ANNEX VII

Requirements to be met by notified bodies

1. ORGANISATIONAL AND GENERAL REQUIREMENTS

1.1. Legal status and organisational structure

1.1.1. Each notified body shall be established under the national law of a Member State, or under the law of a third country with which the Union has concluded an agreement in this respect. Its legal personality and status shall be fully documented. Such documentation shall include information about ownership and the legal or natural persons exercising control over the notified body.

1.1.2. If the notified body is a legal entity that is part of a larger organisation, the activities of that organisation as well as its organisational structure and governance, and the relationship with the notified body shall be clearly documented. In such cases, the requirements of Section 1.2 are applicable to both the notified body and the organisation to which it belongs.

1.1.3. If a notified body wholly or partly owns legal entities established in a Member State or in a third country or is owned by another legal entity, the activities and responsibilities of those entities, as well as their legal and operational relationships with the notified body, shall be clearly defined and documented. Personnel of those entities performing conformity assessment activities under this Regulation shall be subject to the applicable requirements of this Regulation.

1.1.4. The organisational structure, allocation of responsibilities, reporting lines and operation of the notified body shall be such that they ensure that there is confidence in the performance by the notified body and in the results of the conformity assessment activities it conducts.

1.1.5 The notified body shall clearly document its organisational structure and the functions, responsibilities and authority of its top-level management and of other personnel who may have an influence upon the performance by the notified body and upon the results of its conformity assessment activities.

1.1.6 The notified body shall identify the persons in top-level management that have overall authority and responsibility for each of the following:

the provision of adequate resources for conformity assessment activities;
the development of procedures and policies for the operation of the notified body;
the supervision of implementation of the procedures, policies and
quality management systems of the notified body;
the supervision of the notified body’s finances;
the activities and decisions taken by the notified body, including
contractual agreements;
the delegation of authority to personnel and/or committees, where
necessary, for the performance of defined activities;
the interaction with the authority responsible for notified bodies and the obligations regarding communications with other competent
authorities, the Commission and other notified bodies.

1.2. Independence and impartiality

1.2.1. The notified body shall be a third-party body that is independent of the manufacturer of the device in relation to which it performs conformity assessment activities. The notified body shall also be independent of any other economic operator having an interest in the device as well as of any competitors of the manufacturer. This does not preclude the notified body from carrying out conformity assessment activities for competing manufacturers.

1.2.2. The notified body shall be organised and operated so as to safeguard the independence, objectivity and impartiality of its activities. The notified body shall document and implement a structure and procedures for safeguarding impartiality and for promoting and applying the principles of impartiality throughout its organisation, personnel and assessment activities. Such procedures shall provide for the identification, investigation and resolution of any case in which a conflict of interest may arise, including involvement in consultancy services in the field of devices prior to taking up employment with the notified body. The investigation, outcome and its resolution shall be documented.

1.2.3. The notified body, its top-level management and the personnel responsible for carrying out the conformity assessment tasks shall not:

(a)be the designer, manufacturer, supplier, installer, purchaser, owneror 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 asregards the design, construction, marketing or maintenance of devices or processes under assessment, and
(e)be linked to any organisation which itself provides consultancy services as referred to in point (d). Such restriction does not preclude general training activities that are not client specific and that relate to regulation of devices or to related standards.

1.2.4. Involvement in consultancy services in the field of devices prior to taking up employment with a notified body shall be fully documented at the time of employment and potential conflicts of interest shall be monitored and resolved in accordance with this Annex. Personnel who were formerly employed by a specific client, or provided consultancy services in the field of devices to that specific client prior to taking up employment with a notified body, shall not be assigned for conformity assessment activities for that specific client or companies belonging to the same group for a period of three years.

1.2.5. The impartiality of notified bodies, of their top-level management and of the assessment personnel shall be guaranteed. The level of the remuneration of the top-level management and assessment personnel of a notified body and subcontractors, involved in assessment activities shall not depend on the results of the assessments. Notified bodies shall make publicly available the declarations of interest of their top-level management.

1.2.6. If a notified body is owned by a public entity or institution, independence and absence of any conflict of interest shall be ensured and documented between, on the one hand, the authority responsible for notified bodies and/or the competent authority and, on the other hand, the notified body.

1.2.7. The notified body shall ensure and document that the activities of its subsidiaries or subcontractors, or of any associated body, including the activities of its owners do not affect its independence, impartiality or the objectivity of its conformity assessment activities.

1.2.8. The notified body shall operate in accordance with a set of consistent, fair and reasonable terms and conditions, taking into account the interests of small and medium-sized enterprises as defined in Recommendation 2003/361/EC in relation to fees.

1.2.9. The requirements laid down in this Section in no way preclude exchanges of technical information and regulatory guidance between a notified body and a manufacturer applying for conformity assessment.

1.3. Confidentiality

1.3.1. The notified body shall have documented procedures in place ensuring that its personnel, committees, subsidiaries, subcontractors, and any associated body or personnel of external bodies respect the confidentiality of the information which comes into its possession during the performance of conformity assessment activities, except when disclosure is required by law.

1.3.2. The personnel of a notified body shall observe professional secrecy in carrying out their tasks under this Regulation or any provision of national law giving effect to it, except in relation to the authorities responsible for notified bodies, competent authorities for medical devices in the Member States or the Commission. Proprietary rights shall be protected. The notified body shall have documented procedures in place in respect of the requirements of this Section.

1.4. Liability

1.4.1. The notified body shall take out appropriate liability insurance for its conformity assessment activities, unless liability is assumed by the Member State in question in accordance with national law or that Member State is directly responsible for the conformity assessment.

1.4.2. The scope and overall financial value of the liability insurance shall correspond to the level and geographic scope of activities of the notified body and be commensurate with the risk profile of the devices certified by the notified body. The liability insurance shall cover cases where the notified body may be obliged to withdraw, restrict or suspend certificates.

1.5. Financial requirements

The notified body shall have at its disposal the financial resources required to conduct its conformity assessment activities within its scope of designation and related business operations. It shall document and provide evidence of its financial capacity and its long-term economic viability, taking into account, where relevant, any specific circumstances during an initial start-up phase.

1.6. Participation in coordination activities

1.6.1. The notified body shall participate in, or ensure that its assessment personnel is informed of, any relevant standardisation activities and in the activities of the notified body coordination group referred to in Article 49 and that its assessment and decision-making personnel are informed of all relevant legislation, guidance and best practice documents adopted in the framework of this Regulation.

1.6.2. The notified body shall take into consideration guidance and best practice documents.

2. QUALITY MANAGEMENT REQUIREMENTS

2.1. The notified body shall establish, document, implement, maintain and operate a quality management system that is appropriate to the nature, area and scale of its conformity assessment activities and is capable of supporting and demonstrating the consistent fulfilment of the requirements of this Regulation.

2.2. The quality management system of the notified body shall address at least the following:

management system structure and documentation, including policies and objectives for its activities;
policies for assignment of activities and responsibilities to personnel;
assessment and decision-making processes in accordance with the tasks, responsibilities and role of the notified body’s personnel and top-level management;
the planning, conduct, evaluation and, if necessary, adaptation of its
conformity assessment procedures;
control of documents;
control of records;
management reviews;
internal audits;
corrective and preventive actions;
complaints and appeals; and
continuous training.

Where documents are used in various languages, the notified body shall ensure and control that they have the same content.

2.3. The top-level management of the notified body shall ensure that the quality management system is fully understood, implemented and maintained throughout the notified body organisation including subsidiaries and subcontractors involved in conformity assessment activities pursuant to this Regulation.

2.4. The notified body shall require all personnel to formally commit themselves by a signature or equivalent to comply with the procedures defined by the notified body. That commitment shall cover aspects relating to confidentiality and to independence from commercial and other interests, and any existing or prior association with clients. The personnel shall be required to complete written statements indicating their compliance with confidentiality, independence and impartiality principles.

3. RESOURCE REQUIREMENTS

3.1 General

3.1.1. Notified bodies shall be capable of carrying out all the tasks falling to them under this Regulation with the highest degree of professional integrity and the requisite competence in the specific field, whether those tasks are carried out by notified bodies themselves or on their behalf and under their responsibility.

In particular, notified bodies shall have the necessary personnel and possess or have access to all equipment, facilities and competence needed to perform properly the technical, scientific and administrative tasks entailed in the conformity assessment activities in relation to which they have been designated.

