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Document 02017R0745-20230320
Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC (Text with EEA relevance)Text with EEA relevance
Consolidated text: Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC (Text with EEA relevance)Text with EEA relevance
Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC (Text with EEA relevance)Text with EEA relevance
02017R0745 — EN — 20.03.2023 — 003.001
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REGULATION (EU) 2017/745 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC (OJ L 117 5.5.2017, p. 1) |
Amended by:
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Official Journal |
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date |
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REGULATION (EU) 2020/561 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 23 April 2020 |
L 130 |
18 |
24.4.2020 |
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COMMISSION DELEGATED REGULATION (EU) 2023/502 of 1 December 2022 |
L 70 |
1 |
8.3.2023 |
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REGULATION (EU) 2023/607 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 15 March 2023 |
L 80 |
24 |
20.3.2023 |
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Corrected by:
REGULATION (EU) 2017/745 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL
of 5 April 2017
on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC
(Text with EEA relevance)
CHAPTER I
SCOPE AND DEFINITIONS
Article 1
Subject matter and scope
The necessary common specifications shall be adopted by ►M1 26 May 2021 ◄ . They shall apply as from six months after the date of their entry into force or from ►M1 26 May 2021 ◄ , whichever is the latest.
Notwithstanding Article 122, Member States' measures regarding the qualification of the products covered by Annex XVI as medical devices pursuant to Directive 93/42/EEC shall remain valid until the date of application, as referred to in the first subparagraph, of the relevant common specifications for that group of products.
This Regulation also applies to clinical investigations conducted in the Union concerning the products referred to in the first subparagraph.
This Regulation does not apply to:
in vitro diagnostic medical devices covered by Regulation (EU) 2017/746;
medicinal products as defined in point 2 of Article 1 of Directive 2001/83/EC. In deciding whether a product falls under Directive 2001/83/EC or under this Regulation, particular account shall be taken of the principal mode of action of the product;
advanced therapy medicinal products covered by Regulation (EC) No 1394/2007;
human blood, blood products, plasma or blood cells of human origin or devices which incorporate, when placed on the market or put into service, such blood products, plasma or cells, except for devices referred to in paragraph 8 of this Article;
cosmetic products covered by Regulation (EC) No 1223/2009;
transplants, tissues or cells of animal origin, or their derivatives, or products containing or consisting of them; however this Regulation does apply to devices manufactured utilising tissues or cells of animal origin, or their derivatives, which are non-viable or are rendered non-viable;
transplants, tissues or cells of human origin, or their derivatives, covered by Directive 2004/23/EC, or products containing or consisting of them; however this Regulation does apply to devices manufactured utilising derivatives of tissues or cells of human origin which are non-viable or are rendered non-viable;
products, other than those referred to in points (d), (f) and (g), that contain or consist of viable biological material or viable organisms, including living micro-organisms, bacteria, fungi or viruses in order to achieve or support the intended purpose of the product;
food covered by Regulation (EC) No 178/2002.
However, if the action of that substance is principal and not ancillary to that of the device, the integral product shall be governed by Directive 2001/83/EC or Regulation (EC) No 726/2004 of the European Parliament and of the Council ( 1 ), as applicable. In that case, the relevant general safety and performance requirements set out in Annex I to this Regulation shall apply as far as the safety and performance of the device part are concerned.
However, if the device intended to administer a medicinal product and the medicinal product are placed on the market in such a way that they form a single integral product which is intended exclusively for use in the given combination and which is not reusable, that single integral product shall be governed by Directive 2001/83/EC or Regulation (EC) No 726/2004, as applicable. In that case, the relevant general safety and performance requirements set out in Annex I to this Regulation shall apply as far as the safety and performance of the device part of the single integral product are concerned.
However, if the action of those tissues or cells or their derivatives is principal and not ancillary to that of the device and the product is not governed by Regulation (EC) No 1394/2007, the product shall be governed by Directive 2004/23/EC. In that case, the relevant general safety and performance requirements set out in Annex I to this Regulation shall apply as far as the safety and performance of the device part are concerned.
Article 2
Definitions
For the purposes of this Regulation, the following definitions apply:
‘medical device’ means any instrument, apparatus, appliance, software, implant, reagent, material or other article intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the following specific medical purposes:
and which does not achieve its principal intended action by pharmacological, immunological or metabolic means, in or on the human body, but which may be assisted in its function by such means.
The following products shall also be deemed to be medical devices:
‘accessory for a medical device’ means an article which, whilst not being itself a medical device, is intended by its manufacturer to be used together with one or several particular medical device(s) to specifically enable the medical device(s) to be used in accordance with its/their intended purpose(s) or to specifically and directly assist the medical functionality of the medical device(s) in terms of its/their intended purpose(s);
‘custom-made device’ means any device specifically made in accordance with a written prescription of any person authorised by national law by virtue of that person's professional qualifications which gives, under that person's responsibility, specific design characteristics, and is intended for the sole use of a particular patient exclusively to meet their individual conditions and needs.
However, mass-produced devices which need to be adapted to meet the specific requirements of any professional user and devices which are mass-produced by means of industrial manufacturing processes in accordance with the written prescriptions of any authorised person shall not be considered to be custom-made devices;
‘active device’ means any device, the operation of which depends on a source of energy other than that generated by the human body for that purpose, or by gravity, and which acts by changing the density of or converting that energy. Devices intended to transmit energy, substances or other elements between an active device and the patient, without any significant change, shall not be deemed to be active devices.
Software shall also be deemed to be an active device;
‘implantable device’ means any device, including those that are partially or wholly absorbed, which is intended:
by clinical intervention and which is intended to remain in place after the procedure.
Any device intended to be partially introduced into the human body by clinical intervention and intended to remain in place after the procedure for at least 30 days shall also be deemed to be an implantable device;
‘invasive device’ means any device which, in whole or in part, penetrates inside the body, either through a body orifice or through the surface of the body;
‘generic device group’ means a set of devices having the same or similar intended purposes or a commonality of technology allowing them to be classified in a generic manner not reflecting specific characteristics;
‘single-use device’ means a device that is intended to be used on one individual during a single procedure;
‘falsified device’ means any device with a false presentation of its identity and/or of its source and/or its CE marking certificates or documents relating to CE marking procedures. This definition does not include unintentional non-compliance and is without prejudice to infringements of intellectual property rights;
‘procedure pack’ means a combination of products packaged together and placed on the market with the purpose of being used for a specific medical purpose;
‘system’ means a combination of products, either packaged together or not, which are intended to be inter-connected or combined to achieve a specific medical purpose;
‘intended purpose’ means the use for which a device is intended according to the data supplied by the manufacturer on the label, in the instructions for use or in promotional or sales materials or statements and as specified by the manufacturer in the clinical evaluation;
‘label’ means the written, printed or graphic information appearing either on the device itself, or on the packaging of each unit or on the packaging of multiple devices;
‘instructions for use’ means the information provided by the manufacturer to inform the user of a device's intended purpose and proper use and of any precautions to be taken;
‘Unique Device Identifier’ (‘UDI’) means a series of numeric or alphanumeric characters that is created through internationally accepted device identification and coding standards and that allows unambiguous identification of specific devices on the market;
‘non-viable’ means having no potential for metabolism or multiplication;
‘derivative’ means a ‘non-cellular substance’ extracted from human or animal tissue or cells through a manufacturing process. The final substance used for manufacturing of the device in this case does not contain any cells or tissues;
‘nanomaterial’ means a natural, incidental or manufactured material containing particles in an unbound state or as an aggregate or as an agglomerate and where, for 50 % or more of the particles in the number size distribution, one or more external dimensions is in the size range 1-100 nm;
Fullerenes, graphene flakes and single-wall carbon nanotubes with one or more external dimensions below 1 nm shall also be deemed to be nanomaterials;
‘particle’, for the purposes of the definition of nanomaterial in point (18), means a minute piece of matter with defined physical boundaries;
‘agglomerate’, for the purposes of the definition of nanomaterial in point (18), means a collection of weakly bound particles or aggregates where the resulting external surface area is similar to the sum of the surface areas of the individual components;
‘aggregate’, for the purposes of the definition of nanomaterial in point (18), means a particle comprising of strongly bound or fused particles;
‘performance’ means the ability of a device to achieve its intended purpose as stated by the manufacturer;
‘risk’ means the combination of the probability of occurrence of harm and the severity of that harm;
‘benefit-risk determination’ means the analysis of all assessments of benefit and risk of possible relevance for the use of the device for the intended purpose, when used in accordance with the intended purpose given by the manufacturer;
‘compatibility’ is the ability of a device, including software, when used together with one or more other devices in accordance with its intended purpose, to:
perform without losing or compromising the ability to perform as intended, and/or
integrate and/or operate without the need for modification or adaption of any part of the combined devices, and/or
be used together without conflict/interference or adverse reaction.
‘interoperability’ is the ability of two or more devices, including software, from the same manufacturer or from different manufacturers, to:
exchange information and use the information that has been exchanged for the correct execution of a specified function without changing the content of the data, and/or
communicate with each other, and/or
work together as intended.
‘making available on the market’ means any supply of a device, other than an investigational device, for distribution, consumption or use on the Union market in the course of a commercial activity, whether in return for payment or free of charge;
‘placing on the market’ means the first making available of a device, other than an investigational device, on the Union market;
‘putting into service’ means the stage at which a device, other than an investigational device, has been made available to the final user as being ready for use on the Union market for the first time for its intended purpose;
‘manufacturer’ means a natural or legal person who manufactures or fully refurbishes a device or has a device designed, manufactured or fully refurbished, and markets that device under its name or trade mark;
‘fully refurbishing’, for the purposes of the definition of manufacturer, means the complete rebuilding of a device already placed on the market or put into service, or the making of a new device from used devices, to bring it into conformity with this Regulation, combined with the assignment of a new lifetime to the refurbished device;
‘authorised representative’ means any natural or legal person established within the Union who has received and accepted a written mandate from a manufacturer, located outside the Union, to act on the manufacturer's behalf in relation to specified tasks with regard to the latter's obligations under this Regulation;
‘importer’ means any natural or legal person established within the Union that places a device from a third country on the Union market;
‘distributor’ means any natural or legal person in the supply chain, other than the manufacturer or the importer, that makes a device available on the market, up until the point of putting into service;
‘economic operator’ means a manufacturer, an authorised representative, an importer, a distributor or the person referred to in Article 22(1) and 22(3);
‘health institution’ means an organisation the primary purpose of which is the care or treatment of patients or the promotion of public health;
‘user’ means any healthcare professional or lay person who uses a device;
‘lay person’ means an individual who does not have formal education in a relevant field of healthcare or medical discipline;
‘reprocessing’ means a process carried out on a used device in order to allow its safe reuse including cleaning, disinfection, sterilisation and related procedures, as well as testing and restoring the technical and functional safety of the used device;
‘conformity assessment’ means the process demonstrating whether the requirements of this Regulation relating to a device have been fulfilled;
‘conformity assessment body’ means a body that performs third-party conformity assessment activities including calibration, testing, certification and inspection;
‘notified body’ means a conformity assessment body designated in accordance with this Regulation;
‘CE marking of conformity’ or ‘CE marking’ means a marking by which a manufacturer indicates that a device is in conformity with the applicable requirements set out in this Regulation and other applicable Union harmonisation legislation providing for its affixing;
‘clinical evaluation’ means a systematic and planned process to continuously generate, collect, analyse and assess the clinical data pertaining to a device in order to verify the safety and performance, including clinical benefits, of the device when used as intended by the manufacturer;
‘clinical investigation’ means any systematic investigation involving one or more human subjects, undertaken to assess the safety or performance of a device;
‘investigational device’ means a device that is assessed in a clinical investigation;
‘clinical investigation plan’ means a document that describes the rationale, objectives, design, methodology, monitoring, statistical considerations, organisation and conduct of a clinical investigation;
‘clinical data’ means information concerning safety or performance that is generated from the use of a device and is sourced from the following:
‘sponsor’ means any individual, company, institution or organisation which takes responsibility for the initiation, for the management and setting up of the financing of the clinical investigation;
‘subject’ means an individual who participates in a clinical investigation;
‘clinical evidence’ means clinical data and clinical evaluation results pertaining to a device of a sufficient amount and quality to allow a qualified assessment of whether the device is safe and achieves the intended clinical benefit(s), when used as intended by the manufacturer;
‘clinical performance’ means the ability of a device, resulting from any direct or indirect medical effects which stem from its technical or functional characteristics, including diagnostic characteristics, to achieve its intended purpose as claimed by the manufacturer, thereby leading to a clinical benefit for patients, when used as intended by the manufacturer;
‘clinical benefit’ means the positive impact of a device on the health of an individual, expressed in terms of a meaningful, measurable, patient-relevant clinical outcome(s), including outcome(s) related to diagnosis, or a positive impact on patient management or public health;
‘investigator’ means an individual responsible for the conduct of a clinical investigation at a clinical investigation site;
‘informed consent’ means a subject's free and voluntary expression of his or her willingness to participate in a particular clinical investigation, after having been informed of all aspects of the clinical investigation that are relevant to the subject's decision to participate or, in the case of minors and of incapacitated subjects, an authorisation or agreement from their legally designated representative to include them in the clinical investigation;
‘ethics committee’ means an independent body established in a Member State in accordance with the law of that Member State and empowered to give opinions for the purposes of this Regulation, taking into account the views of laypersons, in particular patients or patients' organisations;
‘adverse event’ means any untoward medical occurrence, unintended disease or injury or any untoward clinical signs, including an abnormal laboratory finding, in subjects, users or other persons, in the context of a clinical investigation, whether or not related to the investigational device;
‘serious adverse event’ means any adverse event that led to any of the following:
death,
serious deterioration in the health of the subject, that resulted in any of the following:
life-threatening illness or injury,
permanent impairment of a body structure or a body function,
hospitalisation or prolongation of patient hospitalisation,
medical or surgical intervention to prevent life-threatening illness or injury or permanent impairment to a body structure or a body function,
chronic disease,
foetal distress, foetal death or a congenital physical or mental impairment or birth defect;
‘device deficiency’ means any inadequacy in the identity, quality, durability, reliability, safety or performance of an investigational device, including malfunction, use errors or inadequacy in information supplied by the manufacturer;
‘post-market surveillance’ means all activities carried out by manufacturers in cooperation with other economic operators to institute and keep up to date a systematic procedure to proactively collect and review experience gained from devices they place on the market, make available on the market or put into service for the purpose of identifying any need to immediately apply any necessary corrective or preventive actions;
‘market surveillance’ means the activities carried out and measures taken by competent authorities to check and ensure that devices comply with the requirements set out in the relevant Union harmonisation legislation and do not endanger health, safety or any other aspect of public interest protection;
‘recall’ means any measure aimed at achieving the return of a device that has already been made available to the end user;
‘withdrawal’ means any measure aimed at preventing a device in the supply chain from being further made available on the market;
‘incident’ means any malfunction or deterioration in the characteristics or performance of a device made available on the market, including use-error due to ergonomic features, as well as any inadequacy in the information supplied by the manufacturer and any undesirable side-effect;
‘serious incident’ means any incident that directly or indirectly led, might have led or might lead to any of the following:
the death of a patient, user or other person,
the temporary or permanent serious deterioration of a patient's, user's or other person's state of health,
a serious public health threat;
‘serious public health threat’ means an event which could result in imminent risk of death, serious deterioration in a person's state of health, or serious illness, that may require prompt remedial action, and that may cause significant morbidity or mortality in humans, or that is unusual or unexpected for the given place and time;
‘corrective action’ means action taken to eliminate the cause of a potential or actual non-conformity or other undesirable situation;
‘field safety corrective action’ means corrective action taken by a manufacturer for technical or medical reasons to prevent or reduce the risk of a serious incident in relation to a device made available on the market;
‘field safety notice’ means a communication sent by a manufacturer to users or customers in relation to a field safety corrective action;
‘harmonised standard’ means a European standard as defined in point (1)(c) of Article 2 of Regulation (EU) No 1025/2012;
‘common specifications’ (CS) means a set of technical and/or clinical requirements, other than a standard, that provides a means of complying with the legal obligations applicable to a device, process or system.
Article 3
Amendment of certain definitions
The Commission is empowered to adopt delegated acts in accordance with Article 115 in order to amend the definition of nanomaterial set out in point (18) and the related definitions in points (19), (20) and (21) of Article 2 in the light of technical and scientific progress and taking into account definitions agreed at Union and international level.
Article 4
Regulatory status of products
CHAPTER II
MAKING AVAILABLE ON THE MARKET AND PUTTING INTO SERVICE OF DEVICES, OBLIGATIONS OF ECONOMIC OPERATORS, REPROCESSING, CE MARKING, FREE MOVEMENT
Article 5
Placing on the market and putting into service
With the exception of the relevant general safety and performance requirements set out in Annex I, the requirements of this Regulation shall not apply to devices, manufactured and used only within health institutions established in the Union, provided that all of the following conditions are met:
the devices are not transferred to another legal entity,
manufacture and use of the devices occur under appropriate quality management systems,
the health institution justifies in its documentation that the target patient group's specific needs cannot be met, or cannot be met at the appropriate level of performance by an equivalent device available on the market,
the health institution provides information upon request on the use of such devices to its competent authority, which shall include a justification of their manufacturing, modification and use;
the health institution draws up a declaration which it shall make publicly available, including:
the name and address of the manufacturing health institution;
the details necessary to identify the devices;
a declaration that the devices meet the general safety and performance requirements set out in Annex I to this Regulation and, where applicable, information on which requirements are not fully met with a reasoned justification therefor,
the health institution draws up documentation that makes it possible to have an understanding of the manufacturing facility, the manufacturing process, the design and performance data of the devices, including the intended purpose, and that is sufficiently detailed to enable the competent authority to ascertain that the general safety and performance requirements set out in Annex I to this Regulation are met;
the health institution takes all necessary measures to ensure that all devices are manufactured in accordance with the documentation referred to in point (f), and
the health institution reviews experience gained from clinical use of the devices and takes all necessary corrective actions.
Member States may require that such health institutions submit to the competent authority any further relevant information about such devices which have been manufactured and used on their territory. Member States shall retain the right to restrict the manufacture and the use of any specific type of such devices and shall be permitted access to inspect the activities of the health institutions.
This paragraph shall not apply to devices that are manufactured on an industrial scale.
Article 6
Distance sales
Article 7
Claims
►C1 In the labelling, instructions for use, making available, putting into service and advertising of devices, it shall be prohibited to use text, names, trade marks, pictures and ◄ figurative or other signs that may mislead the user or the patient with regard to the device's intended purpose, safety and performance by:
ascribing functions and properties to the device which the device does not have;
creating a false impression regarding treatment or diagnosis, functions or properties which the device does not have;
failing to inform the user or the patient of a likely risk associated with the use of the device in line with its intended purpose;
suggesting uses for the device other than those stated to form part of the intended purpose for which the conformity assessment was carried out.
Article 8
Use of harmonised standards
The first subparagraph shall also apply to system or process requirements to be fulfilled in accordance with this Regulation by economic operators or sponsors, including those relating to quality management systems, risk management, post-market surveillance systems, clinical investigations, clinical evaluation or post-market clinical follow-up (‘PMCF’).
References in this Regulation to harmonised standards shall be understood as meaning harmonised standards the references of which have been published in the Official Journal of the European Union.
Article 9
Common specifications
Article 10
General obligations of manufacturers
The Commission is empowered to adopt delegated acts in accordance with Article 115 amending, in the light of technical progress, the Annexes II and III.
Upon request by a competent authority, the manufacturer shall, as indicated therein, provide that technical documentation in its entirety or a summary thereof.
A manufacturer with a registered place of business outside the Union shall, in order to allow its authorised representative to fulfil the tasks mentioned in Article 11(3), ensure that the authorised representative has the necessary documentation permanently available.
The quality management system shall cover all parts and elements of a manufacturer's organisation dealing with the quality of processes, procedures and devices. It shall govern the structure, responsibilities, procedures, processes and management resources required to implement the principles and actions necessary to achieve compliance with the provisions of this Regulation.
The quality management system shall address at least the following aspects:
a strategy for regulatory compliance, including compliance with conformity assessment procedures and procedures for management of modifications to the devices covered by the system;
identification of applicable general safety and performance requirements and exploration of options to address those requirements;
responsibility of the management;
resource management, including selection and control of suppliers and sub-contractors;
risk management as set out in in Section 3 of Annex I;
clinical evaluation in accordance with Article 61 and Annex XIV, including PMCF;
product realisation, including planning, design, development, production and service provision;
verification of the UDI assignments made in accordance with Article 27(3) to all relevant devices and ensuring consistency and validity of information provided in accordance with Article 29;
setting-up, implementation and maintenance of a post-market surveillance system, in accordance with Article 83;
handling communication with competent authorities, notified bodies, other economic operators, customers and/or other stakeholders;
processes for reporting of serious incidents and field safety corrective actions in the context of vigilance;
management of corrective and preventive actions and verification of their effectiveness;
processes for monitoring and measurement of output, data analysis and product improvement.
Where the device presents a serious risk, manufacturers shall immediately inform the competent authorities of the Member States in which they made the device available and, where applicable, the notified body that issued a certificate for the device in accordance with Article 56, in particular, of the non-compliance and of any corrective action taken.
If the manufacturer fails to cooperate or the information and documentation provided is incomplete or incorrect, the competent authority may, in order to ensure the protection of public health and patient safety, take all appropriate measures to prohibit or restrict the device's being made available on its national market, to withdraw the device from that market or to recall it until the manufacturer cooperates or provides complete and correct information.
If a competent authority considers or has reason to believe that a device has caused damage, it shall, upon request, facilitate the provision of the information and documentation referred to in the first subparagraph to the potentially injured patient or user and, as appropriate, the patient's or user's successor in title, the patient's or user's health insurance company or other third parties affected by the damage caused to the patient or user, without prejudice to data protection rules and, unless there is an overriding public interest in disclosure, without prejudice to the protection of intellectual property rights.
The competent authority need not comply with the obligation laid down in the third subparagraph where disclosure of the information and documentation referred to in the first subparagraph is ordinarily dealt with in the context of legal proceedings.
Manufacturers shall, in a manner that is proportionate to the risk class, type of device and the size of the enterprise, have measures in place to provide sufficient financial coverage in respect of their potential liability under Directive 85/374/EEC, without prejudice to more protective measures under national law.
Article 11
Authorised representative
The mandate shall require, and the manufacturer shall enable, the authorised representative to perform at least the following tasks in relation to the devices that it covers:
verify that the EU declaration of conformity and technical documentation have been drawn up and, where applicable, that an appropriate conformity assessment procedure has been carried out by the manufacturer;
keep available a copy of the technical documentation, the EU declaration of conformity and, if applicable, a copy of the relevant certificate, including any amendments and supplements, issued in accordance with Article 56, at the disposal of competent authorities for the period referred to in Article 10(8);
comply with the registration obligations laid down in Article 31 and verify that the manufacturer has complied with the registration obligations laid down in Articles 27 and 29;
in response to a request from a competent authority, provide that competent authority with all the information and documentation necessary to demonstrate the conformity of a device, in an official Union language determined by the Member State concerned;
forward to the manufacturer any request by a competent authority of the Member State in which the authorised representative has its registered place of business for samples, or access to a device and verify that the competent authority receives the samples or is given access to the device;
cooperate with the competent authorities on any preventive or corrective action taken to eliminate or, if that is not possible, mitigate the risks posed by devices;
immediately inform the manufacturer about complaints and reports from healthcare professionals, patients and users about suspected incidents related to a device for which they have been designated;
terminate the mandate if the manufacturer acts contrary to its obligations under this Regulation.
Article 12
Change of authorised representative
The detailed arrangements for a change of authorised representative shall be clearly defined in an agreement between the manufacturer, where practicable the outgoing authorised representative, and the incoming authorised representative. That agreement shall address at least the following aspects:
the date of termination of the mandate of the outgoing authorised representative and date of beginning of the mandate of the incoming authorised representative;
the date until which the outgoing authorised representative may be indicated in the information supplied by the manufacturer, including any promotional material;
the transfer of documents, including confidentiality aspects and property rights;
the obligation of the outgoing authorised representative after the end of the mandate to forward to the manufacturer or incoming authorised representative any complaints or reports from healthcare professionals, patients or users about suspected incidents related to a device for which it had been designated as authorised representative.
Article 13
General obligations of importers
In order to place a device on the market, importers shall verify that:
the device has been CE marked and that the EU declaration of conformity of the device has been drawn up;
a manufacturer is identified and that an authorised representative in accordance with Article 11 has been designated by the manufacturer;
the device is labelled in accordance with this Regulation and accompanied by the required instructions for use;
where applicable, a UDI has been assigned by the manufacturer in accordance with Article 27.
Where an importer considers or has reason to believe that a device is not in conformity with the requirements of this Regulation, it shall not place the device on the market until it has been brought into conformity and shall inform the manufacturer and the manufacturer's authorised representative. Where the importer considers or has reason to believe that the device presents a serious risk or is a falsified device, it shall also inform the competent authority of the Member State in which the importer is established.
Article 14
General obligations of distributors
Before making a device available on the market, distributors shall verify that all of the following requirements are met:
the device has been CE marked and that the EU declaration of conformity of the device has been drawn up;
the device is accompanied by the information to be supplied by the manufacturer in accordance with Article 10(11);
for imported devices, the importer has complied with the requirements set out in Article 13(3);
that, where applicable, a UDI has been assigned by the manufacturer.
In order to meet the requirements referred to in points (a), (b) and (d) of the first subparagraph the distributor may apply a sampling method that is representative of the devices supplied by that distributor.
Where a distributor considers or has reason to believe that a device is not in conformity with the requirements of this Regulation, it shall not make the device available on the market until it has been brought into conformity, and shall inform the manufacturer and, where applicable, the manufacturer's authorised representative, and the importer. Where the distributor considers or has reason to believe that the device presents a serious risk or is a falsified device, it shall also inform the competent authority of the Member State in which it is established.
Distributors shall be considered to have fulfilled the obligation referred to in the first subparagraph when the manufacturer or, where applicable, the authorised representative for the device in question provides the required information. Distributors shall cooperate with competent authorities, at their request, on any action taken to eliminate the risks posed by devices which they have made available on the market. Distributors, upon request by a competent authority, shall provide free samples of the device or, where that is impracticable, grant access to the device.
Article 15
Person responsible for regulatory compliance
Manufacturers shall have available within their organisation at least one person responsible for regulatory compliance who possesses the requisite expertise in the field of medical devices. The requisite expertise shall be demonstrated by either of the following qualifications:
a diploma, certificate or other evidence of formal qualification, awarded on completion of a university degree or of a course of study recognised as equivalent by the Member State concerned, in law, medicine, pharmacy, engineering or another relevant scientific discipline, and at least one year of professional experience in regulatory affairs or in quality management systems relating to medical devices;
four years of professional experience in regulatory affairs or in quality management systems relating to medical devices.
Without prejudice to national provisions regarding professional qualifications, manufacturers of custom-made devices may demonstrate the requisite expertise referred to in the first subparagraph by having at least two years of professional experience within a relevant field of manufacturing.
The person responsible for regulatory compliance shall at least be responsible for ensuring that:
the conformity of the devices is appropriately checked, in accordance with the quality management system under which the devices are manufactured, before a device is released;
the technical documentation and the EU declaration of conformity are drawn up and kept up-to-date;
the post-market surveillance obligations are complied with in accordance with Article 10(10);
the reporting obligations referred to in Articles 87 to 91 are fulfilled;
in the case of investigational devices, the statement referred to in Section 4.1 of Chapter II of Annex XV is issued.
Authorised representatives shall have permanently and continuously at their disposal at least one person responsible for regulatory compliance who possesses the requisite expertise regarding the regulatory requirements for medical devices in the Union. The requisite expertise shall be demonstrated by either of the following qualifications:
a diploma, certificate or other evidence of formal qualification, awarded on completion of a university degree or of a course of study recognised as equivalent by the Member State concerned, in law, medicine, pharmacy, engineering or another relevant scientific discipline, and at least one year of professional experience in regulatory affairs or in quality management systems relating to medical devices;
four years of professional experience in regulatory affairs or in quality management systems relating to medical devices.
Article 16
Cases in which obligations of manufacturers apply to importers, distributors or other persons
A distributor, importer or other natural or legal person shall assume the obligations incumbent on manufacturers if it does any of the following:
makes available on the market a device under its name, registered trade name or registered trade mark, except in cases where a distributor or importer enters into an agreement with a manufacturer whereby the manufacturer is identified as such on the label and is responsible for meeting the requirements placed on manufacturers in this Regulation;
changes the intended purpose of a device already placed on the market or put into service;
modifies a device already placed on the market or put into service in such a way that compliance with the applicable requirements may be affected.
The first subparagraph shall not apply to any person who, while not considered a manufacturer as defined in point (30) of Article 2, assembles or adapts for an individual patient a device already on the market without changing its intended purpose.
For the purposes of point (c) of paragraph 1, the following shall not be considered to be a modification of a device that could affect its compliance with the applicable requirements:
provision, including translation, of the information supplied by the manufacturer, in accordance with Section 23 of Annex I, relating to a device already placed on the market and of further information which is necessary in order to market the device in the relevant Member State;
changes to the outer packaging of a device already placed on the market, including a change of pack size, if the repackaging is necessary in order to market the device in the relevant Member State and if it is carried out in such conditions that the original condition of the device cannot be affected by it. In the case of devices placed on the market in sterile condition, it shall be presumed that the original condition of the device is adversely affected if the packaging that is necessary for maintaining the sterile condition is opened, damaged or otherwise negatively affected by the repackaging.
Distributors and importers shall ensure that they have in place a quality management system that includes procedures which ensure that the translation of information is accurate and up-to-date, and that the activities mentioned in points (a) and (b) of paragraph 2 are performed by a means and under conditions that preserve the original condition of the device and that the packaging of the repackaged device is not defective, of poor quality or untidy. The quality management system shall cover, inter alia, procedures ensuring that the distributor or importer is informed of any corrective action taken by the manufacturer in relation to the device in question in order to respond to safety issues or to bring it into conformity with this Regulation.
Article 17
Single-use devices and their reprocessing
By way of derogation from paragraph 2, as regards single-use devices that are reprocessed and used within a health institution, Member States may decide not to apply all of the rules relating to manufacturers' obligations laid down in this Regulation provided that they ensure that:
the safety and performance of the reprocessed device is equivalent to that of the original device and the requirements in points (a), (b), (d), (e), (f), (g) and (h) of Article 5(5) are complied with;
the reprocessing is performed in accordance with CS detailing the requirements concerning:
Member States shall encourage, and may require, health institutions to provide information to patients on the use of reprocessed devices within the health institution and, where appropriate, any other relevant information on the reprocessed devices that patients are treated with.
Member States shall notify the Commission and the other Member States of the national provisions introduced pursuant to this paragraph and the grounds for introducing them. The Commission shall keep the information publicly available.
The name and address of the manufacturer of the original single-use device shall no longer appear on the label, but shall be mentioned in the instructions for use of the reprocessed device.
A Member State that permits reprocessing of single-use devices may maintain or introduce national provisions that are stricter than those laid down in this Regulation and which restrict or prohibit, within its territory, the following:
the reprocessing of single-use devices and the transfer of single-use devices to another Member State or to a third country with a view to their reprocessing;
the making available or further use of reprocessed single-use devices.
