MEDDEV 2.12-2 医疗器械上市后临床跟踪指南

Revision 8 of MEDDEV 2.12-1 explicitly includes IVF/ART devices within the scope of the vigilance system and provides clarity in relation to devices that are not intended to act directly on the individual. The revised guidance will be applicable as of July 2013.
3 SCOPE ............................................................................................................................................. 5 3.1 GENERAL PRINCIPLES ...................................................................................................... 6 3.1.1 FOR MANUFACTURERS .................................................................................................. 6 3.1.2 FOR MANUFACTURERS OF DEVICES THAT ARE NOT INTENDED TO ACT DIRECTLY ON THE INDIVIDUAL ............................................

CE上市后临床跟踪控制程序编制人/日期：审核人/日期：批准人/日期：修订页目录1.目的 (4)2.范围 (4)3.职责 (4)4.程序 (4)5.术语及定义 (4)6.相关文件 (6)7.相关记录 (6)1.目的根据MDR中附录XIV、MEDDEV 2.12-2第2版《医疗器械上市后临床跟踪研究指南》的要求，规范公司的带CE标识的医疗器械是否进行上市后临床跟踪研究以及如何进行研究，特拟定本文件。

2.范围适用于本公司医疗器械产品的CE上市后临床跟踪的制定与管理。

3.职责3.1总经理负责CE上市后临床跟踪（PMCF）计划及评估报告的批准。

3.2管理者代表负责CE上市后临床跟踪（PMCF）计划及评估报告的审核。

3.3研发部及临床专家负责CE上市后临床跟踪（PMCF）计划及上市后临床跟踪评估报告的编制。

3.4质管部负责CE上市后临床跟踪（PMCF）计划及报告的归档管理，及有关法规的更新。

3.5各相关部门按分配执行。

4.术语及定义（来源于MEDDEV 2.12-2第2版）上市后临床跟踪研究（Post Market Clinical Follow-Up Study）:在医疗器械获得CE标记后进行的研究，旨在回答与根据其批准的标签适用时，器械的临床安全性或性能（即残余风险）相关的具体问题5.程序5.1CE上市后临床跟踪（PMCF）的基本要求：上市后临床跟踪（PMCF）是更新临床评价报告的持续过程，并应加入制造商CE上市后监督计划（Post-market Surveillance plan）中，详见《CE上市后监督控制程序》。

上市后临床跟踪（PMCF）的执行应当遵循PMCF计划中的规定并记录的方法。

5.2可以进行上市后临床跟踪研究的情况包括：-创新，例如器械的设计、材料、物质、操作原理、技术或医学适应症是新颖的；-已经完成了上市前临床评估和重新认证的产品发生产品或其预期用途重大变化时；-与产品相关的高风险，如产品的设计、材料、零部件、侵入性及临床程序相关的风险；-高风险的解剖位置；-高风险目标人群，如儿科、老人；-疾病的严重程度/治疗的难易程度；-概括临床调查结果的能力问题；-长期未解决安全性和性能方面的问题；-以往临床调查的结果，包括不良事件或上市后监督活动；-对以前未研究的可能影响利益/风险比例子群的识别，如在不同组群的髋关节植入物；-在上市前合理的随访时间尺度与产品预期寿命之间存在差异情况下的继续验证；-来自文献或其他类似市场器械的数据来源的风险；-与其他医疗产品或治疗的相互作用；-暴露于更大量和更多样化人群的临床使用者时，对器械的安全性和性能进行验证；-出现与设备的安全性或其他性能相关的新信息；-获得CE标志是基于等同性证明的基础上的。

MEDDEV-2.7.1Rev4（最新附中文2016）EUROPEAN COMMISSIONDG Internal Market, Industry, Entrepreneurship and SMEsConsumer, Environmental and Health TechnologiesHealth technology and Cosmetics备注：中文翻译中的临床调查=临床研究，评估=评价、设备=器械、数据=资料MEDDEV 2.7/1 revision 4June 2016GUIDELINES ON MEDICAL DEVICES 医疗器械指南CLINICAL EVALUATION:A GUIDE FOR MANUFACTURERS AND NOTIFIED BODIES UNDER DIRECTIVES 93/42/EEC and 90/385/EECNoteThe present Guidelines are part of a set of Guidelines relating to questions of application of EC-Directives on medical Devices. They are legally not binding. The Guidelines have been carefully drafted through a process of intensive consultation of the various interested parties (competent authorities, Commission services, industries, other interested parties) during which intermediate drafts where circulated and comments were taken up in the document. Therefore, this document reflects positions taken by representatives of interest parties in the medical devices sector. These guidelines incorporate changes introduced by Directive 2007/47/EC amending Council Directive 90/385/EEC and Council Directive93/42/EEC.本指南为一系列与CE—医疗器械指令应用问题相关的指南中的一部分。

1. 欧盟公报 C 136, 4.6.1985, p.1. 2. Recast of the Medical Devices Directives - Summary of the responses of the Public Consultation, Brussels, 5 December 2008 ENTR/F/3/D (2008)
N/A
附录 III
EC 符合性声明（制造商自我 声明）
N/A
公告机构是否介入 YES YES YES YES YES
YES NO
器械风险递增
6
注册和授权代表
98/79/EC 规定欧洲数据库的其中一个职责 是主管当局之间共享关键数据，但目前该 项目仍在进行中。一旦该项目执行，则制 造商只需在其所在国或在其授权代表 (AR) 所在国注册即可。目前，临时取代措施是 要求制造商在初始注册后，通知其他成员 国的主管当局。制造商如果确定了潜在的 目标市场，则需研究该国的具体实施要 求，以确定是否需要通报相关部门。
• “体外诊断医疗器械可以是试剂、试剂 产品、校准物、控制物、试剂盒、器 具、仪器、设备或系统等任何形式的医 疗器械，无论是单独使用或组合使用， 由制造商预期用于体外检测取自人体的 样本，包括血液和其他组织，且其主要 目的是提供如下信息：生理或病理状 态、或有关于先天性异常、或确定潜在 接受者的安全性和兼容性、或监测治疗 措施。”
对于 LIST A 中风险程度最高的器械，需要 有额外的措施来把控风险。在附录 IV 全面 质量保证的符合性评价程序下，每个 LIST A 的器械必须经过详细的技术文件评审， 即 EC 设计审查。无论是参照哪项程序， 在获得 CE 标志后，任一批 LIST A 的产 品在交付市场前，还需进行持续的逐批验 证，以确保器械性能的持续稳定。