Such requirement presupposes at all times and for each conformity assessment procedure and each type of devices in relation to which they have been designated, that the notified body has permanent availability of sufficient administrative, technical and scientific personnel who possess experience and knowledge relating to the relevant devices and the corresponding technologies. Such personnel shall be in sufficient numbers to ensure that the notified body in question can perform the conformity assessment tasks, including the assessment of the medical functionality, clinical evaluations and the performance and safety of devices, for which it has been designated, having regard to the requirements of this Regulation, in particular, those set out in Annex I.

A notified body’s cumulative competences shall be such as to enable it to assess the types of devices for which it is designated. The notified body shall have sufficient internal competence to critically evaluate assessments conducted by external expertise. Tasks which a notified body is precluded from subcontracting are set out in Section 4.1.

Personnel involved in the management of the operation of a notified body’s conformity assessment activities for devices shall have appropriate knowledge to set up and operate a system for the selection of assessment and verification staff, for verification of their competence, for authorisation and allocation of their tasks, for organisation of their initial and ongoing training and for the assignment of their duties and the monitoring of those staff, in order to ensure that personnel who carry out and perform assessment and verification operations are competent to fulfil the tasks required of them.

The notified body shall identify at least one individual within its top-level management as having overall responsibility for all conformity assessment activities in relation to devices.

3.1.2. The notified body shall ensure that personnel involved in conformity assessment activities maintain their qualification and expertise by implementing a system for exchange of experience and a continuous training and education programme.

3.1.3. The notified body shall clearly document the extent and limits of duties and responsibilities and the level of authorisation of the personnel, including any subcontractors and external experts, involved in conformity assessment activities and inform those personnel accordingly.

3.2. Qualification criteria in relation to personnel

3.2.1. The Notified Body shall establish and document qualification criteria and procedures for selection and authorisation of persons involved in conformity assessment activities, including as regards knowledge, experience and other competence required, and the required initial and ongoing training. The qualification criteria shall address the various functions within the conformity assessment process, such as auditing, product evaluation or testing, technical documentation review and decision-making, as well as the devices, technologies and areas, such as biocompatibility, sterilisation, tissues and cells of human and animal origin and clinical evaluation, covered by the scope of designation.

3.2.2. The qualification criteria referred to in Section 3.2.1 shall refer to the scope of a notified body’s designation in accordance with the scope description used by the Member State for the notification referred to in Article 42(3), providing a sufficient level of detail for the required qualification within the subdivisions of the scope description.

Specific qualification criteria shall be defined at least for the assessment of:

the pre-clinical evaluation,
clinical evaluation,
tissues and cells of human and animal origin,
functional safety,
software,
packaging,
devices that incorporate as an integral part a medicinal product,
devices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body and
the different types of sterilisation processes.

3.2.3. The personnel responsible for establishing qualification criteria and for authorising other personnel to perform specific conformity assessment activities shall be employed by the notified body itself and shall not be external experts or subcontracted. They shall have proven knowledge and experience in all of the following:

Union devices legislation and relevant guidance documents;
the conformity assessment procedures provided for in this Regulation;
a broad base of knowledge of device technologies and the design and manufacture of devices;
the notified body’s quality management system, related procedures and the required qualification criteria;
training relevant to personnel involved in conformity assessment activities in relation to devices;
adequate experience in conformity assessments under this Regulation or previously applicable law within a notified body.

3.2.4. The notified body shall have permanent availability of personnel with relevant clinical expertise and where possible such personnel shall be employed by the notified body itself. Such personnel shall be integrated throughout the notified body’s assessment and decision-making process in order to:

identify when specialist input is required for the assessment of the clinical evaluation conducted by the manufacturer and identify appropriately qualified experts;
appropriately train external clinical experts in the relevant requirements of this Regulation, CS, guidance and harmonised standards and
ensure that the external clinical experts are fully aware of the context and implications of their assessment and the advice they provide;
be able to review and scientifically challenge the clinical data contained within the clinical evaluation, and any associated clinical investigations, and appropriately guide external clinical experts in the assessment of the clinical evaluation presented by the manufacturer;
be able to scientifically evaluate and, if necessary, challenge the clinical evaluation presented, and the results of the external clinical experts’ assessment of the manufacturer’s clinical evaluation;
be able to ascertain the comparability and consistency of the assessments of clinical evaluations conducted by clinical experts;
be able to make an assessment of the manufacturer’s clinical evaluation and a clinical judgement of the opinion provided by any external expert and make a recommendation to the notified body’s decision maker; and
be able to draw up records and reports demonstrating that the relevant conformity assessment activities have been appropriately carried out.

3.2.5. The personnel responsible for carrying out product-related reviews (product reviewers), such as technical documentation reviews or type examination, including aspects such as clinical evaluation, biological safety, sterilisation and software validation, shall have all of the following proven qualifications:

successful completion of a university or a technical college degree orequivalent qualification in relevant studies, e.g. medicine, pharmacy,engineering or other relevant sciences;
four years’ professional experience in the field of healthcare products or related activities, such as in manufacturing, auditing or research, of which two years shall be in the design, manufacture, testing or use of the device or technology to be assessed or related to the scientific aspects to be assessed;
knowledge of device legislation, including the general safety and performance requirements set out in Annex I;
appropriate knowledge and experience of relevant harmonised standards, CS and guidance documents;
appropriate knowledge and experience of risk management and related device standards and guidance documents;
appropriate knowledge and experience of clinical evaluation;
appropriate knowledge of the devices which they are assessing;
appropriate knowledge and experience of the conformity assessment procedures laid down in Annexes IX to XI, in particular of the aspects of those procedures for which they are responsible, and adequate
authorisation for carrying out those assessments;
the ability to draw up records and reports demonstrating that the
relevant conformity assessment activities have been appropriately
carried out.

3.2.6. The personnel responsible for carrying out audits of the manufacturer’s quality management system (site auditors) shall have all of the following proven qualifications:

successful completion of a university or a technical college degree orequivalent qualification in relevant studies, such as medicine, pharmacy, engineering or other relevant sciences;
four years’ professional experience in the field of healthcare products or related activities, such as in manufacturing, auditing or research, of which two years shall be in the area of quality management;
appropriate knowledge of devices legislation as well as related harmonised standards, CS and guidance documents;
appropriate knowledge and experience of risk management and related device standards and guidance documents;
appropriate knowledge of quality management systems and related
standards and guidance documents;
appropriate knowledge and experience of the conformity assessment procedures laid down in Annexes IX to XI, in particular of the aspects of those procedures for which they are responsible, and adequate authorisation for carrying out those audits;
training in auditing techniques enabling them to challenge quality management systems;
the ability to draw up records and reports demonstrating that the relevant conformity assessment activities have been appropriately carried out.

3.2.7. The personnel with overall responsibility for final reviews and decision-making on certification shall be employed by the notified body itself and shall not be external experts or be subcontracted. Those personnel shall, as a group, have proven knowledge and comprehensive experience of all of the following:

devices legislation and relevant guidance documents;
the device conformity assessments relevant to this Regulation;
the types of qualifications, experience and expertise relevant to device conformity assessment;
a broad base of knowledge of device technologies, including sufficient experience of conformity assessment of devices being reviewed for certification, the device industry and the design and manufacture of devices;
the notified body’s quality management system, related procedures and the required qualifications for personnel involved;
the ability to draw up records and reports demonstrating that the conformity assessment activities have been appropriately carried out.

3.3. Documentation of qualification, training and authorisation of personnel

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.

3.3.2. For all of its personnel referred to in Sections 3.2.3 to 3.2.7, the notified body shall establish and maintain up to date:

a matrix detailing the authorisations and responsibilities of the personnel in respect of conformity assessment activities; and
records attesting to the required knowledge and experience for the conformity assessment activity for which they are authorised. The records shall contain a rationale for defining the scope of the responsibilities for each of the assessment personnel and records of the conformity assessment activities carried out by each of them.

3.4. Subcontractors and external experts

3.4.1. Notified bodies may, without prejudice to Section 3.2, subcontract certain clearly defined component parts of a conformity assessment activity.

The subcontracting of the auditing of quality management systems or of product related reviews as a whole shall not be permitted; nevertheless parts of those activities may be conducted by subcontractors and external auditors and experts working on behalf of the notified body. The notified body in question shall retain full responsibility for being able to produce appropriate evidence of the competence of subcontractors and experts to fulfil their specific tasks, for making a decision based on a subcontractor’s assessment and for the work conducted by subcontractors and experts on its behalf.