Member States shall notify the Commission and the other Member States of those national provisions. The Commission shall make such information publicly available.
Article 18
Implant card and information to be supplied to the patient with an implanted device
The manufacturer of an implantable device shall provide together with the device the following:
information allowing the identification of the device, including the device name, serial number, lot number, the UDI, the device model, as well as the name, address and the website of the manufacturer;
any warnings, precautions or measures to be taken by the patient or a healthcare professional with regard to reciprocal interference with reasonably foreseeable external influences, medical examinations or environmental conditions;
any information about the expected lifetime of the device and any necessary follow-up;
any other information to ensure safe use of the device by the patient, including the information in point (u) of Section 23.4 of Annex I.
The information referred to in the first subparagraph shall be provided, for the purpose of making it available to the particular patient who has been implanted with the device, by any means that allow rapid access to that information and shall be stated in the language(s) determined by the concerned Member State. The information shall be written in a way that is readily understood by a lay person and shall be updated where appropriate. Updates of the information shall be made available to the patient via the website mentioned in point (a) of the first subparagraph.
In addition, the manufacturer shall provide the information referred to in point (a) of the first subparagraph on an implant card delivered with the device.
Article 19
EU declaration of conformity
Article 20
CE marking of conformity
Article 21
Devices for special purposes
Member States shall not create obstacles to:
investigational devices being supplied to an investigator for the purpose of a clinical investigation if they meet the conditions laid down in Articles 62 to 80 and Article 82, in the implementing acts adopted pursuant to Article 81 and in Annex XV;
custom-made devices being made available on the market if Article 52(8) and Annex XIII have been complied with.
The devices referred to in the first subparagraph shall not bear the CE marking, with the exception of the devices referred to in Article 74.
Member States may require that the manufacturer of a custom-made device submit to the competent authority a list of such devices which have been made available in their territory.
Article 22
Systems and procedure packs
Natural or legal persons shall draw up a statement if they combine devices bearing a CE marking with the following other devices or products, in a manner that is compatible with the intended purpose of the devices or other products and within the limits of use specified by their manufacturers, in order to place them on the market as a system or procedure pack:
other devices bearing the CE marking;
in vitro diagnostic medical devices bearing the CE marking in conformity with Regulation (EU) 2017/746;
other products which are in conformity with legislation that applies to those products only where they are used within a medical procedure or their presence in the system or procedure pack is otherwise justified.
In the statement made pursuant to paragraph 1, the natural or legal person concerned shall declare that:
they verified the mutual compatibility of the devices and, if applicable other products, in accordance with the manufacturers' instructions and have carried out their activities in accordance with those instructions;
they packaged the system or procedure pack and supplied relevant information to users incorporating the information to be supplied by the manufacturers of the devices or other products which have been put together;
the activity of combining devices and, if applicable, other products as a system or procedure pack was subject to appropriate methods of internal monitoring, verification and validation.
Article 23
Parts and components
Article 24
Free movement
Except where otherwise provided for in this Regulation, Member States shall not refuse, prohibit or restrict the making available on the market or putting into service within their territory of devices which comply with the requirements of this Regulation.
CHAPTER III
IDENTIFICATION AND TRACEABILITY OF DEVICES, REGISTRATION OF DEVICES AND OF ECONOMIC OPERATORS, SUMMARY OF SAFETY AND CLINICAL PERFORMANCE, EUROPEAN DATABASE ON MEDICAL DEVICES
Article 25
Identification within the supply chain
Economic operators shall be able to identify the following to the competent authority, for the period referred to in Article 10(8):
any economic operator to whom they have directly supplied a device;
any economic operator who has directly supplied them with a device;
any health institution or healthcare professional to which they have directly supplied a device.
Article 26
Medical devices nomenclature
To facilitate the functioning of the European database on medical devices (‘Eudamed’) as referred to in Article 33, the Commission shall ensure that an internationally recognised medical devices nomenclature is available free of charge to manufacturers and other natural or legal persons required by this Regulation to use that nomenclature. The Commission shall also endeavour to ensure that that nomenclature is available to other stakeholders free of charge, where reasonably practicable.
Article 27
Unique Device Identification system
The Unique Device Identification system (‘UDI system’) described in Part C of Annex VI shall allow the identification and facilitate the traceability of devices, other than custom-made and investigational devices, and shall consist of the following:
production of a UDI that comprises the following:
a UDI device identifier (‘UDI-DI’) specific to a manufacturer and a device, providing access to the information laid down in Part B of Annex VI;
a UDI production identifier (‘UDI-PI’) that identifies the unit of device production and if applicable the packaged devices, as specified in Part C of Annex VI;
placing of the UDI on the label of the device or on its packaging;
storage of the UDI by economic operators, health institutions and healthcare professionals, in accordance with the conditions laid down in paragraphs 8 and 9 of this Article respectively;
establishment of an electronic system for Unique Device Identification (‘UDI database’) in accordance with Article 28.
The Commission shall, by means of implementing acts, designate one or several entities to operate a system for assignment of UDIs pursuant to this Regulation (‘issuing entity’). That entity or those entities shall satisfy all of the following criteria:
the entity is an organisation with legal personality;
its system for the assignment of UDIs is adequate to identify a device throughout its distribution and use in accordance with the requirements of this Regulation;
its system for the assignment of UDIs conforms to the relevant international standards;
the entity gives access to its system for the assignment of UDIs to all interested users in accordance with a set of predetermined and transparent terms and conditions;
the entity undertakes to do the following:
operate its system for the assignment of UDIs for at least 10 years after its designation;
make available to the Commission and to the Member States, upon request, information concerning its system for the assignment of UDIs;
remain in compliance with the criteria for designation and the terms of designation.
When designating issuing entities, the Commission shall endeavour to ensure that UDI carriers, as defined in Part C of Annex VI, are universally readable regardless of the system used by the issuing entity, with a view to minimising financial and administrative burdens for economic operators and health institutions.
Before a device, other than a custom-made or investigational device, is placed on the market the manufacturer shall ensure that the information referred to in Part B of Annex VI of the device in question are correctly submitted and transferred to the UDI database referred to in Article 28.
Economic operators shall store and keep, preferably by electronic means, the UDI of the devices which they have supplied or with which they have been supplied, if those devices belong to:
For devices other than class III implantable devices, Member States shall encourage, and may require, health institutions to store and keep, preferably by electronic means, the UDI of the devices with which they have been supplied.
Member States shall encourage, and may require, healthcare professionals to store and keep preferably by electronic means, the UDI of the devices with which they have been supplied with.
The Commission is empowered to adopt delegated acts in accordance with Article 115:
amending the list of information set out in Part B of Annex VI in the light of technical progress; and
amending Annex VI in the light of international developments and technical progress in the field of Unique Device Identification.
The Commission may, by means of implementing acts, specify the detailed arrangements and the procedural aspects for the UDI system with a view to ensuring its harmonised application in relation to any of the following:
determining the devices, categories or groups of devices to which the obligation laid down in paragraph 8 is to apply;
specifying the data to be included in the UDI-PI of specific devices or device groups;
The implementing acts referred to in the first subparagraph shall be adopted in accordance with the examination procedure referred to in Article 114(3).
When adopting the measures referred to in paragraph 11, the Commission shall take into account all of the following:
confidentiality and data protection as referred to in Articles 109 and 110 respectively;
the risk-based approach;
the cost-effectiveness of the measures;
the convergence of UDI systems developed at international level;
the need to avoid duplications in the UDI system;
the needs of the healthcare systems of the Member States, and where possible, compatibility with other medical device identification systems that are used by stakeholders.
Article 28
UDI database
Article 29
Registration of devices
For the devices referred to in the first subparagraph, the notified body shall include a reference to the Basic UDI-DI on the certificate issued in accordance with point (a) of Section 4 of Chapter I of Annex XII and confirm in Eudamed that the information referred to in Section 2.2 of Part A of Annex VI is correct. After the issuing of the relevant certificate and before placing the device on the market, the manufacturer shall provide the Basic UDI-DI to the UDI database together with the other core data elements referred to in Part B of Annex VI related to that device.
Article 30
Electronic system for registration of economic operators
Where applicable, importers shall inform the relevant authorised representative or manufacturer if the information referred to in paragraph 1 is not included or is incorrect. Importers shall add their details to the relevant entry/entries.
Article 31
Registration of manufacturers, authorised representatives and importers
Article 32
Summary of safety and clinical performance
The summary of safety and clinical performance shall be written in a way that is clear to the intended user and, if relevant, to the patient and shall be made available to the public via Eudamed.
The draft of the summary of safety and clinical performance shall be part of the documentation to be submitted to the notified body involved in the conformity assessment pursuant to Article 52 and shall be validated by that body. After its validation, the notified body shall upload the summary to Eudamed. The manufacturer shall mention on the label or instructions for use where the summary is available.
The summary of safety and clinical performance shall include at least the following aspects:
the identification of the device and the manufacturer, including the Basic UDI-DI and, if already issued, the SRN;
the intended purpose of the device and any indications, contraindications and target populations;
a description of the device, including a reference to previous generation(s) or variants if such exist, and a description of the differences, as well as, where relevant, a description of any accessories, other devices and products, which are intended to be used in combination with the device;
possible diagnostic or therapeutic alternatives;
reference to any harmonised standards and CS applied;
the summary of clinical evaluation as referred to in Annex XIV, and relevant information on post-market clinical follow-up;
suggested profile and training for users;
information on any residual risks and any undesirable effects, warnings and precautions.
Article 33
European database on medical devices
The Commission, after consulting the MDCG, shall set up, maintain and manage the European database on medical devices (‘Eudamed’) for the following purposes:
to enable the public to be adequately informed about devices placed on the market, the corresponding certificates issued by notified bodies and about the relevant economic operators;
to enable unique identification of devices within the internal market and to facilitate their traceability;
to enable the public to be adequately informed about clinical investigations and to enable sponsors of clinical investigations to comply with obligations under Articles 62 to 80, Article 82, and any acts adopted pursuant to Article 81;
to enable manufacturers to comply with the information obligations laid down in Articles 87 to 90 or in any acts adopted pursuant to Article 91;
to enable the competent authorities of the Member States and the Commission to carry out their tasks relating to this Regulation on a well-informed basis and to enhance the cooperation between them.
Eudamed shall include the following electronic systems:
the electronic system for registration of devices referred to in Article 29(4);
the UDI-database referred to in Article 28;
the electronic system on registration of economic operators referred to in Article 30;
the electronic system on notified bodies and on certificates referred to in Article 57;
the electronic system on clinical investigations referred to in Article 73;
the electronic system on vigilance and post-market surveillance referred to in Article 92;
the electronic system on market surveillance referred to in Article 100.
The Commission shall ensure that public parts of Eudamed are presented in a user-friendly and easily-searchable format.
Article 34
Functionality of Eudamed
CHAPTER IV
NOTIFIED BODIES
Article 35
Authorities responsible for notified bodies
Where the authority responsible for notified bodies is a different authority from the national competent authority for medical devices, it shall ensure that the national authority responsible for medical devices is consulted on relevant matters.
Article 36
Requirements relating to notified bodies
In order to meet the requirements referred to in the first subparagraph, notified bodies shall have permanent availability of sufficient administrative, technical and scientific personnel in accordance with Section 3.1.1 of Annex VII and personnel with relevant clinical expertise in accordance with Section 3.2.4 of Annex VII, where possible employed by the notified body itself.
The personnel referred to in Sections 3.2.3 and 3.2.7 of Annex VII shall be employed by the notified body itself and shall not be external experts or subcontractors.
Article 37
Subsidiaries and subcontracting
Article 38
Application by conformity assessment bodies for designation
In respect of the organisational and general requirements and the quality management requirements set out in Sections 1 and 2 of Annex VII, a valid accreditation certificate and the corresponding evaluation report delivered by a national accreditation body in accordance with Regulation (EC) No 765/2008 may be submitted and shall be taken into consideration during the assessment described in Article 39. However, the applicant shall make available all the documentation referred to in the first subparagraph to demonstrate compliance with those requirements upon request.
Article 39
Assessment of the application
The authority responsible for notified bodies shall review the application and supporting documentation in accordance with its own procedures and shall draw up a preliminary assessment report.
The joint assessment team shall be comprised of experts who are competent to assess the conformity assessment activities and the types of devices which are the subject of the application or, in particular when the assessment procedure is initiated in accordance with Article 47(3), to ensure that the specific concern can be appropriately assessed.
The authority responsible for notified bodies together with the joint assessment team shall plan and conduct an on-site assessment of the applicant conformity assessment body and, where relevant, of any subsidiary or subcontractor, located inside or outside the Union, to be involved in the conformity assessment process.
The on-site assessment of the applicant body shall be led by the authority responsible for notified bodies.
At the end of the on-site assessment, the authority responsible for notified bodies shall list for the applicant conformity assessment body the non-compliances resulting from the assessment and summarise the assessment by the joint assessment team.
Within a specified timeframe, the applicant conformity assessment body shall submit to the national authority a corrective and preventive action plan to address the non-compliances.
The authority responsible for notified bodies shall having confirmed the corrective and preventive action plan forward it and its opinion thereon to the joint assessment team. The joint assessment team may request of the authority responsible for notified bodies further clarification and modifications.
The authority responsible for notified bodies shall draw up its final assessment report which shall include:
Article 40
Nomination of experts for joint assessment of applications for notification
Article 41
Language requirements
All documents required pursuant to Articles 38 and 39 shall be drawn up in a language or languages which shall be determined by the Member State concerned.
Member States, in applying the first paragraph, shall consider accepting and using a commonly understood language in the medical field, for all or part of the documentation concerned.
The Commission shall provide translations of the documentation pursuant to Articles 38 and 39, or parts thereof into an official Union language, such as is necessary for that documentation to be readily understood by the joint assessment team appointed in accordance with Article 39(3).
Article 42
Designation and notification procedure
Article 43
Identification number and list of notified bodies
Article 44
Monitoring and re-assessment of notified bodies
The authority responsible for notified bodies shall conduct its monitoring and assessment activities according to an annual assessment plan to ensure that it can effectively monitor the continued compliance of the notified body with the requirements of this Regulation. That plan shall provide a reasoned schedule for the frequency of assessment of the notified body and, in particular, associated subsidiaries and subcontractors. The authority shall submit its annual plan for monitoring or assessment for each notified body for which it is responsible to the MDCG and to the Commission.
The authority responsible for notified bodies shall provide for a systematic follow-up of complaints and other information, including from other Member States, which may indicate non-fulfilment of the obligations by a notified body or its deviation from common or best practice.
The authority responsible for notified bodies of the Member State in which the notified body is established may conduct a complete re-assessment prior to the dates referred to in the first subparagraph, upon request by the notified body or where, based on the results of the annual assessments conducted in accordance with paragraph 4 of this Article, it has concerns regarding the continued fulfilment by the notified body of the requirements set out in Annex VII.
Complete re-assessments that have already started prior to 11 March 2023 shall continue to be conducted, unless the authority responsible for notified bodies of the Member State in which the notified body is established decides to suspend or terminate the ongoing complete re-assessment, taking into account its own resources and the resources of the notified body already spent on the re-assessment, as well as the results of the annual assessments conducted in accordance with paragraph 4 of this Article. Before suspending or terminating an ongoing complete re-assessment, the authority responsible for notified bodies shall hear the notified body concerned.
The summary of the report shall be uploaded to the electronic system referred to in Article 57.
Article 45
Review of notified body assessment of technical documentation and clinical evaluation documentation
Article 46
Changes to designations and notifications
The procedures described in Article 39 and in Article 42 shall apply to extensions of the scope of the designation.
For changes to the designation other than extensions of its scope, the procedures laid down in the following paragraphs shall apply.
The authority responsible for notified bodies shall immediately inform the Commission and the other Member States of any suspension, restriction or withdrawal of a designation.
In the event of restriction, suspension or withdrawal of a designation, the authority responsible for notified bodies shall:
assess the impact on the certificates issued by the notified body;
submit a report on its findings to the Commission and the other Member States within three months of having notified the changes to the designation;
require the notified body to suspend or withdraw, within a reasonable period of time determined by the authority, any certificates which were unduly issued to ensure the safety of devices on the market;
enter into the electronic system referred to in Article 57 information in relation to certificates of which it has required their suspension or withdrawal;
inform the competent authority for medical devices of the Member State in which the manufacturer has its registered place of business through the electronic system referred to in Article 57 of the certificates for which it has required suspension or withdrawal. That competent authority shall take the appropriate measures, where necessary to avoid a potential risk to the health or safety of patients, users or others.
With the exception of certificates unduly issued, and where a designation has been suspended or restricted, the certificates shall remain valid in the following circumstances:
the authority responsible for notified bodies has confirmed, within one month of the suspension or restriction, that there is no safety issue in relation to certificates affected by the suspension or restriction, and the authority responsible for notified bodies has outlined a timeline and actions anticipated to remedy the suspension or restriction; or
the authority responsible for notified bodies has confirmed that no certificates relevant to the suspension will be issued, amended or re-issued during the course of the suspension or restriction, and states whether the notified body has the capability of continuing to monitor and remain responsible for existing certificates issued for the period of the suspension or restriction. In the event that the authority responsible for notified bodies determines that the notified body does not have the capability to support existing certificates issued, the manufacturer shall provide, to the competent authority for medical devices of the Member State in which the manufacturer of the device covered by the certificate has its registered place of business, within three months of the suspension or restriction, a written confirmation that another qualified notified body is temporarily assuming the functions of the notified body to monitor and remain responsible for the certificates during the period of suspension or restriction.
With the exception of certificates unduly issued, and where a designation has been withdrawn, the certificates shall remain valid for a period of nine months in the following circumstances:
where the competent authority for medical devices of the Member State in which the manufacturer of the device covered by the certificate has its registered place of business has confirmed that there is no safety issue associated with the devices in question; and
another notified body has confirmed in writing that it will assume immediate responsibilities for those devices and will have completed assessment of them within twelve months of the withdrawal of the designation.
In the circumstances referred to in the first subparagraph, the competent authority for medical devices of the Member State in which the manufacturer of the device covered by the certificate has its place of business may extend the provisional validity of the certificates for further periods of three months, which altogether shall not exceed twelve months.
The authority or the notified body assuming the functions of the notified body affected by the change of designation shall immediately inform the Commission, the other Member States and the other notified bodies thereof.
Article 47
Challenge to the competence of notified bodies
Where the Member State fails to take the necessary corrective measures, the Commission may, by means of implementing acts, suspend, restrict or withdraw the designation. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 114(3). It shall notify the Member State concerned of its decision and update NANDO and the electronic system referred to in Article 57.
Article 48
Peer review and exchange of experience between authorities responsible for notified bodies
The Commission shall provide for the organisation of exchange of experience and coordination of administrative practice between the authorities responsible for notified bodies. Such exchange shall cover elements including:
development of best practice documents relating to the activities of the authorities responsible for notified bodies;
development of guidance documents for notified bodies in relation to the implementation of this Regulation;
training and qualification of the experts referred to in Article 40;
monitoring of trends relating to changes to notified body designations and notifications and trends in certificate withdrawals and transfers between notified bodies;
monitoring of the application and applicability of scope codes referred to in Article 42(13);
development of a mechanism for peer reviews between authorities and the Commission;
methods of communication to the public on the monitoring and surveillance activities of authorities and the Commission on notified bodies.
Article 49
Coordination of notified bodies
The Commission shall ensure that appropriate coordination and cooperation between notified bodies is put in place and operated in the form of a coordination group of notified bodies in the field of medical devices, including in vitro diagnostic medical devices. This group shall meet on a regular basis and at least annually.
The bodies notified under this Regulation shall participate in the work of that group.
The Commission may establish the specific arrangements for the functioning of the coordination group of notified bodies.
Article 50
List of standard fees
Notified bodies shall establish lists of their standard fees for the conformity assessment activities that they carry out and shall make those lists publicly available.
CHAPTER V
CLASSIFICATION AND CONFORMITY ASSESSMENT
SECTION 1
Classification
Article 51
Classification of devices
The competent authority of the Member State in which the manufacturer has its registered place of business shall notify the MDCG and the Commission of its decision. The decision shall be made available upon request.
At the request of a Member State the Commission shall after consulting the MDCG, decide, by means of implementing acts, on the following:
application of Annex VIII to a given device, or category or group of devices, with a view to determining the classification of such devices;
that a device, or category or group of devices, shall for reasons of public health based on new scientific evidence, or based on any information which becomes available in the course of the vigilance and market surveillance activities be reclassified, by way of derogation from Annex VIII.
SECTION 2
Conformity assessment
Article 52
Conformity assessment procedures
However, for class IIb implantable devices, except sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips and connectors, the assessment of the technical documentation as specified in Section 4 of Annex IX shall apply for every device.
Alternatively, the manufacturer may choose to apply a conformity assessment based on type examination as specified in Annex X coupled with a conformity assessment based on product conformity verification as specified in Annex XI.
Alternatively, the manufacturer may choose to draw up the technical documentation set out in Annexes II and III coupled with a conformity assessment as specified in Section 10 or Section 18 of Annex XI. The assessment of the technical documentation shall apply for at least one representative device for each category of devices.
Manufacturers of class I devices, other than custom-made or investigational devices, shall declare the conformity of their products by issuing the EU declaration of conformity referred to in Article 19 after drawing up the technical documentation set out in Annexes II and III. If those devices are placed on the market in sterile condition, have a measuring function or are reusable surgical instruments, the manufacturer shall apply the procedures set out in Chapters I and III of Annex IX, or in Part A of Annex XI. However, the involvement of the notified body in those procedures shall be limited:
in the case of devices placed on the market in sterile condition, to the aspects relating to establishing, securing and maintaining sterile conditions;
in the case of devices with a measuring function, to the aspects relating to the conformity of the devices with the metrological requirements;
in the case of reusable surgical instruments, to the aspects relating to the reuse of the device, in particular cleaning, disinfection, sterilization, maintenance and functional testing and the related instructions for use.
In addition to the procedure applicable pursuant to the first subparagraph, manufacturers of class III custom-made implantable devices shall be subject to the conformity assessment as specified in Chapter I of Annex IX. Alternatively, the manufacturer may choose to apply a conformity assessment as specified in Part A of Annex XI.
The Commission may, by means of implementing acts, specify detailed arrangements and procedural aspects with a view to ensuring the harmonised application of the conformity assessment procedures by the notified bodies for any of the following aspects:
the frequency and the sampling basis of the assessment of the technical documentation on a representative basis as set out in the third paragraph of Section 2.3 and in Section 3.5 of Annex IX in the case of class IIa and class IIb devices, and in Section 10.2 of Annex XI in the case of class IIa devices;
the minimum frequency of unannounced on-site audits and sample tests to be conducted by notified bodies in accordance with Section 3.4 of Annex IX, taking into account the risk-class and the type of device;
the physical, laboratory or other tests to be carried out by notified bodies in the context of sample tests, assessment of the technical documentation and type examination in accordance with Sections 3.4 and 4.3 of Annex IX, Section 3 of Annex X and Section 15 of Annex XI.
The implementing acts referred to in the first subparagraph shall be adopted in accordance with the examination procedure referred to in Article 114(3).
Article 53
Involvement of notified bodies in conformity assessment procedures
Article 54
Clinical evaluation consultation procedure for certain class III and class IIb devices
In addition to the procedures applicable pursuant to Article 52, a notified body shall also follow the procedure regarding clinical evaluation consultation as specified in Section 5.1 of Annex IX or as referred to in Section 6 of Annex X, as applicable, when performing a conformity assessment of the following devices:
class III implantable devices, and
class IIb active devices intended to administer and/or remove a medicinal product, as referred to in Section 6.4 of Annex VIII (Rule 12).
The procedure referred to in paragraph 1 shall not be required for the devices referred to therein:
in the case of renewal of a certificate issued under this Regulation;
where the device has been designed by modifying a device already marketed by the same manufacturer for the same intended purpose, provided that the manufacturer has demonstrated to the satisfaction of the notified body that the modifications do not adversely affect the benefit-risk ratio of the device; or
where the principles of the clinical evaluation of the device type or category have been addressed in a CS referred to in Article 9 and the notified body confirms that the clinical evaluation of the manufacturer for this device is in compliance with the relevant CS for clinical evaluation of that kind of device.
Article 55
Mechanism for scrutiny of conformity assessments of certain class III and class IIb devices
Article 56
Certificates of conformity
Article 57
Electronic system on notified bodies and on certificates of conformity
The Commission, after consulting the MDCG, shall set up and manage an electronic system to collate and process the following information:
the list of subsidiaries referred to in Article 37(3);
the list of experts referred to in Article 40(2);
the information relating to the notification referred to in Article 42(10) and the amended notifications referred to in Article 46(2);
the list of notified bodies referred to in Article 43(2);
the summary of the report referred to in Article 44(12);
the notifications for conformity assessments and certificates referred to in Articles 54(3) and 55(1);
withdrawal or refusals of applications for the certificates as referred to in Article 53(2) and Section 4.3 of Annex VII;
the information regarding certificates referred to in Article 56(5);
the summary of safety and clinical performance referred to in Article 32.
Article 58
Voluntary change of notified body
In cases where a manufacturer terminates its contract with a notified body and enters into a contract with another notified body in respect of the conformity assessment of the same device, the detailed arrangements for the change of notified body shall be clearly defined in an agreement between the manufacturer, the incoming notified body and, where practicable the outgoing notified body. That agreement shall cover at least the following aspects:
the date on which the certificates issued by the outgoing notified body become invalid;
the date until which the identification number of the outgoing notified body may be indicated in the information supplied by the manufacturer, including any promotional material;
the transfer of documents, including confidentiality aspects and property rights;
the date after which the conformity assessment tasks of the outgoing notified body is assigned to the incoming notified body;
the last serial number or lot number for which the outgoing notified body is responsible.
Article 59
Derogation from the conformity assessment procedures
The Member State may inform the Commission and the other Member States of any authorisation granted in accordance with Article 9(9) of Directive 90/385/EEC or Article 11(13) of Directive 93/42/EEC before 24 April 2020.
On duly justified imperative grounds of urgency relating to the health and safety of humans, the Commission shall adopt immediately applicable implementing acts in accordance with the procedure referred to in Article 114(4).
Article 60
Certificate of free sale
CHAPTER VI
CLINICAL EVALUATION AND CLINICAL INVESTIGATIONS
Article 61
Clinical evaluation
The manufacturer shall specify and justify the level of clinical evidence necessary to demonstrate conformity with the relevant general safety and performance requirements. That level of clinical evidence shall be appropriate in view of the characteristics of the device and its intended purpose.
To that end, manufacturers shall plan, conduct and document a clinical evaluation in accordance with this Article and Part A of Annex XIV.
The manufacturer may not invoke any rights to the views expressed by the expert panel with regard to any future conformity assessment procedure.
A clinical evaluation shall follow a defined and methodologically sound procedure based on the following:
a critical evaluation of the relevant scientific literature currently available relating to the safety, performance, design characteristics and intended purpose of the device, where the following conditions are satisfied:
a critical evaluation of the results of all available clinical investigations, taking duly into consideration whether the investigations were performed under Articles 62 to 80, any acts adopted pursuant to Article 81, and Annex XV; and
a consideration of currently available alternative treatment options for that purpose, if any.
In the case of implantable devices and class III devices, clinical investigations shall be performed, except if:
In this case, the notified body shall check that the PMCF plan is appropriate and includes post market studies to demonstrate the safety and performance of the device.
In addition, clinical investigations need not be performed in the cases referred to in paragraph 6.
A manufacturer of a device demonstrated to be equivalent to an already marketed device not manufactured by him, may also rely on paragraph 4 in order not to perform a clinical investigation provided that the following conditions are fulfilled in addition to what is required in that paragraph:
and the manufacturer of the second device provides clear evidence thereof to the notified body.
The requirement to perform clinical investigations pursuant to paragraph 4 shall not apply to implantable devices and class III devices:
which have been lawfully placed on the market or put into service in accordance with Directive 90/385/EEC or Directive 93/42/EEC and for which the clinical evaluation:
that are sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips or connectors for which the clinical evaluation is based on sufficient clinical data and is in compliance with the relevant product-specific CS, where such a CS is available.
For class III devices and implantable devices, the PMCF evaluation report and, if indicated, the summary of safety and clinical performance referred to in Article 32 shall be updated at least annually with such data.
Article 62
General requirements regarding clinical investigations conducted to demonstrate conformity of devices
Clinical investigations shall be designed, authorised, conducted, recorded and reported in accordance with the provisions of this Article and of Articles 63 to 80, the acts adopted pursuant to Article 81, and Annex XV, where carried out as part of the clinical evaluation for conformity assessment purposes, for one or more of the following purposes:
to establish and verify that, under normal conditions of use, a device is designed, manufactured and packaged in such a way that it is suitable for one or more of the specific purposes listed in point (1) of Article 2, and achieves the performance intended as specified by its manufacturer;
to establish and verify the clinical benefits of a device as specified by its manufacturer;
to establish and verify the clinical safety of the device and to determine any undesirable side-effects, under normal conditions of use of the device, and assess whether they constitute acceptable risks when weighed against the benefits to be achieved by the device.
Member States may choose not to apply the first subparagraph to clinical investigations to be conducted solely on their territory, or on their territory and the territory of a third country, provided that they ensure that the sponsor establishes at least a contact person on their territory in respect of that clinical investigation who shall be the addressee for all communications with the sponsor provided for in this Regulation.
Clinical investigations shall be subject to scientific and ethical review. The ethical review shall be performed by an ethics committee in accordance with national law. Member States shall ensure that the procedures for review by ethics committees are compatible with the procedures set out in this Regulation for the assessment of the application for authorisation of a clinical investigation. At least one lay person shall participate in the ethical review.
A clinical investigation as referred to in paragraph 1 may be conducted only where all of the following conditions are met:
the clinical investigation is the subject of an authorisation by the Member State(s) in which the clinical investigation is to be conducted, in accordance with this Regulation, unless otherwise stated;
an ethics committee, set up in accordance with national law, has not issued a negative opinion in relation to the clinical investigation, which is valid for that entire Member State under its national law;
the sponsor, or its legal representative or a contact person pursuant to paragraph 2, is established in the Union;
vulnerable populations and subjects are appropriately protected in accordance with Articles 64 to 68;
the anticipated benefits to the subjects or to public health justify the foreseeable risks and inconveniences and compliance with this condition is constantly monitored;
the subject or, where the subject is not able to give informed consent, his or her legally designated representative has given informed consent in accordance with Article 63;
the subject or, where the subject is not able to give informed consent, his or her legally designated representative, has been provided with the contact details of an entity where further information can be received in case of need;
the rights of the subject to physical and mental integrity, to privacy and to the protection of the data concerning him or her in accordance with Directive 95/46/EC are safeguarded;
the clinical investigation has been designed to involve as little pain, discomfort, fear and any other foreseeable risk as possible for the subjects, and both the risk threshold and the degree of distress are specifically defined in the clinical investigation plan and constantly monitored;
the medical care provided to the subjects is the responsibility of an appropriately qualified medical doctor or, where appropriate, a qualified dental practitioner or any other person entitled by national law to provide the relevant patient care under clinical investigation conditions;
no undue influence, including that of a financial nature, is exerted on the subject, or, where applicable, on his or her legally designated representatives, to participate in the clinical investigation;
the investigational device(s) in question conform(s) to the applicable general safety and performance requirements set out in Annex I apart from the aspects covered by the clinical investigation and that, with regard to those aspects, every precaution has been taken to protect the health and safety of the subjects. This includes, where appropriate, technical and biological safety testing and pre-clinical evaluation, as well as provisions in the field of occupational safety and accident prevention, taking into consideration the state of the art;
the requirements of Annex XV are fulfilled.
