important for the preparation of the final version of the documents to be used in routine manufacture once the
marketing authorisation is granted.

对于每个生产操作或供应而言，均应有清楚和足够的书面指令和书面记录。指令和记录应使用产品标准文件中特
定的临床研究信息制订。对于常规生产所用文件的最终版本制订而言，一旦上市许可被批准，记录尤其重要。

The relevant information in the product specification file should be used to draft the detailed written instructions on
processing, packaging, quality control testing, and storage, including storage conditions.

产品标准文件中的相关信息应被用来起草详细的加工、包装、质量控制测试和存贮书面指令，包括存贮条件。

5.4 Packaging instructions 包装指令

Investigational medicinal products are normally packed in an individual way for each subject included in the clinical trial.
The number of units to be packaged should be specified prior to the start of the packaging operations, including units
necessary for carrying out quality control and for any retention samples to be kept. Sufficient reconciliations should take
place to ensure that the correct quantity of each product required has been accounted for at each stage of processing.

临床试验药品一般是为临床试验中每个对象采用单独包装方式。要包装的单位数量应在开始包装操作之前即指定，
包括进行质量控制和留样所需的数量。应进行足够的数量衡算以确保每个工艺阶段所需的每个药品的数量都计算
在内且数量正确。

Procedures should describe the specification, generation, testing, security, distribution, handling and retention of any
randomisation code used for packaging investigational medicinal products as well as code-break mechanism. Appropriate
records should be maintained.

程序应描述所有临床试验药品包装所用的所有随机编码的标准、生成、测试、安全、流通、处理和保存，以及断
码机制。应保存适当记录。

5.5 Batch records 批记录

Batch records should be kept in sufficient detail for the sequence of operations to be accurately determined. These records
should contain any relevant remarks which justify procedures used and any changes made, enhance knowledge of the
product, develop the manufacturing operations and document deviations from predefined requirements.

批记录应保存有准确确定的足够详细的操作序列。这些记录应包含有所有相关备注，在其中论证所用程序和所做
变更，增加产品知识，建立生产操作和文件与预定要求的偏差。

Batch manufacturing records should be retained by the manufacturer for at least 5 years after the completion or formal
discontinuation of the last clinical trial in which the batch was used as set out in Article 8(3) of Commission Delegated
Regulation (EU) No 2017/1569.

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依据托管法案 EU2017/1569 第 8（3）条，批生产记录应由生产商保存至使用该批次的最后一个临床试验结束或

正式中止之后 5 年。

6 PRODUCTION 生产

6.1 Packaging materials 包材

Specifications and quality control checks should include measures to guard against unintentional unblinding due to
changes in appearance between different batches of packaging materials.

标准和质量控制检查应包括措施防止由于包材不同批次之间外观变化而无意揭盲。

6.2 Manufacturing operations 生产操作

During development critical parameters should be identified and in-process controls primarily used to control the process.
Provisional production parameters and in- process controls may be deduced from prior experience, including that gained
from earlier development work. Careful consideration by key personnel is called for in order to formulate the necessary
instructions and to adapt them continually to the experience gained in production. Parameters identified and controlled
should be justifiable based on knowledge available at the time.

在研发中，应识别用以控制工艺的关键参数和中控。可以依之前的经验删减临时生产参数和中控，包括从早期研
发工作所获得的经验。为了制订出必要的指令，并持续使用这些指令来在生产中获得经验，关键人员应进行谨慎
的考量。所识别和控制的参数应能基于当时可以获得的知识进行论证。

In line with Article 9(3) of Delegated Regulation, the manufacturing process is not to be validated to the extent necessary for
routine production but shall be validated in its entirety, as far as is appropriate taking into account the stage of product
development. It should be documented in accordance with the requirements detailed in EudraLex, Volume 4, Annex 15.
Article 9(3) of Commission Delegated Regulation (EU) No 2017/1569 states also that the manufacturer shall identify the
process steps that safeguard the safety of the subject and the reliability and robustness of the clinical trial data generated in
the clinical study.