The following activities may not be subcontracted by notified bodies:

review of the qualifications and monitoring of the performance of external experts;
auditing and certification activities where the subcontracting in question is to auditing or certification organisations;
allocation of work to external experts for specific conformity assessment activities; and
final review and decision making functions.

3.4.2 Where a notified body subcontracts certain conformity assessment activities either to an organisation or an individual, it shall have a policy describing the conditions under which subcontracting may take place, and shall ensure that:

the subcontractor meets the relevant requirements of this Annex;
subcontractors and external experts do not further subcontract work to organisations or personnel; and
the natural or legal person that applied for conformity assessment has been informed of the requirements referred to in the first and second indent.

Any subcontracting or consultation of external personnel shall be properly documented, shall not involve any intermediaries and shall be subject to a written agreement covering, among other things, confidentiality and conflicts of interest. The notified body in question shall take full responsibility for the tasks performed by subcontractors.

3.4.3. Where subcontractors or external experts are used in the context of a conformity assessment, in particular regarding novel, invasive and implantable devices or technologies, the notified body in question shall have internal competence in each product area for which it is designated that is adequate for the purpose of leading the overall conformity assessment, verifying the appropriateness and validity of expert opinions and making decisions on certification.

3.5. Monitoring of competences, training and exchange of experience

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.

3.5.2. Notified bodies shall review at regular intervals, the competence of their personnel, identify training needs and draw up a training plan to maintain the required level of qualification and knowledge of individual personnel. That review shall at a minimum, verify that personnel:

are aware of Union and national law in force on devices, relevant harmonised standards, CS, guidance documents and the results of the coordination activities referred to in Section 1.6; and
take part in the internal exchange of experience and the continuous training and education programme referred to in Section 3.1.2.

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:

(a)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;
(b)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;
(c)have documented procedures in relation to advertising of their conformity assessment services. Those procedures shall ensure that advertising or promotional activities in no way imply or are capableof 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;
(d)have documented procedures requiring the review of pre-application information, including the preliminary verification thatthe product is covered by this Regulation and its classification, prior to issuing any quotation to the manufacturer relating to a specific conformity assessment; and
(e)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:

(a)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,
(b)the verification of the qualification of products covered by those applications as devices and their respective classifications,
(c)whether the conformity assessment procedures chosen by the applicant are applicable to the device in question under this Regulation,
(d)the ability of the notified body to assess the application based on its designation, and
(e)the availability of sufficient and appropriate resources.

The outcome of each review of an application shall be documented. Refusals or withdrawals of applications shall be notified to the electronic system referred to in Article 57 and shall be accessible to other notified bodies.

4.4. Allocation of resources

The notified body shall have documented procedures to ensure that all conformity assessment activities are conducted by appropriately authorised and qualified personnel who are sufficiently experienced in the evaluation of the devices, systems and processes and related documentation that are subject to conformity assessment.

For each application, the notified body shall determine the resources needed and identify one individual responsible for ensuring that the assessment of that application is conducted in accordance with the relevant procedures and for ensuring that the appropriate resources including personnel are utilised for each of the tasks of the assessment. The allocation of tasks required to be carried out as part of the conformity assessment and any changes subsequently made to this allocation shall be documented.

4.5. Conformity assessment activities

4.5.1. General

The notified body and its personnel shall carry out the conformity assessment activities with the highest degree of professional integrity and the requisite technical and scientific competence in the specific fields.

The notified body shall have expertise, facilities and documented procedures that are sufficient to effectively conduct the conformity assessment activities for which the notified body in question is designated, taking account of the relevant requirements set out in Annexes IX to XI, and in particular all of the following requirements:

appropriately plan the conduct of each individual project,
ensure that the composition of the assessment teams is such that there is sufficient experience in relation to the technology concerned, and that there is continuous objectivity and independence, and to provide for rotation of the members of the assessment team at appropriate intervals,
specify the rationale for fixing time limits for completion of conformity assessment activities,
assess the manufacturer’s technical documentation and the solutions adopted to meet the requirements laid down in Annex I,
review the manufacturer’s procedures and documentation relating to the evaluation of pre-clinical aspects,
review the manufacturer’s procedures and documentation relating to clinical evaluation,
address the interface between the manufacturer’s risk management
process and its appraisal and analysis of the pre-clinical and clinical
evaluation and to evaluate their relevance for the demonstration of
conformity with the relevant requirements in Annex I,
carry out the specific procedures referred to in Sections 5.2 to 5.4 of
Annex IX,
in the case of class IIa or class IIb devices, assess the technical documentation of devices selected on a representative basis,
plan and periodically carry out appropriate surveillance audits and assessments, carry out or request certain tests to verify the proper functioning of the quality management system and to perform unannounced on site audits,
relating to the sampling of devices, verify that the manufactured device is in conformity with the technical documentation; such requirements shall define the relevant sampling criteria and testing procedure prior to sampling,
evaluate and verify a manufacturer’s compliance with relevant Annexes.

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

(a)As part of the assessment of the quality management system, a notified body shall prior to an audit and in accordance with its documented procedures:
— assess the documentation submitted in accordance with the relevant conformity assessment Annex, and draw up an audit programme which clearly identifies the number and sequence of activities required to demonstrate complete coverage of a manufacturer’s qualitymanagement system and to determine whether it meets the requirements of this Regulation,
— identify links between, and allocation of responsibilities among, the various manufacturing sites, and identify relevant suppliers and/or subcontractors of the manufacturer, and consider the need to specifically audit any of those suppliers or subcontractors or both,
— clearly define, for each audit identified in the audit programme, the objectives, criteria and scope of the audit, and draw up an audit
plan that adequately addresses and takes account of the specific requirements for the devices, technologies and processes involved,
— draw up and keep up to date, for class IIa and class IIb devices, a
sampling plan for the assessment of technical documentation as referred to in Annexes II and III covering the range of such devices covered by the manufacturer’s application. That plan shall ensure that all devices covered by the certificate are sampled over the period of validity of the certificate, and
— select and assign appropriately qualified and authorised personnel for conducting the individual audits. The respective roles,responsibilities and authorities of the team members shall be clearly defined and documented.
(b)Based on the audit programme it has drawn up, the notified body shall, in accordance with its documented procedures:
— audit the manufacturer’s quality management system, in order toverify that the quality management system ensures that the devices
covered conform to the relevant provisions of this Regulation whichapply to devices at every stage, from design through final quality control to ongoing surveillance, and shall determine whether the requirements of this Regulation are met,
— based on relevant technical documentation and in order to determine whether the manufacturer meets the requirements referred to in the relevant conformity assessment Annex, review and audit the manufacturer’s processes and subsystems, in particular for:
— design and development,
— production and process controls,
— product documentation,
— purchasing controls including verification of purchased devices,— corrective and preventive actions, including for post-market surveillance, and
— PMCF,

and review and audit requirements and provisions adopted by the manufacturer, including those in relation to fulfilling the general safety and performance requirements set out in Annex I.

The documentation shall be sampled in such a manner as to reflect the risks associated with the intended use of the device, the complexity of the manufacturing technologies, the range and classes of devices produced and any available post-market surveillance information,

if not already covered by the audit programme, audit the control of processes on the premises of the manufacturer’s suppliers, when the conformity of finished devices is significantly influenced by the activity of suppliers and, in particular when the manufacturer cannot demonstrate sufficient control over its suppliers,
conduct assessments of the technical documentation based on its sampling plan and taking account of Sections 4.5.4. and 4.5.5. for pre-clinical and clinical evaluations, and
the notified body shall ensure that audit findings are appropriately and consistently classified in accordance with the requirements of this Regulation and with relevant standards, or with best practice documents developed or adopted by the MDCG.

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:

the allocation of appropriately qualified and authorised personnel for the examination of individual aspects such as use of the device, biocompatibility, clinical evaluation, risk management, and sterilisation, and
the assessment of conformity of the design with this Regulation, and for taking account of Sections 4.5.4. to 4.5.6. That assessment shall include examination of the implementation by manufacturers of incoming, in- process and final checks and the results thereof. If further tests or other evidence is required for the assessment of conformity with the requirements of this Regulation, the notified body in question shall carry out adequate physical or laboratory tests in relation to the device or request the manufacturer to carry out such tests.