Article 63
Informed consent
Information given to the subject or, where the subject is not able to give informed consent, his or her legally designated representative for the purposes of obtaining his or her informed consent shall:
enable the subject or his or her legally designated representative to understand:
the nature, objectives, benefits, implications, risks and inconveniences of the clinical investigations;
the subject's rights and guarantees regarding his or her protection, in particular his or her right to refuse to participate in and the right to withdraw from the clinical investigation at any time without any resulting detriment and without having to provide any justification;
the conditions under which the clinical investigations is to be conducted, including the expected duration of the subject's participation in the clinical investigation; and
the possible treatment alternatives, including the follow-up measures if the participation of the subject in the clinical investigation is discontinued;
be kept comprehensive, concise, clear, relevant, and understandable to the subject or his or her legally designated representative;
be provided in a prior interview with a member of the investigating team who is appropriately qualified under national law;
include information about the applicable damage compensation system referred to in Article 69; and
include the Union-wide unique single identification number of the clinical investigation referred to in Article 70(1) and information about the availability of the clinical investigation results in accordance with paragraph 6 of this Article.
Article 64
Clinical investigations on incapacitated subjects
In the case of incapacitated subjects who have not given, or have not refused to give, informed consent before the onset of their incapacity, a clinical investigation may be conducted only where, in addition to the conditions set out in Article 62(4), all of the following conditions are met:
the informed consent of their legally designated representative has been obtained;
the incapacitated subjects have received the information referred to in Article 63(2) in a way that is adequate in view of their capacity to understand it;
the explicit wish of an incapacitated subject who is capable of forming an opinion and assessing the information referred to in Article 63(2) to refuse participation in, or to withdraw from, the clinical investigation at any time, is respected by the investigator;
no incentives or financial inducements are given to subjects or their legally designated representatives, except for compensation for expenses and loss of earnings directly related to the participation in the clinical investigation;
the clinical investigation is essential with respect to incapacitated subjects and data of comparable validity cannot be obtained in clinical investigations on persons able to give informed consent, or by other research methods;
the clinical investigation relates directly to a medical condition from which the subject suffers;
there are scientific grounds for expecting that participation in the clinical investigation will produce a direct benefit to the incapacitated subject outweighing the risks and burdens involved.
Article 65
Clinical investigations on minors
A clinical investigation on minors may be conducted only where, in addition to the conditions set out in Article 62(4), all of the following conditions are met:
the informed consent of their legally designated representative has been obtained;
the minors have received the information referred to in Article 63(2) in a way adapted to their age and mental maturity and from investigators or members of the investigating team who are trained or experienced in working with children;
the explicit wish of a minor who is capable of forming an opinion and assessing the information referred to in Article 63(2) to refuse participation in, or to withdraw from, the clinical investigation at any time, is respected by the investigator;
no incentives or financial inducements are given to the subject or his or her legally designated representative except for compensation for expenses and loss of earnings directly related to the participation in the clinical investigation;
the clinical investigation is intended to investigate treatments for a medical condition that only occurs in minors or the clinical investigation is essential with respect to minors to validate data obtained in clinical investigations on persons able to give informed consent or by other research methods;
the clinical investigation either relates directly to a medical condition from which the minor concerned suffers or is of such a nature that it can only be carried out on minors;
there are scientific grounds for expecting that participation in the clinical investigation will produce a direct benefit to the minor subject outweighing the risks and burdens involved;
the minor shall take part in the informed consent procedure in a way adapted to his or her age and mental maturity;
if during a clinical investigation the minor reaches the age of legal competence to give informed consent as defined in national law, his or her express informed consent shall be obtained before that subject can continue to participate in the clinical investigation.
Article 66
Clinical investigations on pregnant or breastfeeding women
A clinical investigation on pregnant or breastfeeding women may be conducted only where, in addition to the conditions set out in Article 62(4), all of the following conditions are met:
the clinical investigation has the potential to produce a direct benefit for the pregnant or breastfeeding woman concerned, or her embryo, foetus or child after birth, outweighing the risks and burdens involved;
where research is undertaken on breastfeeding women, particular care is taken to avoid any adverse impact on the health of the child;
no incentives or financial inducements are given to the subject except for compensation for expenses and loss of earnings directly related to the participation in the clinical investigation.
Article 67
Additional national measures
Member States may maintain additional measures regarding persons performing mandatory military service, persons deprived of liberty, persons who, due to a judicial decision, cannot take part in clinical investigations, or persons in residential care institutions.
Article 68
Clinical investigations in emergency situations
By way of derogation from point (f) of Article 62(4), from points (a) and (b) of Article 64(1) and from points (a) and (b) of Article 65, informed consent to participate in a clinical investigation may be obtained, and information on the clinical investigation may be given, after the decision to include the subject in the clinical investigation, provided that that decision is taken at the time of the first intervention on the subject, in accordance with the clinical investigation plan for that clinical investigation and that all of the following conditions are fulfilled:
due to the urgency of the situation, caused by a sudden life-threatening or other sudden serious medical condition, the subject is unable to provide prior informed consent and to receive prior information on the clinical investigation;
there are scientific grounds to expect that participation of the subject in the clinical investigation will have the potential to produce a direct clinically relevant benefit for the subject resulting in a measurable health-related improvement alleviating the suffering and/or improving the health of the subject, or in the diagnosis of its condition;
it is not possible within the therapeutic window to supply all prior information to and obtain prior informed consent from his or her legally designated representative;
the investigator certifies that he or she is not aware of any objections to participate in the clinical investigation previously expressed by the subject;
the clinical investigation relates directly to the subject's medical condition because of which it is not possible within the therapeutic window to obtain prior informed consent from the subject or from his or her legally designated representative and to supply prior information, and the clinical investigation is of such a nature that it may be conducted exclusively in emergency situations;
the clinical investigation poses a minimal risk to, and imposes a minimal burden on, the subject in comparison with the standard treatment of the subject's condition.
Following an intervention pursuant to paragraph 1 of this Article, informed consent in accordance with Article 63 shall be sought to continue the participation of the subject in the clinical investigation, and information on the clinical investigation shall be given, in accordance with the following requirements:
regarding incapacitated subjects and minors, the informed consent shall be sought by the investigator from his or her legally designated representative without undue delay and the information referred to in Article 63(2) shall be given as soon as possible to the subject and to his or her legally designated representative;
regarding other subjects, the informed consent shall be sought by the investigator without undue delay from the subject or his or her legally designated representative, whichever can be done sooner, and the information referred to in Article 63(2) shall be given as soon as possible to the subject or his or her legally designated representative, as applicable.
For the purposes of point (b) where informed consent has been obtained from the legally designated representative, informed consent to continue the participation in the clinical investigation shall be obtained from the subject as soon as he or she is capable of giving informed consent.
Article 69
Damage compensation
Article 70
Application for clinical investigations
The application shall be submitted by means of the electronic system referred to in Article 73, which shall generate a Union-wide unique single identification number for the clinical investigation, which shall be used for all relevant communication in relation to that clinical investigation. Within 10 days of it receiving the application, the Member State concerned shall notify the sponsor as to whether the clinical investigation falls within the scope of this Regulation and as to whether the application dossier is complete in accordance with Chapter II of Annex XV.
Where the sponsor has not provided comments nor completed the application within the time limit referred to in the first subparagraph, the application shall be deemed to have lapsed. Where the sponsor considers the application does fall under the scope of this Regulation and/or is complete but the Member State concerned does not, the application shall be considered to have been rejected. The Member State concerned shall provide for an appeal procedure in respect of such refusal.
The Member State concerned shall notify the sponsor within five days of receipt of the comments or of the requested additional information, whether the clinical investigation is considered as falling within the scope of this Regulation and the application is complete.
The sponsor may start the clinical investigation in the following circumstances:
in the case of investigational class I devices or in the case of non-invasive class IIa and class IIb devices, unless otherwise stated by national law, immediately after the validation date of the application pursuant to paragraph 5, and provided that a negative opinion which is valid for the entire Member State, under national law, has not been issued by an ethics committee in the Member State concerned in respect of the clinical investigation;
in the case of investigational devices, other than those referred to in point (a), as soon as the Member State concerned has notified the sponsor of its authorisation, and provided that a negative opinion which is valid for the entire Member State, under national law, has not been issued by an ethics committee in the Member State concerned in respect of the clinical investigation. The Member State shall notify the sponsor of the authorisation within 45 days of the validation date referred to in paragraph 5. The Member State may extend this period by a further 20 days for the purpose of consulting with experts.
Article 71
Assessment by Member States
Member States shall assess whether the clinical investigation is designed in such a way that potential remaining risks to subjects or third persons, after risk minimization, are justified, when weighed against the clinical benefits to be expected. They shall, while taking into account applicable CS or harmonised standards, examine in particular:
the demonstration of compliance of the investigational device(s) with the applicable general safety and performance requirements, apart from the aspects covered by the clinical investigation, and whether, with regard to those aspects, every precaution has been taken to protect the health and safety of the subjects. This includes, where appropriate, assurance of technical and biological safety testing and pre-clinical evaluation;
whether the risk-minimisation solutions employed by the sponsor are described in harmonised standards and, in those cases where the sponsor does not use harmonised standards, whether the risk-minimisation solutions provide a level of protection that is equivalent to that provided by harmonised standards;
whether the measures planned for the safe installation, putting into service and maintenance of the investigational device are adequate;
the reliability and robustness of the data generated in the clinical investigation, taking account of statistical approaches, design of the investigation and methodological aspects, including sample size, comparator and endpoints;
whether the requirements of Annex XV are met;
in the case of devices for sterile use, evidence of the validation of the manufacturer's sterilisation procedures or information on the reconditioning and sterilisation procedures which have to be conducted by the investigation site;
the demonstration of the safety, quality and usefulness of any components of animal or human origin or of substances, which may be considered medicinal products in accordance with Directive 2001/83/EC.
Member States shall refuse the authorisation of the clinical investigation if:
the application dossier submitted pursuant to Article 70(1) remains incomplete;
the device or the submitted documents, especially the investigation plan and the investigator's brochure, do not correspond to the state of scientific knowledge, and the clinical investigation, in particular, is not suitable for providing evidence for the safety, performance characteristics or benefit of the device on subjects or patients,
the requirements of Article 62 are not met, or
any assessment under paragraph 3 is negative.
Member States shall provide for an appeal procedure in respect of a refusal pursuant to the first subparagraph.
Article 72
Conduct of a clinical investigation
In order to verify that the rights, safety and well-being of subjects are protected, that the reported data are reliable and robust, and that the conduct of the clinical investigation is in compliance with the requirements of this Regulation, the sponsor shall ensure adequate monitoring of the conduct of a clinical investigation. The extent and nature of the monitoring shall be determined by the sponsor on the basis of an assessment that takes into consideration all characteristics of the clinical investigation including the following:
the objective and methodology of the clinical investigation; and
the degree of deviation of the intervention from normal clinical practice.
Article 73
Electronic system on clinical investigations
The Commission shall, in collaboration with the Member States, set up, manage and maintain an electronic system:
to create the single identification numbers for clinical investigations referred to in Article 70(1);
to be used as an entry point for the submission of all applications or notifications for clinical investigations referred to in Articles 70, 74, 75 and 78 and for all other submission of data, or processing of data in this context;
for the exchange of information relating to clinical investigations in accordance with this Regulation between the Member States and between them and the Commission including the exchange of information referred to in Articles 70 and 76;
for information to be provided by the sponsor in accordance with Article 77, including the clinical investigation report and its summary as required in paragraph 5 of that Article;
for reporting on serious adverse events and device deficiencies and related updates referred to in Article 80.
The information referred to in point (c) of paragraph 1 shall only be accessible to the Member States and the Commission. The information referred to in the other points of that paragraph shall be accessible to the public, unless, for all or parts of that information, confidentiality of the information is justified on any of the following grounds:
protection of personal data in accordance with Regulation (EC) No 45/2001;
protection of commercially confidential information, especially in the investigators brochure, in particular through taking into account the status of the conformity assessment for the device, unless there is an overriding public interest in disclosure;
effective supervision of the conduct of the clinical investigation by the Member State(s) concerned.
Article 74
Clinical investigations regarding devices bearing the CE marking
Article 75
Substantial modifications to clinical investigations
The sponsor may implement the modifications referred to in paragraph 1 at the earliest 38 days after the notification referred to in that paragraph, unless:
the Member State in which the clinical investigation is being or is to be conducted has notified the sponsor of its refusal based on the grounds referred to in Article 71(4) or on considerations of public health, subject and user safety or health, of public policy, or
an ethics committee in that Member State has issued a negative opinion in relation to the substantial modification to the clinical investigation, which, in accordance with national law, is valid for that entire Member State.
Article 76
Corrective measures to be taken by Member States and information exchange between Member States
Where a Member State in which a clinical investigation is being or is to be conducted has grounds for considering that the requirements set out in this Regulation are not met, it may take at least any of the following measures on its territory:
revoke the authorisation for the clinical investigation;
suspend or terminate the clinical investigation;
require the sponsor to modify any aspect of the clinical investigation.
Article 77
Information from the sponsor at the end of a clinical investigation or in the event of a temporary halt or early termination
The clinical investigation report shall be accompanied by a summary presented in terms that are easily understandable to the intended user. Both the report and summary shall be submitted by the sponsor by means of the electronic system referred to in Article 73.
Where, for scientific reasons, it is not possible to submit the clinical investigation report within one year of the end of the investigation, it shall be submitted as soon as it is available. In such case, the clinical investigation plan referred to in Section 3 of Chapter II of Annex XV shall specify when the results of the clinical investigation are going to be available, together with a justification.
In addition, the Commission may issue guidelines for the formatting and sharing of raw data, for cases where the sponsor decides to share raw data on a voluntary basis. Those guidelines may take as a basis and adapt, where possible, existing guidelines for sharing of raw data in the field of clinical investigations.
If the device is not registered in accordance with Article 29 within one year of the summary and the report having been entered into the electronic system pursuant to paragraph 5 of this Article, they shall become publicly accessible at that point in time.
Article 78
Coordinated assessment procedure for clinical investigations
However, the completeness of the documentation referred to in Sections 1.13, 3.1.3, 4.2, 4.3 and 4.4 of Chapter II of Annex XV shall be assessed separately by each Member State concerned in accordance with Article 70(1) to (5).
With regard to documentation other than that referred to in the second subparagraph of paragraph 3, the coordinating Member State shall:
within six days of receipt of the single application, notify the sponsor that it is the coordinating Member State (‘notification date’);
for the purpose of the validation of the application, take into account any considerations submitted within seven days of the notification date by any Member State concerned;
within 10 days of the notification date, assess whether the clinical investigation falls within the scope of this Regulation and whether the application is complete, and shall notify the sponsor accordingly. Article 70(1) and (3) to (5) shall apply to the coordinating Member State in relation to that assessment;
establish the results of its assessment in a draft assessment report to be transmitted within 26 days of the validation date to the Member States concerned. By day 38 after the validation date, the other Member States concerned shall transmit their comments and proposals on the draft assessment report and the underlying application to the coordinating Member State which shall take due account of those comments and proposals in its finalisation of the final assessment report, to be transmitted within 45 days of the validation date to the sponsor and the other Member States concerned.
The final assessment report shall be taken into account by all Member States concerned when deciding on the sponsor's application in accordance with Article 70(7).
Notwithstanding the first subparagraph, a Member State concerned may only disagree with the conclusion of the coordinating Member State concerning the area of coordinated assessment on the following grounds:
when it considers that participation in the clinical investigation would lead to a subject receiving treatment inferior to that received in normal clinical practice in that Member State concerned;
infringement of national law; or
considerations as regards subject safety and data reliability and robustness submitted under point (d) of paragraph 4.
Where one of the Member States concerned disagrees with the conclusion on the basis of the second subparagraph of this paragraph, it shall communicate its disagreement, together with a detailed justification, through the electronic system referred to in Article 73, to the Commission, to all other Member States concerned and to the sponsor.
Article 79
Review of coordinated assessment procedure
By 27 May 2026, the Commission shall submit to the European Parliament and to the Council a report on experience gained from the application of Article 78 and, if necessary, propose a review of Article 78(14) and point (h) of Article 123(3).
Article 80
Recording and reporting of adverse events that occur during clinical investigations
The sponsor shall fully record all of the following:
any adverse event of a type identified in the clinical investigation plan as being critical to the evaluation of the results of that clinical investigation;
any serious adverse event;
any device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention had not occurred, or circumstances had been less fortunate;
any new findings in relation to any event referred to in points (a) to (c).
The sponsor shall report, without delay to all Member States in which the clinical investigation is being conducted, all of the following by means of the electronic system referred to in Article 73:
any serious adverse event that has a causal relationship with the investigational device, the comparator or the investigation procedure or where such causal relationship is reasonably possible;
any device deficiency that might have led to a serious adverse event if appropriate action had not been taken, intervention had not occurred, or circumstances had been less fortunate;
any new findings in relation to any event referred to in points (a) and (b).
The period for reporting shall take account of the severity of the event. Where necessary to ensure timely reporting, the sponsor may submit an initial report that is incomplete followed up by a complete report.
Upon request by any Member State in which the clinical investigation is being conducted, the sponsor shall provide all information referred to in paragraph 1.
Under the direction of the coordinating Member State referred to in Article 78(2), the Member States shall coordinate their assessment of serious adverse events and device deficiencies to determine whether to modify, suspend or terminate the clinical investigation or whether to revoke the authorisation for that clinical investigation.
This paragraph shall not affect the rights of the other Member States to perform their own evaluation and to adopt measures in accordance with this Regulation in order to ensure the protection of public health and patient safety. The coordinating Member State and the Commission shall be kept informed of the outcome of any such evaluation and the adoption of any such measures.
Article 81
Implementing acts
The Commission may, by means of implementing acts, establish the detailed arrangements and procedural aspects necessary for the implementation of this Chapter as regards the following:
harmonised electronic forms for the application for clinical investigations and their assessment as referred to in Articles 70 and 78, taking into account specific categories or groups of devices;
the functioning of the electronic system referred to in Article 73;
harmonised electronic forms for the notification of PMCF investigations as referred to in Article 74(1), and of substantial modifications as referred to in Article 75;
the exchange of information between Member States as referred to in Article 76;
harmonised electronic forms for the reporting of serious adverse events and device deficiencies as referred to in Article 80;
the timelines for the reporting of serious adverse events and device deficiencies, taking into account the severity of the event to be reported as referred to in Article 80;
uniform application of the requirements regarding the clinical evidence or data needed to demonstrate compliance with the general safety and performance requirements set out in Annex I.
The implementing acts referred to in the first paragraph shall be adopted in accordance with the examination procedure referred to in Article 114(3).
Article 82
Requirements regarding other clinical investigations
CHAPTER VII
POST-MARKET SURVEILLANCE, VIGILANCE AND MARKET SURVEILLANCE
SECTION 1
Post-market surveillance
Article 83
Post-market surveillance system of the manufacturer
Data gathered by the manufacturer's post-market surveillance system shall in particular be used:
to update the benefit-risk determination and to improve the risk management as referred to in Chapter I of Annex I;
to update the design and manufacturing information, the instructions for use and the labelling;
to update the clinical evaluation;
to update the summary of safety and clinical performance referred to in Article 32;
for the identification of needs for preventive, corrective or field safety corrective action;
for the identification of options to improve the usability, performance and safety of the device;
when relevant, to contribute to the post-market surveillance of other devices; and
to detect and report trends in accordance with Article 88.
The technical documentation shall be updated accordingly.
Article 84
Post-market surveillance plan
The post-market surveillance system referred to in Article 83 shall be based on a post-market surveillance plan, the requirements for which are set out in ►C2 Section 1 of Annex III. ◄ For devices other than custom-made devices, the post-market surveillance plan shall be part of the technical documentation specified in Annex II.
Article 85
Post-market surveillance report
Manufacturers of class I devices shall prepare a post-market surveillance report summarising the results and conclusions of the analyses of the post-market surveillance data gathered as a result of the post-market surveillance plan referred to in Article 84 together with a rationale and description of any preventive and corrective actions taken. The report shall be updated when necessary and made available to the competent authority upon request.
Article 86
Periodic safety update report
Manufacturers of class IIa, class IIb and class III devices shall prepare a periodic safety update report (‘PSUR’) for each device and where relevant for each category or group of devices summarising the results and conclusions of the analyses of the post-market surveillance data gathered as a result of the post-market surveillance plan referred to in Article 84 together with a rationale and description of any preventive and corrective actions taken. Throughout the lifetime of the device concerned, that PSUR shall set out:
the conclusions of the benefit-risk determination;
the main findings of the PMCF; and
the volume of sales of the device and an estimate evaluation of the size and other characteristics of the population using the device and, where practicable, the usage frequency of the device.
Manufacturers of class IIb and class III devices shall update the PSUR at least annually. That PSUR shall, except in the case of custom-made devices, be part of the technical documentation as specified in Annexes II and III.
Manufacturers of class IIa devices shall update the PSUR when necessary and at least every two years. That PSUR shall, except in the case of custom-made devices, be part of the technical documentation as specified in Annexes II and III.
For custom-made devices, the PSUR shall be part of the documentation referred to in Section 2 of Annex XIII.
SECTION 2
Vigilance
Article 87
Reporting of serious incidents and field safety corrective actions
Manufacturers of devices made available on the Union market, other than investigational devices, shall report, to the relevant competent authorities, in accordance with Articles 92(5) and (7), the following:
any serious incident involving devices made available on the Union market, except expected side-effects which are clearly documented in the product information and quantified in the technical documentation and are subject to trend reporting pursuant to Article 88;
any field safety corrective action in respect of devices made available on the Union market, including any field safety corrective action undertaken in a third country in relation to a device which is also legally made available on the Union market, if the reason for the field safety corrective action is not limited to the device made available in the third country.
The reports referred to in the first subparagraph shall be submitted through the electronic system referred to in Article 92.
The competent authorities shall record centrally at national level reports they receive from healthcare professionals, users and patients.
Where the manufacturer of the device concerned considers that the incident is a serious incident, it shall provide a report in accordance with paragraphs 1 to 5 of this Article on that serious incident to the competent authority of the Member State in which that serious incident occurred and shall take the appropriate follow-up action in accordance with Article 89.
Where the manufacturer of the device concerned considers that the incident is not a serious incident or is an expected undesirable side-effect, which will be covered by trend reporting in accordance with Article 88, it shall provide an explanatory statement. If the competent authority does not agree with the conclusion of the explanatory statement, it may require the manufacturer to provide a report in accordance with paragraphs 1 to 5 of this Article and require it to ensure that appropriate follow-up action is taken in accordance with Article 89.
Article 88
Trend reporting
The manufacturer shall specify how to manage the incidents referred to in the first subparagraph and the methodology used for determining any statistically significant increase in the frequency or severity of such incidents, as well as the observation period, in the post-market surveillance plan referred to in Article 84.
Article 89
Analysis of serious incidents and field safety corrective actions
The manufacturer shall co-operate with the competent authorities and where relevant with the notified body concerned during the investigations referred to in the first subparagraph and shall not perform any investigation which involves altering the device or a sample of the batch concerned in a way which may affect any subsequent evaluation of the causes of the incident, prior to informing the competent authorities of such action.
Upon request by the national competent authority, manufacturers shall provide all documents necessary for the risk assessment.
In the case of devices covered by this Regulation in accordance with point (g) of Article 1(6) and where the serious incident or field safety corrective action may be related to the derivatives of tissues or cells of human origin utilised for the manufacture of the device, and in the case of devices falling under this Regulation pursuant to Article 1(10), the competent authority or the coordinating competent authority referred to in paragraph 9 of this Article shall inform the competent authority for human tissues and cells that was consulted by the notified body in accordance with Article 52(10).
The field safety notice shall allow the correct identification of the device or devices involved, in particular by including the relevant UDIs, and the correct identification, in particular, by including the SRN, if already issued, of the manufacturer that has undertaken the field safety corrective action. The field safety notice shall explain, in a clear manner, without understating the level of risk, the reasons for the field safety corrective action with reference to the device malfunction and associated risks for patients, users or other persons, and shall clearly indicate all the actions to be taken by users.
The manufacturer shall enter the field safety notice in the electronic system referred to in Article 92 through which that notice shall be accessible to the public.
The competent authorities shall actively participate in a procedure in order to coordinate their assessments referred to in paragraph 3 in the following cases:
where there is concern regarding a particular serious incident or cluster of serious incidents relating to the same device or type of device of the same manufacturer in more than one Member State;
where the appropriateness of a field safety corrective action that is proposed by a manufacturer in more than one Member State is in question.
That coordinated procedure shall cover the following:
Unless otherwise agreed between the competent authorities, the coordinating competent authority shall be the competent authority of the Member State in which the manufacturer has its registered place of business.
The coordinating competent authority shall, through the electronic system referred to in Article 92, inform the manufacturer, the other competent authorities and the Commission that it has assumed the role of coordinating authority.
Article 90
Analysis of vigilance data
The Commission shall, in collaboration with the Member States, put in place systems and processes to actively monitor the data available in the electronic system referred to in Article 92, in order to identify trends, patterns or signals in the data that may reveal new risks or safety concerns.
Where a previously unknown risk is identified or the frequency of an anticipated risk significantly and adversely changes the benefit-risk determination, the competent authority or, where appropriate, the coordinating competent authority shall inform the manufacturer, or where applicable the authorised representative, which shall then take the necessary corrective actions.
Article 91
Implementing acts
The Commission may, by means of implementing acts, and after consultation of the MDCG, adopt the detailed arrangements and procedural aspects necessary for the implementation of Articles 85 to 90 and 92 as regards the following:
the typology of serious incidents and field safety corrective actions in relation to specific devices, or categories or groups of devices;
the reporting of serious incidents and field safety corrective actions and field safety notices, and the provision of periodic summary reports, post-market surveillance reports, PSURs and trend reports by manufacturers as referred to in Articles 85, 86, 87, 88 and 89 respectively;
standard structured forms for electronic and non-electronic reporting, including a minimum data set for reporting of suspected serious incidents by healthcare professionals, users and patients;
timelines for the reporting of field safety corrective actions, and for the provision by manufacturers of periodic summary reports and trend reports, taking into account the severity of the incident to be reported as referred to in Article 87;
harmonised forms for the exchange of information between competent authorities as referred to in Article 89;
procedures for the designation of a coordinating competent authority; the coordinated evaluation process, including tasks and responsibilities of the coordinating competent authority and involvement of other competent authorities in this process.
The implementing acts referred to in the first paragraph shall be adopted in accordance with the examination procedure referred to in Article 114(3).
Article 92
Electronic system on vigilance and on post-market surveillance
The Commission shall, in collaboration with the Member States, set up and manage an electronic system to collate and process the following information:
the reports by manufacturers on serious incidents and field safety corrective actions referred to in Article 87(1) and Article 89(5);
the periodic summary reports by manufacturers referred to in Article 87(9);
the reports by manufacturers on trends referred to in Article 88;
the PSURs referred to in Article 86;
the field safety notices by manufacturers referred to in Article 89(8);
the information to be exchanged between the competent authorities of the Member States and between them and the Commission in accordance with Article 89(7) and (9).
That electronic system shall include relevant links to the UDI database.
The reports on field safety corrective actions referred to in point (b) of Article 87(1) shall be automatically transmitted upon receipt via the electronic system referred to in paragraph 1 of this Article to the competent authorities of the following Member States:
the Member States in which the field safety corrective action is being or is to be undertaken;
the Member State in which the manufacturer has its registered place of business.
The periodic summary reports referred to in Article 87(9) shall be automatically transmitted upon receipt via the electronic system referred to in paragraph 1 of this Article to the competent authority of:
the Member State or Member States participating in the coordination procedure in accordance with Article 89(9) and which have agreed on the periodic summary report;
the Member State in which the manufacturer has its registered place of business.
SECTION 3
Market surveillance
Article 93
Market surveillance activities
In order to fulfil the obligations laid down in paragraph 1, the competent authorities:
may require economic operators to, inter alia, make available the documentation and information necessary for the purpose of carrying out the authorities' activities and, where justified, to provide the necessary samples of devices or access to devices free of charge; and
shall carry out both announced and, if necessary, unannounced inspections of the premises of economic operators, as well as suppliers and/or subcontractors, and, where necessary, at the facilities of professional users.
Where appropriate, the competent authorities of the Member States shall agree on work-sharing, joint market surveillance activities and specialisation.
Article 94
Evaluation of devices suspected of presenting an unacceptable risk or other non-compliance
Where the competent authorities of a Member State, based on data obtained by vigilance or market surveillance activities or on other information, have reason to believe that a device:
may present an unacceptable risk to the health or safety of patients, users or other persons, or to other aspects of the protection of public health; or
otherwise does not comply with the requirements laid down in this Regulation,
they shall carry out an evaluation of the device concerned covering all requirements laid down in this Regulation relating to the risk presented by the device, or to any other non-compliance of the device.
The relevant economic operators shall cooperate with the competent authorities.
Article 95
Procedure for dealing with devices presenting an unacceptable risk to health and safety
The competent authorities shall notify the Commission, the other Member States and the notified body referred to in paragraph 2 of this Article, without delay, of those measures, by means of the electronic system referred to in Article 100.
In the event of disagreement with the notified national measure, they shall, without delay, inform the Commission and the other Member States of their objections, by means of the electronic system referred to in Article 100.
In that case, all Member States shall ensure that corresponding appropriate restrictive or prohibitive measures, including withdrawing, recalling or limiting the availability of the device on their national market, are taken without delay in respect of the device concerned.
Article 96
Procedure for evaluating national measures at Union level
Where the Commission does not adopt a decision pursuant to paragraph 1 of this Article within eight months of receipt of the notification referred to in Article 95(4), the national measure shall be considered to be justified.
Article 97
Other non-compliance
Article 98
Preventive health protection measures
Article 99
Good administrative practice
Where action has been taken without the economic operator having had the opportunity to make submissions as referred to in the first subparagraph, it shall be given the opportunity to make submissions as soon as possible and the action taken shall be reviewed promptly thereafter.
Article 100
Electronic system on market surveillance
The Commission, in collaboration with the Member States, shall set up and manage an electronic system to collate and process the following information:
summaries of the results of the surveillance activities referred to in Article 93(4);
the final inspection report referred to in Article 93(7);
information in relation to devices presenting an unacceptable risk to health and safety as referred to in Article 95(2), (4) and (6);
information in relation to non-compliance of products as referred to in Article 97(2);
information in relation to the preventive health protection measures referred to in Article 98(2);
summaries of the results of the reviews and assessments of the market surveillance activities of the Member States referred to in 93(8).
CHAPTER VIII
COOPERATION BETWEEN MEMBER STATES, MEDICAL DEVICE COORDINATION GROUP, EXPERT LABORATORIES, EXPERT PANELS AND DEVICE REGISTERS
Article 101
Competent authorities
The Member States shall designate the competent authority or authorities responsible for the implementation of this Regulation. They shall entrust their authorities with the powers, resources, equipment and knowledge necessary for the proper performance of their tasks pursuant to this Regulation. The Member States shall communicate the names and contact details of the competent authorities to the Commission which shall publish a list of competent authorities.
