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Document 02017R0746-20220128
Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU (Text with EEA relevance)Text with EEA relevance
Consolidated text: Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU (Text with EEA relevance)Text with EEA relevance
Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU (Text with EEA relevance)Text with EEA relevance
02017R0746 — EN — 28.01.2022 — 001.001
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REGULATION (EU) 2017/746 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU (OJ L 117 5.5.2017, p. 176) |
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REGULATION (EU) 2022/112 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 25 January 2022 |
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REGULATION (EU) 2017/746 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL
of 5 April 2017
on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU
(Text with EEA relevance)
CHAPTER I
INTRODUCTORY PROVISIONS
Article 1
Subject matter and scope
This Regulation does not apply to:
products for general laboratory use or research-use only products, unless such products, in view of their characteristics, are specifically intended by their manufacturer to be used for in vitro diagnostic examination;
invasive sampling products or products which are directly applied to the human body for the purpose of obtaining a specimen;
internationally certified reference materials;
materials used for external quality assessment schemes.
Article 2
Definitions
For the purposes of this Regulation, the following definitions apply:
‘medical device’ means ‘medical device’ as defined in point (1) of Article 2 of Regulation (EU) 2017/745;
‘in vitro diagnostic medical device’ means any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, piece of equipment, software or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally for the purpose of providing information on one or more of the following:
concerning a physiological or pathological process or state;
concerning congenital physical or mental impairments;
concerning the predisposition to a medical condition or a disease;
to determine the safety and compatibility with potential recipients;
to predict treatment response or reactions;
to define or monitoring therapeutic measures.
Specimen receptacles shall also be deemed to be in vitro diagnostic medical devices;
‘specimen receptacle’ means a device, whether of a vacuum-type or not, specifically intended by its manufacturer for the primary containment and preservation of specimens derived from the human body for the purpose of in vitro diagnostic examination;
‘accessory for an in vitro diagnostic medical device’ means an article which, whilst not being itself an in vitro diagnostic medical device, is intended by its manufacturer to be used together with one or several particular in vitro diagnostic medical device(s) to specifically enable the in vitro diagnostic 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 in vitro diagnostic medical device(s) in terms of its/their intended purpose(s);
‘device for self-testing’ means any device intended by the manufacturer to be used by lay persons, including devices used for testing services offered to lay persons by means of information society services;
‘device for near-patient testing’ means any device that is not intended for self-testing but is intended to perform testing outside a laboratory environment, generally near to, or at the side of, the patient by a health professional;
‘companion diagnostic’ means a device which is essential for the safe and effective use of a corresponding medicinal product to:
identify, before and/or during treatment, patients who are most likely to benefit from the corresponding medicinal product; or
identify, before and/or during treatment, patients likely to be at increased risk of serious adverse reactions as a result of treatment with the corresponding medicinal product;
‘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 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;
‘kit’ means a set of components that are packaged together and intended to be used to perform a specific in vitro diagnostic examination, or a part thereof;
‘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 or as specified by the manufacturer in the performance 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;
‘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 a device for performance study, 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 a device for performance study, on the Union market;
‘putting into service’ means the stage at which a device, other than a device for performance study, 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 or a distributor;
‘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;
‘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 evidence’ means clinical data and performance 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 benefit’ means the positive impact of a device related to its function, such as that of screening, monitoring, diagnosis or aid to diagnosis of patients, or a positive impact on patient management or public health;
‘scientific validity of an analyte’ means the association of an analyte with a clinical condition or a physiological state;
‘performance of a device’ means the ability of a device to achieve its intended purpose as claimed by the manufacturer. It consists of the analytical and, where applicable, the clinical performance supporting that intended purpose;
‘analytical performance’ means the ability of a device to correctly detect or measure a particular analyte;
‘clinical performance’ means the ability of a device to yield results that are correlated with a particular clinical condition or a physiological or pathological process or state in accordance with the target population and intended user;
‘performance study’ means a study undertaken to establish or confirm the analytical or clinical performance of a device;
‘performance study plan’ means a document that describes the rationale, objectives, design methodology, monitoring, statistical considerations, organisation and conduct of a performance study;
‘performance evaluation’ means an assessment and analysis of data to establish or verify the scientific validity, the analytical and, where applicable, the clinical performance of a device;
‘device for performance study’ means a device intended by the manufacturer to be used in a performance study.
A device intended to be used for research purposes, without any medical objective, shall not be deemed to be a device for performance study;
‘interventional clinical performance study’ means a clinical performance study where the test results may influence patient management decisions and/or may be used to guide treatment;
‘subject’ means an individual who participates in a performance study and whose specimen(s) undergo in vitro examination by a device for performance study and/or by a device used for control purposes;
‘investigator’ means an individual responsible for the conduct of a performance study at a performance study site;
‘diagnostic specificity’ means the ability of a device to recognise the absence of a target marker associated with a particular disease or condition;
‘diagnostic sensitivity’ means the ability of a device to identify the presence of a target marker associated with a particular disease or condition;
‘predictive value’ means the probability that a person with a positive device test result has a given condition under investigation, or that a person with a negative device test result does not have a given condition;
‘positive predictive value’ means the ability of a device to separate true positive results from false positive results for a given attribute in a given population;
‘negative predictive value’ means the ability of a device to separate true negative results from false negative results for a given attribute in a given population;
‘likelihood ratio’ means the likelihood of a given result arising in an individual with the target clinical condition or physiological state compared to the likelihood of the same result arising in an individual without that clinical condition or physiological state;
‘calibrator’ means a measurement reference material used in the calibration of a device;
‘control material’ means a substance, material or article intended by its manufacturer to be used to verify the performance characteristics of a device;
‘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 performance study;
‘informed consent’ means a subject's free and voluntary expression of his or her willingness to participate in a particular performance study, after having been informed of all aspects of the performance study 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 performance study;
‘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, inappropriate patient management decision, 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 performance study, whether or not related to the device for performance study;
‘serious adverse event’ means any adverse event that led to any of the following:
a patient management decision resulting in death or an imminent life-threatening situation for the individual being tested, or in the death of the individual's offspring,
death,
serious deterioration in the health of the individual being tested or the recipient of tested donations or materials, 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 a device for performance study, 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 public 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 harm as a consequence of a medical decision, action taken or not taken on the basis of information or result(s) provided by the device;
‘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
Regulatory status of products
Article 4
Genetic information, counselling and informed consent
CHAPTER II
MAKING AVAILABLE ON THE MARKET AND PUTTING INTO SERVICE OF DEVICES, OBLIGATIONS OF ECONOMIC OPERATORS, 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 laboratory of the health institution is compliant with standard EN ISO 15189 or where applicable national provisions, including national provisions regarding accreditation;
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;
as regards class D devices in accordance with the rules set out in Annex VIII, 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. Member States may apply this provision also to class A, B or C devices in accordance with the rules set out in Annex VIII;
the health institution takes all necessary measures to ensure that all devices are manufactured in accordance with the documentation referred to in point (g); 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 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
In the labelling, instructions for use, making available, putting into service and advertising of devices, it shall be prohibited to use text, names, trademarks, 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, performance studies, clinical evidence or post-market performance follow-up (‘PMPF’).
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 108 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 Section 3 of Annex I;
performance evaluation, in accordance with Article 56 and Annex XIII, including PMPF;
product realisation, including planning, design, development, production and service provision;
verification of the UDI assignments made in accordance with Article 24(3) to all relevant devices and ensuring consistency and validity of information provided in accordance with Article 26;
setting-up, implementation and maintenance of a post-market surveillance system, in accordance with Article 78;
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.
The information supplied in accordance with Section 20 of Annex I with devices for self-testing or near-patient testing shall be easily understandable and provided in the official Union language(s) determined by the Member State in which the device is made available to the user or patient.
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 51, 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 51, at the disposal of competent authorities for the period referred to in Article 10(7);
comply with the registration obligations laid down in Article 28 and verify that the manufacturer has complied with the registration obligations laid down in Article 26;
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 24.
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 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(10);
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 in vitro diagnostic 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 in vitro diagnostic medical devices;
four years of professional experience in regulatory affairs or in quality management systems relating to in vitro diagnostic medical devices.
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(9);
the reporting obligations referred to in Articles 82 to 86 are fulfilled;
in the case of devices for performance studies intended to be used in the context of interventional clinical performance studies or other performance studies involving risks for the subjects, the statement referred to in Section 4.1 of Annex XIV 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 in vitro diagnostic 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 in vitro diagnostic medical devices;
four years of professional experience in regulatory affairs or in quality management systems relating to in vitro diagnostic 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 own 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 (23) 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 20 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
EU declaration of conformity
Article 18
CE marking of conformity
Article 19
Devices for special purposes
Article 20
Parts and components
Article 21
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 22
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(7):
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 23
Medical devices nomenclature
To facilitate the functioning of the European database on medical devices (Eudamed) as referred to in Article 33 of Regulation (EU) 2017/745, 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 24
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 devices for performance studies, 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 respectively;
establishment of an electronic system for Unique Device Identification (‘UDI database’) in accordance with Article 28 of Regulation (EU) 2017/745.
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, health institutions and healthcare professionals.
Before a device, other than a device for performance study, is placed on the market the manufacturer must ensure that the information referred to in Part B of Annex V of the device in question are correctly submitted and transferred to the UDI database referred to in Article 25.
Member States shall encourage, and may require, health care 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 108:
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 107(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 102 and 103 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 health care systems of the Member States, and where possible, compatibility with other medical device identification systems that are used by stakeholders.
Article 25
UDI database
The Commission, after consulting the MDCG, shall set up and manage a UDI database in accordance with the conditions and detailed arrangements provided for in Article 28 of Regulation (EU) 2017/745.
Article 26
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 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 27
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 28
Registration of manufacturers, authorised representatives and importers
Article 29
Summary of safety and performance
The summary of safety and 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 performance shall be part of the documentation to be submitted to the notified body involved in the conformity assessment pursuant to Article 48 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 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, contra-indications 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;
reference to any harmonised standards and CS applied;
the summary of the performance evaluation as referred to in Annex XIII, and relevant information on the PMPF;
the metrological traceability of assigned values;
suggested profile and training for users;
information on any residual risks and any undesirable effects, warnings and precautions.
Article 30
European database on medical devices
Eudamed shall include the following electronic systems:
the electronic system for registration of devices referred to in Article 26;
the UDI database referred to in Article 25;
the electronic system on registration of economic operators referred to in Article 27;
the electronic system on notified bodies and on certificates referred to in Article 52;
the electronic system on performance studies referred to in Article 69,
the electronic system on vigilance and post-market surveillance referred to in Article 87;
the electronic system on market surveillance referred to in Article 95.
CHAPTER IV
NOTIFIED BODIES
Article 31
Authorities responsible for notified bodies
Where the authority responsible for notified bodies is a different authority from the national competent authority for in vitro diagnostic medical devices, it shall ensure that the national authority responsible for in vitro diagnostic medical devices is consulted on relevant matters.
Article 32
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 33
Subsidiaries and subcontracting
Article 34
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 35. However, the applicant shall make available all the documentation referred to in the first subparagraph to demonstrate compliance with those requirements upon request.
Article 35
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 competent 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 43(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 of 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 36
Nomination of experts for joint assessment of applications for notification
Article 37
Language requirements
All documents required pursuant to Articles 34 and 35 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 34 and 35, 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 35(3).
Article 38
Designation and notification procedure
Article 39
Identification number and list of notified bodies
Article 40
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 summary of the report shall be uploaded to the electronic system referred to in Article 52.
Article 41
Review of notified body assessment of technical documentation and performance evaluation documentation
Article 42
Changes to designations and notifications
The procedures described in Article 35 and in Article 38 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 in the electronic system referred to in Article 52 information in relation to certificates of which it has required their suspension or withdrawal;
inform the competent authority for in vitro diagnostic medical devices of the Member State in which the manufacturer has its registered place of business through the electronic system referred to in Article 52 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 in vitro diagnostic 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 in vitro diagnostic 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 national competent authority for in vitro diagnostic medical devices of the Member State in which the manufacturer of the device covered by the certificate has its registered 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 43
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 107(3). It shall notify the Member State concerned of its decision and update NANDO and the electronic system referred to in Article 52.
Article 44
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 36;
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 38(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 45
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 the coordination group of notified bodies, as referred to in Article 49 of Regulation (EU) 2017/745.
The bodies notified under this Regulation shall participate in the work of that group.
Article 46
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
Article 47
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.
Article 48
Conformity assessment procedures
In addition to the procedures referred to in the first subparagraph, for devices for self-testing and near-patient testing, the manufacturer shall follow the procedure for technical documentation assessment set out in Section 5.1 of Annex IX.
In addition to the procedures referred to in the first and second subparagraphs, for companion diagnostics, the notified body shall consult a competent authority designated by the Member States in accordance with Directive 2001/83/EC of the European Parliament and of the Council ( 4 ) or the EMA, as applicable, in accordance with the procedure set out in Section 5.2 of Annex IX.
For companion diagnostics, the notified body shall in particular consult a competent authority designated by the Member States in accordance with Directive 2001/83/EC or the EMA, as applicable, in accordance with the procedure set out in point (k) of Section 3 of Annex X.
In addition to the procedures referred to in the first subparagraph, for devices for self-testing and near-patient testing, the manufacturer shall follow the procedure for technical documentation assessment set out in Section 5.1 of Annex IX.
In addition to the procedures referred to in the first and second subparagraphs, for companion diagnostics the notified body shall for every device follow the procedure for technical documentation assessment laid down in Section 5.2 of Annex IX, and shall apply the procedure for technical documentation assessment laid down in Sections 4.1 to 4.8 of Annex IX and shall consult the competent authority designated by the Member States in accordance with Directive 2001/83/EC or the EMA, as applicable, in accordance with the procedure set out in Section 5.2 of Annex IX.
For companion diagnostics the notified body shall in particular for every device consult a competent authority designated by the Member States in accordance with Directive 2001/83/EC or the EMA, as applicable, in accordance with the procedure set out in point (k) of Section 3 of Annex X.
In addition to the procedures referred to in the first subparagraph, for devices for self-testing and near-patient testing, the manufacturer shall follow the procedure for assessment of the technical documentation set out in Section 5.1 of Annex IX.
However, if those devices are placed on the market in sterile condition, the manufacturer shall apply the procedures set out in Annex IX or in Annex XI. Involvement of the notified body shall be limited to the aspects relating to establishing, securing and maintaining sterile conditions.
The Commission may, by means of implementing acts, specify the 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 third paragraph of Section 2.3. and in Section 3.5 of Annex IX, in the case of class C 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 frequency of samples of the manufactured devices or batches of class D devices to be sent to an EU reference laboratory designated under Article 100 in accordance with Section 4.12 of Annex IX and Section 5.1 of Annex XI; or
the physical, laboratory or other tests to be carried out by notified bodies in the context of sample tests, assessment of technical documentation and type examination in accordance with Sections 3.4 and 4.3 of Annex IX and points (f) and (g) of Section 3. of Annex X.