作者简介：马艳彬，Tel： (024)31606983；E-mail：myb-1027@众所周知，随着现代科技的迅速发展和公众日益增强的健康需求，医疗器械已被广泛应用于疾病的预防、诊断、治疗、监护、康复等医疗卫生技术领域。

但是，与药品一样，医疗器械在给人们带来预期用途的同时也存在着一定的潜在风险。

因此，世界各国在医疗器械上市前，都要对其进行严格的审查，其中临床试验就是验证医疗器械上市前安全性和有效性的核心方法之一。

本文就我国医疗器械浅谈我国医疗器械临床试验中的问题与对策马艳彬，李竹，杨牧，梁文，李非（辽宁省食品药品监督管理局技术审评中心，沈阳110003）zhgysh临床试验实施及监管过程中存在的问题进行探讨、总结和分析，提出了改进的建议和对策。

1 医疗器械临床试验现状简介医疗器械临床试验起源于药品的临床试验。

临床试验（clinical trial）是指所有在人体（病人或健康志愿者）进行药物或器械的系统性研究，其目的是收集试验药物或器械的效用与安全性的相关数据[1]。

国际对医疗器械临床试验的监督管理非常重视。

1962年，《美国Hefauver-Hatris 药品修正案》对临床实验管理进行了规范。

美国食品药品监督管理局（FDA）在1996年还发布了优良临床试验规范（good clinical practice，GCP）。

ISO（国际标准化组织）专门制定了医疗器械临床试验标准（IS0 14155）。

欧盟于2003年发布了医疗器械临床数据评价制造商和授权机构指南（MEDDEV.2.7.1）[1]。

我国的行业标准YY ／T 0297等同采用国际标准ISO 14155-2003。

由于ISO 14155旨在用于世界范围内医疗器械临床试验，用以满足不同国家、地区以及国际管理法规中的技术层面的基本要求，而目前不同国家和地区的法律法规还存在很大差异，因此，ISO 14155中不包括法律法规性的要求，相应的YY/T 0297也是如此。

EUROPEAN COMMISSION 欧盟委员会DG ENTERPRISE DG企业Directorate G 董事会GUnit 4 - Pressure Equipment, Medical Devices, Metrology第4单元-压力设备、医疗器械、计量学医疗器械指南该指南是指实施医疗器械EC指令中所遇到问题的系统指南中的一个。

这些指令与指南之间没有法律效益的关联。

这些指南是通过与各个利益方（包括主管当局，委员会服务机构，行业以及其他利益相关方）进行详尽的征询后谨慎起草的，在这个过程中，草稿有被传阅，相关的建议在文件中加以采纳。

因此，此文件体现了医疗器械各相关方代表的立场。

CEC 临床评估小组5月18日, 2004年医疗器械指令之上市后临床跟踪前言：PMCF的基本原因和目标本文件的目的是指为制造商和通告机构就如何执行PMCF, 和履行上市后监督义务提供指导性意见。

参照医疗器械指令附录II 3. 1, 附录IV 3. 附录V 3, 附录VI 3.1 附录VII 4 (增加参阅AIMDD)。

虽然临床证据是上市前符合性评定程序的基本要素，但重要的是要认识到，这些上市前临床调查存在局限性。

虽然在上市前阶段已经收集了广泛的数据，但是并不能保证制造商能够察觉到不常见的并发症或问题，而这些问题只有在医疗器械被大范围的使用和长期运行后才会显现。

作为医疗器械制造商的质量体系，或上市后监督体系的一个部分，关键就是需识别和调查销售后的医疗器械在使用过程中所具有的风险。

制造商应建立上市后监督系统，并且对每一个产品或产品类都应有明确的PMS（上市后监督）策划。

因此，选择PMCF(上市后临床跟踪)看起来是实现此目的的一个方法。

通过建立一个长期的安全跟踪评审程序和侦查一些可能出现的风险，它可以使病人获得新的疗法，而这些风险仅仅依赖上市前的临床调查（仅仅要求相对很短的时间跟踪）和根据产品经验或产品警惕性都是不能完全充分地察觉到的。

MEDDEV2.12.2rev2...MEDDEV 2.12/2 rev2 January 2012GUIDELINES ON MEDICAL DEVICESPOST MARKET CLINICAL FOLLOW-UP STUDIESA GUIDE FOR MANUFACTURERS AND NOTIFIED BODIES 关于医疗设备指导方针药品上市后临床跟踪研究指导生产商和相关人员NoteThe present Guidelines are part of a set of Guidelines relating to questions of application of EC-Directives on medical Devices. They are legally not binding. The Guidelines have been carefully drafted through a process of intensive consultation of the various interest parties (competent authorities, Commission services, industries, other interested parties) during which intermediate drafts where circulated and comments were taken up in the document. Therefore, this document reflects positions taken by representatives of interest parties in the medical devices sector. 注释本准则是有关欧共体指令对医疗器械的应用问题指引的一部分。

其在法律上不具约束力。

MEDICAL DEVICES: Guidance document
MEDDEV 2.12-1 rev 8 January 2013
GUIDELINES ON A MEDICAL DEVICES VIGILANCE SYSTEM
The present guidelines are part of a set of guidelines relating to questions of application of EC-Directives on MEDICAL DEVICEs. They are legally not binding. The guidelines have been carefully drafted through a process of intensive consultation of the various interested parties (competent authorities, Commission services, industries, other interested parties) during which intermediate drafts were circulated and comments were taken up in the document. Therefore, this document reflects positions taken by representatives of interested parties in the MEDICAL DEVICEs sector.
3 SCOPE ...........................................................................................