Article 102
Cooperation
Article 103
Medical Device Coordination Group
The members of the MDCG shall be chosen for their competence and experience in the field of medical devices and in vitro diagnostic medical devices. They shall represent the competent authorities of the Member States. The names and affiliation of members shall be made public by the Commission.
The alternates shall represent and vote for the members in their absence.
The MDCG shall establish its rules of procedure which shall, in particular, lay down procedures for the following:
Article 104
Support by the Commission
The Commission shall support the functioning of the cooperation between national competent authorities. It shall, in particular, provide for the organisation of exchanges of experience between the competent authorities and provide technical, scientific and logistic support to the MDCG and its sub-groups. It shall organise the meetings of the MDCG and its sub-groups, participate in those meetings and ensure the appropriate follow-up.
Article 105
Tasks of the MDCG
Under this Regulation, the MDCG shall have the following tasks:
to contribute to the assessment of applicant conformity assessment bodies and notified bodies pursuant to the provisions set out in Chapter IV;
to advise the Commission, at its request, in matters concerning the coordination group of notified bodies as established pursuant to Article 49;
to contribute to the development of guidance aimed at ensuring effective and harmonised implementation of this Regulation, in particular regarding the designation and monitoring of notified bodies, application of the general safety and performance requirements and conduct of clinical evaluations and investigations by manufacturers, assessment by notified bodies and vigilance activities;
to contribute to the continuous monitoring of technical progress and assessment of whether the general safety and performance requirements laid down in this Regulation and Regulation (EU) 2017/746 are adequate to ensure safety and performance of devices, and thereby contribute to identifying whether there is a need to amend Annex I to this Regulation;
to contribute to the development of device standards, of CS and of scientific guidelines, including product specific guidelines, on clinical investigation of certain devices in particular implantable devices and class III devices;
to assist the competent authorities of the Member States in their coordination activities in particular in the fields of classification and the determination of the regulatory status of devices, clinical investigations, vigilance and market surveillance including the development and maintenance of a framework for a European market surveillance programme with the objective of achieving efficiency and harmonisation of market surveillance in the Union, in accordance with Article 93;
to provide advice, either on its own initiative or at request of the Commission, in the assessment of any issue related to the implementation of this Regulation;
to contribute to harmonised administrative practice with regard to devices in the Member States.
Article 106
Provision of scientific, technical and clinical opinions and advice
The members of expert panels shall perform their tasks with impartiality and objectivity. They shall neither seek nor take instructions from notified bodies or manufacturers. Each member shall draw up a declaration of interests, which shall be made publicly available.
The Commission shall establish systems and procedures to actively manage and prevent potential conflicts of interest.
The Commission may, by means of implementing acts and following consultation with the MDCG, designate expert laboratories, on the basis of their expertise in:
of specific devices, categories or groups of devices.
The Commission shall only designate expert laboratories for which a Member State or the Joint Research Centre has submitted an application for designation.
Expert laboratories shall satisfy the following criteria:
have adequate and appropriately qualified staff with adequate knowledge and experience in the field of the devices for which they are designated;
possess the necessary equipment to carry out the tasks assigned to them;
have the necessary knowledge of international standards and best practices;
have an appropriate administrative organisation and structure;
ensure that their staff observe the confidentiality of information and data obtained in carrying out their tasks.
Expert panels and expert laboratories may have the following tasks, depending on the requisite needs:
to provide scientific, technical and clinical assistance to the Commission and the MDCG in relation to the implementation of this Regulation;
to contribute to the development and maintenance of appropriate guidance and CS for:
for specific devices, or a category or group of devices, or for specific hazards related to a category or group of devices;
to develop and review clinical evaluation guidance and performance evaluation guidance for performance of conformity assessment in line with the state of the art with regard to clinical evaluation, performance evaluation, physico-chemical characterisation, and microbiological, biocompatibility, mechanical, electrical, electronic or non-clinical toxicological testing;
to contribute to the development of standards at international level, ensuring that such standards reflect the state of the art;
to provide opinions in response to consultations by manufacturers in accordance with Article 61(2), notified bodies and Member States in accordance with paragraphs 11 to 13 of this Article.
to contribute to identification of concerns and emerging issues on the safety and performance of medical devices;
to provide views in accordance with Article 48(4) of Regulation (EU) 2017/746 on the performance evaluation of certain in vitro diagnostic medical devices.
The Commission shall publish the scientific opinion and advice delivered in accordance with paragraphs 9 and 11 of this Article, ensuring consideration of aspects of confidentiality as set out in Article 109. The clinical evaluation guidance referred to in point (c) of paragraph 10 shall be published following consultation with the MDCG.
Article 107
Conflict of interests
Article 108
Device registers and databanks
The Commission and the Member States shall take all appropriate measures to encourage the establishment of registers and databanks for specific types of devices setting common principles to collect comparable information. Such registers and databanks shall contribute to the independent evaluation of the long-term safety and performance of devices, or the traceability of implantable devices, or all of such characteristics.
CHAPTER IX
CONFIDENTIALITY, DATA PROTECTION, FUNDING AND PENALTIES
Article 109
Confidentiality
Unless otherwise provided for in this Regulation and without prejudice to existing national provisions and practices in the Member States on confidentiality, all parties involved in the application of this Regulation shall respect the confidentiality of information and data obtained in carrying out their tasks in order to protect the following:
personal data, in accordance with Article 110;
commercially confidential information and trade secrets of a natural or legal person, including intellectual property rights; unless disclosure is in the public interest;
the effective implementation of this Regulation, in particular for the purpose of inspections, investigations or audits.
Article 110
Data protection
Article 111
Levying of fees
Article 112
Funding of activities related to designation and monitoring of notified bodies
The costs associated with joint assessment activities shall be covered by the Commission. The Commission shall, by means of implementing acts, lay down the scale and structure of recoverable costs and other necessary implementing rules. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 114(3).
Article 113
Penalties
The Member States shall lay down the rules on penalties applicable for infringement of the provisions of this Regulation and shall take all measures necessary to ensure that they are implemented. The penalties provided for shall be effective, proportionate, and dissuasive. The Member States shall notify the Commission of those rules and of those measures by ►M1 25 February 2021 ◄ and shall notify it, without delay, of any subsequent amendment affecting them.
CHAPTER X
FINAL PROVISIONS
Article 114
Committee procedure
Where the committee delivers no opinion, the Commission shall not adopt the draft implementing act and the third subparagraph of Article 5(4) of Regulation (EU) No 182/2011 shall apply.
Article 115
Exercise of the delegation
Article 116
Separate delegated acts for different delegated powers
The Commission shall adopt a separate delegated act in respect of each power delegated to it pursuant to this Regulation.
Article 117
Amendment to Directive 2001/83/EC
In Annex I to Directive 2001/83/EC, point 12 of Section 3.2. is replaced by the following:
‘(12) Where, in accordance with the second subparagraph of Article 1(8) or the second subparagraph of Article 1(9) of Regulation (EU) 2017/745 of the European Parliament and of the Council ( *1 ), a product is governed by this Directive, the marketing authorisation dossier shall include, where available, the results of the assessment of the conformity of the device part with the relevant general safety and performance requirements set out in Annex I to that Regulation contained in the manufacturer's EU declaration of conformity or the relevant certificate issued by a notified body allowing the manufacturer to affix a CE marking to the medical device.
If the dossier does not include the results of the conformity assessment referred to in the first subparagraph and where for the conformity assessment of the device, if used separately, the involvement of a notified body is required in accordance with Regulation (EU) 2017/745, the authority shall require the applicant to provide an opinion on the conformity of the device part with the relevant general safety and performance requirements set out in Annex I to that Regulation issued by a notified body designated in accordance with that Regulation for the type of device in question.
Article 118
Amendment to Regulation (EC) No 178/2002
In the third paragraph of Article 2 of Regulation (EC) No 178/2002, the following point is added:
‘(i) medical devices within the meaning of Regulation (EU) 2017/745 of the European Parliament and of the Council ( *2 ).
Article 119
Amendment to Regulation (EC) No 1223/2009
In Article 2 of Regulation (EC) No 1223/2009, the following paragraph is added:
Article 120
Transitional provisions
Certificates issued by notified bodies in accordance with Directives 90/385/EEC and 93/42/EEC from 25 May 2017 that were still valid on 26 May 2021 and that have not been withdrawn afterwards shall remain valid after the end of the period indicated on the certificate until the date set out in paragraph 3a of this Article applicable for the relevant risk class of the devices. Certificates issued by notified bodies in accordance with those Directives from 25 May 2017 that were still valid on 26 May 2021 and that have expired before 20 March 2023 shall be considered to be valid until the dates set out in paragraph 3a of this Article only if one of the following conditions is fulfilled:
before the date of expiry of the certificate, the manufacturer and a notified body have signed a written agreement in accordance with Section 4.3, second subparagraph, of Annex VII to this Regulation for the conformity assessment in respect of the device covered by the expired certificate or in respect of a device intended to substitute that device;
a competent authority of a Member State has granted a derogation from the applicable conformity assessment procedure in accordance with Article 59(1) of this Regulation or has required the manufacturer, in accordance with Article 97(1) of this Regulation, to carry out the applicable conformity assessment procedure.
Devices which have a certificate that was issued in accordance with Directive 90/385/EEC or Directive 93/42/EEC and that is valid by virtue of paragraph 2 of this Article may be placed on the market or put into service until the following dates:
31 December 2027, for all class III devices, and for class IIb implantable devices except sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips and connectors;
31 December 2028, for class IIb devices other than those covered by point (a) of this paragraph, for class IIa devices, and for class I devices placed on the market in sterile condition or having a measuring function.
Devices referred to in paragraphs 3a and 3b of this Article may be placed on the market or put into service until the dates referred to in those paragraphs only if the following conditions are met:
those devices continue to comply with Directive 90/385/EEC or Directive 93/42/EEC, as applicable;
there are no significant changes in the design and intended purpose;
the devices do not present an unacceptable risk to the health or safety of patients, users or other persons, or to other aspects of the protection of public health;
no later than 26 May 2024, the manufacturer has put in place a quality management system in accordance with Article 10(9);
no later than 26 May 2024, the manufacturer or the authorised representative has lodged a formal application with a notified body in accordance with Section 4.3, first subparagraph, of Annex VII for conformity assessment in respect of a device referred to in paragraph 3a or 3b of this Article or in respect of a device intended to substitute that device, and, no later than 26 September 2024, the notified body and the manufacturer have signed a written agreement in accordance with Section 4.3, second subparagraph, of Annex VII.
No later than 26 September 2024, the notified body that has signed the written agreement referred to in paragraph 3c, point (e), of this Article shall be responsible for the surveillance in respect of the devices covered by the written agreement. Where the written agreement covers a device intended to substitute a device which has a certificate that was issued in accordance with Directive 90/385/EEC or Directive 93/42/EEC, the surveillance shall be conducted in respect of the device that is being substituted.
The arrangements for the transfer of the surveillance from the notified body that issued the certificate to the notified body designated in accordance with Article 42 shall be clearly defined in an agreement between the manufacturer and the notified body designated in accordance with Article 42 and, where practicable, the notified body that issued the certificate. The notified body designated in accordance with Article 42 shall not be responsible for conformity assessment activities carried out by the notified body that issued the certificate.
Article 121
Evaluation
By 27 May 2027, the Commission shall assess the application of this Regulation and produce an evaluation report on the progress towards achievement of the objectives contained herein including an assessment of the resources required to implement this Regulation. Special attention shall be given to the traceability of medical devices through the storage, pursuant to Article 27, of the UDI by economic operators, health institutions and health professionals.
Article 122
Repeal
Without prejudice to Article 120(3) to (3e) and (4) of this Regulation, and without prejudice to the obligations of the Member States and manufacturers as regards vigilance and to the obligations of manufacturers as regards the making available of documentation, under Directives 90/385/EEC and 93/42/EEC, those Directives are repealed with effect from 26 May 2021, with the exception of:
As regards the devices referred to in Article 120(3) to (3e) and (4) of this Regulation, the Directives referred to in the first paragraph of this Article shall continue to apply to the extent necessary for the application of those paragraphs.
Notwithstanding the first paragraph, Regulations (EU) No 207/2012 and (EU) No 722/2012 shall remain in force and continue to apply unless and until repealed by implementing acts adopted by the Commission pursuant to this Regulation.
References to the repealed Directives shall be understood as references to this Regulation and shall be read in accordance with the correlation table laid down in Annex XVII to this Regulation.
Article 123
Entry into force and date of application
By way of derogation from paragraph 2:
Articles 35 to 50 shall apply from 26 November 2017. However, from that date until ►M1 26 May 2021 ◄ , the obligations on notified bodies pursuant to Articles 35 to 50 shall apply only to those bodies which submit an application for designation in accordance with Article 38;
Articles 101 and 103 shall apply from 26 November 2017;
Article 102 shall apply from 26 May 2018;
without prejudice to the obligations on the Commission pursuant to Article 34, where, due to circumstances that could not reasonably have been foreseen when drafting the plan referred to in Article 34(1), Eudamed is not fully functional on ►M1 26 May 2021 ◄ , the obligations and requirements that relate to Eudamed shall apply from the date corresponding to six months after the date of publication of the notice referred to in Article 34(3). The provisions referred to in the preceding sentence are:
Until Eudamed is fully functional, the corresponding provisions of Directives 90/385/EEC and 93/42/EEC shall continue to apply for the purpose of meeting the obligations laid down in the provisions listed in the first paragraph of this point regarding exchange of information including, and in particular, information regarding vigilance reporting, clinical investigations, registration of devices and economic operators, and certificate notifications.
Article 29(4) and Article 56(5) shall apply from 18 months after the later of the dates referred to in point (d);
for implantable devices and for class III devices Article 27(4) shall apply from 26 May 2021. For class IIa and class IIb devices Article 27(4) shall apply from 26 May 2023. For class I devices Article 27(4) shall apply from 26 May 2025;
with regard to reusable devices that are required to bear the UDI carrier on the device itself, Article 27(4) shall apply to:
implantable devices and class III devices from 26 May 2023;
class IIa and class IIb devices from 26 May 2025;
class I devices from 26 May 2027;
The procedure set out in Article 78 shall apply from 26 May 2027, without prejudice to Article 78(14);
Article 120(12) shall apply from 26 May 2019;
Article 59 shall apply from 24 April 2020.
This Regulation shall be binding in its entirety and directly applicable in all Member States.
ANNEXES
|
I |
General safety and performance requirements |
|
II |
Technical documentation |
|
III |
Technical documentation on post-market surveillance |
|
IV |
EU declaration of conformity |
|
V |
CE marking of conformity |
|
VI |
Information to be submitted upon the registration of devices and economic operators in accordance with Articles 29(4) and 31; core data elements to be provided to the UDI database together with the UDI-DI in accordance with Articles 28 and 29;and the UDI system |
|
VII |
Requirements to be met by notified bodies |
|
VIII |
Classification rules |
|
IX |
Conformity assessment based on a quality management system and assessment of the technical documentation |
|
X |
Conformity assessment based on type examination |
|
XI |
Conformity assessment based on product conformity verification |
|
XII |
Certificates issued by a notified body |
|
XIII |
Procedure for custom-made devices |
|
XIV |
Clinical evaluation and post-market clinical follow-up |
|
XV |
Clinical investigations |
|
XVI |
List of groups of products without an intended medical purpose referred to in Article 1(2) |
|
XVII |
Correlation table |
ANNEX I
GENERAL SAFETY AND PERFORMANCE REQUIREMENTS
CHAPTER I
GENERAL REQUIREMENTS
|
1. |
Devices shall achieve the performance intended by their manufacturer and shall be designed and manufactured in such a way that, during normal conditions of use, they are suitable for their intended purpose. They shall be safe and effective and shall not compromise the clinical condition or the safety of patients, or the safety and health of users or, where applicable, other persons, provided that any risks which may be associated with their use constitute acceptable risks when weighed against the benefits to the patient and are compatible with a high level of protection of health and safety, taking into account the generally acknowledged state of the art. |
|
2. |
The requirement in this Annex to reduce risks as far as possible means the reduction of risks as far as possible without adversely affecting the benefit-risk ratio. |
|
3. |
Manufacturers shall establish, implement, document and maintain a risk management system. Risk management shall be understood as a continuous iterative process throughout the entire lifecycle of a device, requiring regular systematic updating. In carrying out risk management manufacturers shall:
(a)
establish and document a risk management plan for each device;
(b)
identify and analyse the known and foreseeable hazards associated with each device;
(c)
estimate and evaluate the risks associated with, and occurring during, the intended use and during reasonably foreseeable misuse;
(d)
eliminate or control the risks referred to in point (c) in accordance with the requirements of Section 4;
(e)
evaluate the impact of information from the production phase and, in particular, from the post-market surveillance system, on hazards and the frequency of occurrence thereof, on estimates of their associated risks, as well as on the overall risk, benefit-risk ratio and risk acceptability; and
(f)
based on the evaluation of the impact of the information referred to in point (e), if necessary amend control measures in line with the requirements of Section 4. |
|
4. |
Risk control measures adopted by manufacturers for the design and manufacture of the devices shall conform to safety principles, taking account of the generally acknowledged state of the art. To reduce risks, Manufacturers shall manage risks so that the residual risk associated with each hazard as well as the overall residual risk is judged acceptable. In selecting the most appropriate solutions, manufacturers shall, in the following order of priority:
(a)
eliminate or reduce risks as far as possible through safe design and manufacture;
(b)
where appropriate, take adequate protection measures, including alarms if necessary, in relation to risks that cannot be eliminated; and
(c)
provide information for safety (warnings/precautions/contra-indications) and, where appropriate, training to users. Manufacturers shall inform users of any residual risks. |
|
5. |
In eliminating or reducing risks related to use error, the manufacturer shall:
(a)
reduce as far as possible the risks related to the ergonomic features of the device and the environment in which the device is intended to be used (design for patient safety), and
(b)
give consideration to the technical knowledge, experience, education, training and use environment, where applicable, and the medical and physical conditions of intended users (design for lay, professional, disabled or other users). |
|
6. |
The characteristics and performance of a device shall not be adversely affected to such a degree that the health or safety of the patient or the user and, where applicable, of other persons are compromised during the lifetime of the device, as indicated by the manufacturer, when the device is subjected to the stresses which can occur during normal conditions of use and has been properly maintained in accordance with the manufacturer's instructions. |
|
7. |
Devices shall be designed, manufactured and packaged in such a way that their characteristics and performance during their intended use are not adversely affected during transport and storage, for example, through fluctuations of temperature and humidity, taking account of the instructions and information provided by the manufacturer. |
|
8. |
All known and foreseeable risks, and any undesirable side-effects, shall be minimised and be acceptable when weighed against the evaluated benefits to the patient and/or user arising from the achieved performance of the device during normal conditions of use. |
|
9. |
For the devices referred to in Annex XVI, the general safety requirements set out in Sections 1 and 8 shall be understood to mean that the device, when used under the conditions and for the purposes intended, does not present a risk at all or presents a risk that is no more than the maximum acceptable risk related to the product's use which is consistent with a high level of protection for the safety and health of persons. |
CHAPTER II
REQUIREMENTS REGARDING DESIGN AND MANUFACTURE
10. Chemical, physical and biological properties
|
10.1. |
Devices shall be designed and manufactured in such a way as to ensure that the characteristics and performance requirements referred to in Chapter I are fulfilled. Particular attention shall be paid to:
(a)
the choice of materials and substances used, particularly as regards toxicity and, where relevant, flammability;
(b)
the compatibility between the materials and substances used and biological tissues, cells and body fluids, taking account of the intended purpose of the device and, where relevant, absorption, distribution, metabolism and excretion;
(c)
the compatibility between the different parts of a device which consists of more than one implantable part;
(d)
the impact of processes on material properties;
(e)
where appropriate, the results of biophysical or modelling research the validity of which has been demonstrated beforehand;
(f)
the mechanical properties of the materials used, reflecting, where appropriate, matters such as strength, ductility, fracture resistance, wear resistance and fatigue resistance;
(g)
surface properties; and
(h)
the confirmation that the device meets any defined chemical and/or physical specifications. |
|
10.2. |
Devices shall be designed, manufactured and packaged in such a way as to minimise the risk posed by contaminants and residues to patients, taking account of the intended purpose of the device, and to the persons involved in the transport, storage and use of the devices. Particular attention shall be paid to tissues exposed to those contaminants and residues and to the duration and frequency of exposure. |
|
10.3. |
Devices shall be designed and manufactured in such a way that they can be used safely with the materials and substances, including gases, with which they enter into contact during their intended use; if the devices are intended to administer medicinal products they shall be designed and manufactured in such a way as to be compatible with the medicinal products concerned in accordance with the provisions and restrictions governing those medicinal products and that the performance of both the medicinal products and of the devices is maintained in accordance with their respective indications and intended use. |
|
10.4. |
Substances 10.4.1. Design and manufacture of devices Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks posed by substances or particles, including wear debris, degradation products and processing residues, that may be released from the device. Devices, or those parts thereof or those materials used therein that:
—
are invasive and come into direct contact with the human body,
—
(re)administer medicines, body liquids or other substances, including gases, to/from the body, or
—
transport or store such medicines, body fluids or substances, including gases, to be (re)administered to the body,
shall only contain the following substances in a concentration that is above 0,1 % weight by weight (w/w) where justified pursuant to Section 10.4.2:
(a)
substances which are carcinogenic, mutagenic or toxic to reproduction (‘CMR’), of category 1A or 1B, in accordance with Part 3 of Annex VI to Regulation (EC) No 1272/2008 of the European Parliament and of the Council ( 5 ), or
(b)
substances having endocrine-disrupting properties for which there is scientific evidence of probable serious effects to human health and which are identified either in accordance with the procedure set out in Article 59 of Regulation (EC) No 1907/2006 of the European Parliament and of the Council ( 6 ) or, once a delegated act has been adopted by the Commission pursuant to the first subparagraph of Article 5(3) of Regulation (EU) No 528/2012 of the European Parliament and the Council ( 7 ), in accordance with the criteria that are relevant to human health amongst the criteria established therein. 10.4.2. Justification regarding the presence of CMR and/or endocrine-disrupting substances The justification for the presence of such substances shall be based upon:
(a)
an analysis and estimation of potential patient or user exposure to the substance;
(b)
an analysis of possible alternative substances, materials or designs, including, where available, information about independent research, peer-reviewed studies, scientific opinions from relevant scientific committees and an analysis of the availability of such alternatives;
(c)
argumentation as to why possible substance and/ or material substitutes, if available, or design changes, if feasible, are inappropriate in relation to maintaining the functionality, performance and the benefit-risk ratios of the product; including taking into account if the intended use of such devices includes treatment of children or treatment of pregnant or breastfeeding women or treatment of other patient groups considered particularly vulnerable to such substances and/or materials; and
(d)
where applicable and available, the latest relevant scientific committee guidelines in accordance with Sections 10.4.3. and 10.4.4. 10.4.3. Guidelines on phthalates For the purposes of Section 10.4., the Commission shall, as soon as possible and by 26 May 2018, provide the relevant scientific committee with a mandate to prepare guidelines that shall be ready before 26 May 2020. The mandate for the committee shall encompass at least a benefit-risk assessment of the presence of phthalates which belong to either of the groups of substances referred to in points (a) and (b) of Section 10.4.1. The benefit-risk assessment shall take into account the intended purpose and context of the use of the device, as well as any available alternative substances and alternative materials, designs or medical treatments. When deemed appropriate on the basis of the latest scientific evidence, but at least every five years, the guidelines shall be updated. 10.4.4. Guidelines on other CMR and endocrine-disrupting substances Subsequently, the Commission shall mandate the relevant scientific committee to prepare guidelines as referred to in Section 10.4.3. also for other substances referred to in points (a) and (b) of Section 10.4.1., where appropriate. 10.4.5. Labelling Where devices, parts thereof or materials used therein as referred to in Section 10.4.1. contain substances referred to in points (a) or (b) of Section 10.4.1. in a concentration above 0,1 % weight by weight (w/w), the presence of those substances shall be labelled on the device itself and/or on the packaging for each unit or, where appropriate, on the sales packaging, with the list of such substances. If the intended use of such devices includes treatment of children or treatment of pregnant or breastfeeding women or treatment of other patient groups considered particularly vulnerable to such substances and/or materials, information on residual risks for those patient groups and, if applicable, on appropriate precautionary measures shall be given in the instructions for use. |
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10.5. |
Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks posed by the unintentional ingress of substances into the device taking into account the device and the nature of the environment in which it is intended to be used. |
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10.6. |
Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks linked to the size and the properties of particles which are or can be released into the patient's or user's body, unless they come into contact with intact skin only. Special attention shall be given to nanomaterials. |
11. Infection and microbial contamination
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11.1. |
Devices and their manufacturing processes shall be designed in such a way as to eliminate or to reduce as far as possible the risk of infection to patients, users and, where applicable, other persons. The design shall:
(a)
reduce as far as possible and appropriate the risks from unintended cuts and pricks, such as needle stick injuries,
(b)
allow easy and safe handling,
(c)
reduce as far as possible any microbial leakage from the device and/or microbial exposure during use, and
(d)
prevent microbial contamination of the device or its content such as specimens or fluids. |
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11.2. |
Where necessary devices shall be designed to facilitate their safe cleaning, disinfection, and/or re-sterilisation. |
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11.3. |
Devices labelled as having a specific microbial state shall be designed, manufactured and packaged to ensure that they remain in that state when placed on the market and remain so under the transport and storage conditions specified by the manufacturer. |
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11.4. |
Devices delivered in a sterile state shall be designed, manufactured and packaged in accordance with appropriate procedures, to ensure that they are sterile when placed on the market and that, unless the packaging which is intended to maintain their sterile condition is damaged, they remain sterile, under the transport and storage conditions specified by the manufacturer, until that packaging is opened at the point of use. It shall be ensured that the integrity of that packaging is clearly evident to the final user. |
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11.5. |
Devices labelled as sterile shall be processed, manufactured, packaged and, sterilised by means of appropriate, validated methods. |
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11.6. |
Devices intended to be sterilised shall be manufactured and packaged in appropriate and controlled conditions and facilities. |
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11.7. |
Packaging systems for non-sterile devices shall maintain the integrity and cleanliness of the product and, where the devices are to be sterilised prior to use, minimise the risk of microbial contamination; the packaging system shall be suitable taking account of the method of sterilisation indicated by the manufacturer. |
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11.8. |
The labelling of the device shall distinguish between identical or similar devices placed on the market in both a sterile and a non-sterile condition additional to the symbol used to indicate that devices are sterile. |
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12. |
Devices incorporating a substance considered to be a medicinal product and devices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body.
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13. |
Devices incorporating materials of biological origin
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14. |
Construction of devices and interaction with their environment
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15. |
Devices with a diagnostic or measuring function
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16. |
Protection against radiation 16.1. General
(a)
Devices shall be designed, manufactured and packaged in such a way that exposure of patients, users and other persons to radiation is reduced as far as possible, and in a manner that is compatible with the intended purpose, whilst not restricting the application of appropriate specified levels for therapeutic and diagnostic purposes.
(b)
The operating instructions for devices emitting hazardous or potentially hazardous radiation shall contain detailed information as to the nature of the emitted radiation, the means of protecting the patient and the user, and on ways of avoiding misuse and of reducing the risks inherent to installation as far as possible and appropriate. Information regarding the acceptance and performance testing, the acceptance criteria, and the maintenance procedure shall also be specified. 16.2. Intended radiation
(a)
Where devices are designed to emit hazardous, or potentially hazardous, levels of ionizing and/or non-ionizing radiation necessary for a specific medical purpose the benefit of which is considered to outweigh the risks inherent to the emission, it shall be possible for the user to control the emissions. Such devices shall be designed and manufactured to ensure reproducibility of relevant variable parameters within an acceptable tolerance.
(b)
Where devices are intended to emit hazardous, or potentially hazardous, ionizing and/or non-ionizing radiation, they shall be fitted, where possible, with visual displays and/or audible warnings of such emissions.
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17. |
Electronic programmable systems — devices that incorporate electronic programmable systems and software that are devices in themselves
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18. |
Active devices and devices connected to them
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19. |
Particular requirements for active implantable devices
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20. |
Protection against mechanical and thermal risks
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21. |
Protection against the risks posed to the patient or user by devices supplying energy or substances
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22. |
Protection against the risks posed by medical devices intended by the manufacturer for use by lay persons
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CHAPTER III
REQUIREMENTS REGARDING THE INFORMATION SUPPLIED WITH THE DEVICE
23. Label and instructions for use
23.1. General requirements regarding the information supplied by the manufacturer
Each device shall be accompanied by the information needed to identify the device and its manufacturer, and by any safety and performance information relevant to the user, or any other person, as appropriate. Such information may appear on the device itself, on the packaging or in the instructions for use, and shall, if the manufacturer has a website, be made available and kept up to date on the website, taking into account the following:
The medium, format, content, legibility, and location of the label and instructions for use shall be appropriate to the particular device, its intended purpose and the technical knowledge, experience, education or training of the intended user(s). In particular, instructions for use shall be written in terms readily understood by the intended user and, where appropriate, supplemented with drawings and diagrams.
The information required on the label shall be provided on the device itself. If this is not practicable or appropriate, some or all of the information may appear on the packaging for each unit, and/or on the packaging of multiple devices.
Labels shall be provided in a human-readable format and may be supplemented by machine-readable information, such as radio-frequency identification (‘RFID’) or bar codes.
Instructions for use shall be provided together with devices. By way of exception, instructions for use shall not be required for class I and class IIa devices if such devices can be used safely without any such instructions and unless otherwise provided for elsewhere in this Section.
Where multiple devices are supplied to a single user and/or location, a single copy of the instructions for use may be provided if so agreed by the purchaser who in any case may request further copies to be provided free of charge.
Instructions for use may be provided to the user in non-paper format (e.g. electronic) to the extent, and only under the conditions, set out in Regulation (EU) No 207/2012 or in any subsequent implementing rules adopted pursuant to this Regulation.
Residual risks which are required to be communicated to the user and/or other person shall be included as limitations, contra-indications, precautions or warnings in the information supplied by the manufacturer.
Where appropriate, the information supplied by the manufacturer shall take the form of internationally recognised symbols. Any symbol or identification colour used shall conform to the harmonised standards or CS. In areas for which no harmonised standards or CS exist, the symbols and colours shall be described in the documentation supplied with the device.
