欧盟临床试验药品IMP GMP指南

翻译： julia 来源：Julia法规翻译

EUROPEAN COMMISSION

Brussels, 8.12.2017

C(2017) 8179 final 

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

中英文PDF下载点击阅读原文。

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 

INTRODUCTION 概述

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

本指南基于法规EU536/2014第63（1）条第二段。

These guidelines complement Commission DelegatedRegulation (EU) 2017/1569 of 23 May 2017 supplementing Regulation (EU) No536/2014 on the good manufacturing practice for investigational medicinal productsfor human use and arrangements for inspections that has as its legal basis the firstsubparagraph 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EU536/2014第63（1）条。

These guidelines lay down appropriate tools to address specificissues concerning investigational medicinal products with regard to good manufacturingpractice. The tools are flexible to provide for changes as knowledge of theprocess 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 inArticle 2(5) of Regulation (EU) No 536/2014 as a medicinal product which isbeing tested or used as a reference, including as a placebo, in a clinicaltrial and manufacturing is defined as total and partial manufacture, as well asthe various processes of dividing up, packaging and labelling (includingblinding) in Article 2(24) of that Regulation.

临床试验药品的定义在法规EU536/2014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 providesthat investigational medicinal products shall be manufactured by applyingmanufacturing practice which ensures the quality of such medicinal products inorder to safeguard the safety of the subject and the reliability and robustnessof clinical data generated in the clinical trial ("good manufacturingpractice").

法规EU536/2014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 medicinalproducts is set out in Commission Delegated Regulation (EU) No 2017/1569 and inthese 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 thecompetent authorities should also take into account the detailed guidelinesreferred to in the second paragraph of Article 47 of Directive 2001/83/EC ,published by the Commission in the "Guide to good manufacturing practice formedicinal products and for investigational medicinal products" (EudraLex, Volume 4). Examplesof applicable parts of EudraLex, Volume 4 to investigational medicinalproducts, not specifically mentioned in these guidelines, are Part I, Chapters2, and 6, and Part III.

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 benoted that Regulation (EU) No 536/2014 does not lay down requirements for goodmanufacturing practice for active substances of investigational medicinalproducts. However, if a clinical trial is to be used to support the applicationfor a marketing authorisation, Part II of EudraLex, Volume 4 would need to beconsidered.

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 asknowledge of the process increases and appropriate to the stage of developmentof 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 thesubjects compared to patients treated with authorised medicinal products. Theapplication of good manufacturing practice for the manufacture and import ofinvestigational medicinal products is intended to ensure that subjects are notplaced at undue risk, and that the results of clinical trials are unaffected byinadequate quality, safety or efficacy arising from unsatisfactory manufactureor import. Equally, it is intended to ensure that there is consistency betweenbatches of the same investigational medicinal product used in the same or differentclinical trials and that changes during the development of an investigational medicinalproduct 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 productsinvolves added complexity in comparison with authorised medicinal products byvirtue of lack of fixed routines, variety of clinical trial designs andconsequent packaging designs. Randomisation and blinding add to that complexityan increased risk of product cross-contamination and mix-up. Furthermore, theremay be incomplete knowledge of the potency and toxicity of the product and alack of full process validation. Moreover, authorised products may be usedwhich have been re-packaged or modified in some way. These challenges requirepersonnel with a thorough understanding of and training in the application ofgood manufacturing practice to investigational medicinal products. Theincreased complexity in manufacturing operations requires a highly effectivequality 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 withgood 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 technical agreement between thesponsor and manufacturer, as referred to in recital 4 of Delegated Regulation62 (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 ofinvestigational 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, Article16 of Commission Delegated Regulation (EU) No 2017/1569 states that the requirementsof good manufacturing practice shall be adapted to the specific characteristicof such products in accordance with a risk-based approach and consistent with goodmanufacturing requirements applicable to authorised advanced therapy medicinalproducts. Those adaptations are addressed in the Guidelines on goodmanufacturing practice for advanced therapy medicinal products. Therefore,these detailed guidelines on good manufacturing practice for investigational medicinalproducts for human use do not apply to manufacture or import of advancedtherapy investigational medicinal products.

对于先进治疗临床试验药品，托管法案EU2017/1569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 isnot 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 ofdissolving or dispersing the investigational medicinal product foradministration of the product to a trial subject, or diluting or mixing theinvestigation medicinal product with some other substance(s) used as a vehiclefor 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 investigationalmedicinal product. An investigational medicinal product must exist before aprocess 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 closein time as possible to administration and has to be defined in the clinicaltrial 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。

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

本指南不适用于法规EU536/2014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 themanufacturer according to Article 5 of Commission Delegated Regulation (EU) No2017/1569 and designed, set-up and verified by the manufacturer should be describedin 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EU2017/1569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 instructionsmay be changed during development but full control and traceability of thechanges should be documented and maintained. Deviations from any predefinedspecifications and instructions should be registered, investigated andcorrective 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 ofsuppliers of starting materials, together with their purchase and acceptance,should be documented as part of the pharmaceutical quality system to ensure theintegrity of the supply chain and protect against falsified products. The levelof supervision should be proportionate to the risks posed by the individualmaterials, taking into account their source, manufacturing process, supplychain complexity and the final use to which the material is put in theinvestigational medicinal product. The supporting evidence for each supplierapproval 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 DelegatedRegulation (EU) No 2017/1569, brings together and contains all of the essentialreference documents to ensure that investigational medicinal products aremanufactured according to good manufacturing practice for investigationalmedicinal products and the clinical trial authorisation. The productsspecification files is one of the essential elements of pharmaceutical qualitysystem.