依据托管法案第 9（3）条，生产工艺不需要验证至常规生产的程度，但应考虑产品研发的阶段验证至适当的完
整程度。应依据欧盟药事法第 4 卷附录 15 中的详细要求进行文件记录。托管法案 EU2017/1569 第 9（3）条也指
出，生产商应识别其工艺步骤，保护试验对象的安全性，以及在临床研究中所生成临床数据的可靠性和稳健性。

To avoid cross-contamination, written cleaning procedures and analytical methods to verify the cleaning process should be
available.

为了避免交叉污染，应制订书面清洁程序和分析方法用以核查清洁工艺。

For sterile products, the validation of sterilising processes should be of the same standards as for authorised medicinal
products and take account of the principles for the manufacture of sterile medicinal products detailed EudraLex, Volume 4,
Annex 1. Likewise, when required, virus inactivation/removal and removal of other impurities of biological origin
should be demonstrated, to assure the safety of biotechnologically derived and biological products by following the
scientific principles and techniques defined in the available guidance in this area.

对于无菌药品，无菌工艺的验证应达到所批准的药品相同的标准，同时考虑欧盟药事法第 4 卷附录 1 中无菌药品

生产的原则。类似地，在需要时，病毒灭活/清除和其它生物来源杂质的清除应得到证明，以通过遵守科学原则
和该领域现有指南中定义的技术来确保生物技术衍生物和生物药品的安全性。

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Validation of aseptic processes presents special problems where the batch size is small; in these cases, the number of
units filled may be the maximum number filled in production. If practicable, and otherwise consistent with simulating the
process, a larger number of units should be filled with media to provide greater confidence in the results obtained. Filling
and sealing is often a manual or semi-automated operation presenting great challenges to sterility so enhanced
attention should be given to operator training and validating the aseptic technique of individual operators.

如果批量过小，无菌工艺的验证可能会有特殊问题，在此情况下，灌装单位数量可以是生产中的最大灌装数量。
如果可行，并且与工艺模拟相一致，应采用培养基灌装更大数量的单位，为所获得的结果提供更大可信度。灌装
和封口通常是手动或半自动操作，对于无菌性会是一个巨大的挑战，因此应提高对操作人员培训和单个操作人员
无菌技术验证的注意。

6.3 Modification of comparator products 对照药品的修改

If a product is modified, data should be available (e.g. Stability, comparative dissolution or bioavailability) to demonstrate
that these changes do not significantly alter the original quality characteristics of the product.

如果对药品进行了修改，则应获取数据（例如，稳定性、可比的溶出或生物利用度）来证明这些变更不会对药品
的原始质量属性造成重大改变。

The expiry date stated for the comparator product in its original packaging might not be applicable to the product where it
has been repackaged in a different container that may not offer equivalent protection, or be compatible with the product. A
suitable retest date, taking into account the nature of the product, the characteristics of the container and the storage
conditions to which the product may be subjected, should be determined by or on behalf of the sponsor. Such a date should
be justified and must not be later than the expiry date of the original package. There should be compatibility of expiry dating
and clinical trial duration.

如果对照药品采用不同容器重新包装，可能无法提供等同的保护，或与药品并不相容，则在其原始包装上所声称
的有效期可能不再适用。应结合药品的属性，容器的特性和药品可能经受的存贮条件，由申办人或其代表确定一
个适当的复验日期。此日期应经过论证，不得迟于原始包装上载明的有效期。有效期与临床试验时长应不冲突。

A reference sample of comparator product, which has been repackaged or over encapsulated for blinding purposes, should
be taken at a point representative of the additional processing and retained, as the additional processing step could have
an impact on stability or be needed for identification purposes in the event of a quality defect investigation, which would not
be covered by the commercial retained sample.

如果为了设盲的目的而将对照药品重新包装或重复套装胶囊，则应在额外加工和保存期间抽取代表性参比样品。
因为额外的加工步骤可能会对稳定性产生影响，或者在有质量缺陷调查时需要进行识别，而这些是在商业化留样
中所无法包括的。

6.4 Blinding operations 设盲操作

Where products are blinded, systems should be in place to ensure that the blind is achieved and maintained while allowing
for identification of "blinded" products, when necessary, including batch numbers of the products before the blinding
operation. Rapid identification of product should also be possible in an emergency. Where the manufacturer has been
delegated the responsibility for generation of randomisation codes, the manufacturer should enable that unblinding
information is available to the appropriate responsible investigator site personnel before investigational medicinal products
are supplied.

