EU GMP指南 第1部分第2章：人员

EUROPEANCOMMISSION

HEALTH ANDCONSUMERS DIRECTORATE-GENERAL

Public Healthand Risk Assessment

MedicinalProduct – quality, safety and efficacy

Brussels, 16August 2013

EudraLex

TheRules Governing Medicinal Products in the European Union

Volume4

EUGuidelines for

GoodManufacturing Practice for

MedicinalProducts for Human and Veterinary Use

Part1

Chapter2: Personnel

人药与兽药GMP指南第2章：人员

Legal basisfor publishing the detailed guidelines:Article 47 of Directive 2001/83/EC on the Community code relating to medicinalproducts for human use and Article 51 of Directive 2001/82/EC on the Communitycode relating to veterinary medicinal products. This document provides guidancefor the interpretation of the principles and guidelines of good manufacturingpractice (GMP) for medicinal products as laid down in Directive 2003/94/EC formedicinal products for human use and Directive 91/412/EEC for veterinary use.

指南细则出版的立法基础：2001/83/EC法令第47款对人用药品的相关要求，2001/82/EC法令第51款兽用药相关的欧共体法规。本文件主要是2003/94/EC法令对人用药和91/412/EEC对兽用药品的GMP原则和指南的解释。

Status of thedocument: Revision

文件状态：修订

Reasons forchanges: Changes have been made in orderto integrate the principles of “Pharmaceutical Quality System” as described inthe ICH Q10 tripartite guideline. A section has been added on consultants

变更理由：变更是为了整合ICHQ10三方协调指南中所描述的“药品质量体系”的原则。增加了顾问部分。

Deadline forcoming into operation: 16 February2014

实施最后期限：2014年2月16日

Principle 原则

Thecorrect manufacture of medicinal products relies upon people. For this reasonthere must be sufficient qualified personnel to carry out all the tasks whichare the responsibility of the manufacturer. Individual responsibilities shouldbe clearly understood by the individuals and recorded. All personnel should beaware of the principles of Good Manufacturing Practice that affect them andreceive initial and continuing training, including hygiene instructions,relevant to their needs.

药品的正确生产依赖于人。因此，生产商应配备充足的有资质的人员承担所有工作。所有员工应明确个人应承担的职责并有书面记录。所有人员应明白与其职责相关的GMP的原则，接受初始及后续培训，包括与其工作相关的卫生要求。

General 通则

2.1The manufacturer should have an adequate number of personnel with the necessaryqualifications and practical experience. Senior management should determine andprovide adequate and appropriate resources (human, financial, materials,facilities and equipment) to implement and maintain the quality managementsystem and continually improve its effectiveness. The responsibilities placedon any one individual should not be so extensive as to present any risk toquality.

生产商应具备足够数量的人员，人员应具备必要的资质和实践经验。高层管理应决定和提供充足的和适当的资源（人员、经济、物料、厂房设施和设备），以实现和维护质量管理体系，并持续提高其有效性。给单个人员的职责不应太多，造成对质量的风险。

2.2The manufacturer must have an organisation chart in which the relationshipsbetween the heads of Production, Quality Control and where applicable Head ofQuality Assurance or Quality Unit referred to in point 2.5 and the position ofthe Qualified Person(s) are clearly shown in the managerial hierarchy.

生产商必须具备组织机构图，根据2.5内容在其中标明生产负责人、QC负责人和QA或质量部门负责人的关系，QP的位置应在管理层级中明确标示。

2.3People in responsible positions should have specific duties recorded in writtenjob descriptions and adequate authority to carry out their responsibilities.Their duties may be delegated to designated deputies of a satisfactoryqualification level. There should be no gaps or unexplained overlaps in theresponsibilities of those personnel concerned with the application of GoodManufacturing Practice.

承担职责的人员应具有指定的任务，任务应在书面岗位职责中记录，并具备足够的权限实现其职责。其职责可以转授予具有令人满意的资质层次的人员。与实施GMP相关人员的职责之间不应有漏项或无法解释的重叠。

2.4Senior management has the ultimate responsibility to ensure an effectivequality management system is in place to achieve the quality objectives, and,that roles, responsibilities, and authorities are defined, communicated andimplemented throughout the organisation. Senior management should establish aquality policy that describes the overall intentions and direction of thecompany related to quality and should ensure continuing suitability andeffectiveness of the quality management system and GMP compliance throughparticipation in management review.