EUROPEAN COMMISSIONDG ENTERPRISEDirectorate GUnit 4 - Pressure Equipment, Medical Devices, MetrologyMEDICAL DEVICES : Guidance documentMEDDEV 2. 1/1April 1994GUIDELINES RELATING TO THE APPLICATION OF :THE COUNCIL DIRECTIVE 90/385/EEC ON ACTIVE IMPLANTABLE MEDICAL DEVICESTHE COUNCIL DIRECTIVE 93/42/EEC ON MEDICAL DEVICESDefinition of "medical devices"Definition of "accessory"Definition of "manufacturer"--- (())---LIST OF CONTENTSI.FIELD OF APPLICATION - DEFINITIONS1.Directive 93/42/EE on medical devices2.Directive 90/385/EEC on active implantable medical devices13.Interface with other directives- medical devices/medicinal products- medical devices/electromagnetic compatibility2- medical devices/personal protective equipment2II.CLASSIFICATION OF MEDICAL DEVICES COVERED BY DIRECTIVE 93/42/EEC3III.CONFORMITY ASSESSMENT PROCEDURES(*):1.CE-marking2.Application-Annex 5-Annex 2. Quality systems. Examination of the design dossier- Annex 33.Conduct of audits44.Format of decisions, design examination certificate5.Technical DossierIV.CUSTOM MADE DEVICES(*):V.DEVICES INTENDED FOR CLINICAL INVESTIGATIONS(*):VI.MEDICAL DEVICE VIGILANCE(*):E OF LANGUAGES(*):VIII.TRANSITIONAL PERIOD(*):1see MEDDEV. 5/93 rev. 22see MEDDEV 13/933see MEDDEV.10/93 rev. 14see MEDDEV. 1/94I.FIELD OF APPLICATION - DEFINITIONS1.Directive 93/42/EEC on medical devices1.1Definition of "medical devices"a)devices - accessoryThe definition of the term "medical device" together with thedefinition of "accessory" is determinant for the delimitation of the fieldof application of Directive 93/42/EEC. A slight difference existsbetween the definition in article 1(2) (a) of Directive 93/42/EEC and inarticle 1(2) of Directive 90/385/EEC.Following the latter directive, accessories are by definition medicaldevices, whilst following Directive 93/42/EEC, a distinction is madebetween "devices" and "accessories". Therefore within the meaning ofDirective 93/42/EEC, accessories are products in their own right and,although being treated as devices (article 1(1)) do not follow, as ageneral rule, the classification of related devices in conjunction withwhich they are used.Accessories are therefore following Directive 93/42/EEC to beclassified in their own right.b)medical purposeMedical devices are defined as articles which are intended to be usedfor a medical purpose. The medical purpose is assigned to a productby the manufacturer. The manufacturer determines through the label,the instruction for use and the promotional material related to a givendevice its specific medical purpose. As the directive aims essentially atthe protection of patients and users, the medical purpose relates ingeneral to finished products regardless of whether they are intendedto be used alone or in combination. This means that the protectionensured by the directive becomes valid for products having a stage ofmanufacture, where they are supplied to the final user.Following this concept, raw materials, components or intermediateproducts are as such normally not medical devices. Such rawmaterials may need to present properties or characteristics which aredeterminant for the safety and quality of finished devices. It istherefore the responsibility of the manufacturer of finished devices toselect and control by adequate means his raw materials orintermediate products (see Annex I, section 7.1; Annex II, section 3.2;Annex V, section 3.2 of Directive 93/42/EEC)Spare parts supplied for replacement of existing components of adevice, the conformity of which has already been established, are notmedical devices. If spare parts, however, change significantly thecharacteristics or performances of a device with regard to its alreadyestablished conformity, such spare parts are to be considered asdevices in their own right.c)customizingThe concept of "finished device" does not imply that a device whenreaching the final user is already in a state ready for use. Prior to usefurther preparatory processing, preparation, configuration,installation, assembling, adaptation or fitting to the needs of the useror patient may be required. Examples :-sterilisation of medical devices supplied non-sterile-assembling of systems-configuration of electronic equipment-preparation of a dental filling-fitting of contact lenses-adaptation of prosthesis to the needs of the patient.The aforementioned activities are normally not manufacturersactivities if they are carried out by the final user as part of the use orpreparation for use. In this context a distinction needs to be madebetween a typical professional activity performed by a healthcareprofessional and processing and assembling activities done by aspecialist for such processing. In the latter case relevant activities maybecome proper manufacturing or assembling activities relevant withinthe meaning of articles 11 and 12.A particular consideration in this context needs to be given for themanufacture of custom-made devices. Custom-made devices (such as dental appliances, prosthesis, hearing-aid inserts) are in most casesone-off devices and the Directive subjects their manufacture to theprocedure of article 11(6) in conjunction with Annex VIII. In thesecases intermediate products specifically intended for this kind ofcustom-made devices may be considered also as medical devices.This applies essentially to dental alloys, dental ceramics, modularcomponents for prosthesis, if the intended purpose of such products is specifically related to medical devices.d)medical - toiletry purposeThe definition of "medical device" should be understood to includeproducts intended to be used principally for a medical use. Thereforeproducts intended to have a toiletry or cosmetic purpose are notmedical devices even though they may be used for prevention of adisease. Examples for products for which a medical purpose cannormally not be established :-tooth brushes, dental sticks, dental floss;-baby diapers, hygiene tampons;-contact lenses without corrective function intended toprovide another colour to the eyes,-bleaching products for teeth [needs to be furtherdiscussed with regard to products intendedspecifically for application by dentists]-instruments for tattooing.Examples for products, where depending on the circumstances, amedical purpose can be established :-incontinence products.e)aids for handicapped personsIn the case of equipment intended for alleviation of or compensationfor a handicap, there must be a direct link between the correctivefunction and the person concerned. Therefore the followingequipment are not medical devices :-acoustic signals at traffic lights,-special water taps, toilet equipment for handicappedf)softwareThe following distinction can be made : software influencing theproper functioning of a device and software used in combination withnon-medical equipment.Software related to the functioning of a medical device may be part ofa device or a device in its own right if it is placed on the marketseparately from the related device.In the case of software intended for use with multipurpose informaticequipment a distinction has to be made between software providingfor a proper diagnostic or therapeutic tool and software for handlinggeneral patient-related data. Only in the first case may a medicalpurpose be determined. Examples for medical devices :-calculation of anatomical sites of the body,-image enhancing software intended for diagnosticpurpose.-software for programming a medical deviceThere is no medical purpose in the case of software used foradministration of general patient datag)multipurpose productsProducts with a multiple purpose which may be used occasionally in amedical environment are normally not medical devices, unless aspecific medical intended purpose is assigned to them. Examples :-multipurpose PC, printer, scanner, ..._magnetoscope, screen.1.2Definition of "accessory"The question whether a product is a "device" or a "accessory" has notpractical consequence. Following article 1(1) of Directive 93/42/EEC,"accessories shall be treated as medical devices in their own right". Therefore the main question is whether a product with a rather remote link to amedical use can still be considered as "accessory" (article 1(2)b) and as amatter of consequence is covered by the directive.The definition of "accessory" requires that the accessory is specificallyintended by the manufacturer of the accessory to be used together with adevice. The intended use of the accessory must be such as to enable a device to be used in accordance with its intended use. Therefore a product can only become an accessory to a medical device if the manufacturer of such aproduct establishes an intended use in conjunction with one or severalmedical devices.Examples for accessories depending on defined circumstances of device-related use :-sterilizers for use in a medical environment,-pouches for packaging re-sterilised medical devices,-specific battery chargers for battery driven electromedicaldevices,-contact lens care products, disinfectants specificallyintended for invasive medical devices-special water treatment device for use in conjunction withdialyzing machines,-gas cylinders/pressure release devices for use inconjunction with anaesthesia machines.1.3Definition of "manufacturer"Users in-house manufacturingThe Directive defines a manufacturer as the natural or legal personresponsible for defined manufacturing activities related to a device with aview to its being placed on the market under the manufacturers own name.The reason for this link with the placing on the market is that the directives aims to subject to its protection requirements the transaction of a device from the sphere of a manufacturer towards the public. The directive does notprovide any specific provisions for the case where a device is manufactured by the user (for example, a hospital) without being transferred to anotherperson. The decision to which extent such in-house manufacturing activities by hospitals are subjected to legal requirements, belongs therefore to thenational legislator. This relates however exclusively to such in-housemanufacturing activities where a device remains within the users, but not to cases where, for example, a hospital produces orthopaedic devices for usewith patients.。