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:

examine and assess the technical documentation taking account of Sections 4.5.4. to 4.5.6., and verify that the type has been manufactured in conformity with that documentation;
establish a test plan identifying all relevant and critical parameters which need to be tested by the notified body or under its responsibility;
document its rationale for the selection of those parameters;
carry out the appropriate examinations and tests in order to verify that the solutions adopted by the manufacturer meet the general safety and performance requirements set out in Annex I. Such examinations and tests shall include all tests necessary to verify that the manufacturer has in fact applied the relevant standards it has opted to use;
agree with the applicant as to where the necessary tests will be performed if they are not to be carried out directly by the notified body; and
assume full responsibility for test results. 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.

Verification by examination and testing of every product

The notified body shall:

(a)have documented procedures, sufficient expertise and facilities for the verification by examination and testing of every product in accordance with Part B of Annex XI;
(b)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:
—verify, for class IIb devices, the conformity of the device with the type described in the EU type-examination certificate and with the requirements of this Regulation which apply to those devices,
— confirm, for class IIa devices, the conformity with the technical documentation referred to in Annexes II and III and with the requirements of this Regulation which apply to those devices;
(c)document its rationale for the selection of the parameters referred to in point (b);
(d)have documented procedures to carry out the appropriate assessments and tests in order to verify the conformity of the device with the requirements of this Regulation by examining and testing every product as specified in Section 15 of Annex XI;
(e)have documented procedures providing for the reaching of an agreement with the applicant concerning when and where necessary tests that are not to be carried out by the notified body itself are to be performed; and
(f)assume full responsibility for test results in accordance with documented procedures; test reports submitted by the manufacturer shall only be taken into account if they have been issued by conformity assessment bodies which are competent and independent of the manufacturer.

4.5.4. Pre-clinical evaluation assessment

The notified body shall have documented procedures in place for the review of the manufacturer’s procedures and documentation relating to the evaluation of pre-clinical aspects. The notified body shall examine, validate and verify that the manufacturer’s procedures and documentation adequately address:

(a)the planning, conduct, assessment, reporting and, where appropriate, updating of the pre-clinical evaluation, in particular of
— the scientific pre-clinical literature search, and
— the pre-clinical testing, for example laboratory testing, simulated use testing, computer modelling, the use of animal models,
(b)the nature and duration of body contact and the specific associated biological risks,
(c)the interface with the risk management process, and
(d)the appraisal and analysis of the available pre-clinical data and its relevance with regard to demonstrating conformity with the relevant requirements in Annex I.

The notified body’s assessment of pre-clinical evaluation procedures and documentation shall address the results of literature searches and all validation, verification and testing performed and conclusions drawn, and shall typically include considering the use of alternative materials and substances and take account of the packaging, stability, including shelf life, of the finished device. Where no new testing has been undertaken by a manufacturer or where there are deviations from procedures, the notified body in question shall critically examine the justification presented by the manufacturer.

4.5.5. Clinical evaluation assessment

The notified body shall have documented procedures in place relating to the assessment of a manufacturer’s procedures and documentation relating to clinical evaluation both for initial conformity assessment and on an ongoing basis. The notified body shall examine, validate and verify that manufacturers’ procedures and documentation adequately address:

the planning, conduct, assessment, reporting and updating of the clinical evaluation as referred to in Annex XIV,
post-market surveillance and PMCF,
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, and
the conclusions drawn with regard to the clinical evidence and drawing up of the clinical evaluation report.

These procedures referred to in the first paragraph shall take into consideration available CS, guidance and best practice documents.

The notified body’s assessment of clinical evaluations as referred to in Annex XIV shall cover:

the intended use specified by the manufacturer and claims for the device defined by it,
the planning of the clinical evaluation,
the methodology for the literature search,
relevant documentation from the literature search,
the clinical investigation,
validity of equivalence claimed in relation to other devices, the demonstration of equivalence, the suitability and conclusions data from equivalent and similar devices,
post-market surveillance and PMCF,
the clinical evaluation report, and
justifications in relation to non-performance of clinical investigations or PMCF.

In relation to clinical data from clinical investigations included within the clinical evaluation, the notified body in question shall ensure that the conclusions drawn by the manufacturer are valid in the light of the approved clinical investigation plan.

The notified body shall ensure that the clinical evaluation adequately addresses the relevant safety and performance requirements provided for in Annex I, that it is appropriately aligned with the risk management requirements, that it is conducted in accordance with Annex XIV and that it is appropriately reflected in the information provided relating to the device.

4.5.6. Specific Procedures

The notified body shall have documented procedures, sufficient expertise and facilities for the procedures referred to in Sections 5 and 6 of Annex IX, Section 6 of Annex X and Section 16 of Annex XI, for which they are designated.

In the case of devices manufactured utilising tissues or cells of animal origin or their derivatives, such as from TSE susceptible species, as referred to in Regulation (EU) No 722/2012, the notified body shall have documented procedures in place that fulfil the requirements laid down in that Regulation, including for the preparation of a summary evaluation report for the relevant competent authority.

4.6. Reporting

The notified body shall:

ensure that all steps of the conformity assessment are documented so that the conclusions of the assessment are clear and demonstrate compliance with the requirements of this Regulation and can represent objective evidence of such compliance to persons that are not themselves involved in the assessment, for example personnel in designating authorities,
ensure that records that are sufficient to provide a discernible audit trail are available for quality management system audits,
clearly document the conclusions of its assessment of clinical evaluation in a clinical evaluation assessment report, and
for each specific project, provide a detailed report which shall be based on a standard format containing a minimum set of elements determined by the MDCG.

The report of the notified body shall:

clearly document the outcome of its assessment and draw clear conclusions from the verification of the manufacturer’s conformity with the requirements of this Regulation,
make a recommendation for a final review and for a final decision to be taken by the notified body; this recommendation shall be signed off by the member of personnel responsible in the notified body, and
be provided to the manufacturer in question.

4.7. Final review

The notified body shall prior to making a final decision:

ensure that the personnel assigned for the final review and decision-making on specific projects are appropriately authorised and are different from the personnel who have conducted the assessments,
verify that the report or reports and supporting documentation needed for decision making, including concerning resolution of non-conformities noted during assessment, are complete and sufficient with respect to the scope of the application, and
verify whether there are any unresolved non-conformities preventing issuance of a certificate.

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:

decide, based on the assessment documentation and additional information available, whether the requirements of this Regulation are fulfilled,
decide, based on the results of its assessment of the clinical evaluation and risk management, whether the post-market surveillance plan, including the PMCF plan, is adequate,
decide on specific milestones for further review by the notified body of the up to date clinical evaluation,
decide whether specific conditions or provisions need to be defined for the certification,
decide, based on the novelty, risk classification, clinical evaluation and conclusions from the risk analysis of the device, on a period of certification not exceeding five years,
clearly document decision making and approval steps including approval by signature of the members of personnel responsible,
clearly document responsibilities and mechanisms for communication of decisions, in particular, where the final signatory of a certificate differs from the decision maker or decision makers or does not fulfil the requirements laid down in Section 3.2.7,
issue a certificate or certificates in accordance with the minimum requirements laid down in Annex XII for a period of validity not exceeding five years and shall indicate whether there are specific conditions or limitations associated with the certification,
issue a certificate or certificates for the applicant alone and shall not issue certificates covering multiple entities, and
ensure that the manufacturer is notified of the outcome of the assessment and the resultant decision and that they are entered into the electronic system referred to in Article 57.

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 approved quality management system or systems or to the product-range covered,
the approved design of a device,
the intended use of or claims made for the device,
the approved type of a device, and
any substance incorporated in or utilised for the manufacturing of a device and being subject to the specific procedures in accordance with Section 4.5.6.

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:

ensure that manufacturers submit for prior approval plans for changes as referred to in the first paragraph and relevant information relating to such changes,
assess the changes proposed and verify whether, after these changes, the quality management system, or the design of a device or type of a device, still meets the requirements of this Regulation, and
notify the manufacturer of its decision and provide a report or as applicable a supplementary report, which shall contain the justified conclusions of its assessment.