The implementing acts referred to in the first subparagraph shall be adopted in accordance with the examination procedure referred to in Article 107(3).
Article 49
Involvement of notified bodies in conformity assessment procedures
Article 50
Mechanism for scrutiny of conformity assessments of class D devices
Article 51
Certificates of conformity
Article 52
Electronic system on notified bodies and on certificates of conformity
For the purposes of this Regulation, the following information shall be collated and processed pursuant to Article 57 of Regulation (EU) 2017/745 in the electronic system set up in accordance with that Article:
the list of subsidiaries referred to in Article 33(2);
the list of experts referred to in Article 36(2);
the information relating to the notification referred to in Article 38(10) and the amended notifications referred to in Article 42(2);
the list of notified bodies referred to in Article 39(2);
the summary of the report referred to in Article 40(12);
the notifications for conformity assessments and certificates referred to in Article 50(1);
withdrawal or refusals of applications for the certificates as referred to in Article 49(2) and Section 4.3 of Annex VII;
the information regarding certificates referred to in Article 51(5);
the summary of safety and performance referred to in Article 29.
Article 53
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 54
Derogation from the conformity assessment procedures
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 107(4).
Article 55
Certificate of free sale
CHAPTER VI
CLINICAL EVIDENCE, PERFORMANCE EVALUATION AND PERFORMANCE STUDIES
Article 56
Performance evaluation and clinical evidence
The manufacturer shall specify and justify the level of the 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 performance evaluation in accordance with this Article and with Part A of Annex XIII.
A performance evaluation shall follow a defined and methodologically sound procedure for the demonstration of the following, in accordance with this Article and with Part A of Annex XIII:
scientific validity;
analytical performance;
clinical performance.
The data and conclusions drawn from the assessment of those elements shall constitute the clinical evidence for the device. The clinical evidence shall be such as to scientifically demonstrate, by reference to the state of the art in medicine, that the intended clinical benefit(s) will be achieved and that the device is safe. The clinical evidence derived from the performance evaluation shall provide scientifically valid assurance, that the relevant general safety and performance requirements set out in Annex I, are fulfilled, under normal conditions of use.
The performance evaluation report for class C and D devices shall be updated when necessary, but at least annually, with the data referred to in the first subparagraph. The summary of safety and performance referred to in Article 29(1) shall be updated as soon as possible, where necessary.
Article 57
General requirements regarding performance studies
Performance studies, including performance studies that use left-over samples, shall be conducted in accordance with applicable law on data protection.
Article 58
Additional requirements for certain performance studies
Any performance study:
in which surgically invasive sample-taking is done only for the purpose of the performance study;
that is an interventional clinical performance study as defined in point (46) of Article 2; or
where the conduct of the study involves additional invasive procedures or other risks for the subjects of the studies,
shall, in addition to meeting the requirements set out in Article 57 and Annex XIII, be designed, authorised, conducted, recorded and reported in accordance with this Article and Articles 59 to 77 and Annex XIV.
Member States may choose not to apply the first subparagraph to performance studies 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 performance study who shall be the addressee for all communications with the sponsor provided for in this Regulation.
A performance study as referred to in paragraph 1 may be conducted only where all of the following conditions are met:
the performance study is the subject of an authorisation by the Member State(s) in which the performance study 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 performance study, 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 4 is established in the Union;
vulnerable populations and subjects are appropriately protected in accordance with Articles 59 to 64;
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 59;
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 performance study 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 performance study plan and constantly monitored;
the medical care provided to the subjects is the responsibility of an appropriately qualified medical doctor or, where appropriate, any other person entitled by national law to provide the relevant patient care under performance study 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 performance study;
where appropriate, biological safety testing reflecting the latest scientific knowledge or any other test deemed necessary in the light of the device's intended purpose has been conducted;
in the case of clinical performance studies, the analytical performance has been demonstrated, taking into consideration the state of the art;
in the case of interventional clinical performance studies, the analytical performance and scientific validity has been demonstrated, taking into consideration the state of the art. Where, for companion diagnostics, the scientific validity is not established, the scientific rationale for the use of the biomarker shall be provided;
the technical safety of the device with regard to its use has been proven, taking into consideration the state of the art as well as provisions in the field of occupational safety and accident prevention;
the requirements of Annex XIV are fulfilled.
Article 59
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 performance study;
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 performance study at any time without any resulting detriment and without having to provide any justification;
the conditions under which the performance study is to be conducted, including the expected duration of the subject's participation in the performance study; and
the possible treatment alternatives, including the follow-up measures if the participation of the subject in the performance study 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; and
include information about the applicable damage compensation system referred to in Article 65;
include the Union-wide unique single identification number for the performance study referred to in Article 66(1) and information about the availability of the performance study results in accordance with paragraph 6 of this Article.
Article 60
Performance studies 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 performance study may be conducted only where, in addition to the conditions set out in Article 58(5), 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 59(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 59(2) to refuse participation in, or to withdraw from, the performance study 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 performance study;
the performance study is essential with respect to incapacitated subjects and data of comparable validity cannot be obtained in performance studies on persons able to give informed consent, or by other research methods;
the performance study relates directly to a medical condition from which the subject suffers;
there are scientific grounds for expecting that participation in the performance study will produce:
a direct benefit to the incapacitated subject outweighing the risks and burdens involved; or
some benefit for the population represented by the incapacitated subject concerned when the performance study will pose only minimal risk to, and will impose minimal burden on, the incapacitated subject concerned in comparison with the standard treatment of the incapacitated subject's condition.
Article 61
Performance studies on minors
A performance study on minors may be conducted only where, in addition to the conditions set out in Article 58(5), 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 59(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 59(2) to refuse participation in, or to withdraw from, the performance study 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 performance study;
the performance study is intended to investigate treatments for a medical condition that only occurs in minors or the performance study is essential with respect to minors to validate data obtained in performance studies on persons able to give informed consent or by other research methods;
the performance study 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 performance study will produce:
a direct benefit to the minor subject outweighing the risks and burdens involved; or
some benefit for the population represented by the minor concerned when the performance study will pose only minimal risk to, and will impose minimal burden on, the minor concerned in comparison with the standard treatment of the minor's condition;
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 performance study the minor reaches the age of legal competence to give informed consent as defined in the national law, his or her express informed consent shall be obtained before that subject can continue to participate in the performance study.
Article 62
Performance studies on pregnant or breastfeeding women
A performance study on pregnant or breastfeeding women may be conducted only where, in addition to the conditions set out in Article 58(5), all of the following conditions are met:
the performance study 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;
if such a performance study has no direct benefit for the pregnant or breastfeeding woman concerned, or her embryo, foetus or child after birth, it can be conducted only if:
a performance study of comparable effectiveness cannot be carried out on women who are not pregnant or breastfeeding;
the performance study contributes to the attainment of results capable of benefitting pregnant or breastfeeding women or other women in relation to reproduction or other embryos, foetuses or children; and
the performance study poses a minimal risk to, and imposes a minimal burden on, the pregnant or breastfeeding woman concerned, her embryo, foetus or child after birth;
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 subjects, except for compensation for expenses and loss of earnings directly related to the participation in the performance study.
Article 63
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 performance studies, or persons in residential care institutions.
Article 64
Performance studies in emergency situations
By way of derogation from point (f) of Article 58(5), from points (a) and (b) of Article 60(1) and from points (a) and (b) of Article 61(1), informed consent to participate in a performance study may be obtained, and information on the performance studies may be given, after the decision to include the subject in the performance study, provided that that decision is taken at the time of the first intervention on the subject, in accordance with the clinical performance study plan for that performance study 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 performance study;
there are scientific grounds to expect that participation of the subject in the performance study 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 performance study previously expressed by the subject;
the performance study 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 performance study is of such a nature that it may be conducted exclusively in emergency situations;
the performance study 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 59 shall be sought to continue the participation of the subject in the performance study, and information on the performance study 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 59(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 59(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 performance study shall be obtained from the subject as soon as he or she is capable of giving informed consent.
Article 65
Damage compensation
Article 66
Application for performance studies
The application shall be submitted by means of the electronic system referred to in Article 69, which shall generate a Union-wide unique single identification number for the performance study which shall be used for all relevant communication in relation to that performance study. Within 10 days of receiving the application, the Member State concerned shall notify the sponsor as to whether the performance study falls within the scope of this Regulation and as to whether the application dossier is complete in accordance with Chapter I of Annex XIV.
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 that the application falls under the scope of this Regulation and/or is complete but the Member State concerned does not agree, 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 performance study is considered as falling within the scope of this Regulation and the application is complete.
The sponsor may start the performance study in the following circumstances:
in the case of performance studies carried out pursuant to point (a) of Article 58(1) and where the specimen collection does not represent a major clinical risk to the subject of the study, unless otherwise stated by national law, immediately after the validation date of application described in paragraph 5 of this Article, 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 performance study;
in the case of performance studies carried out pursuant to points (b) and (c) of Article 58(1) and Article 58(2) or performance studies other than those referred to in point (a) of this paragraph, 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 performance study. The Member State shall notify the sponsor of the authorisation within 45 days of the validation date of the application 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 67
Assessment by Member States
Member States shall assess whether the performance study 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 device(s) for performance study with the applicable general safety and performance requirements, apart from the aspects covered by the performance study, and whether, with regard to those aspects, every precaution has been taken to protect the health and safety of the subjects. This includes, in case of performance studies, the evaluation of the analytical performance, and in case of interventional clinical performance studies, the evaluation of the analytical performance, clinical performance and scientific validity, taking into consideration the state of the art;
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 device for performance study are adequate;
the reliability and robustness of the data generated in the performance study, taking account of statistical approaches, design of the performance study and methodological aspects, including sample size, comparator and endpoints;
whether the requirements of Annex XIV are met.
Member States shall refuse the authorisation of the performance study if:
the application dossier submitted pursuant to Article 66(3) remains incomplete;
the device or the submitted documents, especially the performance study plan and the investigator's brochure, do not correspond to the state of scientific knowledge, and the performance study, 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 58 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 68
Conduct of a performance study
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 performance study is in compliance with the requirements of this Regulation, the sponsor shall ensure adequate monitoring of the conduct of a performance study. 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 performance study including the following:
the objective and methodology of the performance study; and
the degree of deviation of the intervention from normal clinical practice.
Article 69
Electronic system on performance studies
The Commission shall, in collaboration with the Member States, set up, manage and maintain an electronic system:
to create the single identification numbers for performance studies referred to in Article 66(1);
to be used as an entry point for the submission of all applications or notifications for performance studies referred to in Articles 66, 70, 71 and 74 and for all other submission of data, or processing of data in this context;
for the exchange of information relating to performance studies in accordance with this Regulation between the Member States and between them and the Commission including the exchange of information referred to in to Articles 72 and 74;
for information to be provided by the sponsor in accordance with Article 73, including the performance study 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 76.
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 performance study by the Member State(s) concerned.
Article 70
Performance studies regarding devices bearing the CE marking
Article 71
Substantial modifications to performance studies
The sponsor may implement the modifications referred to in paragraph 1 at the earliest 38 days after the notification referred to in paragraph 1, unless:
the Member State in which the performance study is being or is to be conducted has notified the sponsor of its refusal based on the grounds referred to in Article 67(4) or on considerations of public health, of subject and user safety or health, or of public policy; or
an ethics committee in that Member State has issued a negative opinion in relation to the substantial modification to the performance study, which, in accordance with national law, is valid for that entire Member State.
Article 72
Corrective measures to be taken by Member States and information exchange between Member States on performance studies
Where a Member State in which a performance study 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 performance study;
suspend or terminate the performance study;
require the sponsor to modify any aspect of the performance study.
Article 73
Information from the sponsor at the end of a performance study or in the event of a temporary halt or early termination
The performance study 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 69.
Where, for scientific reasons, it is not possible to submit the performance study report within one year of the end of the study, it shall be submitted as soon as it is available. In such case, the clinical performance study plan referred to in Section 2.3.2. of Part A of Annex XIII shall specify when the results of the performance study 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 performance studies.
If the device is not registered in accordance with Article 26 within one year of the summary and the performance study 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 74
Coordinated assessment procedure for performance studies
However, the completeness of the documentation referred to in Sections 1.13, 4.2, 4.3 and 4.4 of Chapter I of Annex XIV and point (c) of Section 2.3.2. of Part A of Annex XIII shall be assessed separately by each Member State concerned in accordance with Article 66(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 performance study falls within the scope of this Regulation and whether the application is complete and shall notify the sponsor accordingly. Article 66(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 66(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 performance study 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 69 to the Commission, to all other Member States concerned, and to the sponsor.
Article 75
Review of the coordinated assessment procedure
By 27 May 2028, the Commission shall submit to the European Parliament and to the Council a report on the experience gained from the application of Article 74 and, if necessary, propose a review of Article 74(14) and point (g) of Article 113(3).
Article 76
Recording and reporting of adverse events that occur during performance studies
The sponsor shall fully record all of the following:
any adverse event of a type identified in the performance study plan as being critical to the evaluation of the results of that performance study;
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 a performance study is being conducted all of the following by means of the electronic system referred to in Article 69:
any serious adverse event that has a causal relationship with the device, the comparator or the study 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 performance study 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 74(2), the Member States shall coordinate their assessment of serious adverse events and device deficiencies to determine whether to modify, suspend or terminate the performance study or whether to revoke the authorisation for that performance study.
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 77
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 performance studies and their assessment as referred to in Articles 66 and 74, taking into account specific categories or groups of devices;
the functioning of the electronic system referred to in Article 69;
harmonised electronic forms for the notification of PMPF studies as referred to in Article 70(1), and of substantial modifications as referred to in Article 71;
the exchange of information between Member States as referred to in Article 72;
harmonised electronic forms for the reporting of serious adverse events and device deficiencies as referred to in Article 76;
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 76;
uniform application of the requirements regarding the clinical evidence/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 107(3).
CHAPTER VII
POST-MARKET SURVEILLANCE, VIGILANCE AND MARKET SURVEILLANCE
Article 78
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 performance evaluation;
to update the summary of safety and performance referred to in Article 29;
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 83.
The technical documentation shall be updated accordingly.
Article 79
Post-market surveillance plan
The post-market surveillance system referred to in Article 78 shall be based on a post-market surveillance plan, the requirements for which are set out in Section 1 of Annex III. The post-market surveillance plan shall be part of the technical documentation specified in Annex II.
Article 80
Post-market surveillance report
Manufacturers of class A and B 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 79 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 notified body and the competent authority upon request.
Article 81
Periodic safety update report
Manufacturers of class C and class D 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 79 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 PMPF; and
the volume of sales of the device and an estimate of the size and other characteristics of the population using the device and, where practicable, the usage frequency of the device.
Manufacturers of class C and D devices shall update the PSUR at least annually. That PSUR shall be part of the technical documentation as specified in Annexes II and III.