EUROPEAN COMMISSIONDG ENTERPRISEDirectorate GGUIDELINES ON POST MARKET CLINICAL FOLLOW-UP上市后临床跟踪指南The present Guidelines are part of a set of Guidelines relating to questions of application of EC-Directives on medical devices. They are legally not binding. The Guidelines have been carefully drafted through a process of intensive consultation of the various interested parties (competent authorities, Commission services, industries, other interested parties) during which intermediate drafts were circulated and comments were taken up in the document. Therefore, this document reflects positions taken by representatives of interested parties in the medical devices sector.本准则是一个有关的欧共体指令对医疗设备的应用问题指引的一部分。

他们在法律上没有约束力。

该指引已审慎草拟通过各有关方面（主管机关，委员会的服务，工业，其他有关各方）在此期间，中间草案分发和评论的文件采取了密集的磋商进程。

因此，这份文件反映了有关各方的代表在该领域采取的医疗设备的位置。

EUROPEAN COMMISSIONDIRECTORATE GENERAL for HEALTH and CONSUMERSConsumer AffairsHealth technology and CosmeticsNoteThe present Guidelines are part of a set of Guidelines relating to questions of application of EC-Directives on medical Devices. They are legally not binding. The Guidelines have been carefully drafted through a process of intensive consultation of the various interest parties (competent authorities, Commission services, industries, other interested parties) during which intermediate drafts where circulated and comments were taken up in the document. Therefore, this document reflects positions taken by representatives of interest parties in the medical devices sector.CONTENTS12341. Introduction (3)52. Scope (4)63. References (4)74. Definitions (6)85. Circumstances where a post market clinical follow up study in indicated (8)96. Elements of a post-market clinical follow up study (10)107. The use of study data (12)118 The role of the notified body in post-market clinical follow up (12)121314Preface15This document is intended to be a guide for manufacturers and Notified Bodies on 16how to carry out Post-Market Clinical Follow-up (PMCF) studies in order to fulfil 17Post-Market Surveillance (PMS) obligations according to Section 3.1 of Annex II, 18Section 3 of Annex IV, Section 3 of Annex V, Section 3.1 of Annex VI or Section 4 19of Annex VII of the Medical Devices Directive (93/42/EEC) and Section 3.1 of 20Annex 2, Section 3 of Annex 4, Section 3.1 of Annex 5 of the Active Implantable 21Medical Devices Directive (90/385/EEC). These Sections refer to requirements of 22Annex X of Directive 93/42/EEC and Annex 7 of Directive 90/385/EEC, respectively.2324Attention is drawn to paragraph 8 of Article 15 of Directive 93/42/EEC which spells 25out the provisions of Article 15 that are not applicable to clinical investigations26conducted using CE-marked devices within their intended use.27Similarly when PMCF studies are conducted using CE marked devices within their28intended use, the provisions of section 2.3.5 of Annex X of Directive 93/42/EEC do 29not apply. However, the provisions of Directive 93/42/EEC concerning information 30and notification of incidents occurring following placing devices on the market are31fully applicable.321. Introduction3334While clinical evidence is an essential element of the premarket conformity 35assessment process to demonstrate conformity to Essential Requirements, it is 36important to recognise that there may be limitations to the clinical data available in 37the pre-market phase. Such limitations may be due to the duration of pre-market 38clinical investigations, the number of subjects and investigators involved in an 39investigation, the relative heterogeneity of subjects and investigators and/or the 40controlled setting of a clinical investigation versus the full range of clinical conditions 41encountered in general medical practice.4243A precondition for placing a product on the market is that conformity to the relevant44Essential Requirements, including a favourable benefit/risk ratio, has been 45demonstrated. The extent of the data that can be gathered in the pre-market phase 46does not necessarily enable the manufacturer to detect rare complications or problems 47that only become apparent after wide-spread or long term use of the device. As part of 48the manufacturer’s quality system, an appropriate post-market surveillance plan is key 49to identifying and investigating residual risks associated with the use of medical 50devices placed on the market. These residual risks should be investigated and assessed 51in the post-market phase through systematic Post-Market Clinical Follow-up (PMCF) 52study(ies).5354Clinical data obtained from post-market surveillance and during PMCF studies by the 55manufacturer are not intended to replace the pre-market data necessary to demonstrate 56conformity with the provisions of the legislation. However, they are critical to update 57the clinical evaluation throughout the life-cycle of the medical device and to ensure 58the long term safety and performance of devices after their placing on the market.5960PMCF studies are one of several options available in post-market surveillance and 61contribute to the risk management process.62636465662. Scope6768The objective of this document is to provide guidance on the appropriate use and 69conduct of PMCF studies to address issues linked to residual risks. The intention is 70not to impose new regulatory requirements.7172PMCF studies are an important element to be considered in PMCF or PMS plans. The 73principles for PMCF studies set out in this guidance are not intended to replace PMCF 74or PMS plans. They are or may be applicable to PMCF studies conducted for other 75purposes.7677This document provides guidance in relation to:78i)the circumstances where a PMCF study is indicated;79ii)the general principles of PMCF studies involving medical devices;80iii) the use of study data (for example to update instructions for use and labelling);81and82iv)the role of a notified body for medical devices in the assessment of PMCF plans 83and of the results obtained from the plans as part of conformity assessment.8485This document does not apply to in vitro diagnostic devices.86873. References8889Council Directive 93/42/EEC of 14 June 1993 concerning medical devices as last 90amended by Directive 2007/47/EC of the European Parliament and of the Council of 915 September 2007.9293Council Directive 90/385/EEC of 20 June 1990 on the approximation of the laws of 94the Member States relating to active implantable medical devices last amended by95Directive 2007/47/EC of the European Parliament and of the Council of 5 September 962007.979899100Interpretative Documents101102MEDDEV 2.7.1 Clinical Evaluation: A Guide for Manufacturers and Notified103Bodies104105106MEDDEV 2.7.1, Appendix 1Evaluation of Clinical Data – A Guide for Manufacturers and107Notified Bodies –Appendix 1: Clinical Evaluation of Coronary 108Stents109110111GHTF Final Documents:112SG1/N41:2005Essential Principles of Safety & Performance of Medical Devices 113SG1/N44:2008The Role of Standards in the Assessment of Medical Devices114SG1/N065:2010Registration of Manufacturers and Other Parties and Listing of 115Medical Devices116SG2/N47:2005Review of Current Requirements on Post-Market Surveillance117SG5/N1:2007Clinical Evidence – Key Definitions and Concepts118SG5/N2:2007Clinical Evaluation119SG5/N3:2010Clinical Investigations120121122International Standards:123EN ISO 14155:2011Clinical investigation of Medical Devices for human subjects 124Good clinical practice; Second edition 2011-02-01125126EN ISO 14971:2009 Application of risk management to medical devices127128Others:129US Department of Health and Human Service, Agency for Healthcare Research 130and Quality:131R egistries for Evaluating Patient Outcomes: a User’s Guide(Executive 132Summary, April 2007).1331341351361374. Definitions138139140Clinical Data1:141The safety and/or performance information that is generated from the use of a 142device.143Clinical data are sourced from:144-clinical investigation(s) of the device concerned; or145-clinical investigation(s) or other studies reported in the scientific literature 146of a similar device for which equivalence to the device in question can be 147demonstrated; or148-published and/or unpublished reports on other clinical experience of either 149the device in question or a similar device for which equivalence to the 150device in question can be demonstrated.151152Clinical Evaluation2:153The assessment and analysis of clinical data pertaining to a medical device to 154verify the clinical safety and performance of the device when used as intended 155by the manufacturer.156157Clinical Evidence2:158The clinical data and the clinical evaluation report pertaining to a medical 159device.160161Clinical Investigation2:162Any systematic investigation or study in or on one or more human subjects, 163undertaken to assess the safety or performance of a medical device.164165Device Registry3:166An organised system that uses observational study methods to collect defined 167clinical data under normal conditions of use relating to one or more devices to 1681Council Directives 90/385/EEC and 93/42/EEC2 GHTF document SG5/N1R8: 2007: Clinical Evidence – Key Definitions and Concepts3GHTF document SG5/N4:2010: Post Market Clinical Follow-Up Studies, based on the definition inAgency for Healthcare Research and Quality, “Registries for Evaluating Patient Outcomes: A User’sGuide”, as modified.evaluate specified outcomes for a population defined by a particular disease, 169condition, or exposure and that serves predetermined scientific, clinical or 170policy purpose(s).171172Note: The term “device registry” as defined in this guidance should not be 173confused with the concept of device registration and listing. (See GHTF 174SG1N065)175176Post-market clinical follow-up (PMCF) study:177A study carried out following the CE marking of a device and intended to 178answer specific questions relating to clinical safety or performance (i.e. residual 179risks) of a device when used in accordance with its approved labelling.180181PMCF plan:182The documented, proactive, organised methods and procedures set up by the 183manufacturer to collect clinical data based on the use of a CE-marked device 184corresponding to a particular design dossier or on the use of a group of medical 185devices belonging to the same subcategory or generic device group as defined 186in Directive 93/42/EEC. The objective is to confirm clinical performance and 187safety throughout the expected lifetime of the medical device, the acceptability 188of identified risks and to detect emerging risks on the basis of factual evidence. 