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如果药品需要被设盲，由应有体系确保达成并维持设盲目的，同时允许“设盲”的药品可以识别，必要时，包括设
盲操作之前的药品批号。紧急情况下还应可以进行药品的快速识别。如果生产商被委托执行随机赋码的工作，则
生产商应有保证具备适当职责的临床试验场所人员在临床药品提供之前可以获得揭盲信息。

Where products are blinded, the expiry date assigned should be stated at the expiry of the shortest dated product so that
the blinding is maintained.

如果药品被设盲，则应在最早到效期的药品效期时宣布所给定的有效期，以维护药品被盲状态。

6.5 Packaging 包装

During packaging of investigational medicinal products, it may be necessary to handle different products on the same
packaging line at the same time. The risk of product unintentional mixing (mix-ups) must be minimised by using appropriate
procedures and/or specialised equipment as appropriate and relevant staff training. Documentation must be sufficient to
demonstrate that appropriate segregation has been maintained during any packaging operations.

在临床药品包装期间，可能需要在相同包装线上同时处理不同药品。应采用适当的程序和/或专用设备（适当时）
和相关的员工培训来最大程度降低药品无意混淆的风险。应有足够的文件记录证明在所有包装操作中均维持有适
当的分隔。

Packaging and labelling of investigational medicinal products are likely to be more complex and more liable to errors which
are also harder to detect than for authorised medicinal products, particularly when blinded products with similar appearance
are used. Precautions against mislabelling such as reconciliation, line clearance, in- process control checks by
appropriately trained staff should accordingly be intensified.

相比批准上市的药品而言，临床药品的包装和标签可能会更复杂，更容易出错，也更难发现错误，尤其是当盲药
使用相似外观时，因此应相应强化由经过适当培训的员工进行物料衡算、清场、中控检查来防止错误标识。

The packaging must ensure that the investigational medicinal product remains in good condition during transport and
storage at intermediate destinations. Any opening or tampering of the outer packaging during transport should be readily
discernible.

包装必须确保临床试验药品在运输及中转站存贮过程中保持在良好状态。所有在运输期间打开或破坏外包装的情
况均应易于辨识。

Re-packaging operations may be performed by authorised personnel at a hospital, health centre or clinic that meet the
requirements of Article 61(5)(a) of Regulation (EU) No 536/2014.

重新包装的操作可以由经过授权的人员在符合法规 EU 536/2014 第 61（5）（a）条要求的医院、卫生中心或诊所

执行。

6.6 Labelling 标签

Labelling of investigation medicinal products shall comply with the requirements of Article 66, 67, 68 and 69 of Regulation
(EU) No 536/2014. A list of information which shall appear on the labelling is set out in Annex VI to the said Regulation. The
labelling operation should be performed at an authorised manufacturing site that complies with the requirements of Article
61(1) of Regulation (EU) No 536/2014.

临床试验药品的标签应符合法规 EU 536/2014 第 66、67、68 和 69 条的要求。标签上应出现的信息清单在上述法

规附录 VI 中已有规定。贴标操作应在符合法规 EU536/2014 第 61（1）条规定经批准的生产场所实施。

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If it becomes necessary to change the expiry date, an additional label should be affixed to the investigational medicinal
product. This additional label should state the new expiry date and repeat the batch number and clinical trial reference
number. It may be superimposed on the old expiry date, but for quality control reasons, not on the original batch number.

如果有必要修改有效期，应在临床试验药品上加贴一个标签。该加贴标签上应声明新的有效期，并重新写明批号
和临床试验索引编号。旧的有效期可以被覆盖掉，但为了质量控制的原因，不应覆盖掉原始的批号。

The re-labelling operation should be performed by appropriately trained staff in accordance with good manufacturing
practice principles and specific standard operating procedures and should be checked by a second person. This additional
labelling should be properly documented in the batch records. To avoid mistakes the additional labelling activity should be
carried out in an area which is partitioned or separated from other activities. A line clearance at the start and end of activity
should be carried out and label reconciliation performed. Any discrepancies observed during reconciliation should be
investigated and accounted for before release.