23.2. Information on the label
The label shall bear all of the following particulars:
the name or trade name of the device;
the details strictly necessary for a user to identify the device, the contents of the packaging and, where it is not obvious for the user, the intended purpose of the device;
the name, registered trade name or registered trade mark of the manufacturer and the address of its registered place of business;
if the manufacturer has its registered place of business outside the Union, the name of the authorised representative and address of the registered place of business of the authorised representative;
where applicable, an indication that the device contains or incorporates:
where applicable, information labelled in accordance with Section 10.4.5.;
the lot number or the serial number of the device preceded by the words LOT NUMBER or SERIAL NUMBER or an equivalent symbol, as appropriate;
the UDI carrier referred to in Article 27(4) and Part C of Annex VI;
an unambiguous indication of t the time limit for using or implanting the device safely, expressed at least in terms of year and month, where this is relevant;
where there is no indication of the date until when it may be used safely, the date of manufacture. This date of manufacture may be included as part of the lot number or serial number, provided the date is clearly identifiable;
an indication of any special storage and/or handling condition that applies;
if the device is supplied sterile, an indication of its sterile state and the sterilisation method;
warnings or precautions to be taken that need to be brought to the immediate attention of the user of the device, and to any other person. This information may be kept to a minimum in which case more detailed information shall appear in the instructions for use, taking into account the intended users;
if the device is intended for single use, an indication of that fact. A manufacturer's indication of single use shall be consistent across the Union;
if the device is a single-use device that has been reprocessed, an indication of that fact, the number of reprocessing cycles already performed, and any limitation as regards the number of reprocessing cycles;
if the device is custom-made, the words ‘custom-made device’;
an indication that the device is a medical device. If the device is intended for clinical investigation only, the words ‘exclusively for clinical investigation’;
in the case of devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed by or locally dispersed in the human body, the overall qualitative composition of the device and quantitative information on the main constituent or constituents responsible for achieving the principal intended action;
for active implantable devices, the serial number, and for other implantable devices, the serial number or the lot number.
23.3. Information on the packaging which maintains the sterile condition of a device (‘sterile packaging’)
The following particulars shall appear on the sterile packaging:
an indication permitting the sterile packaging to be recognised as such,
a declaration that the device is in a sterile condition,
the method of sterilisation,
the name and address of the manufacturer,
a description of the device,
if the device is intended for clinical investigations, the words ‘exclusively for clinical investigations’,
if the device is custom-made, the words ‘custom-made device’,
the month and year of manufacture,
an unambiguous indication of the time limit for using or implanting the device safely expressed at least in terms of year and month, and
an instruction to check the instructions for use for what to do if the sterile packaging is damaged or unintentionally opened before use.
23.4. Information in the instructions for use
The instructions for use shall contain all of the following particulars:
the particulars referred to in points (a), (c), (e), (f), (k), (l), (n) and (r) of Section 23.2;
the device's intended purpose with a clear specification of indications, contra-indications, the patient target group or groups, and of the intended users, as appropriate;
where applicable, a specification of the clinical benefits to be expected.
where applicable, links to the summary of safety and clinical performance referred to in Article 32;
the performance characteristics of the device;
where applicable, information allowing the healthcare professional to verify if the device is suitable and select the corresponding software and accessories;
any residual risks, contra-indications and any undesirable side-effects, including information to be conveyed to the patient in this regard;
specifications the user requires to use the device appropriately, e.g. if the device has a measuring function, the degree of accuracy claimed for it;
details of any preparatory treatment or handling of the device before it is ready for use or during its use, such as sterilisation, final assembly, calibration, etc., including the levels of disinfection required to ensure patient safety and all available methods for achieving those levels of disinfection;
any requirements for special facilities, or special training, or particular qualifications of the device user and/or other persons;
the information needed to verify whether the device is properly installed and is ready to perform safely and as intended by the manufacturer, together with, where relevant:
if the device is supplied sterile, instructions in the event of the sterile packaging being damaged or unintentionally opened before use;
if the device is supplied non-sterile with the intention that it is sterilised before use, the appropriate instructions for sterilisation;
if the device is reusable, information on the appropriate processes for allowing reuse, including cleaning, disinfection, packaging and, where appropriate, the validated method of re-sterilisation appropriate to the Member State or Member States in which the device has been placed on the market. Information shall be provided to identify when the device should no longer be reused, e.g. signs of material degradation or the maximum number of allowable reuses;
an indication, if appropriate, that a device can be reused only if it is reconditioned under the responsibility of the manufacturer to comply with the general safety and performance requirements;
if the device bears an indication that it is for single use, information on known characteristics and technical factors known to the manufacturer that could pose a risk if the device were to be re-used. This information shall be based on a specific section of the manufacturer's risk management documentation, where such characteristics and technical factors shall be addressed in detail. If in accordance with point (d) of Section 23.1. no instructions for use are required, this information shall be made available to the user upon request;
for devices intended for use together with other devices and/or general purpose equipment:
if the device emits radiation for medical purposes:
information that allows the user and/or patient to be informed of any warnings, precautions, contra-indications, measures to be taken and limitations of use regarding the device. That information shall, where relevant, allow the user to brief the patient about any warnings, precautions, contra-indications, measures to be taken and limitations of use regarding the device. The information shall cover, where appropriate:
in the case of devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body and that are absorbed by or locally dispersed in the human body, warnings and precautions, where appropriate, related to the general profile of interaction of the device and its products of metabolism with other devices, medicinal products and other substances as well as contra-indications, undesirable side-effects and risks relating to overdose;
in the case of implantable devices, the overall qualitative and quantitative information on the materials and substances to which patients can be exposed;
warnings or precautions to be taken in order to facilitate the safe disposal of the device, its accessories and the consumables used with it, if any. This information shall cover, where appropriate:
If in accordance with the point (d) of Section 23.1 no instructions for use are required, this information shall be made available to the user upon request;
for devices intended for use by lay persons, the circumstances in which the user should consult a healthcare professional;
for the devices covered by this Regulation pursuant to Article 1(2), information regarding the absence of a clinical benefit and the risks related to use of the device;
date of issue of the instructions for use or, if they have been revised, date of issue and identifier of the latest revision of the instructions for use;
a notice to the user and/or patient that any serious incident that has occurred in relation to the device should be reported to the manufacturer and the competent authority of the Member State in which the user and/or patient is established;
information to be supplied to the patient with an implanted device in accordance with Article 18;
for devices that incorporate electronic programmable systems, including software, or software that are devices in themselves, minimum requirements concerning hardware, IT networks characteristics and IT security measures, including protection against unauthorised access, necessary to run the software as intended.
ANNEX II
TECHNICAL DOCUMENTATION
The technical documentation and, if applicable, the summary thereof to be drawn up by the manufacturer shall be presented in a clear, organised, readily searchable and unambiguous manner and shall include in particular the elements listed in this Annex.
1. DEVICE DESCRIPTION AND SPECIFICATION, INCLUDING VARIANTS AND ACCESSORIES
1.1. Device description and specification
product or trade name and a general description of the device including its intended purpose and intended users;
the Basic UDI-DI as referred to in Part C of Annex VI assigned by the manufacturer to the device in question, as soon as identification of this device becomes based on a UDI system, or otherwise a clear identification by means of product code, catalogue number or other unambiguous reference allowing traceability;
the intended patient population and medical conditions to be diagnosed, treated and/or monitored and other considerations such as patient selection criteria, indications, contra-indications, warnings;
principles of operation of the device and its mode of action, scientifically demonstrated if necessary;
the rationale for the qualification of the product as a device;
the risk class of the device and the justification for the classification rule(s) applied in accordance with Annex VIII;
an explanation of any novel features;
a description of the accessories for a device, other devices and other products that are not devices, which are intended to be used in combination with it;
a description or complete list of the various configurations/variants of the device that are intended to be made available on the market;
a general description of the key functional elements, e.g. its parts/components (including software if appropriate), its formulation, its composition, its functionality and, where relevant, its qualitative and quantitative composition. Where appropriate, this shall include labelled pictorial representations (e.g. diagrams, photographs, and drawings), clearly indicating key parts/components, including sufficient explanation to understand the drawings and diagrams;
a description of the raw materials incorporated into key functional elements and those making either direct contact with the human body or indirect contact with the body, e.g., during extracorporeal circulation of body fluids;
technical specifications, such as features, dimensions and performance attributes, of the device and any variants/configurations and accessories that would typically appear in the product specification made available to the user, for example in brochures, catalogues and similar publications.
1.2. Reference to previous and similar generations of the device
an overview of the previous generation or generations of the device produced by the manufacturer, where such devices exist;
an overview of identified similar devices available on the Union or international markets, where such devices exist.
2. INFORMATION TO BE SUPPLIED BY THE MANUFACTURER
A complete set of:
3. DESIGN AND MANUFACTURING INFORMATION
information to allow the design stages applied to the device to be understood;
complete information and specifications, including the manufacturing processes and their validation, their adjuvants, the continuous monitoring and the final product testing. Data shall be fully included in the technical documentation;
identification of all sites, including suppliers and sub-contractors, where design and manufacturing activities are performed.
4. GENERAL SAFETY AND PERFORMANCE REQUIREMENTS
The documentation shall contain information for the demonstration of conformity with the general safety and performance requirements set out in Annex I that are applicable to the device taking into account its intended purpose, and shall include a justification, validation and verification of the solutions adopted to meet those requirements. The demonstration of conformity shall include:
the general safety and performance requirements that apply to the device and an explanation as to why others do not apply;
the method or methods used to demonstrate conformity with each applicable general safety and performance requirement;
the harmonised standards, CS or other solutions applied; and
the precise identity of the controlled documents offering evidence of conformity with each harmonised standard, CS or other method applied to demonstrate conformity with the general safety and performance requirements. The information referred to under this point shall incorporate a cross-reference to the location of such evidence within the full technical documentation and, if applicable, the summary technical documentation.
5. BENEFIT-RISK ANALYSIS AND RISK MANAGEMENT
The documentation shall contain information on:
the benefit-risk analysis referred to in Sections 1 and 8 of Annex I, and
the solutions adopted and the results of the risk management referred to in Section 3 of Annex I.
6. PRODUCT VERIFICATION AND VALIDATION
The documentation shall contain the results and critical analyses of all verifications and validation tests and/or studies undertaken to demonstrate conformity of the device with the requirements of this Regulation and in particular the applicable general safety and performance requirements.
6.1. Pre-clinical and clinical data
results of tests, such as engineering, laboratory, simulated use and animal tests, and evaluation of published literature applicable to the device, taking into account its intended purpose, or to similar devices, regarding the pre-clinical safety of the device and its conformity with the specifications;
detailed information regarding test design, complete test or study protocols, methods of data analysis, in addition to data summaries and test conclusions regarding in particular:
Where applicable, conformity with the provisions of Directive 2004/10/EC of the European Parliament and of the Council ( 9 ) shall be demonstrated.
Where no new testing has been undertaken, the documentation shall incorporate a rationale for that decision. An example of such a rationale would be that biocompatibility testing on identical materials was conducted when those materials were incorporated in a previous version of the device that has been legally placed on the market or put into service;
the clinical evaluation report and its updates and the clinical evaluation plan referred to in Article 61(12) and Part A of Annex XIV;
the PMCF plan and PMCF evaluation report referred to in Part B of Annex XIV or a justification why a PMCF is not applicable.
6.2. Additional information required in specific cases
Where a device incorporates, as an integral part, a substance which, if used separately, may be considered to be a medicinal product within the meaning of point 2 of Article 1 of Directive 2001/83/EC, including a medicinal product derived from human blood or human plasma, as referred to in the first subparagraph of Article 1(8), a statement indicating this fact. In this case, the documentation shall identify the source of that substance and contain the data of the tests conducted to assess its safety, quality and usefulness, taking account of the intended purpose of the device.
Where a device is manufactured utilising tissues or cells of human or animal origin, or their derivatives, and is covered by this Regulation in accordance with points (f) and (g) of Article 1(6, and where a device incorporates, as an integral part, tissues or cells of human origin or their derivatives that have an action ancillary to that of the device and is covered by this Regulation in accordance with the first subparagraph of Article 1(10), a statement indicating this fact. In such a case, the documentation shall identify all materials of human or animal origin used and provide detailed information concerning the conformity with Sections 13.1. or 13.2., respectively, of Annex I.
In the case of devices that are composed of substances or combinations of substances that are intended to be introduced into the human body and that are absorbed by or locally dispersed in the human body, detailed information, including test design, complete test or study protocols, methods of data analysis, and data summaries and test conclusions, regarding studies in relation to:
In the absence of such studies, a justification shall be provided.
In the case of devices containing CMR or endocrine-disrupting substances referred to in Section 10.4.1 of Annex I, the justification referred to in Section 10.4.2 of that Annex.
In the case of devices placed on the market in a sterile or defined microbiological condition, a description of the environmental conditions for the relevant manufacturing steps. In the case of devices placed on the market in a sterile condition, a description of the methods used, including the validation reports, with respect to packaging, sterilisation and maintenance of sterility. The validation report shall address bioburden testing, pyrogen testing and, if applicable, testing for sterilant residues.
In the case of devices placed on the market with a measuring function, a description of the methods used in order to ensure the accuracy as given in the specifications.
If the device is to be connected to other device(s) in order to operate as intended, a description of this combination/configuration including proof that it conforms to the general safety and performance requirements when connected to any such device(s) having regard to the characteristics specified by the manufacturer.
ANNEX III
TECHNICAL DOCUMENTATION ON POST-MARKET SURVEILLANCE
The technical documentation on post-market surveillance to be drawn up by the manufacturer in accordance with Articles 83 to 86 shall be presented in a clear, organised, readily searchable and unambiguous manner and shall include in particular the elements described in this Annex.
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1. |
The post-market surveillance plan drawn up in accordance with Article 84. The manufacturer shall prove in a post-market surveillance plan that it complies with the obligation referred to in Article 83.
(a)
The post-market surveillance plan shall address the collection and utilization of available information, in particular:
—
information concerning serious incidents, including information from PSURs, and field safety corrective actions;
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records referring to non-serious incidents and data on any undesirable side-effects;
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information from trend reporting;
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relevant specialist or technical literature, databases and/or registers;
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information, including feedbacks and complaints, provided by users, distributors and importers; and
—
publicly available information about similar medical devices.
(b)
The post-market surveillance plan shall cover at least:
—
a proactive and systematic process to collect any information referred to in point (a). The process shall allow a correct characterisation of the performance of the devices and shall also allow a comparison to be made between the device and similar products available on the market;
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effective and appropriate methods and processes to assess the collected data;
—
suitable indicators and threshold values that shall be used in the continuous reassessment of the benefit-risk analysis and of the risk management as referred to in Section 3 of Annex I;
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effective and appropriate methods and tools to investigate complaints and analyse market-related experience collected in the field;
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methods and protocols to manage the incidents subject to the trend report as provided for in Article 88, including the methods and protocols to be used to establish any statistically significant increase in the frequency or severity of incidents as well as the observation period;
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methods and protocols to communicate effectively with competent authorities, notified bodies, economic operators and users;
—
reference to procedures to fulfil the manufacturers obligations laid down in Articles 83, 84 and 86;
—
systematic procedures to identify and initiate appropriate measures including corrective actions;
—
effective tools to trace and identify devices for which corrective actions might be necessary; and
—
a PMCF plan as referred to in Part B of Annex XIV, or a justification as to why a PMCF is not applicable.
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2. |
The PSUR referred to in Article 86 and the post-market surveillance report referred to in Article 85. |
ANNEX IV
EU DECLARATION OF CONFORMITY
The EU declaration of conformity shall contain all of the following information:
Name, registered trade name or registered trade mark and, if already issued, SRN as referred to in Article 31 of the manufacturer, and, if applicable, its authorised representative, and the address of their registered place of business where they can be contacted and their location be established;
A statement that the EU declaration of conformity is issued under the sole responsibility of the manufacturer;
The Basic UDI-DI as referred to in Part C of Annex VI;
Product and trade name, product code, catalogue number or other unambiguous reference allowing identification and traceability of the device covered by the EU declaration of conformity, such as a photograph, where appropriate, as well as its intended purpose. Except for the product or trade name, the information allowing identification and traceability may be provided by the Basic UDI-DI referred to in point 3;
Risk class of the device in accordance with the rules set out in Annex VIII;
A statement that the device that is covered by the present declaration is in conformity with this Regulation and, if applicable, with any other relevant Union legislation that provides for the issuing of an EU declaration of conformity;
References to any CS used and in relation to which conformity is declared;
Where applicable, the name and identification number of the notified body, a description of the conformity assessment procedure performed and identification of the certificate or certificates issued;
Where applicable, additional information;
Place and date of issue of the declaration, name and function of the person who signed it as well as an indication for, and on behalf of whom, that person signed, signature.
ANNEX V
CE MARKING OF CONFORMITY
1. The CE marking shall consist of the initials ‘CE’ taking the following form:
2. If the CE marking is reduced or enlarged, the proportions given in the above graduated drawing shall be respected.
3. The various components of the CE marking shall have substantially the same vertical dimension, which may not be less than 5 mm. This minimum dimension may be waived for small-scale devices.
ANNEX VI
INFORMATION TO BE SUBMITTED UPON THE REGISTRATION OF DEVICES AND ECONOMIC OPERATORS IN ACCORDANCE WITH ARTICLES 29(4) AND 31, CORE DATA ELEMENTS TO BE PROVIDED TO THE UDI DATABASE TOGETHER WITH THE UDI-DI IN ACCORDANCE WITH ARTICLES 28 AND 29, AND THE UDI SYSTEM
PART A
INFORMATION TO BE SUBMITTED UPON THE REGISTRATION OF DEVICES AND ECONOMIC OPERATORS IN ACCORDANCE WITH ARTICLES 29(4) AND 31
Manufacturers or, when applicable, authorised representatives, and, when applicable, importers shall submit the information referred to in Section 1 and shall ensure that the information on their devices referred to in Section 2 is complete, correct and updated by the relevant party.
1. Information relating to the economic operator
type of economic operator(manufacturer, authorised representative, or importer),
name, address and contact details of the economic operator,
where submission of information is carried out by another person on behalf of any of the economic operators mentioned under Section 1.1, the name, address and contact details of that person,
name address and contact details of the person or persons responsible for regulatory compliance referred to in Article 15.
2. Information relating to the device
Basic UDI-DI,
type, number and expiry date of the certificate issued by the notified body and the name or identification number of that notified body and the link to the information that appears on the certificate and was entered by the notified body in the electronic system on notified bodies and certificates,
Member State in which the device is to or has been placed on the market in the Union,
in the case of class IIa, class IIb or class III devices: Member States where the device is or is to be made available,
risk class of the device,
reprocessed single-use device (y/n),
presence of a substance which, if used separately, may be considered to be a medicinal product and name of that substance,
presence of a substance which, if used separately, may be considered to be a medicinal product derived from human blood or human plasma and name of this substance,
presence of tissues or cells of human origin, or their derivatives (y/n),
presence of tissues or cells of animal origin, or their derivatives, as referred to in Regulation (EU) No 722/2012 (y/n),
where applicable, the single identification number of the clinical investigation or investigations conducted in relation to the device or a link to the clinical investigation registration in the electronic system on clinical investigations,
in the case of devices listed in Annex XVI, specification as to whether the intended purpose of the device is other than a medical purpose,
in the case of devices designed and manufactured by another legal or natural person as referred in Article 10(15), the name, address and contact details of that legal or natural person,
in the case of class III or implantable devices, the summary of safety and clinical performance,
status of the device (on the market, no longer placed on the market, recalled, field safety corrective action initiated).
PART B
CORE DATA ELEMENTS TO BE PROVIDED TO THE UDI DATABASE TOGETHER WITH THE UDI-DI IN ACCORDANCE WITH ARTICLES 28 AND 29
The manufacturer shall provide to the UDI database the UDI-DI and all of the following information relating to the manufacturer and the device:
quantity per package configuration,
the Basic UDI-DI as referred to in Article 29 and any additional UDI-DIs,
the manner in which production of the device is controlled (expiry date or manufacturing date, lot number, serial number),
if applicable, the unit of use UDI-DI (where a UDI is not labelled on the device at the level of its unit of use, a ‘unit of use’ DI shall be assigned so as to associate the use of a device with a patient),
name and address of the manufacturer (as indicated on the label),
the SRN issued in accordance with Article 31(2),
if applicable, name and address of the authorised representative (as indicated on the label),
the medical device nomenclature code as provided for in Article 26,
risk class of the device,
if applicable, name or trade name,
if applicable, device model, reference, or catalogue number,
if applicable, clinical size (including volume, length, gauge, diameter),
additional product description (optional),
if applicable, storage and/or handling conditions (as indicated on the label or in the instructions for use),
if applicable, additional trade names of the device,
labelled as a single-use device (y/n),
if applicable, the maximum number of reuses,
device labelled sterile (y/n),
need for sterilisation before use (y/n),
containing latex (y/n),
where applicable, information labelled in accordance with Section 10.4.5 of Annex I,
URL for additional information, such as electronic instructions for use (optional),
if applicable, critical warnings or contra-indications,
status of the device (on the market, no longer placed on the market, recalled, field safety corrective action initiated).
PART C
THE UDI SYSTEM
1. Definitions
Automatic identification and data capture (‘AIDC’)
AIDC is a technology used to automatically capture data. AIDC technologies include bar codes, smart cards, biometrics and RFID.
Basic UDI-DI
The Basic UDI-DI is the primary identifier of a device model. It is the DI assigned at the level of the device unit of use. It is the main key for records in the UDI database and is referenced in relevant certificates and EU declarations of conformity.
Unit of Use DI
The Unit of Use DI serves to associate the use of a device with a patient in instances in which a UDI is not labelled on the individual device at the level of its unit of use, for example in the event of several units of the same device being packaged together.
Configurable device
A configurable device is a device that consists of several components which can be assembled by the manufacturer in multiple configurations. Those individual components may be devices in themselves.
Configurable devices include computed tomography (CT) systems, ultrasound systems, anaesthesia systems, physiological Monitoring systems, radiology information systems (RIS).
Configuration
Configuration is a combination of items of equipment, as specified by the manufacturer, that operate together as a device to achieve an intended purpose. The combination of items may be modified, adjusted or customized to meet specific needs.
Configurations include inter alia:
UDI-DI
The UDI-DI is a unique numeric or alphanumeric code specific to a model of device and that is also used as the ‘access key’ to information stored in a UDI database.
Human Readable Interpretation (‘HRI’)
HRI is a legible interpretation of the data characters encoded in the UDI carrier.
Packaging levels
Packaging levels means the various levels of device packaging that contain a defined quantity of devices, such as a carton or case.
UDI-PI
The UDI-PI is a numeric or alphanumeric code that identifies the unit of device production.
The different types of UDI-PIs include serial number, lot number, software identification and manufacturing or expiry date or both types of date.
Radio Frequency Identification RFID
RFID is a technology that uses communication through the use of radio waves to exchange data between a reader and an electronic tag attached to an object, for the purpose of identification.
Shipping containers
A shipping container is a container in relation to which traceability is controlled by a process specific to logistics systems.
Unique Device Identifier (‘UDI’)
The UDI is a series of numeric or alphanumeric characters that is created through a globally accepted device identification and coding standard. It allows the unambiguous identification of a specific device on the market. The UDI is comprised of the UDI-DI and the UDI-PI.
The word ‘Unique’ does not imply serialisation of individual production units.
UDI carrier
The UDI carrier is the means of conveying the UDI by using AIDC and, if applicable, its HRI.
UDI carriers include, inter alia, ID/linear bar code, 2D/Matrix bar code, RFID.
2. General requirements
|
2.1. |
The affixing of the UDI is an additional requirement — it does not replace any other marking or labelling requirements laid down in Annex I to this Regulation. |
|
2.2. |
The manufacturer shall assign and maintain unique UDIs for its devices. |
|
2.3. |
Only the manufacturer may place the UDI on the device or its packaging. |
|
2.4. |
Only coding standards provided by issuing entities designated by the Commission pursuant to Article 27(2) may be used. |
3. The UDI
|
3.1. |
A UDI shall be assigned to the device itself or its packaging. Higher levels of packaging shall have their own UDI. |
|
3.2. |
Shipping containers shall be exempted from the requirement in Section 3.1. By way of example, a UDI shall not be required on a logistics unit; where a healthcare provider orders multiple devices using the UDI or model number of individual devices and the manufacturer places those devices in a container for shipping or to protect the individually packaged devices, the container (logistics unit) shall not be subject to UDI requirements. |
|
3.3. |
The UDI shall contain two parts: a UDI-DI and a UDI-PI. |
|
3.4. |
The UDI-DI shall be unique at each level of device packaging. |
|
3.5. |
If a lot number, serial number, software identification or expiry date appears on the label, it shall be part of the UDI-PI. If there is also a manufacturing date on the label, it does not need to be included in the UDI-PI. If there is only a manufacturing date on the label, this shall be used as the UDI-PI. |
|
3.6. |
Each component that is considered to be a device and is commercially available on its own shall be assigned a separate UDI unless the components are part of a configurable device that is marked with its own UDI. |
|
3.7. |
Systems and procedure packs as referred to in Article 22 shall be assigned and bear their own UDI. |
|
3.8. |
The manufacturer shall assign the UDI to a device following the relevant coding standard. |
|
3.9. |
A new UDI-DI shall be required whenever there is a change that could lead to misidentification of the device and/or ambiguity in its traceability; in particular, any change of one of the following UDI database data elements shall require a new UDI-DI:
(a)
name or trade name,
(b)
device version or model,
(c)
labelled as single use,
(d)
packaged sterile,
(e)
need for sterilization before use,
(f)
quantity of devices provided in a package,
(g)
critical warnings or contra-indications: e.g. containing latex or DEHP. |
|
3.10. |
Manufacturers that repackage and/or relabel devices, with their own label shall retain a record of the original device manufacturer's UDI. |
4. UDI carrier
|
4.1. |
The UDI carrier (AIDC and HRI representation of the UDI) shall be placed on the label or on the device itself and on all higher levels of device packaging. Higher levels do not include shipping containers. |
|
4.2. |
In the event of there being significant space constraints on the unit of use packaging, the UDI carrier may be placed on the next higher packaging level. |
|
4.3. |
For single-use devices of classes I and IIa packaged and labelled individually, the UDI carrier shall not be required to appear on the packaging but it shall appear on a higher level of packaging, e.g. a carton containing several individually packaged devices. However, when the healthcare provider is not expected to have access, in cases such as in home healthcare settings, to the higher level of device packaging, the UDI shall be placed on the packaging of the individual device. |
|
4.4. |
For devices exclusively intended for retail point of sale the UDI-PIs in AIDC shall not be required to appear on the point of sale packaging. |
|
4.5. |
When AIDC carriers other than the UDI carrier are part of the product labelling, the UDI carrier shall be readily identifiable. |
|
4.6. |
If linear bar codes are used, the UDI-DI and UDI-PI may be concatenated or non-concatenated in two or more bar codes. All parts and elements of the linear bar code shall be distinguishable and identifiable. |
|
4.7. |
If there are significant constraints limiting the use of both AIDC and HRI on the label, only the AIDC format shall be required to appear on the label. For devices intended to be used outside healthcare facilities, such as devices for home care, the HRI shall however appear on the label even if this results in there being no space for the AIDC. |
|
4.8. |
The HRI format shall follow the rules of the UDI code-issuing entity. |
|
4.9. |
If the manufacturer is using RFID technology, a linear or 2D bar code in line with the standard provided by the issuing entities shall also be provided on the label. |
|
4.10. |
Devices that are reusable shall bear a UDI carrier on the device itself. The UDI carrier for reusable devices that require cleaning, disinfection, sterilisation or refurbishing between patient uses shall be permanent and readable after each process performed to make the device ready for the subsequent use throughout the intended lifetime of the device. The requirement of this Section shall not apply to devices in the following circumstances:
(a)
any type of direct marking would interfere with the safety or performance of the device;
(b)
the device cannot be directly marked because it is not technologically feasible. |
|
4.11. |
The UDI carrier shall be readable during normal use and throughout the intended lifetime of the device. |
|
4.12. |
If the UDI carrier is readily readable or, in the case of AIDC, scannable, through the device's packaging, the placing of the UDI carrier on the packaging shall not be required. |
|
4.13. |
In the case of single finished devices made up of multiple parts that must be assembled before their first use, it shall be sufficient to place the UDI carrier on only one part of each device. |
|
4.14. |
The UDI carrier shall be placed in a manner such that the AIDC can be accessed during normal operation or storage. |
|
4.15. |
Bar code carriers that include both a UDI-DI and a UDI-PI may also include essential data for the device to operate or other data. |
5. General principles of the UDI database
|
5.1. |
The UDI database shall support the use of all core UDI database data elements referred to in Part B of this Annex. |
|
5.2. |
Manufacturers shall be responsible for the initial submission and updates of the identifying information and other device data elements in the UDI database. |
|
5.3. |
Appropriate methods/procedures for validation of the data provided shall be implemented. |
|
5.4. |
Manufacturers shall periodically verify the correctness of all of the data relevant to devices they have placed on the market, except for devices that are no longer available on the market. |
|
5.5. |
The presence of the device UDI-DI in the UDI database shall not be assumed to mean that the device is in conformity with this Regulation. |
|
5.6. |
The database shall allow for the linking of all the packaging levels of the device. |
|
5.7. |
The data for new UDI-DIs shall be available at the time the device is placed on the market. |
|
5.8. |
Manufacturers shall update the relevant UDI database record within 30 days of a change being made to an element, which does not require a new UDI-DI. |
|
5.9. |
Internationally-accepted standards for data submission and updates shall, wherever possible, be used by the UDI database. |
|
5.10. |
The user interface of the UDI database shall be available in all official languages of the Union. The use of free-text fields shall, however, be minimized in order to reduce translations. |
|
5.11. |
Data relating to devices that are no longer available on the market shall be retained in the UDI database. |
6. Rules for specific device types
|
6.1. |
Implantable devices:
6.1.1.
Implantable devices shall, at their lowest level of packaging (‘unit packs’), be identified, or marked using AIDC, with a UDI (UDI-DI + UDI-PI);
6.1.2.
The UDI-PI shall have at least the following characteristics:
(a)
the serial number for active implantable devices,
(b)
the serial number or lot number for other implantable devices.
6.1.3.