4.10. Surveillance activities and post-certification monitoring

The notified body shall have documented procedures:

defining how and when surveillance activities of manufacturers are to be conducted. Those procedures shall include arrangements for unannounced on-site audits of manufacturers and, where applicable, subcontractors and suppliers carrying out product tests and the monitoring of compliance with any conditions binding manufacturers and associated with certification decisions, such as updates to clinical data at defined intervals,
for screening relevant sources of scientific and clinical data and post-market information relating to the scope of their designation. Such information shall be taken into account in the planning and conduct of surveillance activities, and
to review vigilance data to which they have access under Article 92(2) in order to estimate its impact, if any, on the validity of existing certificates. The results of the evaluation and any decisions taken shall be thoroughly documented.

The notified body in question shall, upon receipt of information about vigilance cases from a manufacturer or competent authorities, decide which of the following options to apply:

not to take action on the basis that the vigilance case is clearly not related to the certification granted,
observe the manufacturer’s and competent authority’s activities and the results of the manufacturer’s investigation so as to determine whether the certification granted is at risk or whether adequate corrective action has been taken,
perform extraordinary surveillance measures, such as document reviews, short-notice or unannounced audits and product testing, where it is likely that the certification granted is at risk,
increase the frequency of surveillance audits,
review specific products or processes on the occasion of the next audit of the manufacturer, or
take any other relevant measure.

In relation to surveillance audits of manufacturers, the notified body shall have documented procedures to:

conduct surveillance audits of the manufacturer on at least an annual basis which shall be planned and conducted in line with the relevant requirements in Section 4.5,
ensure adequate assessment of the manufacturer’s documentation on, and application of the provisions on, vigilance, the post-market surveillance, and PMCF,
sample and test devices and technical documentation, during audits, according to pre-defined sampling criteria and testing procedures to ensure that the manufacturer continuously applies the approved quality management system,
ensure that the manufacturer complies with the documentation and information obligations laid down in the relevant Annexes and that its procedures take into account best practices in the implementation of quality management systems,
ensure that the manufacturer does not use quality management system or device approvals in a misleading manner,
gather sufficient information to determine if the quality management system continues to comply with the requirements of this Regulation,
ask the manufacturer, if non-conformities are detected, for corrections, corrective actions and, where applicable, preventive actions, and
where necessary, impose specific restrictions on the relevant certificate, or suspend or withdraw it.

The notified body shall, if listed as part of the conditions for certification:

conduct an in-depth review of the clinical evaluation as most recently updated by the manufacturer based on the manufacturer’s post-market surveillance, on its PMCF and on clinical literature relevant to the condition being treated with the device or on clinical literature relevant to similar devices,
clearly document the outcome of the in-depth review and address any specific concerns to the manufacturer or impose any specific conditions on it, and
ensure that the clinical evaluation as most recently updated, is appropriately reflected in the instructions for use and, where applicable, the summary of safety and performance.

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:

(a)all changes to the originally approved device, including changes not yet notified,
(b)experience gained from post-market surveillance,
(c)experience from risk management,
(d)experience from updating the proof of compliance with the general safety and performance requirements set out in Annex I,
(e)experience from reviews of the clinical evaluation, including the results of any clinical investigations and PMCF,
(f)changes to the requirements, to components of the device or to the scientific or regulatory environment,
(g)changes to applied or new harmonised standards, CS or equivalent documents, and
(h)changes in medical, scientific and technical knowledge, such as:
— new treatments,
— changes in test methods,
— new scientific findings on materials and components, including findings on their biocompatibility,
— experience from studies on comparable devices,
— data from registers and registries,
— experience from clinical investigations with comparable devices.

The notified body shall have documented procedures to assess the information referred to in the second paragraph and shall pay particular attention to clinical data from post-market surveillance and PMCF activities undertaken since the previous certification or re-certification, including appropriate updates to manufacturers’ clinical evaluation reports.

For the decision on re-certification, the notified body in question shall use the same methods and principles as for the initial certification decision. If necessary, separate forms shall be established for re-certification taking into account the steps taken for certification such as application and application review.

ANNEX I – General safety and performance requirements

Chapter III (Part 2)

Requirements regarding the information supplied with the device

23.4. Information in the instructions for use

The instructions for use shall contain all of the following particulars:

(a)the particulars referred to in points (a), (c), (e), (f), (k), (l), (n) and (r)of Section 23.2;
(b)the device’s intended purpose with a clear specification of
indications, contra-indications, the patient target group or groups,
and of the intended users, as appropriate;
(c)where applicable, a specification of the clinical benefits to be
expected.
(d)where applicable, links to the summary of safety and clinical
performance referred to in Article 32;
(e)the performance characteristics of the device;
(f)where applicable, information allowing the healthcare professional
to verify if the device is suitable and select the corresponding
software and accessories;
(g)any residual risks, contra-indications and any undesirable side-
effects, including information to be conveyed to the patient in this
regard;
(h)specifications the user requires to use the device appropriately, e.g.
if the device has a measuring function, the degree of accuracy
claimed for it;
(i)details of any preparatory treatment or handling of the device before it is ready for use or during its use, such as sterilisation, final
assembly, calibration, etc., including the levels of disinfection
required to ensure patient safety and all available methods for
achieving those levels of disinfection;
(j)any requirements for special facilities, or special training, or
particular qualifications of the device user and/or other persons;
(k)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, and of any preparatory cleaning or disinfection,
— identification of any consumable components and how to replacethem,
— information on any necessary calibration to ensure that the
device operates properly and safely during its intended lifetime, and — methods for eliminating the risks encountered by persons
involved in installing, calibrating or servicing devices;
(l)if the device is supplied sterile, instructions in the event of the sterile packaging being damaged or unintentionally opened before use;
(m)if the device is supplied non-sterile with the intention that it is
sterilised before use, the appropriate instructions for sterilisation;
(n)if the device is reusable, information on the appropriate processes
for allowing reuse, including cleaning, disinfection, packaging and,where appropriate, the validated method of re-sterilisation
appropriate to the Member State or Member States in which the
device has been placed on the market. Information shall be
provided to identify when the device should no longer be reused,
e.g. signs of material degradation or the maximum number of
allowable reuses;
(o)an indication, if appropriate, that a device can be reused only if it is
reconditioned under the responsibility of the manufacturer to
comply with the general safety and performance requirements;
(p)if the device bears an indication that it is for single use, informationon known characteristics and technical factors known to the
manufacturer that could pose a risk if the device were to be re-used.This information shall be based on a specific section of the
manufacturer’s risk management documentation, where such
characteristics and technical factors shall be addressed in detail. If
in accordance with point (d) of Section 23.1. no instructions for use
are required, this information shall be made available to the user
upon request;
(q)for devices intended for use together with other devices and/or
general purpose equipment:
— information to identify such devices or equipment, in order to
obtain a safe combination, and/or
— information on any known restrictions to combinations of
devices and equipment;
(r)if the device emits radiation for medical purposes:
— detailed information as to the nature, type and where
appropriate, the intensity and distribution of the emitted radiation,
— the means of protecting the patient, user, or other person from
unintended radiation during use of the device;
(s)information that allows the user and/or patient to be informed of
any warnings, precautions, contra- indications, measures to be taken and limitations of use regarding the device. That information shall, where relevant, allow the user to brief the patient about any
warnings, precautions, contra-indications, measures to be taken and
limitations of use regarding the device. The information shall cover,where appropriate:
— warnings, precautions and/or measures to be taken in the event of malfunction of the device or changes in its performance that may
affect safety,
— warnings, precautions and/ormeasures 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,
— 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,
or therapeutic treatment or other procedures such as
electromagnetic interference emitted by the device affecting other
equipment, — if the device is intended to administer medicinal
products, tissues or cells of human or animal origin, or their
derivatives, or biological substances, any limitations or
incompatibility in the choice of substances to be delivered,
— warnings, precautions and/or limitations related to the medicinal
substance or biological material that is incorporated into the device as an integral part of the device; and
— precautions related to materials incorporated into the device thatcontain or consist of CMR substances or endocrine-disrupting
substances, or that could result in sensitisation or an allergic
reaction by the patient or user;
(t)in the case of devices that are composed of substances or of
combinations of substances that are intended to be introduced into
the human body and that are absorbed by or locally dispersed in
the human body, warnings and precautions, where appropriate,
related to the general profile of interaction of the device and its
products of metabolism with other devices, medicinal products and
other substances as well as contra- indications, undesirable side-
effects and risks relating to overdose;
(u)in the case of implantable devices, the overall qualitative and
quantitative information on the materials and substances to which patients can be exposed;
(v)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:
— infection or microbial hazards such as explants, needles or
surgical equipment contaminated with potentially infectious
substances of human origin, and
— physical hazards such as from sharps.
If in accordance with the point (d) of Section 23.1 no instructions for use are required, this information shall be made available to the user upon request;
(w)for devices intended for use by lay persons, the circumstances in
which the user should consult a healthcare professional;
(x)for the devices covered by this Regulation pursuant to Article 1(2),
information regarding the absence of a clinical benefit and the risksrelated to use of the device;
(y)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;
(z)a notice to the user and/or patient that any serious incident that
has occurred in relation to the device should be reported to the
manufacturer and the competent authority of the Member State in which the user and/or patient is established;
(aa)information to be supplied to the patient with an implanted device in accordance with Article 18;
(ab)for devices that incorporate electronic programmable systems,
including software, or software that are devices in themselves,
minimum requirements concerning hardware, IT networks
characteristics and IT security measures, including protection against unauthorised access, necessary to run the software as intended.