189190Residual Risk:191Risk remaining after risk control measures has been taken4 .1921934EN ISO 149711945. Circumstances where a PMCF study is indicated195196Following a proper premarket clinical evaluation, the decision to conduct PMCF 197studies must be based on the identification of possible residual risks and/or unclarity 198on long term clinical performance that may impact the benefit/risk ratio.199200PMCF studies may review issues such as long-term performance and/or safety, the 201occurrence of clinical events (e.g. delayed hypersensitivity reactions, thrombosis), 202events specific to defined patient populations, or the performance and/or safety of the 203device in a more representative population of users and patients.204205Circumstances that may justify PMCF studies include, for example:206∙innovation, e.g., where the design of the device, the materials, substances, 207the principles of operation, the technology or the medical indications are 208novel;209∙significant changes to the products or to its intended use for which pre-210market clinical evaluation and re-certification has been completed;211∙high product related risk e.g. based on design, materials, components, 212invasiveness, clinical procedures;213∙high risk anatomical locations;214∙high risk target populations e.g. paediatrics, elderly;215∙severity of disease/treatment challenges;216∙questions of ability to generalise clinical investigation results;217∙unanswered questions of long-term safety and performance;218219∙results from any previous clinical investigation, including adverse events or from post-market surveillance activities;220∙identification of previously unstudied subpopulations which may show 221different benefit/risk-ratio e.g. hip implants in different ethnic 222populations;223∙continued validation in cases of discrepancy between reasonable 224premarket follow-up time scales and the expected life of the product;225∙risks identified from the literature or other data sources for similar 226marketed devices;227∙interaction with other medical products or treatments;228∙verification of safety and performance of device when exposed to a larger 229and more varied population of clinical users;230∙emergence of new information on safety or performance;231∙where CE marking was based on equivalence.232233PMCF studies may not be required when the medium/long-term safety and clinical 234performance are already known from previous use of the device or where other 235appropriate post-market surveillance activities would provide sufficient data to 236address the risks.2372382392402412426. Elements of a PMCF study243244Post-market clinical follow-up studies are performed on a device within its intended 245use/purpose(s) according to the instructions for use. It is important to note that PMCF 246studies must be conducted according to applicable laws and regulations and should 247involve an appropriate methodology and follow appropriate guidance and standards. 248249PMCF studies must be outlined as a well designed clinical investigation plan or study 250plan, and, as appropriate, include:251∙clearly stated research question(s), objective(s) and related endpoints;252∙scientifically sound design with an appropriate rationale and statistical analysis 253plan;254255∙a plan for conduct according to the appropriate standard(s);256∙a plan for an analysis of the data and for drawing appropriate conclusion(s).257Objectives of PMCF studies258The objective(s) of the study should be stated clearly and should address the residual 259risk(s) identified and be formulated to address one or more specific questions relating 260to the clinical safety or clinical performance of the device. A formal hypothesis 261should be clearly expressed.262263Design of PMCF studies264PMCF studies should be designed to address the objective(s) of the study. The design 265may vary based on the objective(s), study hypothesis research question and endpoints 266and should be scientifically sound to allow for valid conclusions to be drawn.267268PMCF studies can follow several methodologies, for example:269∙the extended follow-up of patients enrolled in premarket investigations;270∙ a new clinical investigation;271∙ a review of data derived from a device registry; or272∙ a review of relevant retrospective data from patients previously exposed to 273the device.274275PMCF studies should have a plan describing the design and methodologies 276appropriate for addressing the stated objectives. The clinical investigation plan/study 277plan should identify and where needed justify at a minimum:278∙the study population (corresponding to the CE-mark scope);279∙inclusion/exclusion criteria;280∙rational and justification of the chosen study design including use of 281controls/control groups (where relevant; randomised or not);282∙the selection of sites and investigators;283∙study objectives and related study endpoints and statistical considerations; 284∙the number of subjects involved;285∙the duration of patient follow-up;286∙the data to be collected;287∙the analysis plan including any interim reporting where appropriate to 288ensure continuous risk management based on clinical data; and289∙procedures/criteria for early study termination;290∙ethical considerations;291∙methods of quality control of data where appropriate.292293The points above may not all apply to a retrospective data review.294295296Implementation of the PMCF study, analysis of data and conclusion(s)297The study should:298∙be executed with adequate control measures to assure compliance with the 299clinical investigation or study plan;300∙include data analysis with conclusions drawn according to the analysis plan by 301someone with appropriate expertise; and302∙have a final report with conclusions relating back to original objective(s) and 303hypothesis/hypotheses.3043053063077. The use of study data308309The data and conclusions derived from the PMCF study are used to provide clinical 310evidence for the clinical evaluation process. This may result in the need to reassess 311whether the device continues to comply with the Essential Requirements. Such 312assessment may result in corrective or preventive actions, for example changes to the 313labelling/instructions for use, changes to manufacturing processes, changes to the 314device design, or public health notifications.3153168 The role of the notified body in PMCF317When auditing the quality system of the manufacturer in the framework of one of the 318conformity assessment annexes of Directive 90/385/EEC or of Directive 93/42/EEC, 319t he Notified Body (NB) shall review the appropriateness of the manufacturer’s 320general post-market surveillance procedures and plans, including plans for PMCF, as 321relevant.322323The Notified Body shall verify that PMCF as part of the overall clinical evaluation is 324conducted by or on behalf of the manufacturer by appropriately competent assessors 325(as per section 10.3 of MEDDEV 2.7/1).326327The NB shall verify that clinical investigations conducted as part of PMCF plans are 328conducted in accordance with the relevant provisions of Annex X (as per Article 15.8 329of 93/42/EEC), related guidance and relevant standards.330331The NB shall as part of its assessment of a specific medical device5:332∙verify that the manufacturer has appropriately considered the need for 333PMCF as part of post market surveillance based on the residual risks 334including those identified from the results of the clinical evaluation and 335from the characteristics of the medical device in accordance with section 5 336of the guidance;337∙verify that PMCF is conducted when clinical evaluation was based 338exclusively on clinical data from equivalent devices for initial conformity 3395 in accordance with Annex II.4, Annex II.7, Annex III, Annex V.6 and Annex VI.6 of Directive93/42/EEC and Annex II.4, Annex II.7, Annex III and Annex V.6 of Directive 90/385/EECassessment and that PMCF addresses the residual risks identified for the 340equivalent devices;341∙assess the appropriateness of any justification presented by a manufacturer 342for not conducting a specific PMCF plan as part of post market surveillance 343and seek appropriate remedy where the justification is not valid;344∙assess the appropriateness of the proposed PMCF plan in demonstrating the 345manufacturer’s stated objectives and addressing the residual risks and issues 346of long term clinical performance and safety identified for the specific 347device;348∙verify that data gathered by the manufacturer from PMCF, whether 349favourable or unfavourable, is being used to actively update the clinical 350evaluation (as well as the risk management system);351∙consider whether, based on the specific device assessment, data obtained 352from PMCF should be transmitted to the NB between scheduled assessment 353activities (e.g. surveillance audit, recertification assessment);354∙consider an appropriate period for certification of the product in order to set 355a particular time point at which PMCF data will be assessed by the NB or 356specific conditions relating to certification for subsequent follow up. (This 357decision may be based on the residual risks, the characteristics presented in 358section 5 and the clinical evaluation presented at the time of initial 359assessment. Conditions the NB may consider could include the need for the 360manufacturer to submit interim reports between certification reviews, of the 361clinical data generated from the PMCF and post-market surveillance 362system).363364。