The UDI of the implantable device shall be identifiable prior to implantation. |
|
6.2. |
Reusable devices requiring cleaning, disinfection, sterilisation or refurbishing between uses
|
|
6.3. |
Systems and procedure packs as referred to in Article 22
|
|
6.4. |
Configurable devices:
|
|
6.5. |
Device Software 6.5.1. UDI assignment Criteria The UDI shall be assigned at the system level of the software. Only software which is commercially available on its own and software which constitutes a device in itself shall be subject to that requirement. The software identification shall be considered to be the manufacturing control mechanism and shall be displayed in the UDI-PI.
|
ANNEX VII
REQUIREMENTS TO BE MET BY NOTIFIED BODIES
1. ORGANISATIONAL AND GENERAL REQUIREMENTS
1.1. Legal status and organisational structure
|
1.1.1. |
Each notified body shall be established under the national law of a Member State, or under the law of a third country with which the Union has concluded an agreement in this respect. Its legal personality and status shall be fully documented. Such documentation shall include information about ownership and the legal or natural persons exercising control over the notified body. |
|
1.1.2. |
If the notified body is a legal entity that is part of a larger organisation, the activities of that organisation as well as its organisational structure and governance, and the relationship with the notified body shall be clearly documented. In such cases, the requirements of Section 1.2 are applicable to both the notified body and the organisation to which it belongs. |
|
1.1.3. |
If a notified body wholly or partly owns legal entities established in a Member State or in a third country or is owned by another legal entity, the activities and responsibilities of those entities, as well as their legal and operational relationships with the notified body, shall be clearly defined and documented. Personnel of those entities performing conformity assessment activities under this Regulation shall be subject to the applicable requirements of this Regulation. |
|
1.1.4. |
The organisational structure, allocation of responsibilities, reporting lines and operation of the notified body shall be such that they ensure that there is confidence in the performance by the notified body and in the results of the conformity assessment activities it conducts. |
|
1.1.5. |
The notified body shall clearly document its organisational structure and the functions, responsibilities and authority of its top-level management and of other personnel who may have an influence upon the performance by the notified body and upon the results of its conformity assessment activities. |
|
1.1.6. |
The notified body shall identify the persons in top-level management that have overall authority and responsibility for each of the following:
—
the provision of adequate resources for conformity assessment activities;
—
the development of procedures and policies for the operation of the notified body;
—
the supervision of implementation of the procedures, policies and quality management systems of the notified body;
—
the supervision of the notified body's finances;
—
the activities and decisions taken by the notified body, including contractual agreements;
—
the delegation of authority to personnel and/or committees, where necessary, for the performance of defined activities;
—
the interaction with the authority responsible for notified bodies and the obligations regarding communications with other competent authorities, the Commission and other notified bodies.
|
1.2. Independence and impartiality
|
1.2.1. |
The notified body shall be a third-party body that is independent of the manufacturer of the device in relation to which it performs conformity assessment activities. The notified body shall also be independent of any other economic operator having an interest in the device as well as of any competitors of the manufacturer. This does not preclude the notified body from carrying out conformity assessment activities for competing manufacturers. |
|
1.2.2. |
The notified body shall be organised and operated so as to safeguard the independence, objectivity and impartiality of its activities. The notified body shall document and implement a structure and procedures for safeguarding impartiality and for promoting and applying the principles of impartiality throughout its organisation, personnel and assessment activities. Such procedures shall provide for the identification, investigation and resolution of any case in which a conflict of interest may arise, including involvement in consultancy services in the field of devices prior to taking up employment with the notified body. The investigation, outcome and its resolution shall be documented. |
|
1.2.3. |
The notified body, its top-level management and the personnel responsible for carrying out the conformity assessment tasks shall not:
(a)
be the designer, manufacturer, supplier, installer, purchaser, owner or maintainer of devices which they assess, nor the authorised representative of any of those parties. Such restriction shall not preclude the purchase and use of assessed devices that are necessary for the operations of the notified body and the conduct of the conformity assessment, or the use of such devices for personal purposes;
(b)
be involved in the design, manufacture or construction, marketing, installation and use, or maintenance of the devices for which they are designated, nor represent the parties engaged in those activities;
(c)
engage in any activity that may conflict with their independence of judgement or integrity in relation to conformity assessment activities for which they are designated;
(d)
offer or provide any service which may jeopardise the confidence in their independence, impartiality or objectivity. In particular, they shall not offer or provide consultancy services to the manufacturer, its authorised representative, a supplier or a commercial competitor as regards the design, construction, marketing or maintenance of devices or processes under assessment, and
(e)
be linked to any organisation which itself provides consultancy services as referred to in point (d). Such restriction does not preclude general training activities that are not client specific and that relate to regulation of devices or to related standards. |
|
1.2.4. |
Involvement in consultancy services in the field of devices prior to taking up employment with a notified body shall be fully documented at the time of employment and potential conflicts of interest shall be monitored and resolved in accordance with this Annex. Personnel who were formerly employed by a specific client, or provided consultancy services in the field of devices to that specific client prior to taking up employment with a notified body, shall not be assigned for conformity assessment activities for that specific client or companies belonging to the same group for a period of three years. |
|
1.2.5. |
The impartiality of notified bodies, of their top-level management and of the assessment personnel shall be guaranteed. The level of the remuneration of the top-level management and assessment personnel of a notified body and subcontractors, involved in assessment activities shall not depend on the results of the assessments. Notified bodies shall make publicly available the declarations of interest of their top-level management. |
|
1.2.6. |
If a notified body is owned by a public entity or institution, independence and absence of any conflict of interest shall be ensured and documented between, on the one hand, the authority responsible for notified bodies and/or the competent authority and, on the other hand, the notified body. |
|
1.2.7. |
The notified body shall ensure and document that the activities of its subsidiaries or subcontractors, or of any associated body, including the activities of its owners do not affect its independence, impartiality or the objectivity of its conformity assessment activities. |
|
1.2.8. |
The notified body shall operate in accordance with a set of consistent, fair and reasonable terms and conditions, taking into account the interests of small and medium-sized enterprises as defined in Recommendation 2003/361/EC in relation to fees. |
|
1.2.9. |
The requirements laid down in this Section in no way preclude exchanges of technical information and regulatory guidance between a notified body and a manufacturer applying for conformity assessment. |
1.3. Confidentiality
|
1.3.1. |
The notified body shall have documented procedures in place ensuring that its personnel, committees, subsidiaries, subcontractors, and any associated body or personnel of external bodies respect the confidentiality of the information which comes into its possession during the performance of conformity assessment activities, except when disclosure is required by law. |
|
1.3.2. |
The personnel of a notified body shall observe professional secrecy in carrying out their tasks under this Regulation or any provision of national law giving effect to it, except in relation to the authorities responsible for notified bodies, competent authorities for medical devices in the Member States or the Commission. Proprietary rights shall be protected. The notified body shall have documented procedures in place in respect of the requirements of this Section. |
1.4. Liability
|
1.4.1. |
The notified body shall take out appropriate liability insurance for its conformity assessment activities, unless liability is assumed by the Member State in question in accordance with national law or that Member State is directly responsible for the conformity assessment. |
|
1.4.2. |
The scope and overall financial value of the liability insurance shall correspond to the level and geographic scope of activities of the notified body and be commensurate with the risk profile of the devices certified by the notified body. The liability insurance shall cover cases where the notified body may be obliged to withdraw, restrict or suspend certificates. |
1.5. Financial requirements
The notified body shall have at its disposal the financial resources required to conduct its conformity assessment activities within its scope of designation and related business operations. It shall document and provide evidence of its financial capacity and its long-term economic viability, taking into account, where relevant, any specific circumstances during an initial start-up phase.
1.6. Participation in coordination activities
|
1.6.1. |
The notified body shall participate in, or ensure that its assessment personnel is informed of, any relevant standardisation activities and in the activities of the notified body coordination group referred to in Article 49 and that its assessment and decision-making personnel are informed of all relevant legislation, guidance and best practice documents adopted in the framework of this Regulation. |
|
1.6.2. |
The notified body shall take into consideration guidance and best practice documents. |
2. QUALITY MANAGEMENT REQUIREMENTS
|
2.1. |
The notified body shall establish, document, implement, maintain and operate a quality management system that is appropriate to the nature, area and scale of its conformity assessment activities and is capable of supporting and demonstrating the consistent fulfilment of the requirements of this Regulation. |
|
2.2. |
The quality management system of the notified body shall address at least the following:
—
management system structure and documentation, including policies and objectives for its activities;
—
policies for assignment of activities and responsibilities to personnel;
—
assessment and decision-making processes in accordance with the tasks, responsibilities and role of the notified body's personnel and top-level management;
—
the planning, conduct, evaluation and, if necessary, adaptation of its conformity assessment procedures;
—
control of documents;
—
control of records;
—
management reviews;
—
internal audits;
—
corrective and preventive actions;
—
complaints and appeals; and
—
continuous training.
Where documents are used in various languages, the notified body shall ensure and control that they have the same content. |
|
2.3. |
The top-level management of the notified body shall ensure that the quality management system is fully understood, implemented and maintained throughout the notified body organisation including subsidiaries and subcontractors involved in conformity assessment activities pursuant to this Regulation. |
|
2.4. |
The notified body shall require all personnel to formally commit themselves by a signature or equivalent to comply with the procedures defined by the notified body. That commitment shall cover aspects relating to confidentiality and to independence from commercial and other interests, and any existing or prior association with clients. The personnel shall be required to complete written statements indicating their compliance with confidentiality, independence and impartiality principles. |
3. RESOURCE REQUIREMENTS
3.1. General
|
3.1.1. |
Notified bodies shall be capable of carrying out all the tasks falling to them under this Regulation with the highest degree of professional integrity and the requisite competence in the specific field, whether those tasks are carried out by notified bodies themselves or on their behalf and under their responsibility. In particular, notified bodies shall have the necessary personnel and possess or have access to all equipment, facilities and competence needed to perform properly the technical, scientific and administrative tasks entailed in the conformity assessment activities in relation to which they have been designated. Such requirement presupposes at all times and for each conformity assessment procedure and each type of devices in relation to which they have been designated, that the notified body has permanent availability of sufficient administrative, technical and scientific personnel who possess experience and knowledge relating to the relevant devices and the corresponding technologies. Such personnel shall be in sufficient numbers to ensure that the notified body in question can perform the conformity assessment tasks, including the assessment of the medical functionality, clinical evaluations and the performance and safety of devices, for which it has been designated, having regard to the requirements of this Regulation, in particular, those set out in Annex I. A notified body's cumulative competences shall be such as to enable it to assess the types of devices for which it is designated. The notified body shall have sufficient internal competence to critically evaluate assessments conducted by external expertise. Tasks which a notified body is precluded from subcontracting are set out in Section 4.1. Personnel involved in the management of the operation of a notified body's conformity assessment activities for devices shall have appropriate knowledge to set up and operate a system for the selection of assessment and verification staff, for verification of their competence, for authorisation and allocation of their tasks, for organisation of their initial and ongoing training and for the assignment of their duties and the monitoring of those staff, in order to ensure that personnel who carry out and perform assessment and verification operations are competent to fulfil the tasks required of them. The notified body shall identify at least one individual within its top-level management as having overall responsibility for all conformity assessment activities in relation to devices. |
|
3.1.2. |
The notified body shall ensure that personnel involved in conformity assessment activities maintain their qualification and expertise by implementing a system for exchange of experience and a continuous training and education programme. |
|
3.1.3. |
The notified body shall clearly document the extent and limits of duties and responsibilities and the level of authorisation of the personnel, including any subcontractors and external experts, involved in conformity assessment activities and inform those personnel accordingly. |
3.2. Qualification criteria in relation to personnel
|
3.2.1. |
The Notified Body shall establish and document qualification criteria and procedures for selection and authorisation of persons involved in conformity assessment activities, including as regards knowledge, experience and other competence required, and the required initial and ongoing training. The qualification criteria shall address the various functions within the conformity assessment process, such as auditing, product evaluation or testing, technical documentation review and decision-making, as well as the devices, technologies and areas, such as biocompatibility, sterilisation, tissues and cells of human and animal origin and clinical evaluation, covered by the scope of designation. |
|
3.2.2. |
The qualification criteria referred to in Section 3.2.1 shall refer to the scope of a notified body's designation in accordance with the scope description used by the Member State for the notification referred to in Article 42(3), providing a sufficient level of detail for the required qualification within the subdivisions of the scope description. Specific qualification criteria shall be defined at least for the assessment of:
—
the pre-clinical evaluation,
—
clinical evaluation,
—
tissues and cells of human and animal origin,
—
functional safety,
—
software,
—
packaging,
—
devices that incorporate as an integral part a medicinal product,
—
devices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body and
—
the different types of sterilisation processes.
|
|
3.2.3. |
The personnel responsible for establishing qualification criteria and for authorising other personnel to perform specific conformity assessment activities shall be employed by the notified body itself and shall not be external experts or subcontracted. They shall have proven knowledge and experience in all of the following:
—
Union devices legislation and relevant guidance documents;
—
the conformity assessment procedures provided for in this Regulation;
—
a broad base of knowledge of device technologies and the design and manufacture of devices;
—
the notified body's quality management system, related procedures and the required qualification criteria;
—
training relevant to personnel involved in conformity assessment activities in relation to devices;
—
adequate experience in conformity assessments under this Regulation or previously applicable law within a notified body.
|
|
3.2.4. |
The notified body shall have permanent availability of personnel with relevant clinical expertise and where possible such personnel shall be employed by the notified body itself. Such personnel shall be integrated throughout the notified body's assessment and decision-making process in order to:
—
identify when specialist input is required for the assessment of the clinical evaluation conducted by the manufacturer and identify appropriately qualified experts;
—
appropriately train external clinical experts in the relevant requirements of this Regulation, CS, guidance and harmonised standards and ensure that the external clinical experts are fully aware of the context and implications of their assessment and the advice they provide;
—
be able to review and scientifically challenge the clinical data contained within the clinical evaluation, and any associated clinical investigations, and appropriately guide external clinical experts in the assessment of the clinical evaluation presented by the manufacturer;
—
be able to scientifically evaluate and, if necessary, challenge the clinical evaluation presented, and the results of the external clinical experts' assessment of the manufacturer's clinical evaluation;
—
be able to ascertain the comparability and consistency of the assessments of clinical evaluations conducted by clinical experts;
—
be able to make an assessment of the manufacturer's clinical evaluation and a clinical judgement of the opinion provided by any external expert and make a recommendation to the notified body's decision maker; and
—
be able to draw up records and reports demonstrating that the relevant conformity assessment activities have been appropriately carried out.
|
|
3.2.5. |
The personnel responsible for carrying out product-related reviews (product reviewers), such as technical documentation reviews or type examination, including aspects such as clinical evaluation, biological safety, sterilisation and software validation, shall have all of the following proven qualifications:
—
successful completion of a university or a technical college degree or equivalent qualification in relevant studies, e.g. medicine, pharmacy, engineering or other relevant sciences;
—
four years' professional experience in the field of healthcare products or related activities, such as in manufacturing, auditing or research, of which two years shall be in the design, manufacture, testing or use of the device or technology to be assessed or related to the scientific aspects to be assessed;
—
knowledge of device legislation, including the general safety and performance requirements set out in Annex I;
—
appropriate knowledge and experience of relevant harmonised standards, CS and guidance documents;
—
appropriate knowledge and experience of risk management and related device standards and guidance documents;
—
appropriate knowledge and experience of clinical evaluation;
—
appropriate knowledge of the devices which they are assessing;
—
appropriate knowledge and experience of the conformity assessment procedures laid down in Annexes IX to XI, in particular of the aspects of those procedures for which they are responsible, and adequate authorisation for carrying out those assessments;
—
the ability to draw up records and reports demonstrating that the relevant conformity assessment activities have been appropriately carried out.
|
|
3.2.6. |
The personnel responsible for carrying out audits of the manufacturer's quality management system (site auditors) shall have all of the following proven qualifications:
—
successful completion of a university or a technical college degree or equivalent qualification in relevant studies, such as medicine, pharmacy, engineering or other relevant sciences;
—
four years' professional experience in the field of healthcare products or related activities, such as in manufacturing, auditing or research, of which two years shall be in the area of quality management;
—
appropriate knowledge of devices legislation as well as related harmonised standards, CS and guidance documents;
—
appropriate knowledge and experience of risk management and related device standards and guidance documents;
—
appropriate knowledge of quality management systems and related standards and guidance documents;
—
appropriate knowledge and experience of the conformity assessment procedures laid down in Annexes IX to XI, in particular of the aspects of those procedures for which they are responsible, and adequate authorisation for carrying out those audits;
—
training in auditing techniques enabling them to challenge quality management systems;
—
the ability to draw up records and reports demonstrating that the relevant conformity assessment activities have been appropriately carried out.
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3.2.7. |
The personnel with overall responsibility for final reviews and decision-making on certification shall be employed by the notified body itself and shall not be external experts or be subcontracted. Those personnel shall, as a group, have proven knowledge and comprehensive experience of all of the following:
—
devices legislation and relevant guidance documents;
—
the device conformity assessments relevant to this Regulation;
—
the types of qualifications, experience and expertise relevant to device conformity assessment;
—
a broad base of knowledge of device technologies, including sufficient experience of conformity assessment of devices being reviewed for certification, the device industry and the design and manufacture of devices;
—
the notified body's quality management system, related procedures and the required qualifications for personnel involved;
—
the ability to draw up records and reports demonstrating that the conformity assessment activities have been appropriately carried out.
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3.3. Documentation of qualification, training and authorisation of personnel
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3.3.1. |
The notified body shall have a procedure in place to fully document the qualification of each member of personnel involved in conformity assessment activities and the satisfaction of the qualification criteria referred to in Section 3.2. Where in exceptional circumstances the fulfilment of the qualification criteria set out in Section 3.2. cannot be fully demonstrated, the notified body shall justify to the authority responsible for notified bodies the authorisation of those members of personnel to carry out specific conformity assessment activities. |
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3.3.2. |
For all of its personnel referred to in Sections 3.2.3 to 3.2.7, the notified body shall establish and maintain up to date:
—
a matrix detailing the authorisations and responsibilities of the personnel in respect of conformity assessment activities; and
—
records attesting to the required knowledge and experience for the conformity assessment activity for which they are authorised. The records shall contain a rationale for defining the scope of the responsibilities for each of the assessment personnel and records of the conformity assessment activities carried out by each of them.
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3.4. Subcontractors and external experts
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3.4.1. |
Notified bodies may, without prejudice to Section 3.2, subcontract certain clearly defined component parts of a conformity assessment activity. The subcontracting of the auditing of quality management systems or of product related reviews as a whole shall not be permitted; nevertheless parts of those activities may be conducted by subcontractors and external auditors and experts working on behalf of the notified body. The notified body in question shall retain full responsibility for being able to produce appropriate evidence of the competence of subcontractors and experts to fulfil their specific tasks, for making a decision based on a subcontractor's assessment and for the work conducted by subcontractors and experts on its behalf. The following activities may not be subcontracted by notified bodies:
—
review of the qualifications and monitoring of the performance of external experts;
—
auditing and certification activities where the subcontracting in question is to auditing or certification organisations;
—
allocation of work to external experts for specific conformity assessment activities; and
—
final review and decision making functions.
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3.4.2. |
Where a notified body subcontracts certain conformity assessment activities either to an organisation or an individual, it shall have a policy describing the conditions under which subcontracting may take place, and shall ensure that:
—
the subcontractor meets the relevant requirements of this Annex;
—
subcontractors and external experts do not further subcontract work to organisations or personnel; and
—
the natural or legal person that applied for conformity assessment has been informed of the requirements referred to in the first and second indent.
Any subcontracting or consultation of external personnel shall be properly documented, shall not involve any intermediaries and shall be subject to a written agreement covering, among other things, confidentiality and conflicts of interest. The notified body in question shall take full responsibility for the tasks performed by subcontractors. |
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3.4.3. |
Where subcontractors or external experts are used in the context of a conformity assessment, in particular regarding novel, invasive and implantable devices or technologies, the notified body in question shall have internal competence in each product area for which it is designated that is adequate for the purpose of leading the overall conformity assessment, verifying the appropriateness and validity of expert opinions and making decisions on certification. |
3.5. Monitoring of competences, training and exchange of experience
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3.5.1. |
The notified body shall establish procedures for the initial evaluation and on-going monitoring of the competence, conformity assessment activities and performance of all internal and external personnel, and subcontractors, involved in conformity assessment activities. |
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3.5.2. |
Notified bodies shall review at regular intervals, the competence of their personnel, identify training needs and draw up a training plan to maintain the required level of qualification and knowledge of individual personnel. That review shall at a minimum, verify that personnel:
—
are aware of Union and national law in force on devices, relevant harmonised standards, CS, guidance documents and the results of the coordination activities referred to in Section 1.6; and
—
take part in the internal exchange of experience and the continuous training and education programme referred to in Section 3.1.2.
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4. PROCESS REQUIREMENTS
4.1. General
The notified body shall have in place documented processes and sufficiently detailed procedures for the conduct of each conformity assessment activity for which it is designated, comprising the individual steps from pre-application activities up to decision making and surveillance and taking into account, when necessary, the respective specificities of the devices.
The requirements laid down in Sections 4.3, 4.4, 4.7 and 4.8 shall be fulfilled as part of the internal activities of notified bodies and shall not be subcontracted.
4.2. Notified body quotations and pre-application activities
The notified body shall:
publish a publicly available description of the application procedure by which manufacturers can obtain certification from it. That description shall include which languages are acceptable for submission of documentation and for any related correspondence;
have documented procedures relating to, and documented details about, fees charged for specific conformity assessment activities and any other financial conditions relating to notified bodies' assessment activities for devices;
have documented procedures in relation to advertising of their conformity assessment services. Those procedures shall ensure that advertising or promotional activities in no way imply or are capable of leading to an inference that their conformity assessment will offer manufacturers earlier market access or be quicker, easier or less stringent than that of other notified bodies;
have documented procedures requiring the review of pre-application information, including the preliminary verification that the product is covered by this Regulation and its classification, prior to issuing any quotation to the manufacturer relating to a specific conformity assessment; and
ensure that all contracts relating to the conformity assessment activities covered by this Regulation are concluded directly between the manufacturer and the notified body and not with any other organisation.
4.3. Application review and contract
The notified body shall require a formal application signed by a manufacturer or an authorised representative containing all of the information and the manufacturer's declarations required by the relevant conformity assessment as referred to in Annexes IX to XI.
The contract between a notified body and a manufacturer shall take the form of a written agreement signed by both parties. It shall be kept by the notified body. This contract shall have clear terms and conditions and contain obligations that enable the notified body to act as required under this Regulation, including an obligation on the manufacturer to inform the notified body of vigilance reports, the right of the notified body to suspend, restrict or withdraw certificates issued and the duty of the notified body to fulfil its information obligations.
The notified body shall have documented procedures to review applications, addressing:
the completeness of those applications with respect to the requirements of the relevant conformity assessment procedure, as referred to in the corresponding Annex, under which approval has been sought,
the verification of the qualification of products covered by those applications as devices and their respective classifications,
whether the conformity assessment procedures chosen by the applicant are applicable to the device in question under this Regulation,
the ability of the notified body to assess the application based on its designation, and
the availability of sufficient and appropriate resources.
The outcome of each review of an application shall be documented. Refusals or withdrawals of applications shall be notified to the electronic system referred to in Article 57 and shall be accessible to other notified bodies.
4.4. Allocation of resources
The notified body shall have documented procedures to ensure that all conformity assessment activities are conducted by appropriately authorised and qualified personnel who are sufficiently experienced in the evaluation of the devices, systems and processes and related documentation that are subject to conformity assessment.
For each application, the notified body shall determine the resources needed and identify one individual responsible for ensuring that the assessment of that application is conducted in accordance with the relevant procedures and for ensuring that the appropriate resources including personnel are utilised for each of the tasks of the assessment. The allocation of tasks required to be carried out as part of the conformity assessment and any changes subsequently made to this allocation shall be documented.
4.5. Conformity assessment activities
4.5.1. General
The notified body and its personnel shall carry out the conformity assessment activities with the highest degree of professional integrity and the requisite technical and scientific competence in the specific fields.
The notified body shall have expertise, facilities and documented procedures that are sufficient to effectively conduct the conformity assessment activities for which the notified body in question is designated, taking account of the relevant requirements set out in Annexes IX to XI, and in particular all of the following requirements:
The notified body shall, where relevant, take into consideration available CS, guidance and best practice documents and harmonised standards, even if the manufacturer does not claim to be in compliance.
4.5.2. Quality management system auditing
As part of the assessment of the quality management system, a notified body shall prior to an audit and in accordance with its documented procedures:
Based on the audit programme it has drawn up, the notified body shall, in accordance with its documented procedures:
4.5.3. Product verification
Assessment of the technical documentation
For assessment of the technical documentation conducted in accordance with Chapter II of Annex IX, notified bodies shall have sufficient expertise, facilities and documented procedures for:
Type-examinations
The notified body shall have documented procedures, sufficient expertise and facilities for the type-examination of devices in accordance with Annex X including the capacity to:
Verification by examination and testing of every product
The notified body shall:
have documented procedures, sufficient expertise and facilities for the verification by examination and testing of every product in accordance with Part B of Annex XI;
establish a test plan identifying all relevant and critical parameters which need to be tested by the notified body or under its responsibility in order to:
document its rationale for the selection of the parameters referred to in point (b);
have documented procedures to carry out the appropriate assessments and tests in order to verify the conformity of the device with the requirements of this Regulation by examining and testing every product as specified in Section 15 of Annex XI;
have documented procedures providing for the reaching of an agreement with the applicant concerning when and where necessary tests that are not to be carried out by the notified body itself are to be performed; and
assume full responsibility for test results in accordance with documented procedures; test reports submitted by the manufacturer shall only be taken into account if they have been issued by conformity assessment bodies which are competent and independent of the manufacturer.
4.5.4. Pre-clinical evaluation assessment
The notified body shall have documented procedures in place for the review of the manufacturer's procedures and documentation relating to the evaluation of pre-clinical aspects. The notified body shall examine, validate and verify that the manufacturer's procedures and documentation adequately address:
the planning, conduct, assessment, reporting and, where appropriate, updating of the pre-clinical evaluation, in particular of
the nature and duration of body contact and the specific associated biological risks,
the interface with the risk management process, and
the appraisal and analysis of the available pre-clinical data and its relevance with regard to demonstrating conformity with the relevant requirements in Annex I.
The notified body's assessment of pre-clinical evaluation procedures and documentation shall address the results of literature searches and all validation, verification and testing performed and conclusions drawn, and shall typically include considering the use of alternative materials and substances and take account of the packaging, stability, including shelf life, of the finished device. Where no new testing has been undertaken by a manufacturer or where there are deviations from procedures, the notified body in question shall critically examine the justification presented by the manufacturer.
4.5.5. Clinical evaluation assessment
The notified body shall have documented procedures in place relating to the assessment of a manufacturer's procedures and documentation relating to clinical evaluation both for initial conformity assessment and on an ongoing basis. The notified body shall examine, validate and verify that manufacturers' procedures and documentation adequately address:
These procedures referred to in the first paragraph shall take into consideration available CS, guidance and best practice documents.
The notified body's assessment of clinical evaluations as referred to in Annex XIV shall cover:
In relation to clinical data from clinical investigations included within the clinical evaluation, the notified body in question shall ensure that the conclusions drawn by the manufacturer are valid in the light of the approved clinical investigation plan.
The notified body shall ensure that the clinical evaluation adequately addresses the relevant safety and performance requirements provided for in Annex I, that it is appropriately aligned with the risk management requirements, that it is conducted in accordance with Annex XIV and that it is appropriately reflected in the information provided relating to the device.
4.5.6. Specific Procedures
The notified body shall have documented procedures, sufficient expertise and facilities for the procedures referred to in Sections 5 and 6 of Annex IX, Section 6 of Annex X and Section 16 of Annex XI, for which they are designated.
In the case of devices manufactured utilising tissues or cells of animal origin or their derivatives, such as from TSE susceptible species, as referred to in Regulation (EU) No 722/2012, the notified body shall have documented procedures in place that fulfil the requirements laid down in that Regulation, including for the preparation of a summary evaluation report for the relevant competent authority.
4.6. Reporting
The notified body shall:
The report of the notified body shall:
4.7. Final review
The notified body shall prior to making a final decision:
4.8. Decisions and Certifications
The notified body shall have documented procedures for decision-making including as regards the allocation of responsibilities for the issuance, suspension, restriction and withdrawal of certificates. Those procedures shall include the notification requirements laid down in Chapter V of this Regulation. The procedures shall allow the notified body in question to:
4.9. Changes and modifications
The notified body shall have documented procedures and contractual arrangements with manufacturers in place relating to the manufacturers' information obligations and the assessment of changes to:
The procedures and contractual arrangements referred to in the first paragraph shall include measures for checking the significance of the changes referred to in the first paragraph.
In accordance with its documented procedures, the notified body in question shall:
4.10. Surveillance activities and post-certification monitoring
The notified body shall have documented procedures:
The notified body in question shall, upon receipt of information about vigilance cases from a manufacturer or competent authorities, decide which of the following options to apply:
In relation to surveillance audits of manufacturers, the notified body shall have documented procedures to:
The notified body shall, if listed as part of the conditions for certification:
4.11. Re-certification
The notified body shall have documented procedures in place relating to the re-certification reviews and the renewal of certificates. Re-certification of approved quality management systems or EU technical documentation assessment certificates or EU type-examination certificates shall occur at least every five years.
The notified body shall have documented procedures relating to renewals of EU technical documentation assessment certificates and EU type-examination certificates and those procedures shall require the manufacturer in question to submit a summary of changes and scientific findings for the device, including:
all changes to the originally approved device, including changes not yet notified,
experience gained from post-market surveillance,
experience from risk management,
experience from updating the proof of compliance with the general safety and performance requirements set out in Annex I,
experience from reviews of the clinical evaluation, including the results of any clinical investigations and PMCF,
changes to the requirements, to components of the device or to the scientific or regulatory environment,
changes to applied or new harmonised standards, CS or equivalent documents, and
changes in medical, scientific and technical knowledge, such as:
The notified body shall have documented procedures to assess the information referred to in the second paragraph and shall pay particular attention to clinical data from post-market surveillance and PMCF activities undertaken since the previous certification or re-certification, including appropriate updates to manufacturers' clinical evaluation reports.
For the decision on re-certification, the notified body in question shall use the same methods and principles as for the initial certification decision. If necessary, separate forms shall be established for re-certification taking into account the steps taken for certification such as application and application review.
ANNEX VIII
CLASSIFICATION RULES
CHAPTER I
DEFINITIONS SPECIFIC TO CLASSIFICATION RULES
1. DURATION OF USE
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1.1. |
‘Transient’ means normally intended for continuous use for less than 60 minutes. |
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1.2. |
‘Short term’ means normally intended for continuous use for between 60 minutes and 30 days. |
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1.3. |
‘Long term’ means normally intended for continuous use for more than 30 days. |
2. INVASIVE AND ACTIVE DEVICES
|
2.1. |
‘Body orifice’ means any natural opening in the body, as well as the external surface of the eyeball, or any permanent artificial opening, such as a stoma. |
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2.2. |
‘Surgically invasive device’ means:
(a)
an invasive device which penetrates inside the body through the surface of the body, including through mucous membranes of body orifices with the aid or in the context of a surgical operation; and
(b)
a device which produces penetration other than through a body orifice. |
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2.3. |
‘Reusable surgical instrument’ means an instrument intended for surgical use in cutting, drilling, sawing, scratching, scraping, clamping, retracting, clipping or similar procedures, without a connection to an active device and which is intended by the manufacturer to be reused after appropriate procedures such as cleaning, disinfection and sterilisation have been carried out. |
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2.4. |
‘Active therapeutic device’ means any active device used, whether alone or in combination with other devices, to support, modify, replace or restore biological functions or structures with a view to treatment or alleviation of an illness, injury or disability. |
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2.5. |
‘Active device intended for diagnosis and monitoring’ means any active device used, whether alone or in combination with other devices, to supply information for detecting, diagnosing, monitoring or treating physiological conditions, states of health, illnesses or congenital deformities. |
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2.6. |
‘Central circulatory system’ means the following blood vessels: arteriae pulmonales, aorta ascendens, arcus aortae, aorta descendens to the bifurcatio aortae, arteriae coronariae, arteria carotis communis, arteria carotis externa, arteria carotis interna, arteriae cerebrales, truncus brachiocephalicus, venae cordis, venae pulmonales, vena cava superior and vena cava inferior. |
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2.7. |
‘Central nervous system’ means the brain, meninges and spinal cord. |
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2.8. |
‘Injured skin or mucous membrane’ means an area of skin or a mucous membrane presenting a pathological change or change following disease or a wound. |
CHAPTER II
IMPLEMENTING RULES
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3.1. |
Application of the classification rules shall be governed by the intended purpose of the devices. |
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3.2. |
If the device in question is intended to be used in combination with another device, the classification rules shall apply separately to each of the devices. ►C1 Accessories for a medical device shall be classified in their own right ◄ separately from the device with which they are used. |
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3.3. |
Software, which drives a device or influences the use of a device, shall fall within the same class as the device. If the software is independent of any other device, it shall be classified in its own right. |
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3.4. |
If the device is not intended to be used solely or principally in a specific part of the body, it shall be considered and classified on the basis of the most critical specified use. |
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3.5. |
If several rules, or if, within the same rule, several sub-rules, apply to the same device based on the device's intended purpose, the strictest rule and sub-rule resulting in the higher classification shall apply. |
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3.6. |
In calculating the duration referred to in Section 1, continuous use shall mean:
(a)
the entire duration of use of the same device without regard to temporary interruption of use during a procedure or temporary removal for purposes such as cleaning or disinfection of the device. Whether the interruption of use or the removal is temporary shall be established in relation to the duration of the use prior to and after the period when the use is interrupted or the device removed; and
(b)
the accumulated use of a device that is intended by the manufacturer to be replaced immediately with another of the same type. |
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3.7. |
A device is considered to allow direct diagnosis when it provides the diagnosis of the disease or condition in question by itself or when it provides decisive information for the diagnosis. |
CHAPTER III
CLASSIFICATION RULES
4. NON-INVASIVE DEVICES
4.1. Rule 1
All non-invasive devices are classified as class I, unless one of the rules set out hereinafter applies.