重新贴标的操作应由经过适当培训的员工依 GMP 原则和特定的标准操作程序执行，并由第二人检查。此额外贴

标操作应在批记录中进行恰当记录。为避免错误，额外加贴标签的操作应在与其它操作分开或隔断的区域执行。
操作前后应清场并对标签进行数量衡算。在衡算过程中发现的任何差异均应进行调查，并在放行前进行考虑。

The re-labelling operation may be performed by authorised personnel at a hospital, health centre or clinic that meet the
requirements of Article 61(5)(a) of Regulation (EU) No 536/2014.

重新贴标的操作可以由经过授权的人员在符合法规 EU 536/2014 第 61（5）（a）条要求的医院、卫生中心或诊所

执行。

7 QUALITY CONTROL 质量控制

According to Article 10 of Commission Delegated Regulation (EU) No 2017/1569, the manufacturer is required to establish
and maintain a quality control system placed under the authority of a person who has the requisite qualifications and is
independent of production.

依据托管法案 EU 2017/1569 第 10 条，生产商应在具备资质并独立于生产的人员授权下建立并维护质量控制体系。

As processes may not be standardised or fully validated, testing takes on more importance in ensuring that each batch
meets the approved specification at the time of testing.

由于工艺可能并未标准化或经过全面验证，在确保测试时每批均符合批准的质量标准中，检测有着更为重要的作
用。

Quality control of the investigational medicinal product, including comparator product, should be performed in accordance
with the information submitted according to Article 25 of Regulation (EU) No 536/2014, as authorised by the Member State.

临床药品包括对照药品的质量控制应依据按法规 EU 536/2014 第 25 条提交并由成员国批准的信息执行。

Verification of the effectiveness of blinding should be performed and recorded.

应核查设盲的有效性并记录。

Retention periods for samples of investigational medicinal products have to fulfil the requirements of Article 10(4) of
Commission Delegated Regulation (EU) No 2017/1569.

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临床试验药品样品的保存期限必须符合托管法案 EU 2017/1569 第 10（4）条的规定。

Samples are retained to fulfil two purposes: firstly, to provide a sample for future analytical testing, and secondly, to provide
a specimen of the finished investigational medicinal product which may be used in the investigation of a product quality
defect. Samples may therefore fall into two categories:

保留样品是为了两个目的：第一，为未来的分析检测提供样品，第二，为可能用于临床的药品的质量缺陷提供样
本。因此，样品被划分为两类：

? Reference sample: a sample of a batch of starting material, packaging material or finished product which is stored for
the purpose of being analysed should the need arise. Where stability permits, reference samples from critical intermediate
stages, e.g. those requiring analytical testing and release, or intermediates which are transported outside of the
manufacturer's control, should be kept.

? 对照样品：起始物料、包材或成品的各批次样品，保存目的是在有需求时进行分析。如果稳定性许可，关键
中间体阶段的对照样品，如需要进行分析测试和放行的中间体，或要运出生产商控制以外的中间体，应加以保存。

? Retention sample: a sample of a fully packaged unit from a batch of finished product. It is stored for identification
purposes. For example, presentation, packaging, labelling, package leaflet, batch number, expiry date should the need
arise during the shelf life of the batch concerned.

? 留样：成品各批次中抽取的完整包装的样品。保存目的是为了识别。例如，在相关批次货架期间需要核查外
观、包装、标签、包装说明书、批号、有效期。

There may be exceptional circumstances where this requirement can be met without retention of duplicate samples, e.g.
where small amounts of a batch are packaged for different markets or in the production of very expensive medicinal
products.

如有例外情形，可不需保留双份样品，例如，不同市场包装批量太小，或者是所生产药品非常昂贵。

For retention samples it is acceptable to store information related to the final packaging as written, photographic or
electronic records, if such records provide sufficient information, e.g. examples of packaging, labelling and any
accompanying documentation to permit investigations associated with the use of the product. In case of electronic records,
the system should comply with the requirements of EudraLex, Volume 4, Annex 11.