上市后跟踪程序的发布和实施产生的文件、记录，按《文件控制程序》、《记录控制程序》的相关规定 执行。行政部确保本程序相关的文件和记录的保存期限为最后一个批次的产品出厂后的满 5 年。
6.0 REFERENCES 相关文件 6.1 上市后临床跟踪计划
ห้องสมุดไป่ตู้
·根据适当标准的实施计划。
·数据分析和得出适当结论的计划。
·临床调查的时机。
5.3.3 上市后临床跟踪研究的目标应被清晰地陈述，应可以解决识别的剩余风险。
5.3.4 上市后临床跟踪研究的设计，可以根据目标、研究假设、调查问题和终结点而变化，并应具备足够的
科学合理性从而可以产生有效的结论。
5.3.5 上市后临床跟踪研究可以采用以下方法之一或其组合：
2.0 SCOPE 范围 适用于本公司带有 CE 标识的医疗器械产品的上市后临床跟踪。
3.0 RESPONSIBILITIES 职责 3.1 管理者代表：负责组织落实产品符合 MDD 93/42/EEC 的要求。 3.2 技术部：负责按本程序及相关法规制定《上市后的临床跟踪计划》及相关文件，并根据汇总上市后的临 床数据，评价现有文件的适合性并修改相关的文件。 3.3 质管部：负责按本程序及相关法规对文件归档保存，负责产品相关的标签的控制。 3.3 市场部：负责审核《上市后的临床跟踪计划》，并在计划批准后按文件要求执行。 3.4 总经理：负责对《上市后的临床跟踪计划》的批准。
1.0 PURPOSE 目的 适当使用和执行上市后临床跟踪研究，来解决与剩余风险相关的问题，及时修改产品标签，
说明书的内容及技术文件，确保产品的持续安全有效，满足欧盟 MEDDEV 2.12 的要求。作为产品质量体系的 一部分，一个适当的市场监督程序，对上市产品识别使用中风险识别和风险研究的关键，特制定本程序。