Article 82
Reporting of serious incidents and field safety corrective actions
Manufacturers of devices, made available on the Union market, other than devices for performance study, shall report, to the relevant competent authorities, in accordance with Articles 87(5) and (7), the following:
any serious incident involving devices made available on the Union market, except expected erroneous results which are clearly documented and quantified in the product information and in the technical documentation and are subject to trend reporting pursuant to Article 83;
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 87.
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 84.
Where the manufacturer of the device concerned considers that the incident is not a serious incident or is to be treated as an increase in expected erroneous results, which will be covered by trend reporting in accordance with to Article 83, 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 84.
Article 83
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 events or change in performance, as well as the observation period, in the post-market surveillance plan referred to in Article 79.
Article 84
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 for all documents necessary for the risk assessment.
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 87 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 87, inform the manufacturer, the other competent authorities and the Commission that it has assumed the role of coordinating authority.
Article 85
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 87, 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 86
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 80 to 85 and 87 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 80, 81, 82, 83 and 84 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 82;
harmonised forms for the exchange of information between competent authorities as referred to in Article 84;
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 107(3).
Article 87
Electronic system on vigilance and 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:
reports by manufacturers on serious incidents and field safety corrective actions referred to in Article 82(1) and Article 84(5);
the periodic summary reports by manufacturers referred to in Article 82(9);
the reports by manufacturers on trends referred to in Article 83;
the PSURs referred to in Article 81;
the field safety notices by manufacturers referred to in Article 84(8);
the information to be exchanged between the competent authorities of the Member States and between them and the Commission in accordance with Article 84(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 82(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 State 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 82(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 84(9) and which have agreed on the periodic summary report;
the Member State in which the manufacturer has its registered place of business.
Article 88
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 89
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 90
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 95.
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 95.
Article 91
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 90(4), the national measure shall be considered to be justified.
Article 92
Other non-compliance
Article 93
Preventive health protection measures
Article 94
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 95
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 88(4);
the final inspection report as referred to in Article 88(7);
information in relation to devices presenting an unacceptable risk to health and safety as referred to in Article 90(2), (4) and (6);
information in relation to non-compliance of products as referred to in Article 92(2);
information in relation to the preventive health protection measures referred to in Article 93(2);
summaries of the results of the reviews and assessments of the market surveillance activities of the Member States referred to in Article 88(8).
CHAPTER VIII
COOPERATION BETWEEN MEMBER STATES, MEDICAL DEVICE COORDINATION GROUP, EU REFERENCE LABORATORIES AND DEVICE REGISTERS
Article 96
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 97
Cooperation
Article 98
Medical Device Coordination Group
The Medical Device Coordination Group (MDCG) established in accordance with the conditions and detailed arrangements referred to in Article 103 and 107 of Regulation (EU) 2017/745 shall carry out, with the support of the Commission as provided in Article 104 of Regulation (EU) 2017/745, the tasks conferred on it under this Regulation as well as those under Regulation (EU) 2017/745.
Article 99
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 45;
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 performance evaluations 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) 2017/745 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 and of CS;
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, performance studies, 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 88;
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 100
The European Union reference laboratories
Within the scope of their designation, the EU reference laboratories shall, where appropriate, have the following tasks:
to verify the performance claimed by the manufacturer and the compliance of class D devices with the applicable CS, when available, or with other solutions chosen by the manufacturer to ensure a level of safety and performance that is at least equivalent, as provided for in the third subparagraph of Article 48(3);
to carry out appropriate tests on samples of manufactured class D devices or batches of class D devices, as provided for in the Section 4.12 of Annex IX and in Section 5.1 of Annex XI;
to provide scientific and technical assistance to the Commission, the MDCG, the Member States and notified bodies in relation to the implementation of this Regulation;
to provide scientific advice regarding the state of the art in relation to specific devices, or a category or group of devices;
to set up and manage a network of national reference laboratories after consulting with the national authorities and publish a list of the participating national reference laboratories and their respective tasks;
to contribute to the development of appropriate testing and analysis methods to be applied for conformity assessment procedures and market surveillance;
to collaborate with notified bodies in the development of best practices for the performance of conformity assessment procedures;
to provide recommendations on suitable reference materials and reference measurement procedures of higher metrological order;
to contribute to the development of CS and of international standards;
to provide scientific opinions in response to consultations by notified bodies in accordance with this Regulation and publish them by electronic means having considered national provisions on confidentiality.
The EU reference laboratories shall satisfy the following criteria:
have adequate and appropriately qualified staff with adequate knowledge and experience in the field of the in vitro diagnostic medical devices for which they are designated;
possess the necessary equipment and reference material 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;
act in the public interest and in an independent manner;
ensure that their staff do not have financial or other interests in the in vitro diagnostic medical device industry which could affect their impartiality, declare any other direct and indirect interests they may have in the in vitro diagnostic medical device industry and update this declaration whenever a relevant change occurs.
The EU reference laboratories shall form a network in order to coordinate and harmonise their working methods as regards testing and assessment. That coordination and harmonisation shall involve:
applying coordinated methods, procedures and processes;
agreeing on the use of same reference materials and common test samples and seroconversion panels;
establishing common assessment and interpretation criteria;
using common testing protocols and assessing the test results using standardised and coordinated evaluation methods;
using standardised and coordinated test reports;
developing, applying and maintaining a peer review system;
organizing regular quality assessment tests (including mutual checks on the quality and comparability of test results);
agreeing on joint guidelines, instructions, procedural instructions or standard operational procedures;
coordinating the introduction of testing methods for new technologies and according to new or amended CS;
reassessing the state of the art on the basis of comparative test results or by further studies, as requested by a Member State or by the Commission.
The Commission may adopt, by means of implementing acts, the detailed arrangements and the amount of a Union financial contribution to the EU reference laboratories, taking into account the objectives of health and safety protection, support of innovation and cost-effectiveness. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 107(3).
The Commission shall specify by means of implementing acts:
detailed rules to facilitate the application of paragraph 2 of this Article and detailed rules to ensure compliance with the criteria referred to in paragraph 4 of this Article.
the structure and the level of the fees referred to in paragraph 7 of this Article which may be levied by an EU reference laboratory for providing scientific opinions in response to consultations by notified bodies and Member States in accordance with this Regulation, taking into account the objectives of human health and safety protection, support of innovation and cost-effectiveness.
Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 107(3).
Article 101
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.
CHAPTER IX
CONFIDENTIALITY, DATA PROTECTION, FUNDING AND PENALTIES
Article 102
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 103;
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 103
Data protection
Article 104
Levying of fees
Article 105
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 107(3).
Article 106
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 25 February 2022 and shall notify it without delay of any subsequent amendment affecting them.
CHAPTER X
FINAL PROVISIONS
Article 107
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 108
Exercise of the delegation
Article 109
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 110
Transitional provisions
Certificates issued by notified bodies in accordance with Directive 98/79/EC from 25 May 2017 shall become void by ►M1 27 May 2025 ◄ .
Devices with a certificate that was issued in accordance with Directive 98/79/EC and which is valid by virtue of paragraph 2 of this Article may be placed on the market or put into service until 26 May 2025.
Devices for which the conformity assessment procedure pursuant to Directive 98/79/EC did not require the involvement of a notified body, for which a declaration of conformity was drawn up prior to 26 May 2022 in accordance with that Directive, and for which the conformity assessment procedure pursuant to this Regulation requires the involvement of a notified body, may be placed on the market or put into service until the following dates:
26 May 2025, for class D devices;
26 May 2026, for class C devices;
26 May 2027, for class B devices;
26 May 2027, for class A devices placed on the market in sterile condition.
By way of derogation from the first subparagraph of this paragraph, the requirements of this Regulation relating to post-market surveillance, market surveillance, vigilance, registration of economic operators and of devices shall apply to devices referred to in the second and third subparagraphs of this paragraph, instead of the corresponding requirements in Directive 98/79/EC.
Without prejudice to Chapter IV and paragraph 1 of this Article, the notified body that issued the certificate referred to in the second subparagraph of this paragraph shall continue to be responsible for the appropriate surveillance in respect of all applicable requirements relating to the devices it has certified.
Devices lawfully placed on the market from 26 May 2022 pursuant to paragraph 3 of this Article may continue to be made available on the market or put into service until the following dates:
26 May 2026, for devices referred to in paragraph 3, second subparagraph, or in paragraph 3, third subparagraph, point (a);
26 May 2027, for devices referred to in paragraph 3, third subparagraph, point (b);
26 May 2028, for devices referred to in paragraph 3, third subparagraph, points (c) and (d).
Article 111
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 devices through the storage, pursuant to Article 24, of the UDI by economic operators, health institutions and health professionals. The evaluation shall also include a review on the functioning of Article 4.
Article 112
Repeal
Without prejudice to Articles 110 (3) and (4) of this Regulation, and without prejudice to the obligations of the Member States and manufacturers as regards vigilance and the obligations of manufacturers as regards the making available of documentation, under Directive 98/79/EC, that Directive is repealed with effect from 26 May 2022 with the exception of:
Article 11, point (c) of Article 12(1) and Article 12(2) and (3) of Directive 98/79/EC, and the obligations relating to vigilance and performance studies provided for in the corresponding Annexes, which are repealed with effect from the later of the dates referred to in Article 113(2) and point (f) of Article 113(3) of this Regulation; and
Article 10, points (a) and (b) of Article 12(1) and Article 15(5) of Directive 98/79/EC, and the obligations relating to registration of devices and economic operators, and certificate notifications provided for in the corresponding Annexes, which are repealed with effect from 18 months after the later of the dates referred to in Article 113(2) and point (f) of Article 113(3) of this Regulation.
As regards the devices referred to in Article 110(3) and (4) of this Regulation, Directive 98/79/EC shall continue to apply until ►M1 26 May 2028 ◄ to the extent necessary for the application of those paragraphs.
Decision 2010/227/EU adopted in implementation of Directives 90/385/EEC, 93/42/EEC and 98/79/EC shall be repealed with effect from the later of the dates referred to in Article 113(2) and point (f) of Article 113(3) of this Regulation.
References to the repealed Directive shall be understood as references to this Regulation and shall be read in accordance with the correlation table laid down in Annex XV.
Article 113
Entry into force and date of application
By way of derogation from paragraph 2:
Articles 26(3) and 51(5) shall apply from 18 months after the later of the dates referred to in point (f);
Articles 31 to 46 and Article 96 shall apply from 26 November 2017. However, from that date until 26 May 2022 the obligations on notified bodies pursuant to Articles 31 to 46 shall apply only to those bodies which submit an application for designation in accordance with Article 34;
Article 97 shall apply from 26 May 2018;
Article 100 shall apply from 25 November 2020;
for class D devices, Article 24(4) shall apply from 26 May 2023. For class B and class C devices Article 24(4) shall apply from 26 May 2025. For class A devices Article 24(4) shall apply from 26 May 2027;
without prejudice to the obligations on the Commission pursuant to Article 34 of Regulation (EU) 2017/745, where, due to circumstances that could not reasonably have been foreseen when drafting the plan referred to in Article 34(1) of that Regulation, Eudamed is not fully functional on 26 May 2022, 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) of that Regulation. The provisions referred to in the preceding sentence are:
Until Eudamed is fully functional the corresponding provisions of Directive 98/79/EC 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 performance studies, vigilance reporting, registration of devices and economic operators, and certificate notifications.
the procedure set out in Article 74 shall apply from 26 May 2029 without prejudice to Article 74(14);
Article 110(10) shall apply from 26 May 2019;
Article 5(5), points (b) and (c) and (e) to (i), shall apply from 26 May 2024;
Article 5(5), point (d), shall apply from 26 May 2028.
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 26(3) and 28, core data elements to be provided to the UDI database together with the UDI-DI in accordance with Articles 25 and 26 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 on assessment of technical documentation |
|
X |
Conformity assessment based on type examination |
|
XI |
Conformity assessment based on production quality assurance |
|
XII |
Certificates issued by a notified body |
|
XIII |
Performance evaluation, performance studies and post-market performance follow-up |
|
XIV |
Interventional clinical performance studies and certain other performance studies |
|
XV |
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, the 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, the 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 effects shall be minimised and be acceptable when weighed against the evaluated potential benefits to the patients and/or the user arising from the intended performance of the device during normal conditions of use. |
CHAPTER II
REQUIREMENTS REGARDING PERFORMANCE, DESIGN AND MANUFACTURE
9. Performance characteristics
|
9.1. |
Devices shall be designed and manufactured in such a way that they are suitable for the purposes referred to in point (2) of Article 2, as specified by the manufacturer, and suitable with regard to the performance they are intended to achieve, taking account of the generally acknowledged state of the art. They shall achieve the performances, as stated by the manufacturer and in particular, where applicable:
(a)
the analytical performance, such as, analytical sensitivity, analytical specificity, trueness (bias), precision (repeatability and reproducibility), accuracy (resulting from trueness and precision), limits of detection and quantitation, measuring range, linearity, cut-off, including determination of appropriate criteria for specimen collection and handling and control of known relevant endogenous and exogenous interference, cross-reactions; and
(b)
the clinical performance, such as diagnostic sensitivity, diagnostic specificity, positive predictive value, negative predictive value, likelihood ratio, expected values in normal and affected populations. |
|
9.2. |
The performance characteristics of the device shall be maintained during the lifetime of the device as indicated by the manufacturer. |
|
9.3. |
Where the performance of devices depends on the use of calibrators and/or control materials, the metrological traceability of values assigned to calibrators and/or control materials shall be assured through suitable reference measurement procedures and/or suitable reference materials of a higher metrological order. Where available, metrological traceability of values assigned to calibrators and control materials shall be assured to certified reference materials or reference measurement procedures. |
|
9.4. |
The characteristics and performances of the device shall be specifically checked in the event that they may be affected when the device is used for the intended use under normal conditions:
(a)
for devices for self-testing, performances obtained by laypersons;
(b)
for devices for near-patient testing, performances obtained in relevant environments (for example, patient home, emergency units, ambulances). |
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 the possibility of impairment of analytical performance due to physical and/or chemical incompatibility between the materials used and the specimens, analyte or marker to be detected (such as biological tissues, cells, body fluids and micro-organisms), taking account of the intended purpose of the device. |
|
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 as to reduce to a level as low as reasonably practicable the risks posed by substances or particles, including wear debris, degradation products and processing residues, that may be released from the device. Special attention shall be given to substances which are carcinogenic, mutagenic or toxic to reproduction (‘CMR’), in accordance with Part 3 of Annex VI to Regulation (EC) No 1272/2008 of the European Parliament and of the Council ( 6 ), and to substances having endocrine disrupting properties for which there is scientific evidence of probable serious effects to human health and which are identified in accordance with the procedure set out in Article 59 of Regulation (EC) No 1907/2006 of the European Parliament and of the Council ( 7 ). |
|
10.4. |
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. |
11. Infection and microbial contamination
|
11.1. |
Devices and their manufacturing processes shall be designed in such a way as to eliminate or reduce as far as possible the risk of infection to the user or, where applicable, other persons. The design shall:
(a)
allow easy and safe handling;
(b)
reduce as far as possible any microbial leakage from the device and/or microbial exposure during use; and, where necessary
(c)
prevent microbial contamination of the device during use and, in the case of specimen receptacles, the risk of contamination of the specimen. |
|
11.2. |
Devices labelled either as sterile or as having a specific microbial state shall be designed, manufactured and packaged to ensure that their sterile condition or microbial state is maintained under the transport and storage conditions specified by the manufacturer until that packaging is opened at the point of use, unless the packaging which maintains their sterile condition or microbial state is damaged. |
|
11.3. |
Devices labelled as sterile shall be processed, manufactured, packaged and, sterilised by means of appropriate, validated methods. |
|
11.4. |
Devices intended to be sterilised shall be manufactured and packaged in appropriate and controlled conditions and facilities. |
|
11.5. |
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. |
|
11.6. |
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. |
12. Devices incorporating materials of biological origin
Where devices include tissues, cells and substances of animal, human or microbial origin, the selection of sources, the processing, preservation, testing and handling of tissues, cells and substances of such origin and control procedures shall be carried out so as to provide safety for user or other person.