对于留样，与最终包装有关的存储信息可以是书面的、图片的和电子的记录，只要此类记录能提供足够的信息即
可，例如，包装、标签和所有随货文件记录的样例，以使得与药品使用有关的调查可以进行。如果采用电子记录，
则系统应符合欧盟药事法第 4 卷附录 11 的要求。

Where reference samples and retention samples are presented identically, i.e. as fully packaged units, the samples may be
regarded as interchangeable.

如果对照样品和留样其实是相同样品，即，都是完整包装后的单位，则样品可以互换。

Samples are not expected of an investigational medicinal product which is an unblinded comparator in its original
packaging and sourced from the authorised supply chain in the EU or of a product which holds a marketing authorisation
granted by a national competent authority in the EU or by the European Commission.

来源于 EU 内批准的供应链，或持有 EU 的 NCA 或 EC 颁发的上市许可的对照药品，未设盲且仍在其原始包装中

用作临床试验药品时不需留样。

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The storage location of samples should be defined in a technical agreement between the sponsor and the manufacturer(s)
and should allow timely access by the competent authorities.

样品的存贮位置应在申办人与生产商的技术协议中指定，并允许药监当局及时进出。

Reference samples of finished product should be stored under defined storage conditions in the EU or in a third country
where appropriate arrangements have been made by the Union with the exporting country to ensure that the manufacturer
of the investigational medicinal product applies standards of good manufacturing practice at least equivalent to those laid
down by the Union. In exceptional circumstances, the reference samples of the finished product may be stored by the
manufacturer in another third country, in which case this should be justified and documented in a technical agreement
between the sponsor, the importer in the EU and that manufacturer in the third country.

成品的对照样品应存贮在指定的存贮条件下，可以在 EU 内或在已与 EU 与出口国有适当安排的第三国，以确保

临床试验药品的生产商执行了至少等同于 EU 所设定的 GMP 标准。在例外情形下，成品的对照样品可以由生产
商存放在第三国，此时应进行论证并在申办人、EU 进口商和第三国生产商之间的技术协议中有书面记录。

The reference sample should be of sufficient size to perform, on at least two occasions, all critical quality attribute tests as
defined in the investigational medicinal product dossier authorised by the Member State. Any exception to this should be
justified to, and agreed with, the national competent authority.

对照样品的数量应足够执行至少 2 次在成员国批准的临床试验药品批件中所指定的全部关键质量属性检测。所有
例外情况均应进行论证，并经国家药监机构同意。

8 RELEASE OF BATCHES 批放行

Release of investigational medicinal products should not occur until after the qualified person has certified in line with
Article 62(1) of Regulation (EU) No 536/2014 that the requirements of Article 63(1) and (3) of Regulation (EU) No 536/2014
and those set out in Article 12 of the Commission Delegated Regulation (EU) No 2017/1569 are met.

临床试验药品必须在 QP 按法规 EU 536/2014 第 62（1）条规定认证，证明符合法规 EU536/2014 第 63（1）和（3）

条要求以及托管法案 EU 2017/1569 第 12 条规定后才可放行。

The duties of the qualified person in relation to investigational medicinal products are affected by the different
circumstances that can arise and are referred to below:

QP 与临床试验药品有关的职责受到不同情形的影响，列出如下：

i. Product manufactured within the EU but not subject to an EU marketing authorisation: the duties are laid down in
Article 62 of Regulation (EU) No 536/2014 and Article 12(1)(a) of the Delegated Regulation;

在 EU 境内生产但并不受 EU 上市许可约束的药品，其义务依托管法案第 12（1）（a）条和法规 EU 536/2014 第

62 条规定；

ii. Product sourced from the open market within the EU in accordance with Article 80(b) of Directive 2001/83/EC and
subject to a marketing authorisation granted by a competent authority in the EU, regardless of manufacturing origin: the
duties are as described above. However, the scope of the certification can be limited to assuring that the products are in
accordance with the authorisation of the clinical trial and any subsequent processing carried out by the manufacturer for the
purpose of blinding, trial-specific packaging and labelling.