欧盟医疗器械警戒系统指南——杨悦汤涵令狐昌黎刘东旭译从2008年1月1日起，欧盟开始实施新的《医疗器械警戒系统指南》（MEDDEV2.12/1-第五版，2007年4月发布，以下简称《指南》）。

该《指南》是在2001年4月发布的《欧盟医疗器械指令》（MEDDEV2.12/1-第四版，以下简称《指令》）基础上修订的，修订内容包括：1.将医疗器械全球协调行动任务组（GHTF）国际法规中关于医疗器械警戒及售后监督的指南性文件予以考虑，并将其相关内容转换成适用于欧盟的条款；2.介绍了欧盟医疗器械数据库（EUDAMED）；3.根据2001年《指令》实施的经验修改了一些规范性文件。

一、《指南》简介《指南》的主要内容有欧盟体系中医疗器械事件报告、评价及现场安全纠正措施（Field Safety Corrective Actions，以下简称FSCA），即医疗器械警戒系统的全部内容。

建立医疗器械警戒系统的主要目的是通过降低事件复发率的可能性来提高对患者、器械使用者及其他人的健康和安全的保护。

要达到这一目标，需有关部门通过对上报的不良事件进行评价，并利用适当的信息发布防止此类事件的重复发生或者减轻事件后果。

该《指南》旨在促进以下指令对医疗器械警戒系统所要求内容的统一应用和实施：1.有源植入式医疗器械指令（the Directive for Active Implantable Medical Devices，简称AIMD），90/385/EEC；2.医疗器械指令（the Directive for Medical Devices，简称MDD），93/42/EEC；3.体外诊断医疗器械指令（the In Vitro Diagnostic Medical Devices Directive，简称IVDD），98/79/EC。

现场安全纠正措施（FSCA）、现场安全通报（FSN）、错误使用和非正常使用均为该《指南》新加入的内容，目的是为了在促进医疗器械全球协调行动工作组（GHTF）制定的法规与欧盟环境相协调过程中，强化和明确欧盟医疗器械警戒系统。

MDR医疗器械法规考核试题一、选择题1.下列产品中,属于MDR指令适用范围的是（）［多选题］。

A、新冠抗原检测试剂B、连接呼吸机使用的面罩，C、用于化妆的美瞳√D、用于实时监测呼吸的软件V2.在MDR/IVDR规定中，以下附录规定了CE技术文件的具体内容（）［多选题］。

A、附录IB、附录DVC、附录ΠI√D、附录IV3.针对（）医疗器械,制造商需要编写PSUR（PeriodiCSafetyUPdaterePc）rt）并提交给公告机构评审。

［多选题］*A、I类医疗器械B、Hb类医疗器械√C、IIa类医疗器械√D、所有医疗器械4.针对（）医疗器械，在需要在发证前完成"C1inica1eva1uationConSUItationProCedUre"。

［多选题］*A、In类植入性医疗器械√B、∏a类医疗器械C、∏b类控制药物使用医疗器械√D、所有医疗器械5.11a类和IIb类医疗器械需要在（）之前，带有UDI编码才可销售［单选题］。

A、2019-05-26B、2023-05-26C、2023-05-26√D、2025-05-266.医疗器械进行符合性声明（Dec1arationofconformity）包含的内容（）侈选题］。

A、附录I+附录UB、附录IVVC、附录IXChaPter1D、产品的分类和分类规则V7.11a类医疗器械的定期安全更新报告PeriOdiCSafetyUPdaterePort（PSUR）需要最少每（泽更新一次，并提供给公告机构审查。

［单选题］*A、一B、二√C、ΞD、四8.对于医疗器械的CE技术文件保存的要求有？（）A、要保存在欧盟境内√B、仅由制造商保存即可C、在最后一个器械投放市场后，至少10年，可植入器械至少15年√D、在最后一个器械投放市场后，至少5年9.欧盟的Eudamed数据库将会包含以下信息（）［多选题］。

A、UDI-D1数据库B、SRN数据库√C、公告机构资质及CE证书查询数据库√D、临床研究数据库√E、警戒系统及市场抽查数据库V1（λ根据描述，请选择正确的经济运营商类型，把欧洲境外的产品投放欧洲市场的人（）［单选题］。