4.2. Rule 2
All non-invasive devices intended for channelling or storing blood, body liquids, cells or tissues, liquids or gases for the purpose of eventual infusion, administration or introduction into the body are classified as class IIa:
In all other cases, such devices are classified as class I.
4.3. Rule 3
All non-invasive devices intended for modifying the biological or chemical composition of human tissues or cells, blood, other body liquids or other liquids intended for implantation or administration into the body are classified as class IIb, unless the treatment for which the device is used consists of filtration, centrifugation or exchanges of gas, heat, in which case they are classified as class IIa.
All non-invasive devices consisting of a substance or a mixture of substances intended to be used in vitro in direct contact with human cells, tissues or organs taken from the human body or used in vitro with human embryos before their implantation or administration into the body are classified as class III.
4.4. Rule 4
All non-invasive devices which come into contact with injured skin or mucous membrane are classified as:
This rule applies also to the invasive devices that come into contact with injured mucous membrane.
5. INVASIVE DEVICES
5.1. Rule 5
All invasive devices with respect to body orifices, other than surgically invasive devices, which are not intended for connection to an active device or which are intended for connection to a class I active device are classified as:
All invasive devices with respect to body orifices, other than surgically invasive devices, intended for connection to a class IIa, class IIb or class III active device, are classified as class IIa.
5.2. Rule 6
All surgically invasive devices intended for transient use are classified as class IIa unless they:
5.3. Rule 7
All surgically invasive devices intended for short-term use are classified as class IIa unless they:
5.4. Rule 8
All implantable devices and long-term surgically invasive devices are classified as class IIb unless they:
6. ACTIVE DEVICES
6.1. Rule 9
All active therapeutic devices intended to administer or exchange energy are classified as class IIa unless their characteristics are such that they may administer energy to or exchange energy with the human body in a potentially hazardous way, taking account of the nature, the density and site of application of the energy, in which case they are classified as class IIb.
All active devices intended to control or monitor the performance of active therapeutic class IIb devices, or intended directly to influence the performance of such devices are classified as class IIb.
All active devices intended to emit ionizing radiation for therapeutic purposes, including devices which control or monitor such devices, or which directly influence their performance, are classified as class IIb.
All active devices that are intended for controlling, monitoring or directly influencing the performance of active implantable devices are classified as class III.
6.2. Rule 10
Active devices intended for diagnosis and monitoring are classified as class IIa:
Active devices intended to emit ionizing radiation and intended for diagnostic or therapeutic radiology, including interventional radiology devices and devices which control or monitor such devices, or which directly influence their performance, are classified as class IIb.
6.3. Rule 11
Software intended to provide information which is used to take decisions with diagnosis or therapeutic purposes is classified as class IIa, except if such decisions have an impact that may cause:
Software intended to monitor physiological processes is classified as class IIa, except if it is intended for monitoring of vital physiological parameters, where the nature of variations of those parameters is such that it could result in immediate danger to the patient, in which case it is classified as class IIb.
All other software is classified as class I.
6.4. Rule 12
All active devices intended to administer and/or remove medicinal products, body liquids or other substances to or from the body are classified as class IIa, unless this is done in a manner that is potentially hazardous, taking account of the nature of the substances involved, of the part of the body concerned and of the mode of application in which case they are classified as class IIb.
6.5. Rule 13
All other active devices are classified as class I.
7. SPECIAL RULES
7.1. Rule 14
All devices incorporating, as an integral part, a substance which, if used separately, can be considered to be a medicinal product, as defined in point 2 of Article 1 of Directive 2001/83/EC, including a medicinal product derived from human blood or human plasma, as defined in point 10 of Article 1 of that Directive, and that has an action ancillary to that of the devices, are classified as class III.
7.2. Rule 15
All devices used for contraception or prevention of the transmission of sexually transmitted diseases are classified as class IIb, unless they are implantable or long term invasive devices, in which case they are classified as class III.
7.3. Rule 16
All devices intended specifically to be used for disinfecting, cleaning, rinsing or, where appropriate, hydrating contact lenses are classified as class IIb.
All devices intended specifically to be used for disinfecting or sterilising medical devices are classified as class IIa, unless they are disinfecting solutions or washer-disinfectors intended specifically to be used for disinfecting invasive devices, as the end point of processing, in which case they are classified as class IIb.
This rule does not apply to devices that are intended to clean devices other than contact lenses by means of physical action only.
7.4. Rule 17
Devices specifically intended for recording of diagnostic images generated by X-ray radiation are classified as class IIa.
7.5. Rule 18
All devices manufactured utilising tissues or cells of human or animal origin, or their derivatives, which are non-viable or rendered non-viable, are classified as class III, unless such devices are manufactured utilising tissues or cells of animal origin, or their derivatives, which are non-viable or rendered non-viable and are devices intended to come into contact with intact skin only.
7.6. Rule 19
All devices incorporating or consisting of nanomaterial are classified as:
7.7. Rule 20
All invasive devices with respect to body orifices, other than surgically invasive devices, which are intended to administer medicinal products by inhalation are classified as class IIa, unless their mode of action has an essential impact on the efficacy and safety of the administered medicinal product or they are intended to treat life-threatening conditions, in which case they are classified as class IIb.
7.8. Rule 21
Devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed by or locally dispersed in the human body are classified as:
7.9. Rule 22
Active therapeutic devices with an integrated or incorporated diagnostic function which significantly determines the patient management by the device, such as closed loop systems or automated external defibrillators, are classified as class III.
ANNEX IX
CONFORMITY ASSESSMENT BASED ON A QUALITY MANAGEMENT SYSTEM AND ON ASSESSMENT OF TECHNICAL DOCUMENTATION
CHAPTER I
QUALITY MANAGEMENT SYSTEM
|
1. |
The manufacturer shall establish, document and implement a quality management system as described in Article 10(9) and maintain its effectiveness throughout the life cycle of the devices concerned. The manufacturer shall ensure the application of the quality management system as specified in Section 2 and shall be subject to audit, as laid down in Sections 2.3 and 2.4, and to surveillance as specified in Section 3. |
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2. |
Quality management system assessment
|
|
3. |
Surveillance assessment
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CHAPTER II
ASSESSMENT OF THE TECHNICAL DOCUMENTATION
4. Assessment of the technical documentation applicable to class III devices and to the class IIb devices referred to in the second subparagraph of Article 52(4)
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4.1. |
In addition to the obligations laid down in Section 2, the manufacturer shall lodge with the notified body an application for assessment of the technical documentation relating to the device which it plans to place on the market or put into service and which is covered by the quality management system referred to in Section 2. |
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4.2. |
The application shall describe the design, manufacture and performance of the device in question. It shall include the technical documentation as referred to in Annexes II and III. |
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4.3. |
►C1 The notified body shall assess the technical documentation using staff with proven knowledge ◄ and experience regarding the technology concerned and its clinical application. The notified body may require the application to be completed by having further tests carried out or requesting further evidence to be provided to allow assessment of conformity with the relevant requirements of the Regulation. The notified body shall carry out adequate physical or laboratory tests in relation to the device or request the manufacturer to carry out such tests. |
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4.4. |
The notified body shall review the clinical evidence presented by the manufacturer in the clinical evaluation report and the related clinical evaluation that was conducted. The notified body shall employ device reviewers with sufficient clinical expertise and, if necessary, use external clinical experts with direct and current experience relating to the device in question or the clinical condition in which it is utilised, for the purposes of that review. |
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4.5. |
The notified body shall, in circumstances in which the clinical evidence is based partly or totally on data from devices which are claimed to be equivalent to the device under assessment, assess the suitability of using such data, taking into account factors such as new indications and innovation. The notified body shall clearly document its conclusions on the claimed equivalence, and on the relevance and adequacy of the data for demonstrating conformity. For any characteristic of the device claimed as innovative by the manufacturer or for new indications, the notified body shall assess to what extent specific claims are supported by specific pre-clinical and clinical data and risk analysis. |
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4.6. |
The notified body shall verify that the clinical evidence and the clinical evaluation are adequate and shall verify the conclusions drawn by the manufacturer on the conformity with the relevant general safety and performance requirements. That verification shall include consideration of the adequacy of the benefit-risk determination, the risk management, the instructions for use, the user training and the manufacturer's post-market surveillance plan, and include a review of the need for, and the adequacy of, the PMCF plan proposed, where applicable. |
|
4.7. |
Based on its assessment of the clinical evidence, the notified body shall consider the clinical evaluation and the benefit-risk determination, and whether specific milestones need to be defined to allow the notified body to review updates to the clinical evidence that result from post-market surveillance and PMCF data. |
|
4.8. |
The notified body shall clearly document the outcome of its assessment in the clinical evaluation assessment report. |
|
4.9. |
The notified body shall provide the manufacturer with a report on the technical documentation assessment, including a clinical evaluation assessment report. If the device conforms to the relevant provisions of this Regulation, the notified body shall issue an EU technical documentation assessment certificate. The certificate shall contain the conclusions of the technical documentation assessment, the conditions of the certificate's validity, the data needed for identification of the approved design, and, where appropriate, a description of the intended purpose of the device. |
|
4.10. |
Changes to the approved device shall require approval from the notified body which issued the EU technical documentation assessment certificate where such changes could affect the safety and performance of the device or the conditions prescribed for use of the device. Where the manufacturer plans to introduce any of the above-mentioned changes it shall inform the notified body which issued the EU technical documentation assessment certificate thereof. The notified body shall assess the planned changes and decide whether the planned changes require a new conformity assessment in accordance with Article 52 or whether they could be addressed by means of a supplement to the EU technical documentation assessment certificate. In the latter case, the notified body shall assess the changes, notify the manufacturer of its decision and, where the changes are approved, provide it with a supplement to the EU technical documentation assessment certificate. |
5. Specific additional procedures
5.1. Assessment procedure for certain class III and class IIb devices
For class III implantable devices, and for class IIb active devices intended to administer and/or remove a medicinal product as referred to in Section 6.4. of Annex VIII (Rule 12), the notified body shall, having verified the quality of clinical data supporting the clinical evaluation report of the manufacturer referred to in Article 61(12), prepare a clinical evaluation assessment report which sets out its conclusions concerning the clinical evidence provided by the manufacturer, in particular concerning the benefit-risk determination, the consistency of that evidence with the intended purpose, including the medical indication or indications and the PMCF plan referred to in Article 10(3) and Part B of Annex XIV.
The notified body shall transmit its clinical evaluation assessment report, along with the manufacturer's clinical evaluation documentation, referred to in points (c) and (d) of Section 6.1 of Annex II, to the Commission.
The Commission shall immediately transmit those documents to the relevant expert panel referred to in Article 106.
The notified body may be requested to present its conclusions as referred to in point (a) to the expert panel concerned.
The expert panel shall decide, under the supervision of the Commission, on the basis of all of the following criteria:
the novelty of the device or of the related clinical procedure involved, and the possible major clinical or health impact thereof;
a significantly adverse change in the benefit-risk profile of a specific category or group of devices due to scientifically valid health concerns in respect of components or source material or in respect of the impact on health in the case of failure of the device;
a significantly increased rate of serious incidents reported in accordance with Article 87 in respect of a specific category or group of devices,
whether to provide a scientific opinion on the clinical evaluation assessment report of the notified body based on the clinical evidence provided by the manufacturer, in particular concerning the benefit-risk determination, the consistency of that evidence with the medical indication or indications and the PMCF plan. That scientific opinion shall be provided within a period of 60 days, starting on the day of receipt of the documents from the Commission as referred to in point (a). The reasons for the decision to provide a scientific opinion on the basis of the criteria in points (i), (ii) and (iii) shall be included in the scientific opinion. Where the information submitted is not sufficient for the expert panel to reach a conclusion, this shall be stated in the scientific opinion.
The expert panel may decide, under the supervision of the Commission, on the basis of the criteria laid down in point (c) not to provide a scientific opinion, in which case it shall inform the notified body as soon as possible and in any event within 21 days of receipt of the documents as referred to in point (a) from the Commission. The expert panel shall within that time limit provide the notified body and the Commission with the reasons for its decision, whereupon the notified body may proceed with the certification procedure of that device.
The expert panel shall within 21 days of receipt of the documents from the Commission notify the Commission, through Eudamed whether it intends to provide a scientific opinion, pursuant to point (c), or whether it intends not to provide a scientific opinion, pursuant to point (d).
Where no opinion has been delivered within a period of 60 days, the notified body may proceed with the certification procedure of the device in question.
The notified body shall give due consideration to the views expressed in the scientific opinion of the expert panel. Where the expert panel finds that the level of clinical evidence is not sufficient or otherwise gives rise to serious concerns about the benefit-risk determination, the consistency of that evidence with the intended purpose, including the medical indication(s), and with the PMCF plan, the notified body shall, if necessary, advise the manufacturer to restrict the intended purpose of the device to certain groups of patients or certain medical indications and/or to impose a limit on the duration of validity of the certificate, to undertake specific PMCF studies, to adapt the instructions for use or the summary of safety and performance, or to impose other restrictions in its conformity assessment report, as appropriate. The notified body shall provide a full justification where it has not followed the advice of the expert panel in its conformity assessment report and the Commission shall without prejudice to Article 109 make both the scientific opinion of the expert panel and the written justification provided by the notified body publicly available via Eudamed.
The Commission, after consultation with the Member States and relevant scientific experts shall provide guidance for expert panels for consistent interpretation of the criteria in point (c) before ►M1 26 May 2021 ◄ .
5.2. Procedure in the case of devices incorporating a medicinal substance
Where a device incorporates, as an integral part, a substance which, if used separately, may be considered to be a medicinal product within the meaning of point 2 of Article 1 of Directive 2001/83/EC, including a medicinal product derived from human blood or human plasma and that has an action ancillary to that of the device, the quality, safety and usefulness of the substance shall be verified by analogy with the methods specified in Annex I to Directive 2001/83/EC.
Before issuing an EU technical documentation assessment certificate, the notified body shall, having verified the usefulness of the substance as part of the device and taking account of the intended purpose of the device, seek a scientific opinion from one of the competent authorities designated by the Member States in accordance with Directive 2001/83/EC or from the EMA, either of which to be referred to in this Section as ‘the medicinal products authority consulted’ depending on which has been consulted under this point, on the quality and safety of the substance including the benefit or risk of the incorporation of the substance into the device. Where the device incorporates a human blood or plasma derivative or a substance that, if used separately, may be considered to be a medicinal product falling exclusively within the scope of the Annex to Regulation (EC) No 726/2004, the notified body shall seek the opinion of the EMA.
When issuing its opinion, the medicinal products authority consulted shall take into account the manufacturing process and the data relating to the usefulness of incorporation of the substance into the device as determined by the notified body.
The medicinal products authority consulted shall provide its opinion to the notified body within 210 days of receipt of all the necessary documentation.
The scientific opinion of the medicinal products authority consulted, and any possible update of that opinion, shall be included in the documentation of the notified body concerning the device. The notified body shall give due consideration to the views expressed in the scientific opinion when making its decision. The notified body shall not deliver the certificate if the scientific opinion is unfavourable and shall convey its final decision to the medicinal products authority consulted.
Before any change is made with respect to an ancillary substance incorporated in a device, in particular related to its manufacturing process, the manufacturer shall inform the notified body of the changes. That notified body shall seek the opinion of the medicinal products authority consulted, in order to confirm that the quality and safety of the ancillary substance remain unchanged. The medicinal products authority consulted shall take into account the data relating to the usefulness of incorporation of the substance into the device as determined by the notified body, in order to ensure that the changes have no negative impact on the risk or benefit previously established concerning the incorporation of the substance into the device. The medicinal products authority consulted shall provide its opinion within 60 days after receipt of all the necessary documentation regarding the changes. The notified body shall not deliver the supplement to the EU technical documentation assessment certificate if the scientific opinion provided by the medicinal products authority consulted is unfavourable. The notified body shall convey its final decision to the medicinal products authority consulted.
Where the medicinal products authority consulted obtains information on the ancillary substance, which could have an impact on the risk or benefit previously established concerning the incorporation of the substance into the device, it shall advise the notified body as to whether this information has an impact on the risk or benefit previously established concerning the incorporation of the substance into the device. The notified body shall take that advice into account in reconsidering its assessment of the conformity assessment procedure.
5.3. Procedure in the case of devices manufactured utilising, or incorporating, tissues or cells of human or animal origin, or their derivatives, that are non-viable or rendered non-viable
5.3.1. Tissues or cells of human origin or their derivatives
For devices manufactured utilising derivatives of tissues or cells of human origin that are covered by this Regulation in accordance with point (g) of Article 1(6) and for devices that incorporate, as an integral part, tissues or cells of human origin, or their derivatives, covered by Directive 2004/23/EC, that have an action ancillary to that of the device, the notified body shall, prior to issuing an EU technical documentation assessment certificate, seek a scientific opinion from one of the competent authorities designated by the Member States in accordance with Directive 2004/23/EC (‘human tissues and cells competent authority’) on the aspects relating to the donation, procurement and testing of tissues or cells of human origin or their derivatives. The notified body shall submit a summary of the preliminary conformity assessment which provides, among other things, information about the non-viability of the human tissues or cells in question, their donation, procurement and testing and the risk or benefit of the incorporation of the tissues or cells of human origin or their derivatives into the device.
Within 120 days of receipt of all the necessary documentation, the human tissues and cells competent authority shall provide to the notified body its opinion.
The scientific opinion of the human tissues and cells competent authority, and any possible update, shall be included in the documentation of the notified body concerning the device. The notified body shall give due consideration to the views expressed in the scientific opinion of the human tissues and cells competent authority when making its decision. The notified body shall not deliver the certificate if that scientific opinion is unfavourable. It shall convey its final decision to the human tissues and cells competent authority concerned.
Before any change is made with respect to non-viable tissues or cells of human origin or their derivatives incorporated in a device, in particular relating to their donation, testing or procurement, the manufacturer shall inform the notified body of the intended changes. The notified body shall consult the authority that was involved in the initial consultation, in order to confirm that the quality and safety of the tissues or cells of human origin or their derivatives incorporated in the device are maintained. The human tissues and cells competent authority concerned shall take into account the data relating to the usefulness of incorporation of the tissues or cells of human origin or their derivatives into the device as determined by the notified body, in order to ensure that the changes have no negative impact on the established benefit-risk ratio of the addition of the tissues or cells of human origin or their derivatives in the device. It shall provide its opinion within 60 days of receipt of all the necessary documentation regarding the intended changes. The notified body shall not deliver a supplement to the EU technical documentation assessment certificate if the scientific opinion is unfavourable and shall convey its final decision to the human tissues and cells competent authority concerned.
5.3.2. Tissues or cells of animal origin or their derivatives
In the case of devices manufactured utilising animal tissue which is rendered non-viable or utilising non-viable products derived from animal tissue, as referred to in Regulation (EU) No 722/2012, the notified body shall apply the relevant requirements laid down in that Regulation.
5.4. Procedure in the case of devices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body
The quality and safety of devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed by, or locally dispersed in, the human body, shall be verified where applicable and only in respect of the requirements not covered by this Regulation, in accordance with the relevant requirements laid down in Annex I to Directive 2001/83/EC for the evaluation of absorption, distribution, metabolism, excretion, local tolerance, toxicity, interaction with other devices, medicinal products or other substances and potential for adverse reactions.
In addition, for devices, or their products of metabolism, that are systemically absorbed by the human body in order to achieve their intended purpose, the notified body shall seek a scientific opinion from one of the competent authorities designated by the Member States in accordance with Directive 2001/83/EC or from the EMA, either of which to be referred to in this Section as ‘the medicinal products authority consulted’ depending on which has been consulted under this point, on the compliance of the device with the relevant requirements laid down in Annex I to Directive 2001/83/EC.
The opinion of the medicinal products authority consulted shall be drawn up within 150 days of receipt of all the necessary documentation.
The scientific opinion of the medicinal products authority consulted, and any possible update, shall be included in the documentation of the notified body concerning the device. The notified body shall give due consideration to the views expressed in the scientific opinion when making its decision and shall convey its final decision to the medicinal products authority consulted.
6. Batch verification in the case of devices incorporating, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma as referred to in Article 1(8)
Upon completing the manufacture of each batch of devices that incorporate, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma as referred to in the first subparagraph of Article 1(8), the manufacturer shall inform the notified body of the release of the batch of devices and send it the official certificate concerning the release of the batch of human blood or plasma derivative used in the device, issued by a Member State laboratory or a laboratory designated for that purpose by a Member State in accordance with Article 114(2) of Directive 2001/83/EC.
CHAPTER III
ADMINISTRATIVE PROVISIONS
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7. |
The manufacturer or, where the manufacturer does not have a registered place of business in a Member State, its authorised representative shall, for a period ending no sooner than 10 years, and in the case of implantable devices no sooner than 15 years, after the last device has been placed on the market, keep at the disposal of the competent authorities:
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the EU declaration of conformity,
—
the documentation referred to in the fifth indent of Section 2.1 and in particular the data and records arising from the procedures referred to in point (c) of the second paragraph of Section 2.2,
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information on the changes referred to in Section 2.4,
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the documentation referred to in Section 4.2, and
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the decisions and reports from the notified body as referred to in this Annex.
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8. |
Each Member State shall require that the documentation referred to in Section 7 is kept at the disposal of competent authorities for the period indicated in that Section in case a manufacturer, or its authorised representative, established within its territory goes bankrupt or ceases its business activity prior to the end of that period. |
ANNEX X
CONFORMITY ASSESSMENT BASED ON TYPE-EXAMINATION
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1. |
EU type-examination is the procedure whereby a notified body ascertains and certifies that a device, including its technical documentation and relevant life cycle processes and a corresponding representative sample of the device production envisaged, fulfils the relevant provisions of this Regulation. |
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2. |
Application The manufacturer shall lodge an application for assessment with a notified body. The application shall include:
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the name of the manufacturer and address of the registered place of business of the manufacturer and, if the application is lodged by the authorised representative, the name of the authorised representative and the address of its registered place of business,
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the technical documentation referred to in Annexes II and III. The applicant shall make a representative sample of the device production envisaged (‘type’) available to the notified body. The notified body may request other samples as necessary, and
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a written declaration that no application has been lodged with any other notified body for the same type, or information about any previous application for the same type that was refused by another notified body or was withdrawn by the manufacturer or its authorised representative before that other notified body made its final assessment.
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3. |
Assessment The notified body shall:
(a)
examine the application by using staff with proven knowledge and experience regarding the technology concerned and its clinical application. The notified body may require the application to be completed by having further tests carried out or requesting further evidence to be provided to allow assessment of conformity with the relevant requirements of this Regulation. The notified body shall carry out adequate physical or laboratory tests in relation to the device or request the manufacturer to carry out such tests;
(b)
examine and assess the technical documentation for conformity with the requirements of this Regulation that are applicable to the device and verify that the type has been manufactured in conformity with that documentation; it shall also record the items designed in conformity with the applicable standards referred to in Article 8 or with applicable CS, and record the items not designed on the basis of the relevant standards referred to in Article 8 or of the relevant CS;
(c)
review the clinical evidence presented by the manufacturer in the clinical evaluation report in accordance with Section 4 of Annex XIV. The notified body shall employ device reviewers with sufficient clinical expertise and, if necessary, use external clinical experts with direct and current experience relating to the device in question or to the clinical condition in which it is utilised, for the purposes of that review;
(d)
in circumstances in which the clinical evidence is based partly or totally on data from devices which are claimed to be similar or equivalent to the device under assessment, assess the suitability of using such data, taking into account factors such as new indications and innovation. The notified body shall clearly document its conclusions on the claimed equivalence, and on the relevance and adequacy of the data for demonstrating conformity;
(e)
clearly document the outcome of its assessment in a pre-clinical and clinical evaluation assessment report as part of the EU type examination report referred to in point (i);
(f)
carry out or arrange for the appropriate assessments and the physical or laboratory tests necessary to verify whether the solutions adopted by the manufacturer meet the general safety and performance requirements laid down in this Regulation, in the event that the standards referred to in Article 8 or the CS have not been applied. Where the device has to be connected to another device or devices in order to operate as intended, proof shall be provided that it conforms to the general safety and performance requirements when connected to any such device or devices having the characteristics specified by the manufacturer;
(g)
carry out or arrange for the appropriate assessments and the physical or laboratory tests necessary to verify whether, in the event that the manufacturer has chosen to apply the relevant harmonised standards, those standards have actually been applied;
(h)
agree with the applicant on the place where the necessary assessments and tests are to be carried out; and
(i)
draw up an EU type-examination report on the results of the assessments and tests carried out under points (a) to (g). |
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4. |
Certificate If the type conforms to this Regulation, the notified body shall issue an EU type-examination certificate. The certificate shall contain the name and address of the manufacturer, the conclusions of the type examination assessment, the conditions of the certificate's validity and the data needed for identification of the type approved. The certificate shall be drawn up in accordance with Annex XII. The relevant parts of the documentation shall be annexed to the certificate and a copy kept by the notified body. |
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5. |
Changes to the type
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6. |
Specific additional procedures Section 5 of Annex IX shall apply with the proviso that any reference to an EU technical documentation assessment certificate shall be understood as a reference to an EU type-examination certificate. |
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7. |
Administrative provisions The manufacturer or, where the manufacturer does not have a registered place of business in a Member State, its authorised representative shall, for a period ending no sooner than 10 years, and in the case of implantable devices no sooner than 15 years, after the last device has been placed on the market, keep at the disposal of the competent authorities:
—
the documentation referred to in the second indent of Section 2,
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information on the changes referred to in Section 5, and
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copies of EU type-examination certificates, scientific opinions and reports and their additions/supplements.
Section 8 of Annex IX shall apply. |
ANNEX XI
CONFORMITY ASSESSMENT BASED ON PRODUCT CONFORMITY VERIFICATION
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1. |
The objective of the conformity assessment based on product conformity verification is to ensure that devices conform to the type for which an EU type-examination certificate has been issued, and that they meet the provisions of this Regulation which apply to them. |
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2. |
Where an EU type-examination certificate has been issued in accordance with Annex X, the manufacturer may either apply the procedure set out in Part A (production quality assurance) or the procedure set out in Part B (product verification) of this Annex. |
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3. |
By way of derogation from Sections 1 and 2 above, the procedures in this Annex coupled with the drawing up of technical documentation as set out in Annexes II and III may also be applied by manufacturers of class IIa devices. |
PART A
PRODUCTION QUALITY ASSURANCE
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4. |
The manufacturer shall ensure that the quality management system approved for the manufacture of the devices concerned is implemented, shall carry out a final verification, as specified in Section 6, and shall be subject to the surveillance referred to in Section 7. |
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5. |
When the manufacturer fulfils the obligations laid down in Section 4, it shall draw up and keep an EU declaration of conformity in accordance with Article 19 and Annex IV for the device covered by the conformity assessment procedure. By issuing an EU declaration of conformity, the manufacturer shall be deemed to ensure and to declare that the device concerned conforms to the type described in the EU type-examination certificate and meets the requirements of this Regulation which apply to the device. |
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6. |
Quality management system
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7. |
Surveillance Section 3.1, the first, second and fourth indents of Section 3.2, Sections 3.3, 3.4, 3.6 and 3.7 of Annex IX shall apply. In the case of class III devices, surveillance shall also include a check that the quantities of produced or purchased raw material or crucial components approved for the type and correspond to the quantities of finished devices. |
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8. |
Batch verification in the case of devices incorporating, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma referred to in Article 1(8). Upon completing the manufacture of each batch of devices that incorporate, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma referred to in the first subparagraph of Article 1(8), the manufacturer shall inform the notified body of the release of the batch of devices and send it the official certificate concerning the release of the batch of human blood or plasma derivative used in the device, issued by a Member State laboratory or a laboratory designated for that purpose by a Member State in accordance with Article 114(2) of Directive 2001/83/EC. |
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9. |
Administrative provisions The manufacturer or, where the manufacturer does not have a registered place of business in a Member State, its authorised representative shall, for a period ending no sooner than 10 years, and in the case of implantable devices no sooner than 15 years, after the last device has been placed on the market, keep at the disposal of the competent authorities:
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the EU declaration of conformity,
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the documentation referred to in the fifth indent of Section 2.1 of Annex IX,
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the documentation referred to in the eighth indent of Section 2.1 of Annex IX, including the EU type-examination certificate referred to in Annex X,
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information on the changes referred to in Section 2.4 of Annex IX, and
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the decisions and reports from the notified body as referred to in Sections 2.3, 3.3 and 3.4 of Annex IX.
Section 8 of Annex IX shall apply. |
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10. |
Application to class IIa devices
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PART B
PRODUCT VERIFICATION
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11. |
Product verification shall be understood to be the procedure whereby after examination of every manufactured device, the manufacturer, by issuing an EU declaration of conformity in accordance with Article 19 and Annex IV, shall be deemed to ensure and to declare that the devices which have been subject to the procedure set out in Sections 14 and 15 conform to the type described in the EU type-examination certificate and meet the requirements of this Regulation which apply to them. |
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12. |
The manufacturer shall take all the measures necessary to ensure that the manufacturing process produces devices which conform to the type described in the EU type-examination certificate and to the requirements of the Regulation which apply to them. Prior to the start of manufacture, the manufacturer shall prepare documents defining the manufacturing process, in particular as regards sterilisation where necessary, together with all routine, pre-established procedures to be implemented to ensure homogeneous production and, where appropriate, conformity of the devices with the type described in the EU type-examination certificate and with the requirements of this Regulation which apply to them. In addition, for devices placed on the market in a sterile condition, and only for those aspects of the manufacturing process designed to secure and maintain sterility, the manufacturer shall apply the provisions of Sections 6 and 7. |
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13. |
The manufacturer shall undertake to institute and keep up to date a post-market surveillance plan, including a PMCF plan, and the procedures ensuring compliance with the obligations of the manufacturer resulting from the provisions on vigilance and post-market surveillance system set out in Chapter VII. |
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14. |
The notified body shall carry out the appropriate examinations and tests in order to verify the conformity of the device with the requirements of the Regulation by examining and testing every product as specified in Section 15. The examinations and tests referred to in the first paragraph of this Section shall not apply to aspects of the manufacturing process designed to secure sterility. |
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15. |
Verification by examination and testing of every product
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16. |
Batch verification in the case of devices incorporating, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma referred to in Article 1(8). Upon completing the manufacture of each batch of devices that incorporate, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma referred to in the first subparagraph of Article 1(8), the manufacturer shall inform the notified body of the release of the batch of devices and send it the official certificate concerning the release of the batch of human blood or plasma derivative used in the device, issued by a Member State laboratory or a laboratory designated for that purpose by a Member State in accordance with Article 114(2) of Directive 2001/83/EC. |
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17. |
Administrative provisions The manufacturer or its authorised representative shall, for a period ending no sooner than 10 years, and in the case of implantable devices no sooner than 15 years, after the last device has been placed on the market, keep at the disposal of the competent authorities:
—
the EU declaration of conformity,
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the documentation referred to in Section 12,
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the certificate referred to in Section 15.2, and
—
the EU type-examination certificate referred to in Annex X.