高层管理对保证具备质量管理体系以达到质量目标具有最终职责，其角色、职责、权限应在组织范围内进行定义、沟通和实施。高层管理应建立质量方针，在其中描述公司整体质量相关意图和方向，应通过参与管理评审保证质量管理体系持续适用和有效性，保证GMP符合性。

Key Personnel 关键人员

2.5Senior Management should appoint Key Management Personnel including the head ofProduction, the head of Quality Control, and if at least one of these personsis not responsible for the duties described in Article 51 of Directive2001/83/EC[1], an adequate number, but at least one, Qualified Person(s)designated for the purpose. Normally, key posts should be occupied by full-timepersonnel. The heads of Production and Quality Control must be independent fromeach other. In large organisations, it may be necessary to delegate some of thefunctions listed in 2.6 and 2.7. Additionally depending on the size andorganizational structure of the company, a separate Head of Quality Assuranceor Head of the Quality Unit may be appointed. Where such a function existsusually some of the responsibilities described in 2.6, 2.7 and 2.8 are sharedwith the Head of Quality Control and Head of Production and senior managementshould therefore take care that roles, responsibilities, and authorities aredefined.

高层管理应任命关键管理人员，包括生产负责人、QC负责人，如果这些人中的至少一个不承担2001/83/EC第51款中描述的职责，则应有充足数量，至少一个人应任命为QP。一般来说，关键岗位应由全职人员担任。生产和QC负责人必须相互独立。如果组织机构庞大，可能需要任命2.6和2.7中所列的职责人员。另外，依据各公司规模和组织结构不同，可能需要分别任命QA或QU负责人。如果存在这种功能，一般2.6，2.7和2.8中描述的职责会由QC负责人和生产负责人分担，高层管理则需要保证对这些职位的角色、责任和权限进行定义。

2.6The duties of the Qualified Person(s) are described in Article 51 of Directive2001/83/EC, and can be summarised as follows:

QP的责任在2001/83/EC第51款中已有描述，可以归纳如下

a)for medicinal products manufactured within the European Union, a QualifiedPerson must ensure that each batch has been manufactured and checked incompliance with the laws in force in that Member State and in accordance withthe requirements of the marketing authorisation[2];

在欧共体之内生产的药品，必须有一具备资格人员QP，保证每批产品均按照其所在成员国法规和上市许可的要求进行生产和检查。

(b)in the case of medicinal products coming from third countries, irrespective ofwhether the product has been manufactured in the European Union a QualifiedPerson must ensure that each production batch has undergone in a Member State afull qualitative analysis, a quantitative analysis of at least all the activesubstances and all the other tests or checks necessary to ensure the quality ofmedicinal products in accordance with the requirements of the marketingauthorisation. The Qualified Person must certify in a register or equivalentdocument, as operations are carried out and before any release, that eachproduction batch satisfies the provisions of Article 51.

如果药品来源于欧共体之外的国家，不管该产品是否在欧共体内生产，QP必须保证所有生产批次均在某个成员国接受了全面质量检查，至少对所有活性物质进行了定量分析，进行了所有其它必要的检测或检查，以保证药品符合上市许可的要求。QP必须签发一份登记的文件或等同的文件，以保证在放行前所有操作均已完成，所有生产批准均满足第51款的要求。

Thepersons responsible for these duties must meet the qualification requirementslaid down in Article 49[3] of the same Directive, they shall be permanently andcontinuously at the disposal of the holder of the Manufacturing Authorisationto carry out their responsibilities.

上述职责负责人的资质应符合同样法令第49款中的要求，人员应在上市许可持有人公司长期持续行使其职责。

Theresponsibilities of a Qualified Person may be delegated, but only to otherQualified Person(s).

QP的职责可以转授权，但只能是转授权给其它QP。

Guidanceon the role of the Qualified Person is elaborated in Annex 16.

QP的角色指南在附件16中说明。

2.7The head of the Production Department generally has the followingresponsibilities:

生产部门负责人一般具有如下职责

i.         To ensure that products are producedand stored according to the appropriate documentation in order to obtain therequired quality;

保证产品的生产和存贮符合适当的文件的要求，以获得所需的品质。

ii.       To approve the instructions relating toproduction operations and to ensure their strict implementation;

批准与生产操作有关的指令，保证其被严格遵守。

iii.      To ensure that the production records areevaluated and signed by an authorized person;

保证生产记录由经授权的人员评估并签字。

iv.     To ensure the qualification andmaintenance of his department, premises and equipment;

保证生产部门、厂房设施和设备得到确认和维护。

v.       To ensure that the appropriatevalidations are done;

保证已进行了适当的验证。

vi.     To ensure that the required initial andcontinuing training of his department personnel is carried out and adaptedaccording to need.