In particular, safety with regard to microbial and other transmissible agents shall be addressed by implementation of validated methods of elimination or inactivation in the course of the manufacturing process. This might not apply to certain devices if the activity of the microbial and other transmissible agent are integral to the intended purpose of the device or when such elimination or inactivation process would compromise the performance of the device.
13. Construction of devices and interaction with their environment
|
13.1. |
If the device is intended for use in combination with other devices or equipment, the whole combination, including the connection system, shall be safe and shall not impair the specified performances of the devices. Any restrictions on use applying to such combinations shall be indicated on the label and/or in the instructions for use. |
|
13.2. |
Devices shall be designed and manufactured in such a way as to remove or reduce as far as possible:
(a)
the risk of injury, in connection with their physical features, including the volume/pressure ratio, dimensional and where appropriate ergonomic features;
(b)
risks connected with reasonably foreseeable external influences or environmental conditions, such as magnetic fields, external electrical and electromagnetic effects, electrostatic discharge, radiation associated with diagnostic or therapeutic procedures, pressure, humidity, temperature, variations in pressure and acceleration or radio signal interferences;
(c)
the risks associated with the use of the device when it comes into contact with materials, liquids, and substances, including gases, to which it is exposed during normal conditions of use;
(d)
the risks associated with the possible negative interaction between software and the IT environment within which it operates and interacts;
(e)
the risks of accidental ingress of substances into the device;
(f)
the risk of incorrect identification of specimens and the risk of erroneous results due to, for example, confusing colour and/or numeric and/or character codings on specimen receptacles, removable parts and/or accessories used with devices in order to perform the test or assay as intended;
(g)
the risks of any foreseeable interference with other devices. |
|
13.3. |
Devices shall be designed and manufactured in such a way as to minimise the risks of fire or explosion during normal use and in single fault condition. Particular attention shall be paid to devices the intended use of which includes exposure to or use in association with flammable or explosive substances or substances which could cause combustion. |
|
13.4. |
Devices shall be designed and manufactured in such a way that adjustment, calibration, and maintenance can be done safely and effectively. |
|
13.5. |
Devices that are intended to be operated together with other devices or products shall be designed and manufactured in such a way that the interoperability and compatibility are reliable and safe. |
|
13.6. |
Devices shall be designed and manufactured in such a way as to facilitate their safe disposal and the safe disposal of related waste substances by users, or other person. To that end, manufacturers shall identify and test procedures and measures as a result of which their devices can be safely disposed after use. Such procedures shall be described in the instructions for use. |
|
13.7 |
The measuring, monitoring or display scale (including colour change and other visual indicators) shall be designed and manufactured in line with ergonomic principles, taking account of the intended purpose, users and the environmental conditions in which the devices are intended to be used. |
14. Devices with a measuring function
|
14.1. |
Devices having a primary analytical measuring function shall be designed and manufactured in such a way as to provide appropriate analytical performance in accordance with point (a) of Section 9.1 of Annex I, taking into account the intended purpose of the device. |
|
14.2. |
The measurements made by devices with a measuring function shall be expressed in legal units conforming to the provisions of Council Directive 80/181/EEC ( 8 ). |
15. Protection against radiation
|
15.1. |
Devices shall be designed, manufactured and packaged in such a way that exposure of users or other persons to radiation (intended, unintended, stray or scattered) 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 diagnostic purposes. |
|
15.2. |
When devices are intended to emit hazardous, or potentially hazardous, ionizing and/or non-ionizing radiation, they shall as far as possible be:
(a)
designed and manufactured in such a way as to ensure that the characteristics and the quantity of radiation emitted can be controlled and/or adjusted; and
(b)
fitted with visual displays and/or audible warnings of such emissions. |
|
15.3. |
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 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. Electronic programmable systems — devices that incorporate electronic programmable systems and software that are devices in themselves
|
16.1. |
Devices that incorporate electronic programmable systems, including software, or software that are devices in themselves, shall be designed to ensure repeatability, reliability and performance in line with their intended use. In the event of a single fault condition, appropriate means shall be adopted to eliminate or reduce as far as possible consequent risks or impairment of performance. |
|
16.2. |
For devices that incorporate software or for software that are devices in themselves, the software shall be developed and manufactured in accordance with the state of the art taking into account the principles of development life cycle, risk management, including information security, verification and validation. |
|
16.3. |
Software referred to in this Section that is intended to be used in combination with mobile computing platforms shall be designed and manufactured taking into account the specific features of the mobile platform (e.g. size and contrast ratio of the screen) and the external factors related to their use (varying environment as regards level of light or noise). |
|
16.4. |
Manufacturers shall set out minimum requirements concerning hardware, IT networks characteristics and IT security measures, including protection against unauthorised access, necessary to run the software as intended. |
17. Devices connected to or equipped with an energy source
|
17.1. |
For devices connected to or equipped with an energy source, in the event of a single fault condition, appropriate means shall be adopted to eliminate or reduce as far as possible consequent risks. |
|
17.2. |
Devices where the safety of the patient depends on an internal power supply shall be equipped with a means of determining the state of the power supply and an appropriate warning or indication for when the capacity of the power supply becomes critical. If necessary, such warning or indication shall be given prior to the power supply becoming critical. |
|
17.3. |
Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks of creating electromagnetic interference which could impair the operation of the device in question or other devices or equipment in the intended environment. |
|
17.4. |
Devices shall be designed and manufactured in such a way as to provide a level of intrinsic immunity to electromagnetic interference such that is adequate to enable them to operate as intended. |
|
17.5. |
Devices shall be designed and manufactured in such a way as to avoid as far as possible the risk of accidental electric shocks to the user, or other person both during normal use of the device and in the event of a single fault condition in the device, provided the device is installed and maintained as indicated by the manufacturer. |
18. Protection against mechanical and thermal risks
|
18.1. |
Devices shall be designed and manufactured in such a way as to protect users and other persons against mechanical risks. |
|
18.2. |
Devices shall be sufficiently stable under the foreseen operating conditions. They shall be suitable to withstand stresses inherent to the foreseen working environment, and to retain this resistance during the expected lifetime of the devices, subject to any inspection and maintenance requirements as indicated by the manufacturer. |
|
18.3. |
Where there are risks due to the presence of moving parts, risks due to break-up or detachment, or leakage of substances, then appropriate protection means shall be incorporated. Any guards or other means included with the device to provide protection, in particular against moving parts, shall be secure and shall not interfere with access for the normal operation of the device, or restrict routine maintenance of the device as intended by the manufacturer. |
|
18.4. |
Devices shall be designed and manufactured in such a way as to reduce to the lowest possible level the risks arising from vibration generated by the devices, taking account of technical progress and of the means available for limiting vibrations, particularly at source, unless the vibrations are part of the specified performance. |
|
18.5. |
Devices shall be designed and manufactured in such a way as to reduce to the lowest possible level the risks arising from the noise emitted, taking account of technical progress and of the means available to reduce noise, particularly at source, unless the noise emitted is part of the specified performance. |
|
18.6. |
Terminals and connectors to the electricity, gas or hydraulic and pneumatic energy supplies which the user or other person has to handle, shall be designed and constructed in such a way as to minimise all possible risks. |
|
18.7. |
Errors likely to be made when fitting or refitting certain parts which could be a source of risk shall be made impossible by the design and construction of such parts or, failing this, by information given on the parts themselves and/or their housings. The same information shall be given on moving parts and/or their housings where the direction of movement needs to be known in order to avoid a risk. |
|
18.8. |
Accessible parts of devices (excluding the parts or areas intended to supply heat or reach given temperatures) and their surroundings shall not attain potentially dangerous temperatures under normal conditions of use. |
19. Protection against the risks posed by devices intended for self-testing or near-patient testing
|
19.1. |
Devices intended for self-testing or near-patient testing shall be designed and manufactured in such a way that they perform appropriately for their intended purpose taking into account the skills and the means available to the intended user and the influence resulting from variation that can be reasonably anticipated in the intended user's technique and environment. The information and instructions provided by the manufacturer shall be easy for the intended user to understand and apply in order to correctly interpret the result provided by the device and to avoid misleading information. In the case of near-patient testing, the information and the instructions provided by the manufacturer shall make clear the level of training, qualifications and/or experience required by the user. |
|
19.2. |
Devices intended for self-testing or near-patient testing shall be designed and manufactured in such a way as to:
(a)
ensure that the device can be used safely and accurately by the intended user at all stages of the procedure if necessary after appropriate training and/or information; and
(b)
reduce as far as possible the risk of error by the intended user in the handling of the device and, if applicable, the specimen, and also in the interpretation of the results. |
|
19.3. |
Devices intended for self-testing and near-patient testing shall, where feasible, include a procedure by which the intended user:
(a)
can verify that, at the time of use, the device will perform as intended by the manufacturer; and
(b)
be warned if the device has failed to provide a valid result. |
CHAPTER III
REQUIREMENTS REGARDING INFORMATION SUPPLIED WITH THE DEVICE
20. Label and instructions for use
20.1. 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. If individual full labelling of each unit is not practicable, the information shall be set out 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 or bar codes.
Instructions for use shall be provided together with devices. However, in duly justified and exceptional cases instructions for use shall not be required or may be abbreviated if the device can be used safely and as intended by the manufacturer without any such instructions for use.
Where multiple devices, with the exception of devices intended for self-testing or near-patient testing, 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.
When the device is intended for professional use only, instructions for use may be provided to the user in non-paper format (e.g. electronic), except when the device is intended for near-patient testing.
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, taking into account the intended users. 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.
In the case of devices containing a substance or a mixture which may be considered as being dangerous, taking account of the nature and quantity of its constituents and the form under which they are present, relevant hazard pictograms and labelling requirements of Regulation (EC) No 1272/2008 shall apply. Where there is insufficient space to put all the information on the device itself or on its label, the relevant hazard pictograms shall be put on the label and the other information required by Regulation (EC) No 1272/2008 shall be given in the instructions for use.
The provisions of Regulation (EC) No 1907/2006 on the safety data sheet shall apply, unless all relevant information, as appropriate, is already made available in the instructions for use.
20.2. 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 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 its authorised representative and the address of the registered place of business of the authorised representative;
an indication that the device is an in vitro diagnostic medical device, or if the device is a ‘device for performance study’, an indication of that fact;
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 as referred to in Article 24 and Part C of Annex VI;
an unambiguous indication of the time limit for using the device safely, without degradation of performance, expressed at least in terms of year and month and, where relevant, the day, in that order;
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;
where relevant, an indication of the net quantity of contents, expressed in terms of weight or volume, numerical count, or any combination of thereof, or other terms which accurately reflect the contents of the package;
an indication of any special storage and/or handling condition that applies;
where appropriate, an indication of the sterile state of the device and the sterilisation method, or a statement indicating any special microbial state or state of cleanliness;
warnings or precautions to be taken that need to be brought to the immediate attention of the user of the device or 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 instructions for use are not provided in paper form in accordance with point (f) of Section 20.1, a reference to their accessibility (or availability), and where applicable the website address where they can be consulted;
where applicable, any particular operating instructions;
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 intended for self-testing or near-patient testing, an indication of that fact;
where rapid assays are not intended for self-testing or near-patient testing, the explicit exclusion hereof;
where device kits include individual reagents and articles that are made available as separate devices, each of those devices shall comply with the labelling requirements contained in this Section and with the requirements of this Regulation;
the devices and separate components shall be identified, where applicable in terms of batches, to allow all appropriate action to detect any potential risk posed by the devices and detachable components. As far as practicable and appropriate, the information shall be set out on the device itself and/or, where appropriate, on the sales packaging;
the label for devices for self-testing shall bear the following particulars:
the type of specimen(s) required to perform the test (e.g. blood, urine or saliva);
the need for additional materials for the test to function properly;
contact details for further advice and assistance.
The name of devices for self-testing shall not reflect an intended purpose other than that specified by the manufacturer.
20.3. 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,
the month and year of manufacture,
an unambiguous indication of the time limit for using the device safely, expressed at least in terms of year and month and, where relevant, the day, in that order,
an instruction to check the instructions for use for what to do if the sterile packaging is damaged or unintentionally opened before use.
20.4. Information in the instructions for use
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20.4.1. |
The instructions for use shall contain all of the following particulars:
(a)
the name or trade name of the device;
(b)
the details strictly necessary for the user to uniquely identify the device;
(c)
the device's intended purpose:
(i)
what is detected and/or measured;
(ii)
its function (e.g. screening, monitoring, diagnosis or aid to diagnosis, prognosis, prediction, companion diagnostic);
(iii)
the specific information that is intended to be provided in the context of:
—
a physiological or pathological state;
—
congenital physical or mental impairments;
—
the predisposition to a medical condition or a disease;
—
the determination of the safety and compatibility with potential recipients;
—
the prediction of treatment response or reactions;
—
the definition or monitoring of therapeutic measures;
(iv)
whether it is automated or not;
(v)
whether it is qualitative, semi-quantitative or quantitative;
(vi)
the type of specimen(s) required;
(vii)
where applicable, the testing population; and
(viii)
for companion diagnostics, the International Non-proprietary Name (INN) of the associated medicinal product for which it is a companion test.
(d)
an indication that the device is an in vitro diagnostic medical device, or, if the device is a ‘device for performance study’, an indication of that fact;
(e)
the intended user, as appropriate (e.g. self-testing, near patient and laboratory professional use, healthcare professionals);
(f)
the test principle;
(g)
a description of the calibrators and controls and any limitation upon their use (e.g. suitable for a dedicated instrument only);
(h)
a description of the reagents and any limitation upon their use (e.g. suitable for a dedicated instrument only) and the composition of the reagent product by nature and amount or concentration of the active ingredient(s) of the reagent(s) or kit as well as a statement, where appropriate, that the device contains other ingredients which might influence the measurement;
(i)
a list of materials provided and a list of special materials required but not provided;
(j)
for devices intended for use in combination with or installed with or connected to other devices and/or general purpose equipment:
—
information to identify such devices or equipment, in order to obtain a validated and safe combination, including key performance characteristics, and/or
—
information on any known restrictions to combinations of devices and equipment.