ANNEX I – General safety and performance requirements

Chapter II

Requirements regarding design and manufacture

10. Chemical, physical and biological properties

10.1. Devices shall be designed and manufactured in such a way as to ensure that the characteristics and performance requirements referred to in Chapter I are fulfilled. Particular attention shall be paid to:

(a)the choice of materials and substances used, particularly as regards toxicity and, where relevant, flammability;
(b)the compatibility between the materials and substances used and
biological tissues, cells and body fluids, taking account of the
intended purpose of the device and, where relevant, absorption,
distribution, metabolism and excretion;
(c)the compatibility between the different parts of a device which
consists of more than one implantable part;
(d)the impact of processes on material properties;
(e)where appropriate, the results of biophysical or modelling research
the validity of which has been demonstrated beforehand;
(f)the mechanical properties of the materials used, reflecting, where
appropriate, matters such as strength, ductility, fracture resistance, wear resistance and fatigue resistance;
(g)surface properties; and
(h)the confirmation that the device meets any defined chemical and/orphysical specifications.

10.2. Devices shall be designed, manufactured and packaged in such a way as to minimise the risk posed by contaminants and residues to patients, taking account of the intended purpose of the device, and to the persons involved in the transport, storage and use of the devices. Particular attention shall be paid to tissues exposed to those contaminants and residues and to the duration and frequency of exposure.

10.3. Devices shall be designed and manufactured in such a way that they can be used safely with the materials and substances, including gases, with which they enter into contact during their intended use; if the devices are intended to administer medicinal products they shall be designed and manufactured in such a way as to be compatible with the medicinal products concerned in accordance with the provisions and restrictions governing those medicinal products and that the performance of both the medicinal products and of the devices is maintained in accordance with their respective indications and intended use.

10.4. Substances

10.4.1. Design and manufacture of devices

Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks posed by substances or particles, including wear debris, degradation products and processing residues, that may be released from the device.

Devices, or those parts thereof or those materials used therein that:

are invasive and come into direct contact with the human body,
(re)administer medicines, body liquids or other substances, including gases, to/from the body, or
transport or store such medicines, body fluids or substances,
including gases, to be (re)administered to the body,

shall only contain the following substances in a concentration that is above 0,1 % weight by weight (w/w) where justified pursuant to Section 10.4.2:

(a)substances which are carcinogenic, mutagenic or toxic to
reproduction (‘CMR’), of category 1A or 1B, in accordance with Part 3 of Annex VI to Regulation (EC) No 1272/2008 of the European
Parliament and of the Council (1), or
(b)substances having endocrine-disrupting properties for which there
is scientific evidence of probable serious effects to human health
and which are identified either in accordance with the procedure
set out in Article 59 of Regulation (EC) No 1907/2006 of the European Parliament and of the Council (2) or, once a delegated act has been
adopted by the Commission pursuant to the first subparagraph of
Article 5(3) of Regulation (EU) No 528/2012 of the European
Parliament and the Council (3), in accordance with the criteria that
are relevant to human health amongst the criteria established
therein.

(1) 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).

(2) Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) (OJ L 396, 30.12.2006, p. 1).

(3) Regulation (EU) No 528/2012 of the European Parliament and the Council of 22 May 2012 concerning the making available on the market of and use of biocidal products (OJ L 167, 27.6.2012, p. 1).

10.4.2. Justification regarding the presence of CMR and/or endocrine-disrupting substances

(a)an analysis and estimation of potential patient or user exposure to
the substance;
(b)an analysis of possible alternative substances, materials or designs,
including, where available, information about independent
research, peer-reviewed studies, scientific opinions from relevant
scientific committees and an analysis of the availability of such
alternatives;
(c)argumentation as to why possible substance and/ or material
substitutes, if available, or design changes, if feasible, are
inappropriate in relation to maintaining the functionality,
performance and the benefit-risk ratios of the product; including
taking into account if the intended use of such devices includes
treatment of children or treatment of pregnant or breastfeeding
women or treatment of other patient groups considered particularlyvulnerable to such substances and/or materials; and
(d)where applicable and available, the latest relevant scientific committee guidelines in accordance with Sections 10.4.3. and 10.4.4.

10.4.3. Guidelines on phthalates

For the purposes of Section 10.4., the Commission shall, as soon as possible and by 26 May 2018, provide the relevant scientific committee with a mandate to prepare guidelines that shall be ready before 26 May 2020. The mandate for the committee shall encompass at least a benefit-risk assessment of the presence of phthalates which belong to either of the groups of substances referred to in points (a) and (b) of Section 10.4.1. The benefit-risk assessment shall take into account the intended purpose and context of the use of the device, as well as any available alternative substances and alternative materials, designs or medical treatments. When deemed appropriate on the basis of the latest scientific evidence, but at least every five years, the guidelines shall be updated.

10.4.4. Guidelines on other CMR and endocrine-disrupting substances

Subsequently, the Commission shall mandate the relevant scientific committee to prepare guidelines as referred to in Section 10.4.3. also for other substances referred to in points (a) and (b) of Section 10.4.1., where appropriate.

10.4.5. Labelling

Where devices, parts thereof or materials used therein as referred to in Section 10.4.1. contain substances referred to in points (a) or (b) of Section 10.4.1. in a concentration above 0,1 % weight by weight (w/w), the presence of those substances shall be labelled on the device itself and/or on the packaging for each unit or, where appropriate, on the sales packaging, with the list of such substances. If the intended use of such devices includes treatment of children or treatment of pregnant or breastfeeding women or treatment of other patient groups considered particularly vulnerable to such substances and/or materials, information on residual risks for those patient groups and, if applicable, on appropriate precautionary measures shall be given in the instructions for use.

10.5. Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks posed by the unintentional ingress of substances into the device taking into account the device and the nature of the environment in which it is intended to be used.

10.6. Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks linked to the size and the properties of particles which are or can be released into the patient’s or user’s body, unless they come into contact with intact skin only. Special attention shall be given to nanomaterials.

11. Infection and microbial contamination

11.1. Devices and their manufacturing processes shall be designed in such a way as to eliminate or to reduce as far as possible the risk of infection to patients, users and, where applicable, other persons. The design shall:

(a)reduce as far as possible and appropriate the risks from unintendedcuts and pricks, such as needle stick injuries,
(b)allow easy and safe handling,
(c)reduce as far as possible any microbial leakage from the device and/or microbial exposure during use, and
(d)prevent microbial contamination of the device or its content such asspecimens or fluids.

11.2. Where necessary devices shall be designed to facilitate their safe cleaning, disinfection, and/or re-sterilisation.

11.3. Devices labelled as having a specific microbial state shall be designed, manufactured and packaged to ensure that they remain in that state when placed on the market and remain so under the transport and storage conditions specified by the manufacturer.

11.4. Devices delivered in a sterile state shall be designed, manufactured and packaged in accordance with appropriate procedures, to ensure that they are sterile when placed on the market and that, unless the packaging which is intended to maintain their sterile condition is damaged, they remain sterile, under the transport and storage conditions specified by the manufacturer, until that packaging is opened at the point of use. It shall be ensured that the integrity of that packaging is clearly evident to the final user.

11.5. Devices labelled as sterile shall be processed, manufactured, packaged and, sterilised by means of appropriate, validated methods.