保证生产部门人员所需的初始和后续培训已实施，满足需要。

2.8The head of Quality Control generally has the following responsibilities:

质量控制负责人一般具有如下职责

i.         To approve or reject, as he sees fit,starting materials, packaging materials, intermediate, bulk and finishedproducts;

批准或拒收，由负责人判定，起始物料、包装材料、中间体、散装和制剂成品。

ii.       To ensure that all necessary testing iscarried out and the associated records evaluated;

保证实施所有必须的测试，并对相关记录进行评价。

iii.      To approve specifications, samplinginstructions, test methods and other Quality Control procedures;

批准质量标准、取样指令、检验方法和其它质量控制程序。

iv.     To approve and monitor any contractanalysts;

批准及监控所有合同分析人员

v.       To ensure the qualification andmaintenance of his department, premises and equipment;

保证质量部门、设施和设备得到确认和维护

vi.     To ensure that the appropriate validationsare done;

保证已进行适当的验证

vii.    To ensure that the required initial andcontinuing training of his department personnel is carried out and adaptedaccording to need.

保证质量部门人员所需的初始和后续培训已实施，满足需要。

Otherduties of Quality Control are summarised in Chapter 6.

质量控制的其它职责在第6章中进行了归纳。

2.9The heads of Production, Quality Control and where relevant, Head of QualityAssurance or Head of Quality Unit, generally have some shared, or jointlyexercised, responsibilities relating to quality including in particular thedesign, effective implementation, monitoring and maintenance of the qualitymanagement system. These may include, subject to any national regulations:

生产部门、质量控制部门负责人，及质量保证或质量部门负责人（适当时），一般会共同承担，或联合进行一些与质量相关的职责，包括质量管理体系的设计、有效实施、监控和维护。这些职责可能会包括，受到所有国家法规的约束。

i.         The authorisation of writtenprocedures and other documents, including amendments;

书面程序和其它文件，包括修订内容的批准

ii.       The monitoring and control of themanufacturing environment;

生产环境的监控和控制

iii.      Plant hygiene;

工厂卫生

iv.     Process validation;

工艺验证

v.       Training;

培训

vi.     The approval and monitoring of suppliersof materials;

原料供应商的批准和监控

vii.    The approval and monitoring of contractmanufacturers and providers of other GMP related outsourced activities;

对分包生产商和提供其它GMP相关外包服务提供商的批准和监控，

viii.  The designation and monitoring of storageconditions for materials and products;

原料和产品存贮条件的设计和监控

ix.     The retention of records;

记录保存

x.       The monitoring of compliance with therequirements of Good Manufacturing Practice;

GMP符合性监控

xi.     The inspection, investigation, and takingof samples, in order to monitor factors which may affect product quality;

检查、调查和取样，以监控产品质量影响因素

xii.    Participation in management reviews ofprocess performance, product quality and of the quality management system andadvocating continual improvement

参与工艺性能、产品质量、质量管理体系和倡议持续改进的管理评审

xiii.  Ensuring that a timely and effectivecommunication and escalation process exists to raise quality issues to theappropriate levels of management.

保证及时有效沟通，加强现有向适当级别管理层提出质量议题的通道

Training 培训

2.10The manufacturer should provide training for all the personnel whose dutiestake them into production and storage areas or into control laboratories(including the technical, maintenance and cleaning personnel), and for otherpersonnel whose activities could affect the quality of the product.

生产商应该给所有在生产和存贮区工作的人员和化验室工作的人员（包括技术人员、维修人员和清洁人员）以及其他工作行为可能会影响到产品质量的人员进行培训。

2.11Besides the basic training on the theory and practice of the quality managementsystem and Good Manufacturing Practice, newly recruited personnel shouldreceive training appropriate to the duties assigned to them. Continuingtraining should also be given, and its practical effectiveness should beperiodically assessed. Training programmes should be available, approved byeither the head of Production or the head of Quality Control, as appropriate.Training records should be kept.

对新进的人员除了进行GMP的理论和实践方面的基本培训外，还要进行与所承担的工作直接相关的培训。培训应该是一项持续进行的工作，并需要定期对培训的结果进行评估。应制定培训计划，并由生产负责人或质量负责人批准。培训活动要进行记录。

2.12Personnel working in areas where contamination is a hazard, e.g. clean areas orareas where highly active, toxic, infectious or sensitising materials arehandled, should be given specific training.