(k)
an indication of any special storage (e.g. temperature, light, humidity, etc.) and/or handling conditions which apply;
(l)
in-use stability which may include the storage conditions, and shelf life following the first opening of the primary container, together with the storage conditions and stability of working solutions, where this is relevant;
(m)
if the device is supplied as sterile, an indication of its sterile state, the sterilisation method and instructions in the event of the sterile packaging being damaged before use;
(n)
information that allows the user to be informed of any warnings, precautions, measures to be taken and limitations of use regarding the device. That information shall cover, where appropriate:
(i)
warnings, precautions and/or measures to be taken in the event of malfunction of the device or its degradation as suggested by changes in its appearance that may affect performance,
(ii)
warnings, precautions and/or measures to be taken as regards the exposure to reasonably foreseeable external influences or environmental conditions, such as magnetic fields, external electrical and electromagnetic effects, electrostatic discharge, radiation associated with diagnostic or therapeutic procedures, pressure, humidity, or temperature,
(iii)
warnings, precautions and/or measures to be taken as regards the risks of interference posed by the reasonably foreseeable presence of the device during specific diagnostic investigations, evaluations, therapeutic treatment or other procedures such as electromagnetic interference emitted by the device affecting other equipment,
(iv)
precautions related to materials incorporated into the device that contain or consist of CMR substances, or endocrine disrupting substances or that could result in sensitisation or an allergic reaction by the patient or user,
(v)
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,
(vi)
if the device is reusable, information on the appropriate processes to allow reuse, including cleaning, disinfection, decontamination, packaging and, where appropriate, the validated method of re-sterilisation. Information shall be provided to identify when the device should no longer be reused, such as signs of material degradation or the maximum number of allowable reuses;
(o)
any warnings and/or precautions related to potentially infectious material that is included in the device;
(p)
where relevant, requirements for special facilities, such as a clean room environment, or special training, such as on radiation safety, or particular qualifications of the intended user;
(q)
conditions for collection, handling, and preparation of the specimen;
(r)
details of any preparatory treatment or handling of the device before it is ready for use, such as sterilisation, final assembly, calibration, etc., for the device to be used as intended by the manufacturer;
(s)
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:
—
details of the nature, and frequency, of preventive and regular maintenance, including cleaning and disinfection;
—
identification of any consumable components and how to replace them;
—
information on any necessary calibration to ensure that the device operates properly and safely during its intended lifetime;
—
methods for mitigating the risks encountered by persons involved in installing, calibrating or servicing devices.
(t)
where applicable, recommendations for quality control procedures;
(u)
the metrological traceability of values assigned to calibrators and control materials, including identification of applied reference materials and/or reference measurement procedures of higher order and information regarding maximum (self-allowed) batch to batch variation provided with relevant figures and units of measure;
(v)
assay procedure including calculations and interpretation of results and where relevant if any confirmatory testing shall be considered; where applicable, the instructions for use shall be accompanied by information regarding batch to batch variation provided with relevant figures and units of measure;
(w)
analytical performance characteristics, such as analytical sensitivity, analytical specificity, trueness (bias), precision (repeatability and reproducibility), accuracy (resulting from trueness and precision), limits of detection and measurement range, (information needed for the control of known relevant interferences, cross-reactions and limitations of the method), measuring range, linearity and information about the use of available reference measurement procedures and materials by the user;
(x)
clinical performance characteristics as defined in Section 9.1 of this Annex;
(y)
the mathematical approach upon which the calculation of the analytical result is made;
(z)
where relevant, clinical performance characteristics, such as threshold value, diagnostic sensitivity and diagnostic specificity, positive and negative predictive value;
(aa)
where relevant, reference intervals in normal and affected populations;
(ab)
information on interfering substances or limitations (e.g. visual evidence of hyperlipidaemia or haemolysis, age of specimen) that may affect the performance of the device;
(ac)
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:
(i)
infection or microbial hazards, such as consumables contaminated with potentially infectious substances of human origin;
(ii)
environmental hazards such as batteries or materials that emit potentially hazardous levels of radiation);
(iii)
physical hazards such as explosion.
(ad)
the name, registered trade name or registered trade mark of the manufacturer and the address of its registered place of business at which he can be contacted and its location be established, together with a telephone number and/or fax number and/or website address to obtain technical assistance;
(ae)
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, with a clear indication of the introduced modifications;
(af)
a notice to the user that any serious incident that has occurred in relation to the device shall be reported to the manufacturer and the competent authority of the Member State in which the user and/or the patient is established;
(ag)
where device kits include individual reagents and articles that may be made available as separate devices, each of these devices shall comply with the instructions for use requirements contained in this Section and with the requirements of this Regulation;
(ah)
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. |
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20.4.2 |
In addition, the instructions for use for devices intended for self-testing shall comply with all of the following principles:
(a)
details of the test procedure shall be given, including any reagent preparation, specimen collection and/or preparation and information on how to run the test and interpret the results;
(b)
specific particulars may be omitted provided that the other information supplied by the manufacturer is sufficient to enable the user to use the device and to understand the result(s) produced by the device;
(c)
the device's intended purpose shall provide sufficient information to enable the user to understand the medical context and to allow the intended user to make a correct interpretation of the results;
(d)
the results shall be expressed and presented in a way that is readily understood by the intended user;
(e)
information shall be provided with advice to the user on action to be taken (in case of positive, negative or indeterminate result), on the test limitations and on the possibility of false positive or false negative result. Information shall also be provided as to any factors that can affect the test result such as age, gender, menstruation, infection, exercise, fasting, diet or medication;
(f)
the information provided shall include a statement clearly directing that the user should not take any decision of medical relevance without first consulting the appropriate healthcare professional, information on disease effects and prevalence, and, where available, information specific to the Member State(s) where the device is placed on the market on where a user can obtain further advice such as national helplines, websites;
(g)
for devices intended for self-testing used for the monitoring of a previously diagnosed existing disease or condition, the information shall specify that the patient should only adapt the treatment if he has received the appropriate training to do so. |
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 purpose of the device which may include information on:
what is to be detected and/or measured;
its function such as screening, monitoring, diagnosis or aid to diagnosis, prognosis, prediction, companion diagnostic;
the specific disorder, condition or risk factor of interest that it is intended to detect, define or differentiate;
whether it is automated or not;
whether it is qualitative, semi-quantitative or quantitative;
the type of specimen(s) required;
where applicable, the testing population;
the intended user;
in addition, for companion diagnostics, the relevant target population and the associated medicinal product(s).
the description of the principle of the assay method or the principles of operation of the instrument;
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;
the description of the components and where appropriate, the description of the reactive ingredients of relevant components such as antibodies, antigens, nucleic acid primers;
and where applicable:
the description of the specimen collection and transport materials provided with the device or descriptions of specifications recommended for use;
for instruments of automated assays: the description of the appropriate assay characteristics or dedicated assays;
for automated assays: a description of the appropriate instrumentation characteristics or dedicated instrumentation;
a description of any software to be used with the device;
a description or complete list of the various configurations/variants of the device that are intended to be made available on the market;
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 the device.
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
the label or labels on the device and on its packaging, such as single unit packaging, sales packaging, transport packaging in the case of specific management conditions, in the languages accepted in the Member States where the device is envisaged to be sold;
the instructions for use in the languages accepted in the Member States where the device is envisaged to be sold.
3. DESIGN AND MANUFACTURING INFORMATION
3.1. Design information
Information to allow the design stages applied to the device to be understood shall include:
a description of the critical ingredients of the device such as antibodies, antigens, enzymes and nucleic acid primers provided or recommended for use with the device;
for instruments, a description of major subsystems, analytical technology such as operating principles and control mechanisms, dedicated computer hardware and software;
for instruments and software, an overview of the entire system;
for software, a description of the data interpretation methodology, namely the algorithm;
for devices intended for self-testing or near-patient testing, a description of the design aspects that make them suitable for self-testing or near-patient testing.
3.2. Manufacturing information
information to allow the manufacturing processes such as production, assembly, final product testing, and packaging of the finished device to be understood. More detailed information shall be provided for the audit of the quality management system or other applicable conformity assessment procedures;
identification of all sites, including suppliers and sub-contractors, where 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 also 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;
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. BENFIT-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.
This includes:
6.1. Information on analytical performance of the device
6.1.1. Specimen type
This Section shall describe the different specimen types that can be analysed, including their stability such as storage, where applicable specimen transport conditions and, with a view to time-critical analysis methods, information on the timeframe between taking the specimen and its analysis and storage conditions such as duration, temperature limits and freeze/thaw cycles.
6.1.2. Analytical performance characteristics
6.1.2.1. Accuracy of measurement
Trueness of measurement
This Section shall provide information on the trueness of the measurement procedure and summarise the data in sufficient detail to allow an assessment of the adequacy of the means selected to establish the trueness. Trueness measures apply to both quantitative and qualitative assays only when a certified reference material or certified reference method is available.
Precision of measurement
This Section shall describe repeatability and reproducibility studies.
6.1.2.2. Analytical sensitivity
This Section shall include information about the study design and results. It shall provide a description of specimen type and preparation including matrix, analyte levels, and how levels were established. The number of replicates tested at each concentration shall also be provided as well as a description of the calculation used to determine assay sensitivity.
6.1.2.3. Analytical specificity
This Section shall describe interference and cross reactivity studies performed to determine the analytical specificity in the presence of other substances/agents in the specimen.
Information shall be provided on the evaluation of potentially interfering and cross-reacting substances or agents on the assay, on the tested substance or agent type and its concentration, specimen type, analyte test concentration, and results.
Interferents and cross-reacting substances or agents, which vary greatly depending on the assay type and design, could derive from exogenous or endogenous sources such as:
substances used for patient treatment such as medicinal products;
substances ingested by the patient such as alcohol, foods;
substances added during specimen preparation such as preservatives, stabilisers;
substances encountered in specific specimen types such as haemoglobin, lipids, bilirubin, proteins;
analytes of similar structure such as precursors, metabolites or medical conditions unrelated to the test condition including specimens negative for the assay but positive for a condition that can mimic the test condition.
6.1.2.4. Metrological traceability of calibrator and control material values
6.1.2.5. Measuring range of the assay
This Section shall include information on the measuring range regardless of whether the measuring systems are linear or non-linear, including the limit of detection and describe information on how the range and detection limit were established.
This information shall include a description of specimen type, number of specimens, number of replicates, and specimen preparation including information on the matrix, analyte levels and how levels were established. If applicable, a description of any high dose hook effect and the data supporting the mitigation such as dilution steps shall be added.
6.1.2.6. Definition of assay cut-off
This Section shall provide a summary of analytical data with a description of the study design including methods for determining the assay cut-off, such as:
the population(s) studied: demographics, selection, inclusion and exclusion criteria, number of individuals included;
method or mode of characterisation of specimens; and
statistical methods such as Receiver Operator Characteristic (ROC) to generate results and if applicable, define grey-zone/equivocal zone.
6.1.3. The analytical performance report referred to in Annex XIII.
6.2. Information on clinical performance and clinical evidence. Performance Evaluation Report
The documentation shall contain the performance evaluation report, which includes the reports on the scientific validity, the analytical and the clinical performance, as referred to in Annex XIII, together with an assessment of those reports.
The clinical performance study documents referred to in Section 2 of Part A of Annex XIII shall be included and/or fully referenced in the technical documentation.
6.3. Stability (excluding specimen stability)
This Section shall describe claimed shelf life, in use stability and shipping stability studies.
6.3.1. Claimed shelf-life
This Section shall provide information on stability testing studies to support the shelf life that is claimed for the device. Testing shall be performed on at least three different lots manufactured under conditions that are essentially equivalent to routine production conditions. The three lots do not need to be consecutive. Accelerated studies or extrapolated data from real time data are acceptable for initial shelf life claims but shall be followed up with real time stability studies.
Such detailed information shall include:
the study report including the protocol, number of lots, acceptance criteria and testing intervals;
where accelerated studies have been performed in anticipation of the real time studies, the method used for accelerated studies shall be described;
the conclusions and claimed shelf life.
6.3.2. In-use stability
This Section shall provide information on in-use stability studies for one lot reflecting actual routine use of the device, regardless of whether real or simulated. This may include open vial stability and/or, for automated instruments, on board stability.
In the case of automated instrumentation, if calibration stability is claimed, supporting data shall be included.
Such detailed information shall include:
the study report (including the protocol, acceptance criteria and testing intervals);
the conclusions and claimed in-use stability.
6.3.3. Shipping stability
This Section shall provide information on shipping stability studies for one lot of devices to evaluate the tolerance of devices to the anticipated shipping conditions.
Shipping studies may be done under real and/or simulated conditions and shall include variable shipping conditions such as extreme heat and/or cold.
Such information shall describe:
the study report (including the protocol, acceptance criteria);
the method used for simulated conditions;
the conclusion and recommended shipping conditions.
6.4. Software verification and validation
The documentation shall contain evidence of the validation of the software, as it is used in the finished device. Such information shall typically include the summary results of all verification, validation and testing performed in-house and applicable in an actual user environment prior to final release. It shall also address all of the different hardware configurations and, where applicable, operating systems identified in the labelling.
6.5. Additional information required in specific cases
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 regard 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 containing tissues, cells and substances of animal, human or microbial origin, information on the origin of such material and on the conditions in which it was collected.
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 equipment in order to operate as intended, a description of the resulting combination including proof that it conforms to the general safety and performance requirements set out in Annex I when connected to any such equipment 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 78 to 81 shall be presented in a clear, organised, readily searchable and unambiguous manner and shall include in particular the elements described in this Annex.
1. The post-market surveillance plan drawn up in accordance with Article 79.
The manufacturer shall prove in a post-market surveillance plan that it complies with the obligation referred to in Article 78.
The post-market surveillance plan shall address the collection and utilisation of available information, in particular:
The post-market surveillance plan shall cover at least:
2. The PSUR referred to in Article 81 and the post-market surveillance report referred to in Article 80.
ANNEX IV
EU DECLARATION OF CONFORMITY
The EU declaration of conformity shall contain the following information:
Name, registered trade name or registered trade mark and, if already issued, SRN referred to in Article 28 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 26(3) AND 28, CORE DATA ELEMENTS TO BE PROVIDED TO THE UDI DATABASE TOGETHER WITH THE UDI-DI IN ACCORDANCE WITH ARTICLES 25 AND 26 AND THE UDI SYSTEM
PART A
INFORMATION TO BE SUBMITTED UPON THE REGISTRATION OF DEVICES AND ECONOMIC OPERATORS IN ACCORDANCE WITH ARTICLES 26(3) AND 28
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 shall or has been placed on the market in the Union,
in the case of class B, class C or class D devices: Member States where the device is or is to be made available,
presence of tissues, cells, or, their derivatives, of human origin (y/n),
presence of tissues, cells or their derivatives of animal origin as referred to in Regulation (EU) No 722/2012(y/n),
presence of cells or substances of microbial origin (y/n),
risk class of the device,
where applicable, the single identification number of the performance study,
in the case of devices designed and manufactured by another legal or natural person as referred in Article 10(14), the name, address and contact details of that legal or natural person,
in the case of class C or D devices, the summary of safety and performance,
status of the device (on the market, no longer placed on the market, recalled, field safety corrective Action initiated),
indication as to whether the device is a ‘new’ device.