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药品来源于 EU 内开放市场，符合法规 2001/83/EC 要求，受到 EU 某合法药监机构颁发的上市许可的约束，生产

来源地无关：其义务如上述。但是，认证的范围可以限于确保药品符合临床试验批件，以及生产商为了设盲、试
验特定包装和贴标目的所执行的后续加工操作。

iii. Product imported directly from a third country: the duties are laid down in Article 62 of Regulation (EU) No 536/2014
and Article 12(1)(b) of Delegated Regulation. Where investigational medicinal products are imported from a third country
and they are subject to agreements concluded between the Union and that country, such as a Mutual Recognition
Agreement (MRA), equivalent standards of good manufacturing practice apply provided any such agreement is operational
for investigational medicinal products. In the absence of a MRA, the qualified person should determine that equivalent
standards of good manufacturing practice apply through knowledge of the quality system employed at the manufacturer.
This knowledge is normally acquired through audit of the manufacturer's quality systems. In either case, the qualified
person may then certify on the basis of documentation supplied by the manufacturer in the third country and document the
rational for certification.

直接从第三国进口的药品：其义务依法规 EU 536/2014 第 62 条和托管法规第 12（1）（b）条。如果临床试验药

品是从第三国进口，该国与 EU 有协议，如互认协议（MRA），其国家实施了 GMP 等同标准，且该协议对临床
试验药品有效。如果没有 MRA，则 QP 应通过对生产商所采用质量体系的了解来确定其应用了等同 GMP 标准。
该了解一般是通过对生产商的质量体系进行审计来获得的。另外，QP 也可以基于第三国生产商提供的文件来认
证，并且书面记录下认证的合理理由。

The information in the product specification file should form the basis for assessment of the suitability for certification and
release of a particular batch by the qualified person and should therefore be accessible to him or her.

产品标准文件中的信息应组成评估认证是否适当，QP 放行一个特定批次是否适当的基础。因此，QP 应可以获得

该文件。

Assessment by the qualified person of each batch for certification prior to release should take account of the principles
detailed in EudraLex, Volume 4, Annex 16 and may include as appropriate:

QP 对各批在放行前为了认证而进行的评估应考虑欧盟药事法第 4 卷附录 16 中所述的原则，恰当时可以包括以

下：

a. Batch records, including control reports, in-process test reports and release reports demonstrating compliance
with the product specification file, the order, protocol and randomisation code. These records should include all
deviations or planned changes, and any consequent additional checks and tests, and should be completed and
endorsed by the staff authorised to do so according to the quality system; 批记录，包括检验记录、中控测试
报告和放行报告，证明符合产品标准文件、订单、方案和随机编码。这些记录应包括所有偏差和计划内
变更，以及之后的所有附加检查和测试，并应由经过授权的员工依据质量体系填写完成和签名认可；

b. Production conditions; 生产条件

c. Cleaning records; 清洁记录

d. The qualification status of facilities, validation status of processes and methods; 设施的确认状态、工艺和方法
的验证状态

e. Examination of finished packs; 成品包装的检查

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f. The results of any analyses or tests performed after importation, where relevant; （如相关）所有进口之后所实
施的分析和测试结果

g. Stability plan and reports; 稳定性计划和报告

h. The source and verification of conditions of storage and shipment; 存贮和发运的来源和条件核查

i. Audit reports concerning the quality system of the manufacturer; 生产商的质量体系审计报告

j. Documents certifying that the manufacturer is authorised to manufacture investigational medicinal product for
export by the appropriate authorities in the third country; 由第三国药监认证生产商经批准可以生产临床试验
药品用于出口的文件

k. Where relevant, regulatory requirements for marketing authorisation, good manufacturing practice standards
applicable and any official verification of compliance with good manufacturing practice; （如相关）上市许可法
规需求、适用 GMP 标准和任何 GMP 合规性官方证书

l. Verification of the supply chain including manufacturing, packaging, labelling and testing sites for the
investigational medicinal products; 供应链核查，包括临床试验药品的生产、包装、标签和测试场所

m.All factors of which the qualified person is aware that are relevant to the quality of the batch. QP 明了该批次质量
相关信息的所有要素

The relevance of the above elements is affected by the country of origin of the product, the manufacturer, the status of the
product, i.e. with or without a marketing authorisation granted by competent authorities in the EU or in a third country, and
the phase of development of the product.