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 fileshould be available at the start of manufacturing of the first batch ofinvestigational 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。

The product specification file should be continuallyupdated as development of the product proceeds, ensuring appropriatetraceability to the previous versions. It should include or refer to at leastthe 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.     Specificationsand 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.     Manufacturingmethods;

生产方法

iii.    In-processtesting and methods;

中控检测和方法

iv.    Approvedlabel copy;

批准过的标签副本

v.     Relevantclinical trial authorisations and amendments thereof, clinical trial protocoland 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.    Relevanttechnical 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.   Stabilityplan and reports;

稳定性计划和报告

viii.  Details ofplans and arrangements for reference and retention samples;

对照品和留样的详细计划和安排

ix.    Storage andtransport conditions;

运输和存贮条件

x.    Details of thesupply chain including manufacturing, packaging, labelling and testing sitesfor the investigational medicinal products, preferably in the format of acomprehensive 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 norexclusive.

上述文件清单并不是完全的。

The contents of the product specification file will varydepending 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。

Where different manufacturing steps are carried out atdifferent locations under the responsibility of different qualified persons, itis acceptable to maintain separate files limited to information of relevance tothe activities at the respective locations. The manufacturing site should haveaccess 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 inArticle 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EU2017/1569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 beappropriately 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 themanufacturing or import of investigational medicinal products is small, thereshould be, for each batch, separate people responsible for production andquality 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 ofqualification set out in Article 49(2) and (3) of Directive 2001/83/EC, as perArticle 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 outin Article 62 of Regulation (EU) No 536/2015 and further elaborated in Article12 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 ofinvestigational medicinal products for use in the clinical trial should ensurethat there are systems in place that meet the requirements of goodmanufacturing practice and should have a broad knowledge of pharmaceuticaldevelopment, 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 befully understood for investigational medicinal products and this reinforces theneed to minimise all risks of cross-contamination. The design of equipment andpremises, inspection/test methods and acceptance limits to be used aftercleaning should reflect the nature of these risks and take account of thequality risk management principles detailed in EudraLex, Volume 4, Part I,Chapters 3 and 5.

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 indecisions 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 apotency and toxicological evaluation, should be used to assess and control thecross-contamination risks presented by the investigational medicinal productsmanufactured. 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/equipmentdesign and use;

设备/设备设计和使用

ii.     personneland material flow;

人流和物流

iii.    microbiologicalcontrols;

微生物控制

iv.    physio-chemicalcharacteristics of the active substance;

活性物质的理化特性

v.     processcharacteristics;

工艺特性

vi.    cleaningprocesses;

清洁工艺

vii.   analytical  capabilities relative  to  the relevant  limits  established from  the evaluation of theinvestigational 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 inaccordance 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 linewith the principles detailed in EudraLex, Volume 4, Part I, Chapter 4. Theretention period for instructions and records required to demonstratecompliance with good manufacturing practice should be defined according to thetype of document while complying with the requirement of Article 8 ofCommission Delegated Regulation (EU) No 2017/1569, where relevant. In line withArticle 8(1) of the above mentioned Delegated Regulation the documentationshall be consisted with the Product Specification File. Documents which arepart of the Products Specification File shall be retained for the period of atleast 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EU2017/1569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 documentretention of the clinical trial master file according to Article 58 ofRegulation (EU) No 536/2014 and is required to retain such documentation for atleast 25 years after the end of the trial. If the sponsor and the manufacturerare not the same entity, the sponsor has to make appropriate arrangements withthe manufacturer to fulfil the sponsor’s requirement to retain the clinicaltrial master file. Arrangement for retention of such documents and the type ofdocuments to be retained should be defined in an agreement between the sponsorand manufacturer.

依据法规EU536/2014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, immediatepackaging materials, intermediate products, bulk products and finishedproducts, manufacturing formulae and processing and packing instructions shouldbe as comprehensive as possible given the current state of knowledge. Theyshould be re-assessed during development and updated as necessary. Each newversion should take into account the latest data, current technology used,regulatory and pharmacopoeial developments and should allow traceability to theprevious document. Any changes should be carried out according to a writtenprocedure which should address any implications for product quality such asstability and bioequivalence. The approval process for instructions and changesthereof 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 theconsequences of a change on product quality and on any on-going clinical trialsshould 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 forinvestigational medicinal products as part of the batch documentation. Theorder should request the processing and/or packaging of a certain number ofunits and/or their distribution and be given by or on behalf of the sponsor tothe manufacturer. The order should be in writing, though it may be transmittedby electronic means, and be precise enough to avoid any ambiguity. It should beformally authorised by the sponsor or his representative and refer to theproduct specification file and the relevant clinical trial protocol asappropriate.

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 processinginstructions 生产处方和加工指令

For every manufacturing operation or supply there shouldbe clear and adequate written instructions and written records which areprepared using the specific clinical study information detailed in the productspecification file. Records are particularly important for the preparation ofthe final version of the documents to be used in routine manufacture once themarketing 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 specificationfile 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 inan individual way for each subject included in the clinical trial. The numberof units to be packaged should be specified prior to the start of the packagingoperations, including units necessary for carrying out quality control and forany retention samples to be kept. Sufficient reconciliations should take placeto ensure that the correct quantity of each product required has been accountedfor 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 randomisationcode used for packaging investigational medicinal products as well ascode-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 thesequence of operations to be accurately determined. These records shouldcontain any relevant remarks which justify procedures used and any changesmade, enhance knowledge of the product, develop the manufacturing operationsand 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 themanufacturer for at least 5 years after the completion or formaldiscontinuation of the last clinical trial in which the batch was used as setout in Article 8(3) of Commission Delegated Regulation (EU) No 2017/1569.

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。