A device shall be considered to be ‘new’ if:
there has been no such device continuously available on the Union market during the previous three years for the relevant analyte or other parameter;
the procedure involves analytical technology not continuously used in connection with a given analyte or other parameter on the Union market during the previous three years.
indication as to whether the device is intended for self-testing or near-patient testing.
PART B
CORE DATA ELEMENTS TO BE PROVIDED TO THE UDI DATABASE TOGETHER WITH THE UDI-DI IN ACCORDANCE WITH ARTICLES 25 AND 26
The manufacturer shall provide to the UDI database the UDI-DI and the following information relating to the manufacturer and the device:
quantity per package configuration,
the Basic UDI-DI as referred to in Article 24(6) 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’ UDI-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 28(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 23,
risk class of the device,
if applicable, name or trade name,
if applicable, device model, reference, or catalogue number,
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),
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 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.
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 customised to meet specific needs.
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 fixed quantity of devices, such as a carton or case.
Production Identifier (UDI-PI)
The UDI-PI is a numeric or alphanumeric code that identifies the unit of device production.
The different types of UDI-PI(s) 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 24(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. |
Kits 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. |
|
3.10. |
Manufacturers that repackage 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 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 class A and class B devices 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 packages. 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. |
|
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 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. |
|
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 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 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 minimised 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. Reusable devices that are part of kits and that require cleaning, disinfection, sterilisation or refurbishing between uses
|
6.1.1. |
The UDI of such devices shall be placed on the device and shall be readable after each procedure to make the device ready for the next use; |
|
6.1.2. |
The UDI-PI characteristics such as the lot or serial number shall be defined by the manufacturer. |
6.2. Device software
6.2.1. 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.
|
6.2.2. |
A new UDI-DI shall be required whenever there is a modification that changes:
(a)
the original performance,
(b)
the safety or the intended use of the software.
(c)
interpretation of data. Such modifications include new or modified algorithms, database structures, operating platform, architecture or new user interfaces or new channels for interoperability. |
|
6.2.3. |
Minor software revisions shall require a new UDI-PI and not a new UDI-DI: Minor software revisions are generally associated with bug fixes, usability enhancements that are not for safety purposes, security patches or operating efficiency.
Minor software revisions shall be identified by a manufacturer-specific form of identification.
|
|
6.2.4. |
UDI placement criteria for software
(a)
where the software is delivered on a physical medium, for example via a CD or DVD, each packaging level shall bear the human readable and AIDC representation of the complete UDI. The UDI that is applied to the physical medium containing the software and its packaging shall be identical to the UDI assigned to the system level software;
(b)
the UDI shall be provided on a readily accessible screen for the user in an easily-readable plain-text format such as an ‘about’ file, or included on the start-up screen;
(c)
software lacking a user interface such as middleware for image conversion, shall be capable of transmitting the UDI through an application programming interface (API);
(d)
only the human readable portion of the UDI shall be required in electronic displays of the software. The marking of UDI using AIDC shall not be required in the electronic displays such as ‘about’ menu, splash screen, etc.;
(e)
the human readable format of the UDI for the software shall include the application identifiers (AI) for the standard used by the issuing entities, so as to assist the user in identifying the UDI and determining which standard is being used to create the UDI. |
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 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:
(a)
provision of adequate resources for conformity assessment activities;
(b)
development of procedures and policies for the operation of the notified body;
(c)
supervision of implementation of the procedures, policies and quality management systems of the notified body;
(d)
supervision of the notified body's finances;
(e)
activities and decisions taken by the notified body, including contractual agreements;
(f)
delegation of authority to personnel and/or committees, where necessary, for the performance of defined activities;
(g)
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 the devices or processes under assessment; and
(e)
be linked to any organisation which itself provides consultancy services as referred to in the point (d). Such restriction shall not preclude general training activities that are not client specific and that relate to regulation of devices s 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 interests 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 interests 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 shall 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 the 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 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 requirement 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 their 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 of Regulation (EU) 2017/745 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:
(a)
management system structure and documentation, including policies and objectives for its activities;
(b)
policies for assignment of activities and responsibilities to personnel;
(c)
assessment and decision-making processes in accordance with the tasks, responsibilities and role of the notified body's personnel and top-level management;
(d)
the planning, conduct, evaluation and, if necessary, adaptation of its conformity assessment procedures;
(e)
control of documents;
(f)
control of records;
(g)
management reviews;
(h)
internal audits;
(i)
corrective and preventive actions;
(j)
complaints and appeals;
(k)
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 the notified body itself or on its behalf and under its 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, performance 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 their assignment of their duties and 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 to 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, decision-making, and batch release, as well as the devices, technologies and areas, such as biocompatibility, sterilisation, self and near patient-testing, companion diagnostics and performance 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 the notified body's designation in accordance with the scope description used by the Member State for the notification referred to in Article 38(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:
—
biological safety,
—
performance evaluation,
—
devices for self and near patient testing,
—
companion diagnostics,
—
functional safety,
—
software,
—
packaging, 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 performance 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 performance evaluation, and any associated performance study, and appropriately guide external clinical experts in the assessment of the performance evaluation presented by the manufacturer;
—
be able to scientifically evaluate and, if necessary, challenge the performance evaluation presented, and the results of the external clinical experts' assessment of the manufacturer's performance evaluation;
—
be able to ascertain the comparability and consistency of the assessments of performance evaluation conducted by clinical experts;
—
be able to make an assessment of the manufacturer's performance 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 performance evaluation, biological safety, sterilisation and software validation, shall have all the following proven qualifications:
—
successful completion of a university or a technical college degree or an 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 design, manufacture, testing or use of devices 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 performance 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;
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appropriate knowledge of quality management systems and related l devices standards and guidance documents;
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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;
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training in auditing techniques enabling them to challenge quality management systems;
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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, as a group, shall have proven knowledge and comprehensive experience of all of the following:
—
devices legislation and relevant guidance documents;
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device conformity assessments relevant to this Regulation;
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the types of qualifications, experience and expertise relevant to device conformity assessment;
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a broad base of knowledge of device technologies, including sufficient experience of the conformity assessment of devices being reviewed for certification, the device industry and the design and manufacture of devices;
—
the notified body's quality system, related procedures and the required qualifications for personnel involved;
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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;
—
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;
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auditing and certification activities where the subcontracting in question is to auditing or certification organisations;
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allocation of work to external experts for specific conformity assessment activities;
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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;
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subcontractors and external experts do not further subcontract work to organisations or personnel;
—
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 devices or technologies, the notified body in question shall have adequate 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 as a minimum, verify that personnel:
—
are aware of the 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;
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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 its 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;
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 52 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 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, 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 batch
The notified body shall:
have documented procedures, sufficient expertise and facilities for the verification by examination and testing of every product batch in accordance with Annexes IX and 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 batch as specified in Section 5 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;
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. Performance evaluation assessment
The assessment by notified bodies of 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 have been deviations from procedures, the notified body in question shall critically examine the justification presented by the manufacturer.
The notified body shall have documented procedures in place relating to the assessment of a manufacturer's procedures and documentation relating to performance evaluation both for initial conformity assessment and on an ongoing basis. The notified body shall examine, validate and verify that the manufacturer's procedures and documentation adequately address:
the planning, conduct, assessment, reporting and updating of the performance evaluation as referred to in Annex XIII,
post-market surveillance and post-market performance follow up,
the interface with the risk management process,
the appraisal and analysis of the available data and its relevance with regard to demonstrating conformity with the relevant requirements in Annex I,
the conclusions drawn with regard to the clinical evidence and drawing up of the performance evaluation report.
The procedures referred to in the second paragraph shall take into consideration available CS, guidance and best practice documents.
The notified body's assessment of performance evaluations as referred to in Annex XIII shall cover:
In relation to data from performance studies included within the performance evaluation, the notified body in question shall ensure that the conclusions drawn by the manufacturer are valid in the light of the approved performance study plan.
The notified body shall ensure that the performance evaluation adequately addresses the relevant safety and performance requirements provided for in Annex I, that it is appropriately aligned with the risk management requirements and that it is conducted in accordance with Annex XIII and that it is appropriately reflected in the information provided relating to the device.
4.5.5. Specific Procedures
The notified body shall have documented procedures, sufficient expertise and facilities for the procedures referred to in Section 5 of Annex IX, for which they are designated.
In the case of companion diagnostics, the notified body shall have documented procedures in place that aim to fulfil the requirements of this Regulation in relation to consultation of the EMA or a medicinal products competent authority during its assessment of such types of device.
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 on 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 performance evaluation, including the results of any performance studies and PMPF,
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 PMPF activities undertaken since the previous certification or re-certification, including appropriate updates to manufacturers' performance evaluation reports.
For the decision on the 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 to be taken for certification, such as application and application review.
ANNEX VIII
CLASSIFICATION RULES
1. IMPLEMENTING RULES
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1.1. |
Application of the classification rules shall be governed by the intended purpose of the devices. |
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1.2. |
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. |
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1.3. |
Accessories for an in vitro diagnostic medical device shall be classified in their own right separately from the device with which they are used. |
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1.4. |
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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1.5. |
Calibrators intended to be used with a device shall be classified in the same class as the device. |
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1.6. |
Control materials with quantitative or qualitative assigned values intended for one specific analyte or multiple analytes shall be classified in the same class as the device. |
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1.7. |
The manufacturer shall take into consideration all classification and implementation rules in order to establish the proper classification for the device. |
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1.8. |
Where a manufacturer states multiple intended purposes for a device, and as a result the device falls into more than one class, it shall be classified in the higher class. |
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1.9. |
If several classification rules apply to the same device, the rule resulting in the higher classification shall apply. |
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1.10. |
Each of the classification rules shall apply to first line assays, confirmatory assays and supplemental assays. |
2. CLASSIFICATION RULES
2.1. Rule 1
Devices intended to be used for the following purposes are classified as class D:
2.2. Rule 2
►C2 Devices intended to be used for blood grouping, or to determine foeto-maternal blood group incompatibility, or for tissue typing to ensure the immunological compatibility of blood, ◄ blood components, cells, tissue or organs that are intended for transfusion or transplantation or cell administration, are classified as class C, except when intended to determine any of the following markers:
in which case they are classified as class D.
2.3. Rule 3
Devices are classified as class C if they are intended:
for detecting the presence of, or exposure to, a sexually transmitted agent;
for detecting the presence in cerebrospinal fluid or blood of an infectious agent without a high or suspected high risk of propagation;
for detecting the presence of an infectious agent, if there is a significant risk that an erroneous result would cause death or severe disability to the individual, foetus or embryo being tested, or to the individual's offspring;
for pre-natal screening of women in order to determine their immune status towards transmissible agents;
for determining infective disease status or immune status, where there is a risk that an erroneous result would lead to a patient management decision resulting in a life-threatening situation for the patient or for the patient's offspring;
to be used as companion diagnostics;
to be used for disease staging, where there is a risk that an erroneous result would lead to a patient management decision resulting in a life-threatening situation for the patient or for the patient's offspring;
to be used in screening, diagnosis, or staging of cancer;
for human genetic testing;
for monitoring of levels of medicinal products, substances or biological components, when there is a risk that an erroneous result will lead to a patient management decision resulting in a life-threatening situation for the patient or for the patient's offspring;
for management of patients suffering from a life-threatening disease or condition;
for screening for congenital disorders in the embryo or foetus;
for screening for congenital disorders in new-born babies where failure to detect and treat such disorders could lead to life-threatening situations or severe disabilities.
2.4. Rule 4
Devices intended for self-testing are classified as class C, except for devices for the detection of pregnancy, for fertility testing and for determining cholesterol level, and devices for the detection of glucose, erythrocytes, leucocytes and bacteria in urine, which are classified as class B.
Devices intended for near-patient testing are classified in their own right.
2.5. Rule 5
The following devices are classified as class A:
products for general laboratory use, accessories which possess no critical characteristics, buffer solutions, washing solutions, and general culture media and histological stains, intended by the manufacturer to make them suitable for in vitro diagnostic procedures relating to a specific examination;
instruments intended by the manufacturer specifically to be used for in vitro diagnostic procedures;
specimen receptacles.
2.6. Rule 6
Devices not covered by the above-mentioned classification rules are classified as class B.
2.7. Rule 7
Devices which are controls without a quantitative or qualitative assigned value are classified as class B.