11.6. Devices intended to be sterilised shall be manufactured and packaged in appropriate and controlled conditions and facilities.

11.7. Packaging systems for non-sterile devices shall maintain the integrity and cleanliness of the product and, where the devices are to be sterilised prior to use, minimise the risk of microbial contamination; the packaging system shall be suitable taking account of the method of sterilisation indicated by the manufacturer.

11.8. The labelling of the device shall distinguish between identical or similar devices placed on the market in both a sterile and a non-sterile condition additional to the symbol used to indicate that devices are sterile.

12. Devices incorporating a substance considered to be a medicinal product and devices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body.

12.1. In the case of devices referred to in the first subparagraph of Article 1(8), the quality, safety and usefulness of the substance which, if used separately, would be considered to be a medicinal product within the meaning of point (2) of Article 1 of Directive 2001/83/EC, shall be verified by analogy with the methods specified in Annex I to Directive 2001/83/EC, as required by the applicable conformity assessment procedure under this Regulation.

12.2. Devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body, and that are absorbed by or locally dispersed in the human body shall comply, where applicable and in a manner limited to the aspects not covered by this Regulation, with the relevant requirements laid down in Annex I to Directive 2001/83/EC for the evaluation of absorption, distribution, metabolism, excretion, local tolerance, toxicity, interaction with other devices, medicinal products or other substances and potential for adverse reactions, as required by the applicable conformity assessment procedure under this Regulation.

13. Devices incorporating materials of biological origin

13.1. For devices manufactured utilising derivatives of tissues or cells of human origin which are non-viable or are rendered non-viable covered by this Regulation in accordance with point (g) of Article 1(6), the following shall apply:

(a)donation, procurement and testing of the tissues and cells shall be
done in accordance with Directive 2004/23/EC;
(b)processing, preservation and any other handling of those tissues and cells or their derivatives shall be carried out so as to provide safety
for patients, users and, where applicable, other persons. In
particular, safety with regard to viruses and other transmissible
agents shall be addressed by appropriate methods of sourcing and
by implementation of validated methods of elimination or
inactivation in the course of the manufacturing process;
(c)the traceability system for those devices shall be complementary
and compatible with the traceability and data protection
requirements laid down in Directive 2004/23/EC and in Directive
2002/98/EC.

13.2. For devices manufactured utilising tissues or cells of animal origin, or their derivatives, which are non-viable or rendered non-viable the following shall apply:

(a)where feasible taking into account the animal species, tissues and
cells of animal origin, or their derivatives, shall originate from
animals that have been subjected to veterinary controls that are
adapted to the intended use of the tissues. Information on the
geographical origin of the animals shall be retained by
manufacturers;
(b)sourcing, processing, preservation, testing and handling of tissues,
cells and substances of animal origin, or their derivatives, shall be
carried out so as to provide safety for patients, users and, where
applicable, other persons. In particular safety with regard to virusesand other transmissible agents shall be addressed by
implementation of validated methods of elimination or viral
inactivation in the course of the manufacturing process, except
when the use of such methods would lead to unacceptable
degradation compromising the clinical benefit of the device;
(c)in the case of devices manufactured utilising tissues or cells of
animal origin, or their derivatives, as referred to in Regulation (EU) No 722/2012 the particular requirements laid down in that
Regulation shall apply.

13.3. For devices manufactured utilising non-viable biological substances other than those referred to in Sections 13.1 and 13.2, the processing, preservation, testing and handling of those substances shall be carried out so as to provide safety for patients, users and, where applicable, other persons, including in the waste disposal chain. In particular, safety with regard to viruses and other transmissible agents shall be addressed by appropriate methods of sourcing and by implementation of validated methods of elimination or inactivation in the course of the manufacturing process.

14. Construction of devices and interaction with their environment

14.1. 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 performance of the devices. Any restrictions on use applying to such combinations shall be indicated on the label and/or in the instructions for use. Connections which the user has to handle, such as fluid, gas transfer, electrical or mechanical coupling, shall be designed and constructed in such a way as to minimise all possible risks, such as misconnection.

14.2. 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 risks of reciprocal interference with other devices normally used in the investigations or for the treatment given; and
(g)risks arising where maintenance or calibration are not possible (as with implants), from ageing of materials used or loss of accuracy of any measuring or control mechanism.

14.3. 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.

14.4. Devices shall be designed and manufactured in such a way that adjustment, calibration, and maintenance can be done safely and effectively.

14.5. 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.

14.6. Any measurement, monitoring or display scale 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.

14.7. 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 the user, patient 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.

15. Devices with a diagnostic or measuring function

15.1. Diagnostic devices and devices with a measuring function, shall be designed and manufactured in such a way as to provide sufficient accuracy, precision and stability for their intended purpose, based on appropriate scientific and technical methods. The limits of accuracy shall be indicated by the manufacturer.

15.2. 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 (1).

(1) 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).

16. Protection against radiation

16.1. General

(a)Devices shall be designed, manufactured and packaged in such a
way that exposure of patients, users and other persons to radiation
is reduced as far as possible, and in a manner that is compatible
with the intended purpose, whilst not restricting the application of
appropriate specified levels for therapeutic and diagnostic purposes.
(b)The operating instructions for devices emitting hazardous or
potentially hazardous radiation shall contain detailed information
as to the nature of the emitted radiation, the means of protecting the patient and the user, and on ways of avoiding misuse and of
reducing the risks inherent to installation as far as possible and
appropriate. Information regarding the acceptance and
performance testing, the acceptance criteria, and the maintenance
procedure shall also be specified.

16.1. Intended radiation

(a)Where devices are designed to emit hazardous, or potentially
hazardous, levels of ionizing and/or non- ionizing radiation
necessary for a specific medical purpose the benefit of which is
considered to outweigh the risks inherent to the emission, it shall bepossible for the user to control the emissions. Such devices shall be
designed and manufactured to ensure reproducibility of relevant
variable parameters within an acceptable tolerance.
(b)Where devices are intended to emit hazardous, or potentially
hazardous, ionizing and/or non-ionizing radiation, they shall be
fitted, where possible, with visual displays and/or audible warnings of such emissions.

16.3. Devices shall be designed and manufactured in such a way that exposure of patients, users and other persons to the emission of unintended, stray or scattered radiation is reduced as far as possible. Where possible and appropriate, methods shall be selected which reduce the exposure to radiation of patients, users and other persons who may be affected.

16.4. Ionising radiation

(a)Devices intended to emit ionizing radiation shall be designed and
manufactured taking into account the requirements of the Directive2013/59/Euratom laying down basic safety standards for protection
against the dangers arising from exposure to ionising radiation.
(b)Devices intended to emit ionising radiation shall be designed and
manufactured in such a way as to ensure that, where possible,
taking into account the intended use, the quantity, geometry and
quality of the radiation emitted can be varied and controlled, and, ifpossible, monitored during treatment.
(c)Devices emitting ionising radiation intended for diagnostic radiology shall be designed and manufactured in such a way as to achieve an
image and/or output quality that are appropriate to the intended
medical purpose whilst minimising radiation exposure of the patient and user.
(d)Devices that emit ionising radiation and are intended for
therapeutic radiology shall be designed and manufactured in such
a way as to enable reliable monitoring and control of the delivered
dose, the beam type, energy and, where appropriate, the quality of
radiation.

17. Electronic programmable systems — devices that incorporate electronic programmable systems and software that are devices in themselves

17.1. 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.

17.2. 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.

17.3. 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).

17.4. 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.

18. Active devices and devices connected to them

18.1. For non-implantable active devices, in the event of a single fault condition, appropriate means shall be adopted to eliminate or reduce as far as possible consequent risks.

18.2. 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.

18.3. Devices where the safety of the patient depends on an external power supply shall include an alarm system to signal any power failure.

18.4. Devices intended to monitor one or more clinical parameters of a patient shall be equipped with appropriate alarm systems to alert the user of situations which could lead to death or severe deterioration of the patient’s state of health.

18.5. 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.

18.6. 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.

18.7. 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 patient, user or any 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.

18.8. Devices shall be designed and manufactured in such a way as to protect, as far as possible, against unauthorised access that could hamper the device from functioning as intended.