在污染高危区域工作的人员，如洁净区或处理高活性、毒性、感染或过敏性材料的区域，需要进行特别培训。

2.13Visitors or untrained personnel should, preferably, not be taken into theproduction and quality control areas. If this is unavoidable, they should begiven information in advance, particularly about personal hygiene and theprescribed protective clothing. They should be closely supervised.

参观人员和未经培训的人员，最好不要进入生产区或质量控制区，如果不可避免，他们必须事先进行培训，特别是针对人员洁净和个人防护用品的使用方面。同时陪同他们进行密切指导。

2.14The pharmaceutical quality system and all the measures capable of improving itsunderstanding and implementation should be fully discussed during the trainingsessions.

对药品质量体系的概念，和所有其他有助于理解和应用的方法，都应该在培训中进行全面的讨论。

PersonnelHygiene 人员卫生

2.15Detailed hygiene programmes should be established and adapted to the differentneeds within the factory. They should include procedures relating to thehealth, hygiene practices and clothing of personnel. These procedures should beunderstood and followed in a very strict way by every person whose duties takehim into the production and control areas. Hygiene programmes should bepromoted by management and widely discussed during training sessions.

应建立详细的卫生清洁程序，适用于工厂的各种需要。应包括健康、清洁方法和工作服使用方面的操作程序。在生产区或质量控制区工作人员必须对这些程序理解并严格执行，卫生规程必须由管理层进行审定，并在培训过程中进行广泛的讨论。

2.16All personnel should receive medical examination upon recruitment. It must bethe manufacturer’s responsibility that there are instructions ensuring thathealth conditions that can be of relevance to the quality of products come tothe manufacturer’s knowledge. After the first medical examination, examinationsshould be carried out when necessary for the work and personal health.

所有人员在入职时均应进行健康检查。生产商必须根据自己的产品情况，制定相关的人员卫生要求。在首次健康检查之后，还要在工作需要的时候或个人健康状况需要的时候进行检查。

2.17Steps should be taken to ensure as far as is practicable that no personaffected by an infectious disease or having open lesions on the exposed surfaceof the body is engaged in the manufacture of medicinal products.

采取有效的防御措施，保证参与药品生产人员没有传染病和体表暴露伤口。

2.18Every person entering the manufacturing areas should wear protective garmentsappropriate to the operations to be carried out.

所有进入生产区域的人员均应着与生产操作相适当的防护性工作服

2.19Eating, drinking, chewing or smoking, or the storage of food, drink, smokingmaterials or personal medication in the production and storage areas should beprohibited. In general, any unhygienic practice within the manufacturing areasor in any other area where the product might be adversely affected should beforbidden.

禁止在生产区域和仓贮区域吃东西、喝饮料、嚼东西和吸烟，存贮食品、饮料、吸烟用品，个人药用品。一般，在生产区域和其它所有其它相关区域应禁止出现一切不卫生，可能会对产品产生不良影响的东西。

2.20Direct contact should be avoided between the operator’s hands and the exposedproduct as well as with any part of the equipment that comes into contact withthe products.

操作人员应避免裸手操作产品，以及会与产品直接接触的所有设备部件

2.21Personnel should be instructed to use the hand-washing facilities.

要对人员进行洗手设施使用方面的培训。

2.22Any specific requirements for the manufacture of special groups of products,for example sterile preparations, are covered in the annexes.

所有对特定类别产品，例如无菌制剂，的特定生产要求在附件中说明

Consultants 顾问

2.23Consultants should have adequate education, training, and experience, or anycombination thereof, to advise on the subject for which they are retained.

顾问应在其所指导的主题范围内具有足够的教育、培训和经验，或兼具上述要求。

Recordsshould be maintained stating the name, address, qualifications, and type ofservice provided by these consultants.

应保留相关记录，说明顾问的姓名、地址、资质，以及提供的服务类型。

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[1] Article 55 of Directive 2001/82/EC

[2]According to Article 51 paragraph 1 ofDirective 2001/83/EC), the batches of medicinal products which have undergonesuch controls in a Member State shall be exempt from the controls if they aremarketed in another Member State, accompanied by the control reports signed bythe qualified person..根据2001/83/EC第51款第1段，在某一成员国根据其要求进行控制的药品批次，如果随货有QP签名的控制报告，在另一成员国上市，则在上市国的控制要求可以免除。

[3] Article 53 of Directive 2001/82/EC

谢谢分享，辛苦