ANNEX IX
CONFORMITY ASSESSMENT BASED ON A QUALITY MANAGEMENT SYSTEM AND ON ASSESSMENT OF TECHNICAL DOCUMENTATION
CHAPTER I
QUALITY MANAGEMENT SYSTEM
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1. |
The manufacturer shall establish, document and implement a quality management system, as described in Article 10(8), 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
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3. |
Surveillance assessment
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CHAPTER II
ASSESSMENT OF THE TECHNICAL DOCUMENTATION
4. Assessment of the technical documentation of class B, C and D devices and batch verification applicable to class D devices
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4.1. |
In addition to the obligation laid down in Section 2, the manufacturer of devices shall lodge with the notified body an application for the 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. In the case of devices for self-testing or near-patient testing, the application shall also include the aspects referred to in point (b) of Section 5.1. |
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4.3. |
►C1 The notified body shall assess the technical documentation using staff with proven knowledge ◄ and experience in the evaluation of the technology, and the devices concerned and the evaluation of clinical evidence. 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. |
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4.4. |
The notified body shall review the clinical evidence presented by the manufacturer in the performance evaluation report and the related performance evaluation that was conducted. The notified body shall use employed device reviewers with sufficient clinical expertise and including external clinical experts with direct and current experience relating to the clinical application of the device in question 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. |
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4.6. |
The notified body shall verify that the clinical evidence and the performance 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 PMPF plan proposed, where applicable. |
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4.7. |
Based on its assessment of the clinical evidence, the notified body shall consider the performance 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 PMPF data. |
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4.8. |
The notified body shall clearly document the outcome of its assessment in the performance evaluation assessment report. |
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4.9. |
Before issuing an EU technical documentation assessment certificate, the notified body shall request an EU reference laboratory, where designated in accordance with Article 100, to verify the performance claimed by the manufacturer and the compliance of the device with the CS, where available, or with other solutions chosen by the manufacturer to ensure a level of safety and performance that is at least equivalent. The verification shall include laboratory tests by the EU reference laboratory as referred to in Article 48(5). In addition, the notified body shall, in the cases referred to in Article 48(6) of this Regulation, consult the relevant experts referred to in Article 106 of Regulation (EU) 2017/745 in accordance with the procedure laid down in Article 48(6) of this Regulation on the performance evaluation report of the manufacturer. The EU reference laboratory shall provide a scientific opinion within 60 days. The scientific opinion of the EU reference laboratory and, where applicable, the views of the experts consulted, pursuant to the procedure laid down in Article 48(6), and any possible updates shall be included in the documentation of the notified body concerning the device. The notified body shall, when making its decision, give due consideration to the views expressed in the scientific opinion of the EU reference laboratory, and, where applicable, to the views expressed by the experts consulted pursuant to Article 48(6). The notified body shall not deliver the certificate if the scientific opinion of the EU reference laboratory is unfavourable. |
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4.10. |
The notified body shall provide the manufacturer with a report on the technical documentation assessment, including a performance 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 device, and, where appropriate, a description of the intended purpose of the device. |
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4.11. |
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 48 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. Where the changes could affect compliance with the CS or with other solutions chosen by the manufacturer which were approved through the EU technical documentation assessment certificate, the notified body shall consult the EU reference laboratory that was involved in the initial consultation, in order to confirm that compliance with the CS or with other solutions chosen by the manufacturer, to ensure a level of safety and performance that is at least equivalent, is maintained. The EU reference laboratory shall provide a scientific opinion within 60 days. |
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4.12. |
To verify conformity of manufactured class D devices, the manufacturer shall carry out tests on each manufactured batch of devices. After the conclusion of the controls and tests, it shall forward to the notified body, without delay, the relevant reports on those tests. Furthermore, the manufacturer shall make the samples of manufactured batches of devices available to the notified body in accordance with pre-agreed conditions and detailed arrangements which shall include that the notified body or the manufacturer shall send samples of the manufactured batches of devices to the EU reference laboratory, where such a laboratory has been designated in accordance with Article 100, to carry out appropriate tests. The EU reference laboratory shall inform the notified body about its findings. |
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4.13. |
The manufacturer may place the devices on the market, unless the notified body communicates to the manufacturer within the agreed timeframe, but not later than 30 days after reception of the samples, any other decision, including in particular any condition of validity of delivered certificates. |
5. Assessment of the technical documentation of specific types of devices
5.1. Assessment of the technical documentation of class B, C and D devices for self-testing and near-patient testing
The manufacturer of class B, C and D devices for self-testing and near-patient testing shall lodge with the notified body an application for the assessment of the technical documentation.
The application shall enable the design of the device characteristics and performance(s) to be understood and shall enable conformity with the design-related requirements of this Regulation to be assessed. It shall include:
test reports, including results of studies carried out with intended users;
where practicable, an example of the device; if required, the device shall be returned on completion of the technical documentation assessment;
data showing the suitability of the device in view of its intended purpose for self-testing or near patient-testing;
the information to be provided with the device on its label and its instructions for use.
The notified body may require the application to be completed by carrying out further tests or by providing further proof to allow assessment of conformity with the requirements of this Regulation.
The notified body shall verify the compliance of the device with the relevant requirements set out in Annex I of this Regulation.
The notified body shall assess the application, by using staff, employed by it, with proven knowledge and experience regarding the technology concerned and the intended purpose of the device and provide the manufacturer with a technical documentation 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 assessment, the conditions of its validity, the data needed for the identification of the approved devices and, where appropriate, a description of the intended purpose of the device.
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 48 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.
5.2. Assessment of the technical documentation of companion diagnostics
The manufacturer of a companion diagnostic shall lodge with the notified body an application for the assessment of the technical documentation. The notified body shall assess that application in accordance with the procedure laid down in Sections 4.1 to 4.8 of this Annex.
The application shall enable the characteristics and performance of the device to be understood, and shall enable conformity with the design-related requirements of this Regulation to be assessed, in particular, with regard to the suitability of the device in relation to the medicinal product concerned.
The notified body shall, before issuing an EU technical documentation assessment certificate for the companion diagnostic and on the basis of the draft summary of safety and performance and the draft instructions for use, 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, regarding the suitability of the device in relation to the medicinal product concerned. Where the medicinal product falls exclusively within the scope of the Annex to Regulation (EC) No 726/2004 of the European Parliament and of the Council ( 9 ), the notified body shall seek the opinion of the EMA. If the medicinal product concerned is already authorised, or if an application for its authorisation has been submitted, the notified body shall consult the medicinal products authority, or the EMA, that is responsible for the authorisation.
The medicinal products authority consulted shall provide its opinion, within 60 days of receipt of all the necessary documentation. This 60-day period may be extended once for a further 60 days on justified grounds. The opinion 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 scientific opinion referred to in point (d) when making its decision. The notified body shall convey its final decision to the medicinal products authority consulted. The EU technical documentation assessment certificate shall be delivered in accordance with point (e) of Section 5.1.
Before changes affecting the performance and/or the intended use and/or the suitability of the device in relation to the medicinal product concerned are made, the manufacturer shall inform the notified body of the changes. The notified body shall assess the planned changes and decide whether the planned changes require a new conformity assessment in accordance with Article 48 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 and seek the opinion of the medicinal products authority consulted. The medicinal products authority consulted shall give its opinion within 30 days of receipt of the all the necessary documentation regarding the changes. A supplement to the EU technical documentation assessment certificate shall be issued in accordance with point (f) of Section 5.1.
CHAPTER III
ADMINISTRATIVE PROVISIONS
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6. |
The manufacturer or, where the manufacturer does not have a registered place of business in a Member State, it's authorised representative shall, for a period ending no sooner than 10 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. 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 Sections 4.2. and point (b) of Section 5.1., and
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the decisions and reports from the notified body as referred to in this Annex.
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|
7. |
Each Member State shall require that the documentation referred to in Section 6 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:
—
the name of the manufacturer and the address of its registered place of business 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,
—
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,
—
in the case of devices for self-testing or near-patient testing, test reports, including results of studies carried out with intended users, and data showing the handling suitability of the device in relation to its intended purpose for self-testing or near patient-testing,
—
where practicable, an example of the device. If required, the device shall be returned on completion of the technical documentation assessment;
—
data showing the suitability of the device in relation to its intended purpose for self-testing or near-patient testing,
—
the information to be provided with the device on its label and its instructions for use, and
—
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.
|
|
3. |
Assessment The notified body shall:
(a)
examine the application, by using staff with proven knowledge and experience in the evaluation of the technology, and the devices concerned and the evaluation of clinical evidence. 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 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 performance evaluation report in accordance with Section 1.3.2 of Annex XIII. 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 clinical application of the device in question for the purposes of that review;
(d)
in circumstances in which the clinical evidence is partly or totally based 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 the performance evaluation assessment report referred to in Section 4.8 of Annex IX;
(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;
(i)
draw up an EU type-examination report on the results of the assessments and tests carried out under points (a) to (g);
(j)
in the case of class D devices, request the EU reference laboratory, where designated in accordance with Article 100, to verify the performance claimed by the manufacturer and the compliance of the device with the CS, where available, or with other solutions chosen by the manufacturer to ensure a level of safety and performance that is at least equivalent. The verification shall include laboratory tests by the EU reference laboratory in accordance with Article 48(5). In addition, the notified body shall, in the cases referred to in Article 48(6) of this Regulation, consult the relevant experts referred to in Article 106 of Regulation (EU) 2017/745 following the procedure laid down in Article 48(6) of this Regulation on the performance evaluation report of the manufacturer. The EU reference laboratory shall provide a scientific opinion within 60 days. The scientific opinion of the EU reference laboratory and, where the procedure laid down in Article 48(6) is applicable, the views of the experts consulted, and any possible updates 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 EU reference laboratory, and, where applicable, to the views expressed by the experts consulted in accordance with Article 48(6), when making its decision. The notified body shall not deliver the certificate if the scientific opinion of the EU reference laboratory is unfavourable;
(k)
for companion diagnostics, seek the opinion, on the basis of the draft summary of safety and performance and the draft instructions for use, of one of the competent authorities designated by the Member States in accordance with Directive 2001/83/EC or the EMA (either of which to be hereinafter referred to as ‘the medicinal products authority consulted’ depending on which has been consulted under this point) on the suitability of the device in relation to the medicinal product concerned. Where the medicinal product falls exclusively within the scope of the Annex of Regulation (EC) No 726/2004, the notified body shall consult the EMA. If the medicinal product concerned is already authorised, or if an application for its authorisation has been submitted, the notified body shall consult the medicinal products competent authority, or the EMA, that is responsible for the authorisation. The medicinal products authority consulted shall deliver its opinion within 60 days of receipt of all the necessary documentation. This 60-day period may be extended once for a further 60 days on justified grounds. The 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 opinion expressed by the medicinal products authority consulted when making its decision. It shall convey its final decision to the medicinal products authority consulted; and
(l)
draw up an EU type-examination report on the results of the assessments and tests carried out, and scientific opinions provided under, points (a) to (k), including a performance evaluation assessment report for class C or class D devices or covered by the third indent of Section 2. |
|
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 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. |
|
5. |
Changes to the type
|
|
6. |
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, 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,
—
information on the changes referred to in Section 5,
—
copies of EU type-examination certificates, scientific opinions and reports and their additions/supplements.
Section 7 of Annex IX shall apply. |
ANNEX XI
CONFORMITY ASSESSMENT BASED ON PRODUCTION QUALITY ASSURANCE
|
1. |
The manufacturer shall ensure that the quality management system approved for the manufacture of the devices concerned is implemented, shall carry out final verification, as specified in Section 3, and shall be subject to the surveillance referred to in Section 4. |
|
2. |
When the manufacturer fulfils the obligations laid down in Section 1, it shall draw up and keep an EU declaration of conformity in accordance with Article 17 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 meets the requirements of this Regulation which apply to the device, and in the case of class C and class D devices that undergo a type examination, conforms to the type described in the EU type-examination certificate. |
|
3. |
Quality management system
|
|
4. |
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. |
|
5. |
Verification of manufactured class D devices
|
|
6. |
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 after the last device has been placed on the market, keep at the disposal of the competent authorities:
—
the EU declaration of conformity,
—
the documentation referred to in the fifth indent of Section 2.1 of Annex IX,
—
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,
—
information on the changes referred to in Section 2.4 of Annex IX, and
—
the decisions and reports from the notified body as referred to in Sections 2.3., 3.3. and 3.4. of Annex IX.
Section 7 of Annex IX shall apply. |
ANNEX XII
CERTIFICATES ISSUED BY A NOTIFIED BODY
CHAPTER I
GENERAL REQUIREMENTS
Certificates shall be drawn up in one of the official languages of the Union.
Each certificate shall refer to only one conformity assessment procedure.
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 27.
The scope of the certificates shall unambiguously describe the device or devices covered:
EU technical documentation assessment certificates and EU type-examination certificates shall include a clear identification, including the name, model and type, of the device or devices, the intended purpose as indicated 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 24(6).
EU quality management system certificates and EU production quality assurance certificates shall include the identification of the devices or groups of devices, the risk classification and the intended purpose.
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.
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.
EU quality management system certificates and EU production quality assurance certificates for class A sterile devices shall include a statement that the audit by the notified body was limited to the aspects of manufacture concerned with securing and maintaining sterile conditions.
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 Article 28(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 this Annex;
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
PERFORMANCE EVALUATION, PERFORMANCE STUDIES AND POST-MARKET PERFORMANCE FOLLOW-UP
PART A
PERFORMANCE EVALUATION AND PERFORMANCE STUDIES
1. PERFORMANCE EVALUATION
Performance evaluation of a device is a continuous process by which data are assessed and analysed to demonstrate the scientific validity, analytical performance and clinical performance of that device for its intended purpose as stated by the manufacturer. To plan, continuously conduct and document a performance evaluation, the manufacturer shall establish and update a performance evaluation plan. The performance evaluation plan shall specify the characteristics and the performance of the device and the process and criteria applied to generate the necessary clinical evidence.
The performance evaluation shall be thorough and objective, considering both favourable and unfavourable data.
Its depth and extent shall be proportionate and appropriate to the characteristics of the device including the risks, risk class, performance and its intended purpose.
1.1. Performance evaluation plan
As a general rule, the performance evaluation plan shall include at least:
Where any of the above mentioned elements are not deemed appropriate in the Performance Evaluation Plan due to the specific device characteristics a justification shall be provided in the plan.
1.2. Demonstration of the scientific validity and the analytical and clinical performance:
As a general methodological principle the manufacturer shall:
1.2.1. Demonstration of the scientific validity
The manufacturer shall demonstrate the scientific validity based on one or a combination of the following sources:
The scientific validity of the analyte or marker shall be demonstrated and documented in the scientific validity report.
1.2.2. Demonstration of the analytical performance
The manufacturer shall demonstrate the analytical performance of the device in relation to all the parameters described in point (a) of Section 9.1 of Annex I, unless any omission can be justified as not applicable.
As a general rule, the analytical performance shall always be demonstrated on the basis of analytical performance studies.
For novel markers or other markers without available certified reference materials or reference measurement procedures, it may not be possible to demonstrate trueness. If there are no comparative methods, different approaches may be used if demonstrated to be appropriate, such as comparison to some other well-documented methods or the composite reference standard. In the absence of such approaches, a clinical performance study comparing performance of the novel device to the current clinical standard practice is required.
Analytical performance shall be demonstrated and documented in the analytical performance report.
1.2.3. Demonstration of the clinical performance
The manufacturer shall demonstrate the clinical performance of the device in relation to all the parameters described in point (b) of Section 9.1. of Annex I, unless any omission can be justified as not applicable.
Demonstration of the clinical performance of a device shall be based on one or a combination of the following sources:
Clinical performance studies shall be performed unless due justification is provided for relying on other sources of clinical performance data.
Clinical performance shall be demonstrated and documented in the clinical performance report.
1.3. Clinical evidence and performance evaluation report
|
1.3.1. |
The manufacturer shall assess all relevant scientific validity, analytical and clinical performance data to verify the conformity of its device with the general safety and performance requirements as referred to in Annex I. The amount and quality of that data shall allow the manufacturer to make a qualified assessment whether the device will achieve the intended clinical benefit or benefits and safety, when used as intended by the manufacturer. The data and conclusions drawn from this assessment shall constitute the clinical evidence for the device. The clinical evidence shall scientifically demonstrate that the intended clinical benefit or benefits and safety will be achieved according to the state of the art in medicine. |
|
1.3.2. |
Performance evaluation report The clinical evidence shall be documented in a performance evaluation report. This report shall include the scientific validity report, the analytical performance report, the clinical performance report and an assessment of those reports allowing demonstration of the clinical evidence. The performance evaluation report shall in particular include:
—
the justification for the approach taken to gather the clinical evidence;
—
the literature search methodology and the literature search protocol and literature search report of a literature review;
—
the technology on which the device is based, the intended purpose of the device and any claims made about the device's performance or safety;
—
the nature and extent of the scientific validity and the analytical and clinical performance data that has been evaluated;
—
the clinical evidence as the acceptable performances against the state of the art in medicine;
—
any new conclusions derived from PMPF reports in accordance with Part B of this Annex.
|
|
1.3.3. |
The clinical evidence and its assessment in the performance evaluation report shall be updated throughout the life cycle of the device concerned with data obtained from the implementation of the manufacturer's PMPF plan in accordance with Part B of this Annex, as part of the performance evaluation and the post-market surveillance system referred to in Article 10(9). The performance evaluation report shall be part of the technical documentation. Both favourable and unfavourable data considered in the performance evaluation shall be included in the technical documentation. |
2. CLINICAL PERFORMANCE STUDIES
2.1. Purpose of clinical performance studies
The purpose of clinical performance studies is to establish or confirm aspects of device performance which cannot be determined by analytical performance studies, literature and/or previous experience gained by routine diagnostic testing. This information is used to demonstrate compliance with the relevant general safety and performance requirements with respect to clinical performance. When clinical performance studies are conducted, the data obtained shall be used in the performance evaluation process and be part of the clinical evidence for the device.