欧盟MDR临床评价和上市后临床跟踪欧盟MDR（Medical Device Regulation）是一项新的医疗器械法规，在2024年5月26日正式实施。

MDR为欧盟成员国监管机构提供了更为严格的要求，旨在确保医疗器械的安全性和有效性，并提高对患者的保护。

其中包括MDR对临床评价和上市后临床跟踪的规定。

首先，MDR对临床评价提出了更为严格的要求。

根据新法规，制造商需要进行一系列的临床评价来证明其产品的安全性和有效性。

临床评价应基于最新的医学和科学知识，并遵循科学方法和伦理原则。

此外，评价还应评估产品与患者的兼容性，以及产品在实际使用中的性能和效果。

临床评价的核心是临床试验，这是一项研究设计，旨在评估医疗器械在患者身上的安全性和有效性。

根据MDR的要求，试验应以符合道德要求的方式进行，并采取必要的措施保护参与者的权益。

此外，试验结果应具有科学和统计学的可信性，并进行详细的数据分析和结果报告。

除了临床评价，MDR还要求制造商进行上市后的临床跟踪。

这意味着一旦产品获得市场准入，制造商需要跟踪产品在实际使用中的性能和安全性，并及时收集和分析相关数据。

制造商还应与患者、医生和其他相关利益相关方进行沟通，以了解产品在实际使用中的效果和问题，并采取相应的改进措施。

总之，欧盟MDR对临床评价和上市后临床跟踪提出了更为严格的要求。

制造商需要进行临床评价以证明产品的安全性和有效性，并使用科学方法和伦理原则进行临床试验。

同时，制造商还需要进行上市后的临床跟踪，及时收集和分析相关数据，并与相关利益相关者进行沟通和合作。

这些规定旨在确保医疗器械的安全性和有效性，提高对患者的保护。

1、目的适当使用和执行上市后临床跟踪研究，来解决与剩余风险相关的问题，及时修改产品标签，说明书的内容及技术文件，确保产品的持续安全有效，满足欧盟MEDDEV 2.12/2 rev2（《GUIDELINES ON MEDICAL DEVICES：POST MARKET CLINICAL FOLLOW-UP STUDIES A GUIDE FOR MANUFACTURERS AND NOTIFIED BODIES》January 2012发布）的要求。

作为产品质量体系的一部分，一个适当的市场监督程序，对上市产品识别使用中风险识别和风险研究的关键，特制定本程序。

2、范围适用于本公司带有CE标识的医疗器械产品的销售后的临床数据跟踪。

3、职责3.1 管理者代表：负责组织落实产品符合MDD 93/42/EEC 的要求。

3.2 工程部：负责按本程序及相关法规制定《上市后的临床跟踪计划》及相关文件，并根据汇总上市后的临床数据，评价现有文件的适合性并修改相关的文件。

3.3 品管部：负责按本程序及相关法规对文件归档保存，负责产品相关的标签的控制。

3.3 业务部：负责审核《上市后的临床跟踪计划》，并在计划批准后按文件要求执行。

3.4 总经理：负责对《上市后的临床跟踪计划》的批准。

4、定义4.1 临床调查：在一个或更多的人类受试者上进行的任何系统性的调查或研究，从而评估医疗设备的安全性和性能。

4.2 上市后临床跟踪研究：跟随着设备的CE标记而执行的研究，其意图是回答与设备依照批准的标签使用时的临床安全性和性能(如剩余风险)相关的特定问题。

4.3 PMCF计划：制造商建立的备用证明文件的、前瞻性的、有组织的方法和程序，其根据与特定设计档案一致的CE标记产品的使用或属于相同亚类或MDD93/42/EEC指令中定义的一般设备组的一组医疗设备的使用来收集临床数据。

它的目标是在医疗设备的预期生命期中巩固临床表现和安全性和经鉴定的风险的可接受性，以及在事实证据的基础上探测产生的风险。

产品上市后跟踪管理程序（ISO13485）1.0⽬的为了识别和调查本公司的医疗器械产品上市销售后的医疗器械在使⽤过程中所具有的风险,特制定本程序。

2.0范围适⽤于本公司所有已经上市销售的医疗器械产品的上市后的临床监督。

3.0依据根据MEDDEV 2.12-2 进⾏。

4.0权责管理者代表：负责组织制定上市临床跟踪的计划及组织实施。

总经理：负责批准上市后临床跟踪的计划及为上市后临床跟踪提供保障和资源。

研发部、品质部、业务部：配合进⾏产品上市后临床跟踪计划及措施的实施。

5.0程序5.1 上市后临床跟踪策划：5.1.1针对公司的每⼀种上市后的医疗器械产品都应该策划，由公司管理者代表组织制订。

5.1.2在制订上市后临床跟踪计划时可以通过以下⽅式或渠道进⾏：对所有收到的投诉及不良事件的数据，系统的进⾏评审。

对制造商和发布的⽂献提供的所有信息来源进⾏评估。

对上市后的性能进⾏监测。

对上市前试验的病⼈的预期跟踪观察在器械已投放市场后，对⼀群有代表性病⼈进⾏前瞻性研究的⽅式进⾏对患者或使⽤者进⾏开放式的调查。

5.1.3这个计划需要考虑以下内容：临床调查的结果，包括识别的不良事件。

器械的平均预期寿命。

器械制造商的声明。

声明的等同性能。

适⽤的新信息。

当实施上市后临床跟踪时，须依据产品的⽤户⼿册，执⾏预产品预期暗⽰的⽤途。

对上市后的临床研究必须考虑到相应国家的法规。

5.1.4 上市后临床跟踪计划制定后由总经理负责批准。

5.2 上市后临床跟踪的实施：在上市后临床跟踪计划被批准后，由管理者代表根据划的内容组织相关⼈员进⾏按计划实施。

当实施PMCF时，须依据产品的⽤户⼿册，执⾏预产品预期暗⽰的⽤途。

对上市后的临床研究必须考虑到相应国家的法规。

在跟踪期间，应考虑到产品暗⽰的平均预期寿命，本公司各医疗器械产品的使⽤寿命具体见产品的设计⽂件或说明书。

5.3 信息评价：管理者代表应组织相关⼈员对收集到的信息进⾏及时评价及定期总结评价，并应保持评价的结果。