上述要素的相关性受到药品原产国、生产商、药品状态的影响，即有无 EU 或第三国官方药监机构颁发的上市许
可，以及药品的研发阶段。

Where investigational medicinal products are produced and packaged at different sites under the supervision of different
qualified persons, sharing of responsibilities amongst qualified persons in relation to compliance of a batch must be defined
in a document formally agreed by all parties.

如果临床试验药品是在不同 QP 监管下的不同场所生产和包装，则必须在各方正式同意的文件中定义各 QP 在一
个批次合规性认证中相关职责分担。

Where required to support certification, the qualified person has to ensure that investigational medicinal products have
been stored and transported under conditions to maintain product quality and supply chain security. Relevant situations
may include short expiry date products released prior to final qualified person certification, or where return of investigational
medicinal products to an authorised manufacturer for re-labelling and re-packaging remains a possibility.

如果为了支持认证，QP 必须确保临床试验药品曾经的存贮和运输条件能维持药品质量和供应链安全。相关情形
可能包括较短有效期药品在最终 QP 认证之前放行，或者是退回至授权生产商的临床试验药品还可以进行重新贴
标和重新包装时。

The qualified person is not required to certify re-packaging or re-labelling carried out pursuant to Article 61(5)(a) of
Regulation (EU) No 536/2014.

QP 不需要认证对依据法规 EU 536/2014 第 61（5）（a）条规定所执行的重新包装或重新贴标操作。

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Where the manufacturer is delegated by the sponsor to perform the regulatory release in addition to certification by the
qualified person, the arrangements should be defined in an agreement between the sponsor and the manufacturer.
Relevant clinical trial authorisation and amendment information should be available for reference in the
product specification file and the manufacturer should ensure the necessary clinical trial authorisations are in place and
prior to shipping product for use in the trial.

如果生产商受到申办人委托，在 QP 认证以外还进行法规放行，则应在申办人与生产商之间的协议中明确其安排。
相关临床试验批件和修改信息应可以获得，并在产品标准文件中引用，生产商则应确保在发运试验用药品之前具
备所需的临床试验批件。

After certification by the qualified person, investigational medicinal products should be stored and transported under
conditions to maintain product quality and supply chain security.

在 QP 认证之后，临床试验药品应在指定条件下运输和存贮，以维护药品质量和供应链安全。

9 OUTSOURCED OPERATIONS 委外操作

Activities which are outsourced should be defined, agreed and controlled by written contracts between the contract giver
and the party to whom the operations are outsourced in accordance with Article 13 of Delegated Regulation and the
principles detailed in EudraLex Volume 4, Part I, Chapter 7.

外包活动应依据欧盟药事法第 4 卷第一部分第 7 章中详细说明的原则以及托管法规第 13 条，在委托方与受托方

之间的书面合同内定义、同意和受控。

10 COMPLAINTS 投诉

There should be written procedures describing the actions to be taken upon receipt of a complaint at the manufacturing,
storage or importation site. All complaints should be documented and assessed to establish if they represent a potential
quality defect or other issue. The procedures should ensure that the sponsor is able to assess the complaints to determine
if they justify the reporting of a serious breach, as required by Article 52 of Regulation (EU) No 536/2014.

应有书面程序描述在生产、存贮或进口场所收到投诉时要采取的措施。所有投诉均应心灵深处和评估，以确定其
是否是潜在的质量缺陷或其它问题。程序应确保申办人可以依法规 EU 536/2014 第 52 条对投诉进行评估以确定其
是否报告的是一起严重偏差。

The investigation of quality defect should be performed in accordance with the principles detailed in EudraLex, Volume 4,
Part I, Chapter 8.

质量缺陷的调查应依据欧盟药事法第 4 卷第一部分第 8 章中详述的原则执行。

The conclusions of the investigation should be discussed between the manufacturer and the sponsor, if different, in a timely
manner. This should involve the qualified person and those responsible for the relevant clinical trial in order to asses any
potential impact on the trial, product development and on subjects.