2.2. Ethical considerations for clinical performance studies
Each step in the clinical performance study, 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.
2.3. Methods for clinical performance studies
2.3.1. Clinical performance study design type
Clinical performance studies shall be designed in such a way as to maximize the relevance of the data while minimising potential bias.
2.3.2. Clinical performance study plan
Clinical performance studies shall be performed on the basis of a clinical performance study plan (CPSP).
The CPSP shall define the rationale, objectives, design and proposed analysis, methodology, monitoring, conduct and record-keeping of the clinical performance study. It shall contain in particular the following information:
the single identification number of the clinical performance study, as referred to in Article 66(1);
identification of the sponsor, including the name, address of the registered place of business and contact details of the sponsor and, if applicable, the name, address of the registered place of business and contact details of its contact person or legal representative pursuant to Article 58(4) established in the Union;
information on the investigator or investigators, namely principal, coordinating or other investigator; qualifications; contact details, and investigation site or sites, such as number, qualification, contact details and, in the case of devices for self-testing, the location and number of lay persons involved;
the starting date and scheduled duration for the clinical performance study;
identification and description of the device, its intended purpose, the analyte or analytes or marker or markers, the metrological traceability, and the manufacturer;
information about the type of specimens under investigation;
overall synopsis of the clinical performance study, its design type, such as observational, interventional, together with the objectives and hypotheses of the study, reference to the current state of the art in diagnosis and/or medicine;
a description of the expected risks and benefits of the device and of the clinical performance study in the context of the state of the art in clinical practice, and with the exception of studies using left-over samples, the medical procedures involved and patient management;
the instructions for use of the device or test protocol, the necessary training and experience of the user, the appropriate calibration procedures and means of control, the indication of any other devices, medical devices, medicinal product or other articles to be included or excluded and the specifications on any comparator or comparative method used as reference;
description of and justification for the design of the clinical performance study, its scientific robustness and validity, including the statistical design, and details of measures to be taken to minimise bias, such as randomisation, and management of potential confounding factors;
the analytical performance in accordance with point (a) of Section 9.1 of Chapter I of Annex I with justification for any omission;
parameters of clinical performance in accordance with point (b) of Section 9.1 of Annex I to be determined, with justification for any omission; and with the exception of studies using left-over samples the specified clinical outcomes/endpoints (primary/secondary) used with a justification and the potential implications for individual health and/or public health management decisions;
information on the performance study population: specifications of the subjects, selection criteria, size of performance study population, representativity of target population and, if applicable, information on vulnerable subjects involved, such as children, pregnant women, immuno-compromised or elderly subjects;
information on use of data out of left over specimens banks, genetic or tissue banks, patient or disease registries etc. with description of reliability and representativity and statistical analysis approach; assurance of relevant method for determining the true clinical status of patient specimens;
monitoring plan;
data management;
decision algorithms;
policy regarding any amendments, including those in accordance with Article 71, to or deviations from the CPSP, with a clear prohibition of use of waivers from the CPSP;
accountability regarding the device, in particular control of access to the device, follow-up in relation to the device used in the clinical performance study and the return of unused, expired or malfunctioning devices;
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 performance studies as well as with the applicable regulatory requirements;
description of the informed consent process, including a copy of the patient information sheet and consent forms;
procedures for safety recording and reporting, including definitions of recordable and reportable events, and procedures and timelines for reporting;
criteria and procedures for suspension or early termination of the clinical performance study;
criteria and procedures for follow up of subjects following completion of a performance study, procedures for follow up of subjects in the case of suspension or early termination, procedures for follow up of subjects who have withdrawn their consent and procedures for subjects lost to follow up;
procedures for communication of test results outside the study, including communication of test results to the performance study subjects;
policy as regards the establishment of the clinical performance study report and publication of results in accordance with the legal requirements and the ethical principles referred to in Section 2.2;
list of the technical and functional features of the device indicating those that are covered by the performance study;
bibliography.
If part of the information referred to in the second paragraph is submitted in a separate document, it shall be referenced in the CPSP. For studies using left-over samples, points (u), (x), (y) and (z) shall not apply.
Where any of the elements referred to in the second paragraph are not deemed appropriate for inclusion in the CPSP due to the specific study design chosen, such as use of left-over samples versus interventional clinical performance studies, a justification shall be provided.
2.3.3. Clinical performance study report
A clinical performance study report, signed by a medical practitioner or any other authorised person responsible, shall contain documented information on the clinical performance study protocol plan, results and conclusions of the clinical performance study, including negative findings. The results and conclusions shall be transparent, free of bias and clinically relevant. The report shall contain sufficient information to enable it to be understood by an independent party without reference to other documents. The report shall also include as appropriate any protocol amendments or deviations, and data exclusions with the appropriate rationale.
3. OTHER PERFORMANCE STUDIES
By analogy, the performance study plan referred to in Section 2.3.2, and the performance study report, referred to in Section 2.3.3, shall be documented for other performance studies than clinical performance studies.
PART B
POST-MARKET PERFORMANCE FOLLOW-UP
|
4. |
PMPF shall be understood to be a continuous process that updates the performance evaluation referred to in Article 56 and Part A of this Annex and shall be specifically addressed in the manufacturer's post-market surveillance plan. When conducting PMPF, the manufacturer shall proactively collect and evaluate performance and relevant scientific data from the use 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, performance and scientific validity throughout the expected lifetime of the device, of ensuring the continued acceptability of the benefit-risk ratio and of detecting emerging risks on the basis of factual evidence. |
|
5. |
PMPF shall be performed pursuant to a documented method laid down in a PMPF plan.
|
|
6. |
The manufacturer shall analyse the findings of the PMPF and document the results in a PMPF evaluation report that shall update the performance evaluation report and be part of the technical documentation. |
|
7. |
The conclusions of the PMPF evaluation report shall be taken into account for the performance evaluation referred to in Article 56 and Part A of this Annex and in the risk management referred to in Section 3 of Annex I. If, through the PMPF, the need for preventive and/or corrective measures has been identified, the manufacturer shall implement them. |
|
8. |
If PMPF is not deemed appropriate for a specific device then a justification shall be provided and documented within the performance evaluation report. |
ANNEX XIV
INTERVENTIONAL CLINICAL PERFORMANCE STUDIES AND CERTAIN OTHER PERFORMANCE STUDIES
CHAPTER I
DOCUMENTATION REGARDING THE APPLICATION FOR INTERVENTIONAL CLINICAL PERFORMANCE STUDIES AND OTHER PERFORMANCE STUDIES INVOLVING RISKS FOR THE SUBJECTS OF THE STUDIES
For devices intended to be used in the context of interventional clinical performance studies or other performance studies involving risks for the subjects of the studies, the sponsor shall draw up and submit the application in accordance with Article 58 accompanied by the following documents:
Application form
The application form shall be duly filled in, containing the following information:
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 58(4) 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 performance evaluation and, if applicable, of its authorised representative;
title of the performance study;
single identification number in accordance with Article 66(1);
status of the performance study, such as. the first submission, resubmission, significant amendment;
details and/ or reference to the performance study plan, such as including details of the design phase of the performance study;
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 performance study is to be conducted as part of a multicentre or multinational study at the time of application;
brief description of the device for performance study, its classification and other information necessary for the identification of the device and device type;
summary of the performance study plan;
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 performance study in accordance with the performance study plan;
details of the anticipated start date and duration of the performance study;
details to identify the notified body, if already involved at the stage of application for the performance study;
confirmation that the sponsor is aware that the competent authority may contact the ethics committee that is assessing or has assessed the application;
the statement referred to in Section 4.1.
Investigator's brochure
The investigator's brochure (IB) shall contain the information on the device for performance study that is relevant for the study 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 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.
Analytical performance.
Existing clinical data, in particular:
Summary of the benefit-risk analysis and the risk management, including information regarding known or foreseeable risks and warnings.
In the case of devices that include tissues, cells and substances of human, animal or microbial origins detailed information on the tissues, cells and substances, and on the compliance with the relevant general safety and performance requirements and the specific risk management in relation to those tissues, cells and substances.
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 performance study and in particular information on any deviation from normal clinical practice.
Performance study plan as referred to in Sections 2 and 3 of Annex XIII.
Other information
A signed statement by the natural or legal person responsible for the manufacture of the device for performance study that the device in question conforms to the general safety and performance requirements laid down in Annex I apart from the aspects covered by the clinical performance study and that, with regard to those aspects, every precaution has been taken to protect the health and safety of the subject.
Where applicable according to national law, a copy of the opinion or opinions of the ethics committee or committees concerned. Where under 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.
Proof of insurance cover or indemnification of subjects in case of injury, pursuant to Article 65 and the corresponding national law.
Documents to be used to obtain informed consent, including the patient information sheet and the informed consent document.
Description of the arrangements to comply with the applicable rules on the protection and confidentiality of personal data, in particular:
Full details of the available technical documentation, for example detailed risk analysis/management documentation or specific test reports shall be submitted to the competent authority reviewing an application upon request.
CHAPTER II
OTHER OBLIGATIONS OF THE SPONSOR
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 I of this Annex. If the sponsor is not the natural or legal person responsible for the manufacture of the device intended for performance study, that obligation may be fulfilled by that person on behalf of the sponsor.
The sponsor shall have an agreement in place to ensure that any serious adverse events or any other event as referred to in Article 76(2) are reported by the investigator or investigators to the sponsor in a timely manner.
The documentation mentioned in this Annex shall be kept for a period of time of at least 10 years after the clinical performance study with the device in question has ended, or, in the event that the device is subsequently placed on the market, for at least 10 years after the last device has been placed on the market.
Each Member State shall require that the documentation referred to in this Annex is kept at the disposal of the competent authorities for the period indicated in the first subparagraph in case the sponsor, or his contact person, established within its territory, goes bankrupt or ceases its activity prior to the end of this period.
The sponsor shall appoint a monitor that is independent of the investigation site to ensure that the clinical performance study is conducted in accordance with the Clinical Performance Study Plan, the principles of good clinical practice and this Regulation.
The sponsor shall complete the follow-up of investigation subjects.
ANNEX XV
CORRELATION TABLE
|
Directive 98/79/EC |
This Regulation |
|
Article 1(1) |
Article 1(1) |
|
Article 1(2) |
Article 2 |
|
Article 1(3) |
points (54) and (55) of Article 2 |
|
Article 1(4) |
— |
|
Article 1(5) |
Article 5(4) and (5) |
|
Article 1(6) |
Article 1(9) |
|
Article 1(7) |
Article 1(5) |
|
Article 2 |
Article 5(1) |
|
Article 3 |
Article 5(2) |
|
Article 4(1) |
Article 21 |
|
Article 4(2) |
Article 19(1) and (2) |
|
Article 4(3) |
Article 19(3) |
|
Article 4(4) |
Article 10(10) |
|
Article 4(5) |
Article 18(6) |
|
Article 5(1) |
Article 8(1) |
|
Article 5(2) |
— |
|
Article 5(3) |
Article 9 |
|
Article 6 |
— |
|
Article 7 |
Article 107 |
|
Article 8 |
Articles 89 and 92 |
|
Article 9(1) first subparagraph |
Article 48(10) first subparagraph |
|
Article 9(1) second subparagraph |
Article 48(3) second subparagraph, Article 48(7) second subparagraph and Article 48(9) second subparagraph |
|
Article 9(2) |
Article 48(3) to (6) |
|
Article 9(3) |
Article 48(3) to (9) |
|
Article 9(4) |
Article 5(6) |
|
Article 9(5) |
— |
|
Article 9(6) |
Article 11(3) and (4) |
|
Article 9(7) |
Article 10(7) |
|
Article 9(8) |
Article 49(1) |
|
Article 9(9) |
Article 49(4) |
|
Article 9(10) |
Article 51(2) |
|
Article 9(11) |
Article 48(12) |
|
Article 9(12) |
Article 54(1) |
|
Article 9(13) |
Article 48(2) |
|
Article 10(1) and (2), second sentence of Article 10(3) and Article 10(4) |
Articles 26(3), 27 and 28 |
|
Article 10(3), first sentence |
Article 11(1) |
|
Article 11(1) |
Articles 82(1) and 84(2) |
|
Article 11(2) |
Article 82(10) and Article 82(11) first subparagraph |
|
Article 11(3) |
Article 84(7) |
|
Article 11(4) |
— |
|
Article 11(5) |
Article 86 |
|
Article 12 |
Article 30 |
|
Article 13 |
Article 93 |
|
Article 14(1)(a) |
— |
|
Article 14(1)(b) |
Article 47(3) and (6) |
|
Article 14(2) |
— |
|
Article 14(3) |
— |
|
Article 15(1) |
Article 38 and Article 39 |
|
Article 15(2) |
Article 32 |
|
Article 15(3) |
Article 40(2) and (4) |
|
Article 15(4) |
— |
|
Article 15(5) |
Article 51(5) |
|
Article 15(6) |
Article 51(4) |
|
Article 15(7) |
Article 34(2) and Article 40(2) |
|
Article 16 |
Article 18 |
|
Article 17 |
Articles 89 to 92 |
|
Article 18 |
Article 94 |
|
Article 19 |
Article 102 |
|
Article 20 |
Article 97 |
|
Article 21 |
— |
|
Article 22 |
— |
|
Article 23 |
— |
|
Article 24 |
— |
( 1 ) Directive 2006/42/EC of the European Parliament and of the Council of 17 May 2006 on machinery (OJ L 157, 9.6.2006, p. 24).
( 2 ) Directive 2011/24/EU of the European Parliament and of the Council of 9 March 2011 on the application of patients' rights in cross-border healthcare (OJ L 88, 4.4.2011, p. 45).
( 3 ) Commission Recommendation of 6 May 2003 concerning the definition of micro, small and medium-sized enterprises (OJ L 124, 20.5.2003, p. 36).
( 4 ) Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use (OJ L 311, 28.11.2001, p. 67).
( 5 ) 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).
( 6 ) 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).
( 7 ) 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 136, 29.5.2007, p. 3).
( 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 ) 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).