Section 8 of Annex IX shall apply. |
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18. |
Application to class IIa devices
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ANNEX XII
CERTIFICATES ISSUED BY A NOTIFIED BODY
CHAPTER I
GENERAL REQUIREMENTS
1. Certificates shall be drawn up in one of the official languages of the Union.
2. Each certificate shall refer to only one conformity assessment procedure.
3. Certificates shall only be issued to one manufacturer. The name and address of the manufacturer included in the certificate shall be the same as that registered in the electronic system referred to in Article 30.
4. The scope of the certificates shall unambiguously identify the device or devices covered:
EU technical documentation assessment certificates, EU type-examination certificates and EU product verification certificates shall include a clear identification, including the name, model and type, of the device or devices, the intended purpose, as included by the manufacturer in the instructions for use and in relation to which the device has been assessed in the conformity assessment procedure, risk classification and the Basic UDI-DI as referred to in Article 27(6);
EU quality management system certificates and EU quality assurance certificates shall include the identification of the devices or groups of devices, the risk classification, and, for class IIb devices, the intended purpose.
5. The notified body shall be able to demonstrate on request, which (individual) devices are covered by the certificate. The notified body shall set up a system that enables the determination of the devices, including their classification, covered by the certificate.
6. Certificates shall contain, if applicable, a note that, for the placing on the market of the device or devices it covers, another certificate issued in accordance with this Regulation is required.
7. EU quality management system certificates and EU quality assurance certificates for class I devices for which the involvement of a notified body is required pursuant to Article 52(7) shall include a statement that the audit by the notified body of the quality management system was limited to the aspects required under that paragraph.
8. Where a certificate is supplemented, modified or re-issued, the new certificate shall contain a reference to the preceding certificate and its date of issue with identification of the changes.
CHAPTER II
MINIMUM CONTENT OF THE CERTIFICATES
name, address and identification number of the notified body;
name and address of the manufacturer and, if applicable, of the authorised representative;
unique number identifying the certificate;
if already issued, the SRN of the manufacturer referred to in to Article 31(2);
date of issue;
date of expiry;
data needed for the unambiguous identification of the device or devices where applicable as specified in Section 4 of Part I;
if applicable, reference to any previous certificate as specified in Section 8 of Chapter I;
reference to this Regulation and the relevant Annex in accordance with which the conformity assessment has been carried out;
examinations and tests performed, e.g. reference to relevant CS, harmonised standards, test reports and audit report(s);
if applicable, reference to the relevant parts of the technical documentation or other certificates required for the placing on the market of the device or devices covered;
if applicable, information about the surveillance by the notified body;
conclusions of the notified body's conformity assessment with regard to the relevant Annex;
conditions for or limitations to the validity of the certificate;
legally binding signature of the notified body in accordance with the applicable national law.
ANNEX XIII
PROCEDURE FOR CUSTOM-MADE DEVICES
1. For custom-made devices, the manufacturer or its authorised representative shall draw up a statement containing all of the following information:
2. The manufacturer shall undertake to keep available for the competent national authorities documentation that indicates its manufacturing site or sites and allows an understanding to be formed of the design, manufacture and performance of the device, including the expected performance, so as to allow assessment of conformity with the requirements of this Regulation.
3. The manufacturer shall take all the measures necessary to ensure that the manufacturing process produces devices which are manufactured in accordance with the documentation referred to in Section 2.
4. The statement referred to in the introductory part of Section 1 shall be kept for a period of at least 10 years after the device has been placed on the market. In the case of implantable devices, the period shall be at least 15 years.
Section 8 of Annex IX shall apply.
5. The manufacturer shall review and document experience gained in the post-production phase, including from PMCF as referred to in Part B of Annex XIV, and implement appropriate means to apply any necessary corrective action, In that context, it shall report in accordance with Article 87(1) to the competent authorities any serious incidents or field safety corrective actions or both as soon as it learns of them.
ANNEX XIV
CLINICAL EVALUATION AND POST-MARKET CLINICAL FOLLOW-UP
PART A
CLINICAL EVALUATION
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1. |
To plan, continuously conduct and document a clinical evaluation, manufacturers shall:
(a)
establish and update a clinical evaluation plan, which shall include at least:
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an identification of the general safety and performance requirements that require support from relevant clinical data;
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a specification of the intended purpose of the device;
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a clear specification of intended target groups with clear indications and contra-indications;
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a detailed description of intended clinical benefits to patients with relevant and specified clinical outcome parameters;
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a specification of methods to be used for examination of qualitative and quantitative aspects of clinical safety with clear reference to the determination of residual risks and side-effects;
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an indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device;
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an indication how benefit-risk issues relating to specific components such as use of pharmaceutical, non-viable animal or human tissues, are to be addressed; and
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a clinical development plan indicating progression from exploratory investigations, such as first-in-man studies, feasibility and pilot studies, to confirmatory investigations, such as pivotal clinical investigations, and a PMCF as referred to in Part B of this Annex with an indication of milestones and a description of potential acceptance criteria;
(b)
identify available clinical data relevant to the device and its intended purpose and any gaps in clinical evidence through a systematic scientific literature review;
(c)
appraise all relevant clinical data by evaluating their suitability for establishing the safety and performance of the device;
(d)
generate, through properly designed clinical investigations in accordance with the clinical development plan, any new or additional clinical data necessary to address outstanding issues; and
(e)
analyse all relevant clinical data in order to reach conclusions about the safety and clinical performance of the device including its clinical benefits. |
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2. |
The clinical evaluation shall be thorough and objective, and take into account both favourable and unfavourable data. Its depth and extent shall be proportionate and appropriate to the nature, classification, intended purpose and risks of the device in question, as well as to the manufacturer's claims in respect of the device. |
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3. |
A clinical evaluation may be based on clinical data relating to a device for which equivalence to the device in question can be demonstrated. The following technical, biological and clinical characteristics shall be taken into consideration for the demonstration of equivalence:
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Technical: the device is of similar design; is used under similar conditions of use; has similar specifications and properties including physicochemical properties such as intensity of energy, tensile strength, viscosity, surface characteristics, wavelength and software algorithms; uses similar deployment methods, where relevant; has similar principles of operation and critical performance requirements;
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Biological: the device uses the same materials or substances in contact with the same human tissues or body fluids for a similar kind and duration of contact and similar release characteristics of substances, including degradation products and leachables;
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Clinical: the device is used for the same clinical condition or purpose, including similar severity and stage of disease, at the same site in the body, in a similar population, including as regards age, anatomy and physiology; has the same kind of user; has similar relevant critical performance in view of the expected clinical effect for a specific intended purpose.
The characteristics listed in the first paragraph shall be similar to the extent that there would be no clinically significant difference in the safety and clinical performance of the device. Considerations of equivalence shall be based on proper scientific justification. It shall be clearly demonstrated that manufacturers have sufficient levels of access to the data relating to devices with which they are claiming equivalence in order to justify their claims of equivalence. |
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4. |
The results of the clinical evaluation and the clinical evidence on which it is based shall be documented in a clinical evaluation report which shall support the assessment of the conformity of the device. The clinical evidence together with non-clinical data generated from non-clinical testing methods and other relevant documentation shall allow the manufacturer to demonstrate conformity with the general safety and performance requirements and shall be part of the technical documentation for the device in question. Both favourable and unfavourable data considered in the clinical evaluation shall be included in the technical documentation. |
PART B
POST-MARKET CLINICAL FOLLOW-UP
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5. |
PMCF shall be understood to be a continuous process that updates the clinical evaluation referred to in Article 61 and Part A of this Annex and shall be addressed in the manufacturer's post-market surveillance plan. When conducting PMCF, the manufacturer shall proactively collect and evaluate clinical data from the use in or on humans of a device which bears the CE marking and is placed on the market or put into service within its intended purpose as referred to in the relevant conformity assessment procedure, with the aim of confirming the safety and performance throughout the expected lifetime of the device, of ensuring the continued acceptability of identified risks and of detecting emerging risks on the basis of factual evidence. |
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6. |
PMCF shall be performed pursuant to a documented method laid down in a PMCF plan.
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7. |
The manufacturer shall analyse the findings of the PMCF and document the results in a PMCF evaluation report that shall be part of the clinical evaluation report and the technical documentation. |
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8. |
The conclusions of the PMCF evaluation report shall be taken into account for the clinical evaluation referred to in Article 61 and Part A of this Annex and in the risk management referred to in Section 3 of Annex I. If, through the PMCF, the need for preventive and/or corrective measures has been identified, the manufacturer shall implement them. |
ANNEX XV
CLINICAL INVESTIGATIONS
CHAPTER I
GENERAL REQUIREMENTS
1. Ethical principles
Each step in the clinical investigation, from the initial consideration of the need for and justification of the study to the publication of the results, shall be carried out in accordance with recognised ethical principles.
2. Methods
|
2.1. |
Clinical investigations shall be performed on the basis of an appropriate plan of investigation reflecting the latest scientific and technical knowledge and defined in such a way as to confirm or refute the manufacturer's claims regarding the safety, performance and aspects relating to benefit-risk of devices as referred to in Article 62(1); the clinical investigations shall include an adequate number of observations to guarantee the scientific validity of the conclusions. The rationale for the design and chosen statistical methodology shall be presented as further described in Section 3.6 of Chapter II of this Annex. |
|
2.2. |
The procedures used to perform the clinical investigation shall be appropriate to the device under investigation. |
|
2.3. |
The research methodologies used to perform the clinical investigation shall be appropriate to the device under investigation. |
|
2.4. |
Clinical investigations shall be performed in accordance with the clinical investigation plan by a sufficient number of intended users and in a clinical environment that is representative of the intended normal conditions of use of the device in the target patient population. Clinical investigations shall be in line with the clinical evaluation plan as referred to in Part A of Annex XIV. |
|
2.5. |
All the appropriate technical and functional features of the device, in particular those involving safety and performance, and their expected clinical outcomes shall be appropriately addressed in the investigational design. A list of the technical and functional features of the device and the related expected clinical outcomes shall be provided. |
|
2.6. |
The endpoints of the clinical investigation shall address the intended purpose, clinical benefits, performance and safety of the device. The endpoints shall be determined and assessed using scientifically valid methodologies. The primary endpoint shall be appropriate to the device and clinically relevant. |
|
2.7. |
Investigators shall have access to the technical and clinical data regarding the device. Personnel involved in the conduct of an investigation shall be adequately instructed and trained in the proper use of the investigational device, and as regards the clinical investigation plan and good clinical practice. This training shall be verified and where necessary arranged by the sponsor and documented appropriately. |
|
2.8. |
The clinical investigation report, signed by the investigator, shall contain a critical evaluation of all the data collected during the clinical investigation, and shall include any negative findings. |
CHAPTER II
DOCUMENTATION REGARDING THE APPLICATION FOR CLINICAL INVESTIGATION
For investigational devices covered by Article 62, the sponsor shall draw up and submit the application in accordance with Article 70 accompanied by the following documents:
1. Application form
The application form shall be duly filled in, containing information regarding:
name, address and contact details of the sponsor and, if applicable, name, address and contact details of its contact person or legal representative in accordance with Article 62(2) established in the Union;
if different from those in Section 1.1, name, address and contact details of the manufacturer of the device intended for clinical investigation and, if applicable, of its authorised representative;
title of the clinical investigation;
status of the clinical investigation application (i.e. first submission, resubmission, significant amendment);
details and/or reference to the clinical evaluation plan;
If the application is a resubmission with regard to a device for which an application has been already submitted, the date or dates and reference number or numbers of the earlier application or in the case of significant amendment, reference to the original application. The sponsor shall identify all of the changes from the previous application together with a rationale for those changes, in particular, whether any changes have been made to address conclusions of previous competent authority or ethics committee reviews;
if the application is submitted in parallel with an application for a clinical trial in accordance with Regulation (EU) No 536/2014, reference to the official registration number of the clinical trial;
identification of the Member States and third countries in which the clinical investigation is to be conducted as part of a multicentre or multinational study at the time of application;
a brief description of the investigational device, its classification and other information necessary for the identification of the device and device type;
information as to whether the device incorporates a medicinal substance, including a human blood or plasma derivative or whether it is manufactured utilising non-viable tissues or cells of human or animal origin, or their derivatives;
summary of the clinical investigation plan including the objective or objectives of the clinical investigation, the number and gender of subjects, criteria for subject selection, whether there are subjects under 18 years of age, design of the investigation such as controlled and/or randomised studies, planned dates of commencement and of completion of the clinical investigation;
if applicable, information regarding a comparator device, its classification and other information necessary for the identification of the comparator device;
evidence from the sponsor that the clinical investigator and the investigational site are capable of conducting the clinical investigation in accordance with the clinical investigation plan;
details of the anticipated start date and duration of the investigation;
details to identify the notified body, if already involved at the stage of application for a clinical investigation;
confirmation that the sponsor is aware that the competent authority may contact the ethics committee that is assessing or has assessed the application; and
the statement referred to in Section 4.1.
2. Investigator's Brochure
The investigator's brochure (IB) shall contain the clinical and non-clinical information on the investigational device that is relevant for the investigation and available at the time of application. Any updates to the IB or other relevant information that is newly available shall be brought to the attention of the investigators in a timely manner. The IB shall be clearly identified and contain in particular the following information:
Identification and description of the device, including information on the intended purpose, the risk classification and applicable classification rule pursuant to Annex VIII, design and manufacturing of the device and reference to previous and similar generations of the device.
Manufacturer's instructions for installation, maintenance, maintaining hygiene standards and for use, including storage and handling requirements, as well as, to the extent that such information is available, information to be placed on the label, and instructions for use to be provided with the device when placed on the market. In addition, information relating to any relevant training required.
Pre-clinical evaluation based on relevant pre-clinical testing and experimental data, in particular regarding in-design calculations, in vitro tests, ex vivo tests, animal tests, mechanical or electrical tests, reliability tests, sterilisation validation, software verification and validation, performance tests, evaluation of biocompatibility and biological safety, as applicable.
Existing clinical data, in particular:
Summary of the benefit-risk analysis and the risk management, including information regarding known or foreseeable risks, any undesirable side-effects, contraindications and warnings.
In the case of devices that incorporate a medicinal substance, including a human blood or plasma derivative or devices manufactured utilising non-viable tissues or cells of human or animal origin, or their derivatives, detailed information on the medicinal substance or on the tissues, cells or their derivatives, and on the compliance with the relevant general safety and performance requirements and the specific risk management in relation to the substance or tissues, cells or their derivatives, as well as evidence for the added value of incorporation of such constituents in relation to the clinical benefit and/or safety of the device.
A list detailing the fulfilment of the relevant general safety and performance requirements set out in Annex I, including the standards and CS applied, in full or in part, as well as a description of the solutions for fulfilling the relevant general safety and performance requirements, in so far as those standards and CS have not or have only been partly fulfilled or are lacking.
A detailed description of the clinical procedures and diagnostic tests used in the course of the clinical investigation and in particular information on any deviation from normal clinical practice.
3. Clinical Investigation Plan
The clinical investigation plan (CIP) shall set out the rationale, objectives, design methodology, monitoring, conduct, record-keeping and the method of analysis for the clinical investigation. It shall contain in particular the information as laid down in this Annex. If part of this information is submitted in a separate document, it shall be referenced in the CIP.
3.1. General
|
3.1.1. |
Single identification number of the clinical investigation, as referred to in Article 70(1). |
|
3.1.2. |
Identification of the sponsor — name, address and contact details of the sponsor and, where applicable, the name, address and contact details of the sponsor's contact person or legal representative in accordance with Article 62(2) established in the Union. |
|
3.1.3. |
Information on the principal investigator at each investigational site, the coordinating investigator for the investigation, the address details for each investigational site and the emergency contact details for the principal investigator at each site. The roles, responsibilities and qualifications of the various kinds of investigators shall be specified in the CIP. |
|
3.1.4. |
A brief description of how the clinical investigation is financed and a brief description of the agreement between the sponsor and the site. |
|
3.1.5. |
Overall synopsis of the clinical investigation, in an official Union language determined by the Member State concerned. |
|
3.2. |
Identification and description of the device, including its intended purpose, its manufacturer, its traceability, the target population, materials coming into contact with the human body, the medical or surgical procedures involved in its use and the necessary training and experience for its use, background literature review, the current state of the art in clinical care in the relevant field of application and the proposed benefits of the new device. |
|
3.3. |
Risks and clinical benefits of the device to be examined, with justification of the corresponding expected clinical outcomes in the clinical investigation plan. |
|
3.4. |
Description of the relevance of the clinical investigation in the context of the state of the art of clinical practice. |
|
3.5. |
Objectives and hypotheses of the clinical investigation. |
|
3.6. |
Design of the clinical investigation with evidence of its scientific robustness and validity.
|
|
3.7. |
Statistical considerations, with justification, including a power calculation for the sample size, if applicable. |
|
3.8. |
Data management. |
|
3.9. |
Information about any amendments to the CIP. |
|
3.10. |
Policy regarding follow-up and management of any deviations from the CIP at the investigational site and clear prohibition of use of waivers from the CIP. |
|
3.11. |
Accountability regarding the device, in particular control of access to the device, follow-up in relation to the device used in the clinical investigation and the return of unused, expired or malfunctioning devices. |
|
3.12. |
Statement of compliance with the recognised ethical principles for medical research involving humans, and the principles of good clinical practice in the field of clinical investigations of devices, as well as with the applicable regulatory requirements. |
|
3.13. |
Description of the Informed consent process. |
|
3.14. |
Safety reporting, including definitions of adverse events and serious adverse events, device deficiencies, procedures and timelines for reporting. |
|
3.15. |
Criteria and procedures for follow-up of subjects following the end, temporary halt or early termination of an investigation, for follow-up of subjects who have withdrawn their consent and procedures for subjects lost to follow-up. Such procedures shall for implantable devices, cover as a minimum traceability. |
|
3.16. |
A description of the arrangements for taking care of the subjects after their participation in the clinical investigation has ended, where such additional care is necessary because of the subjects' participation in the clinical investigation and where it differs from that normally expected for the medical condition in question. |
|
3.17. |
Policy as regards the establishment of the clinical investigation report and publication of results in accordance with the legal requirements and the ethical principles referred to in Section 1 of Chapter I. |
|
3.18. |
List of the technical and functional features of the device, with specific mention of those covered by the investigation. |
|
3.19. |
Bibliography. |
4. Other information
|
4.1. |
A signed statement by the natural or legal person responsible for the manufacture of the investigational device that the device in question conforms to the general safety and performance requirements apart from the aspects covered by the clinical investigation and that, with regard to those aspects, every precaution has been taken to protect the health and safety of the subject. |
|
4.2. |
Where applicable according to national law, copy of the opinion or opinions of the ethics committee or committees concerned. Where according to national law the opinion or opinions of the ethics committee or committees is not required at the time of the submission of the application, a copy of the opinion or opinions shall be submitted as soon as available. |
|
4.3. |
Proof of insurance cover or indemnification of subjects in case of injury, pursuant to Article 69 and the corresponding national law. |
|
4.4. |
Documents to be used to obtain informed consent, including the patient information sheet and the informed consent document. |
|
4.5. |
Description of the arrangements to comply with the applicable rules on the protection and confidentiality of personal data, in particular:
—
organisational and technical arrangements that will be implemented to avoid unauthorised access, disclosure, dissemination, alteration or loss of information and personal data processed;
—
a description of measures that will be implemented to ensure confidentiality of records and personal data of subjects; and
—
a description of measures that will be implemented in case of a data security breach in order to mitigate the possible adverse effects.
|
|
4.6. |
Full details of the available technical documentation, for example detailed risk analysis/management documentation or specific test reports, shall, upon request, be submitted to the competent authority reviewing an application. |
CHAPTER III
OTHER OBLIGATIONS OF THE SPONSOR
|
1. |
The sponsor shall undertake to keep available for the competent national authorities any documentation necessary to provide evidence for the documentation referred to in Chapter II of this Annex. If the sponsor is not the natural or legal person responsible for the manufacture of the investigational device, that obligation may be fulfilled by that person on behalf of the sponsor. |
|
2. |
The Sponsor shall have an agreement in place to ensure that any serious adverse events or any other event as referred to in Article 80(2) are reported by the investigator or investigators to the sponsor in a timely manner. |
|
3. |
The documentation mentioned in this Annex shall be kept for a period of at least 10 years after the clinical investigation with the device in question has ended, or, in the event that the device is subsequently placed on the market, at least 10 years after the last device has been placed on the market. In the case of implantable devices, the period shall be at least 15 years. Each Member State shall require that this documentation is kept at the disposal of the competent authorities for the period referred to in the first subparagraph in case the sponsor, or its contact person or legal representative as referred to in Article 62(2) established within its territory, goes bankrupt or ceases its activity prior to the end of this period. |
|
4. |
The Sponsor shall appoint a monitor that is independent from the investigational site to ensure that the investigation is conducted in accordance with the CIP, the principles of good clinical practice and this Regulation. |
|
5. |
The Sponsor shall complete the follow-up of investigation subjects. |
|
6. |
The Sponsor shall provide evidence that the investigation is being conducted in line with good clinical practice, for instance through internal or external inspection. |
|
7. |
The Sponsor shall prepare a clinical investigation report which includes at least the following:
—
Cover/introductory page or pages indicating the title of the investigation, the investigational device, the single identification number, the CIP number and the details with signatures of the coordinating investigators and the principal investigators from each investigational site.
—
Details of the author and date of the report.
—
A summary of the investigation covering the title, purpose of the investigation, description of the investigation, investigational design and methods used, the results of the investigation and conclusion of the investigation. The completion date of the investigation, and in particular details of early termination, temporary halts or suspensions of investigations.
—
Investigational device description, in particular clearly defined intended purpose.
—
A summary of the clinical investigation plan covering objectives, design, ethical aspects, monitoring and quality measures, selection criteria, target patient populations, sample size, treatment schedules, follow-up duration, concomitant treatments, statistical plan, including hypothesis, sample size calculation and analysis methods, as well as a justification.
—
Results of the clinical investigation covering, with rationale and justification, subject demographics, analysis of results related to chosen endpoints, details of subgroup analysis, as well as compliance with the CIP, and covering follow-up of missing data and of patients withdrawing from the clinical investigation, or lost to follow-up.
—
Summary of serious adverse events, adverse device effects, device deficiencies and any relevant corrective actions.
—
Discussion and overall conclusions covering safety and performance results, assessment of risks and clinical benefits, discussion of clinical relevance in accordance with clinical state of the art, any specific precautions for specific patient populations, implications for the investigational device, limitations of the investigation.
|
ANNEX XVI
LIST OF GROUPS OF PRODUCTS WITHOUT AN INTENDED MEDICAL PURPOSE REFERRED TO IN ARTICLE 1(2)
1. Contact lenses or other items intended to be introduced into or onto the eye.
2. Products intended to be totally or partially introduced into the human body through surgically invasive means for the purpose of modifying the anatomy or fixation of body parts with the exception of tattooing products and piercings.
3. Substances, combinations of substances, or items intended to be used for facial or other dermal or mucous membrane filling by subcutaneous, submucous or intradermal injection or other introduction, excluding those for tattooing.
4. Equipment intended to be used to reduce, remove or destroy adipose tissue, such as equipment for liposuction, lipolysis or lipoplasty.
5. High intensity electromagnetic radiation (e.g. infra-red, visible light and ultra-violet) emitting equipment intended for use on the human body, including coherent and non-coherent sources, monochromatic and broad spectrum, such as lasers and intense pulsed light equipment, for skin resurfacing, tattoo or hair removal or other skin treatment.
6. Equipment intended for brain stimulation that apply electrical currents or magnetic or electromagnetic fields that penetrate the cranium to modify neuronal activity in the brain.
ANNEX XVII
CORRELATION TABLE
|
Council Directive 90/385/EEC |
Council Directive 93/42/EEC |
This Regulation |
|
Article 1(1) |
Article 1(1) |
Article 1(1) |
|
Article 1(2) |
Article 1(2) |
Article 2 |
|
Article 1(3) |
Article 1(3) first subparagraph |
Article 1(9) first subparagraph |
|
— |
Article 1(3) second subparagraph |
Article 1(9) second subparagraph |
|
Article 1(4) and (4a) |
Article 1(4) and (4a) |
Article 1(8) first subparagraph |
|
Article 1(5) |
Article 1(7) |
Article 1(11) |
|
Article 1(6) |
Article 1(5) |
Article 1(6) |
|
— |
Article 1(6) |
— |
|
— |
Article 1(8) |
Article 1(13) |
|
Article 2 |
Article 2 |
Article 5(1) |
|
Article 3 first paragraph |
Article 3 first paragraph |
Article 5(2) |
|
Article 3 second paragraph |
Article 3 second paragraph |
Article 1(12) |
|
Article 4(1) |
Article 4(1) |
Article 24 |
|
Article 4(2) |
Article 4(2) |
Article 21(1) and (2) |
|
Article 4(3) |
Article 4(3) |
Article 21(3) |
|
Article 4(4) |
Article 4(4) |
Article 10(11) |
|
Article 4(5)(a) |
Article 4(5) first subparagraph |
Article 20(6) |
|
Article 4(5)(b) |
Article 4(5) second subparagraph |
— |
|
Article 5(1) |
Article 5(1) |
Article 8(1) |
|
Article 5(2) |
Article 5(2) |
Article 8(2) |
|
Article 6(1) |
Articles 5(3) and 6 |
— |
|
Article 6(2) |
Article 7(1) |
Article 114 |
|
Article 7 |
Article 8 |
Articles 94 to 97 |
|
— |
Article 9 |
Article 51 |
|
Article 8(1) |
Article 10(1) |
Articles 87(1) and 89 (2) |
|
Article 8(2) |
Article 10(2) |
Article 87(10) and Article 87(11) first subparagraph |
|
Article 8(3) |
Article 10(3) |
Article 89(7) |
|
Article 8(4) |
Article 10(4) |
Article 91 |
|
Article 9(1) |
Article 11(1) |
Article 52(3) |
|
— |
Article 11(2) |
Article 52(6) |
|
— |
Article 11(3) |
Article 52(4) and (5) |
|
— |
Article 11(4) |
— |
|
— |
Article 11(5) |
Article 52(7) |
|
Article 9(2) |
Article 11 (6) |
Article 52(8) |
|
Article 9(3) |
Article 11(8) |
Article 11(3) |
|
Article 9(4) |
Article 11(12) |
Article 52(12) |
|
Article 9(5) |
Article 11(7) |
— |
|
Article 9(6) |
Article 11(9) |
Article 53(1) |
|
Article 9(7) |
Article 11(10) |
Article 53(4) |
|
Article 9(8) |
Article 11(11) |
Article 56(2) |
|
Article 9(9) |
Article 11(13) |
Article 59 |
|
Article 9(10) |
Article 11(14) |
Article 4(5) and Article 122 third paragraph |
|
— |
Article 12 |
Article 22 |
|
— |
Article 12a |
Article 17 |
|
Article 9a(1) first indent |
Article 13(1)(c) |
— |
|
Article 9a(1) second indent |
Article 13(1)(d) |
Article 4(1) |
|
— |
Article 13(1)(a) |
Article 51(3)(a) and Article 51(6) |
|
— |
Article 13(1)(b) |
Article 51(3)(b) and Article 51(6) |
|
Article 10 |
Article 15 |
Articles 62 to 82 |
|
Article 10a(1), second sentence of Article 10a(2) and Article 10a(3) |
Article 14(1), second sentence of Article 14(2) and Article 14(3) |
Articles 29(4), 30 and 31 |
|
Article 10a(2), first sentence |
Article 14(2) first sentence |
Article 11(1) |
|
Article 10b |
Article 14a |
Articles 33 and 34 |
|
Article 10c |
Article 14b |
Article 98 |
|
Article 11(1) |
Article 16(1) |
Articles 42 and 43 |
|
Article 11(2) |
Article 16(2) |
Article 36 |
|
Article 11(3) |
Article 16(3) |
Article 46(4) |
|
Article 11(4) |
Article 16(4) |
— |
|
Article 11(5) |
Article 16(5) |
Article 56(5) |
|
Article 11(6) |
Article 16(6) |
Article 56(4) |
|
Article 11(7) |
Article 16(7) |
Articles 38(2) and 44(2) |
|
Article 12 |
Article 17 |
Article 20 |
|
Article 13 |
Article 18 |
Articles 94 to 97 |
|
Article 14 |
Article 19 |
Article 99 |
|
Article 15 |
Article 20 |
Article 109 |
|
Article 15a |
Article 20a |
Article 102 |
|
Article 16 |
Article 22 |
— |
|
Article 17 |
Article 23 |
— |
|
— |
Article 21 |
— |
( 1 ) Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (OJ L 136, 30.4.2004, p. 1).
( 2 ) Directive 2006/42/EC of the European Parliament and of the Council of 17 May 2006 on machinery, and amending Directive 95/16/EC (OJ L 157, 9.6.2006, p. 24).
( 3 ) Commission Recommendation 2003/361/ΕC of 6 May 2003 concerning the definition of micro, small and medium-sized enterprises (OJ L 124, 20.5.2003, p. 36).
( 4 ) Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC (OJ L 158, 27.5.2014, p. 1).
( *1 ) Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC (OJ L 117, 5.5.2017, p. 1).’.
( *2 ) Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC (OJ L 117, 5.5.2017, p. 1).’.
( 5 ) Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006 ( OJ L 353, 31.12.2008, p. 1).
( 6 ) Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) (OJ L 396, 30.12.2006, p. 1).
( 7 ) Regulation (EU) No 528/2012 of the European Parliament and the Council of 22 May 2012 concerning the making available on the market of and use of biocidal products (OJ L 167, 27.6.2012, p. 1).
( 8 ) Council Directive 80/181/EEC of 20 December 1979 on the approximation of the laws of the Member States relating to units of measurement and on the repeal of Directive 71/354/EEC (OJ L 39, 15.2.1980, p. 40).
( 9 ) Directive 2004/10/EC of the European Parliament and of the Council of 11 February 2004 on the harmonisation of laws, regulations and administrative provisions relating to the application of the principles of good laboratory practice and the verification of their applications for tests on chemical substances (OJ L 50, 20.2.2004, p. 44).