如果生产商和申办人得出的结论不同，则双方应及时对调查结论进行讨论。QP 和其它相关临床试验负责人应参
与其中，以评估是否对试验、药品研发和试验对象有潜在影响。

11 RECALLS AND RETURNS 召回和退货

11.1 Recalls 召回
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Procedures for retrieving investigational medicinal products and documenting this retrieval should in line with Article 14 of
the Delegated Regulation be agreed by the sponsor in cooperation with the manufacturer, where different. The
manufacturer, investigator and the sponsor's representative need to understand their obligations under the retrieval
procedure. The procedures for retrieval of investigational medicinal products should be in accordance with the
principles detailed in EudraLex, Volume 4, Part I, Chapter 8.

收回临床试验药品和记录此类收回操作的程序应符合托管法规第 14 条规定，并由申办人与生产商协商同意（如
持不同意见）。生产商、临床试验人和申办人代表需要理解回收程序中各自的义务。临床试验药品的回收程序应
符合欧盟药事法第 4 卷第一部分第 8 章的总则要求。

To facilitate recall, a detailed inventory of the shipments made by the manufacturer should be maintained.

为有利召回，应保存生产商所做详细货运清单。

11.2 Returns 退货

Returned investigational medicinal products should be clearly identified and stored in an appropriately controlled, dedicated
area. Inventory records of returned products should be kept.

退回临床试验药品应清楚标识，并存贮在适当控制的专用区域。应保存退货的库存记录。

11.3 Destruction 销毁

The manufacturer or sponsor’s representative should destroy investigational medicinal products only with prior written
authorisation by the sponsor. The arrangements for destruction of investigational medicinal products have to be described
in the protocol. Any arrangement between sponsor and manufacturer in this regard should be defined in their technical
agreement.

只有当申办人有书面授权时，生产商或申办人代表才可以销毁临床试验药品。对临床试验药品的销毁安排必须在
方案中进行描述。与此相关的所有安排均应在生产商和申办人之间的技术协议中规定。

Destruction of unused investigational medicinal products should be carried out only after reconciliation of delivered, used
and recovered products and after investigation and satisfactory explanation of any discrepancies upon which the
reconciliation has been accepted.

未用临床试验药品的销毁只有在发货数量、使用数量和回收数量衡算之后才可以执行。如有任何数量差异，则需
在调查并得到令人满意的解释使得衡算结果可以接受之后才可执行销毁。

Records of destruction operations should be retained, including a dated certificate of destruction or a receipt for destruction
to the sponsor. These documents should clearly identify or allow traceability to the batches and/or patient numbers involved
and the actual quantities destroyed.

应保存销毁操作的记录，包括有日期的销毁证书，或给申办人的销毁收据。这些文件应清楚识别或可追溯至销毁
涉及的批次和/或患者数量以及实际销毁数量。

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GLOSSARY OF TERMS APPLICABLE TO THESE GUIDELINES 本指南适用术语

Terms 术语 Definition 定义

Campaign manufacturing Manufacturing a series of batches of the same product in sequence in a given period of
time followed by an appropriate (validated) cleaning procedure.

周期生产 在给定的时间段内依序生产相同药品的一系列批次，然后执行适当的（经过验证
的）清洁程序。

Comparator product An investigational medicinal product used as a reference, including as a placebo, in a

clinical trial.

对照药品 临床试验中用作对照的临床试验药品，包括安慰剂。

Expiry date The date placed on the container/labels of an investigational medicinal products
designating the time during which the investigational medicinal products is expected to
remain within established shelf life specifications if stored under defined conditions, and
after which it should not be used.

有效期 临床试验药品的容器/标签上放置的日期，在该日期内临床试验药品如果存贮在指
定条件下则预期可以保持其货架期质量标准。超出该日期则不得使用。

Order The order should request the processing and/or packaging of a certain number of units
and/or their shipment and be given by or on behalf of the sponsor to the manufacturer.

订单 订单应要求加工和/或包装一定数量单位和/或其发货，是由申办人或其代表发给
生产商的。

Randomisation The process of assigning trial subjects to treatment or control groups using an element
of chance to determine the assignments in order to reduce bias.

随机分组 将试验对象采用随机方式分入治疗组或控制组以降低偏差的过程。

Retest date The date when a material should be re-examined to ensure that it is still suitable for use.

复测期 一个物料需要重新检验以确保其仍适合使用的日期。

Shipping The operation of packaging for and sending of ordered medicinal products for
clinical trials.

发运 打包发送所订临床试验药品的操作。

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