19. Particular requirements for active implantable devices

19.1. Active implantable devices shall be designed and manufactured in such a way as to remove or minimize as far as possible:

(a)risks connected with the use of energy sources with particular
reference, where electricity is used, to insulation, leakage currents
and overheating of the devices,
(b)risks connected with medical treatment, in particular those
resulting from the use of defibrillators or high- frequency surgical
equipment, and
(c)risks which may arise where maintenance and calibration are
impossible, including:
— excessive increase of leakage currents,
— ageing of the materials used,
— excess heat generated by the device,
— decreased accuracy of any measuring or control mechanism.

19.2. Active implantable devices shall be designed and manufactured in such a way as to ensure

if applicable, the compatibility of the devices with the substances
they are intended to administer, and
the reliability of the source of energy.

19.3. Active implantable devices and, if appropriate, their component parts shall be identifiable to allow any necessary measure to be taken following the discovery of a potential risk in connection with the devices or their component parts.

19.4. Active implantable devices shall bear a code by which they and their manufacturer can be unequivocally identified (particularly with regard to the type of device and its year of manufacture); it shall be possible to read this code, if necessary, without the need for a surgical operation.

20. Protection against mechanical and thermal risks

20.1. Devices shall be designed and manufactured in such a way as to protect patients and users against mechanical risks connected with, for example, resistance to movement, instability and moving parts.

20.2. 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.

20.3. 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.

20.4. 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.

20.5. 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.

20.6 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.

21. Protection against the risks posed to the patient or user by devices supplying energy or substances

21.1. Devices for supplying the patient with energy or substances shall be designed and constructed in such a way that the amount to be delivered can be set and maintained accurately enough to ensure the safety of the patient and of the user.

21.2. Devices shall be fitted with the means of preventing and/or indicating any inadequacies in the amount of energy delivered or substances delivered which could pose a danger. Devices shall incorporate suitable means to prevent, as far as possible, the accidental release of dangerous levels of energy or substances from an energy and/or substance source.

21.3. The function of the controls and indicators shall be clearly specified on the devices. Where a device bears instructions required for its operation or indicates operating or adjustment parameters by means of a visual system, such information shall be understandable to the user and, as appropriate, the patient.

22. Protection against the risks posed by medical devices intended by the manufacturer for use by lay persons

22.1. Devices for use by lay persons 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 lay persons and the influence resulting from variation that can be reasonably anticipated in the lay person’s technique and environment. The information and instructions provided by the manufacturer shall be easy for the lay person to understand and apply.

22.2. Devices for use by lay persons shall be designed and manufactured in such a way as to:

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,
reduce, as far as possible and appropriate, the risk from unintended cuts and pricks such as needle stick injuries, and
reduce as far as possible the risk of error by the intended user in thehandling of the device and, if applicable, in the interpretation of the
results.

22.3. Devices for use by lay persons shall, where appropriate, include a procedure by which the lay person:

can verify that, at the time of use, the device will perform as
intended by the manufacturer, and
if applicable, is warned if the device has failed to provide a valid
result.

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 associatedwith each device;
(c)estimate and evaluate the risks associated with, and occurring
during, the intended use and during reasonably foreseeable misuse;
(d)eliminate or control the risks referred to in point (c) in accordance with the requirements of Section 4;
(e)evaluate the impact of information from the production phase and,
in particular, from the post-market surveillance system, on hazards and the frequency of occurrence thereof, on estimates of their
associated risks, as well as on the overall risk, benefit-risk ratio and risk acceptability; and
(f)based on the evaluation of the impact of the information referred to in point (e), if necessary amend control measures in line with the
requirements of Section 4.

4. Risk control measures adopted by manufacturers for the design and manufacture of the devices shall conform to safety principles, taking account of the generally acknowledged state of the art. To reduce risks, Manufacturers shall manage risks so that the residual risk associated with each hazard as well as the overall residual risk is judged acceptable. In selecting the most appropriate solutions, manufacturers shall, in the following order of priority:

(a)eliminate or reduce risks as far as possible through safe design and manufacture;
(b)where appropriate, take adequate protection measures, including
alarms if necessary, in relation to risks that cannot be eliminated;
and
(c)provide information for safety (warnings/precautions/contra-
indications) and, where appropriate, training to users.

Manufacturers shall inform users of any residual risks.

5. In eliminating or reducing risks related to use error, the manufacturer shall:

(a)reduce as far as possible the risks related to the ergonomic features
of the device and the environment in which the device is intended to be used (design for patient safety), and
(b)give consideration to the technical knowledge, experience,
education, training and use environment, where applicable, and themedical and physical conditions of intended users (design for lay,
professional, disabled or other users).

6. The characteristics and performance of a device shall not be adversely affected to such a degree that the health or safety of the patient or the user and, where applicable, of other persons are compromised during the lifetime of the device, as indicated by the manufacturer, when the device is subjected to the stresses which can occur during normal conditions of use and has been properly maintained in accordance with the manufacturer’s instructions.

7. Devices shall be designed, manufactured and packaged in such a way that their characteristics and performance during their intended use are not adversely affected during transport and storage, for example, through fluctuations of temperature and humidity, taking account of the instructions and information provided by the manufacturer.

8. All known and foreseeable risks, and any undesirable side-effects, shall be minimised and be acceptable when weighed against the evaluated benefits to the patient and/or user arising from the achieved performance of the device during normal conditions of use.

9. For the devices referred to in Annex XVI, the general safety requirements set out in Sections 1 and 8 shall be understood to mean that the device, when used under the conditions and for the purposes intended, does not present a risk at all or presents a risk that is no more than the maximum acceptable risk related to the product’s use which is consistent with a high level of protection for the safety and health of persons.

MDR – Article 82 – Requirements regarding other clinical investigations

Article 82

Requirements regarding other clinical investigations

1. Clinical investigations, not performed pursuant to any of the purposes listed in Article 62(1), shall comply with the provisions of Article 62 (2) and (3), points (b), (c), (d), (f), (h), and (l) of Article 62(4) and Article 62(6).

2. In order to protect the rights, safety, dignity and well-being of subjects and the scientific and ethical integrity of clinical investigations not performed for any of the purposes listed in Article 62(1), each Member State shall define any additional requirements for such investigations, as appropriate for each Member State concerned.

MDR – Article 62 – General requirements regarding clinical investigations conducted to demonstrate conformity of devices

Article 62

General requirements regarding clinical investigations conducted to demonstrate conformity of devices

1. Clinical investigations shall be designed, authorised, conducted, recorded and reported in accordance with the provisions of this Article and of Articles 63 to 80, the acts adopted pursuant to Article 81, and Annex XV, where carried out as part of the clinical evaluation for conformity assessment purposes, for one or more of the following purposes:

(a)to establish and verify that, under normal conditions of use, a device is designed, manufactured and packaged in such a way that it is
suitable for one or more of the specific purposes listed in point (1) of Article 2, and achieves the performance intended as specified by itsmanufacturer;
(b)to establish and verify the clinical benefits of a device as specified by its manufacturer;
(c)to establish and verify the clinical safety of the device and to determine any undesirable side-effects, under normal conditions of use of the device, and assess whether they constitute acceptable risks when weighed against the benefits to be achieved by the device.

2. Where the sponsor of a clinical investigation is not established in the Union, that sponsor shall ensure that a natural or legal person is established in the Union as its legal representative. Such legal representative shall be responsible for ensuring compliance with the sponsor’s obligations pursuant to this Regulation, and shall be the addressee for all communications with the sponsor provided for in this Regulation. Any communication with that legal representative shall be deemed to be a communication with the sponsor.

Member States may choose not to apply the first subparagraph to clinical investigations to be conducted solely on their territory, or on their territory and the territory of a third country, provided that they ensure that the sponsor establishes at least a contact person on their territory in respect of that clinical investigation who shall be the addressee for all communications with the sponsor provided for in this Regulation.

3. Clinical investigations shall be designed and conducted in such a way that the rights, safety, dignity and well-being of the subjects participating in a clinical investigation are protected and prevail over all other interests and the clinical data generated are scientifically valid, reliable and robust.

Clinical investigations shall be subject to scientific and ethical review. The ethical review shall be performed by an ethics committee in accordance with national law. Member States shall ensure that the procedures for review by ethics committees are compatible with the procedures set out in this Regulation for the assessment of the application for authorisation of a clinical investigation. At least one lay person shall participate in the ethical review.

4. A clinical investigation as referred to in paragraph 1 may be conducted only where all of the following conditions are met:

(a)the clinical investigation is the subject of an authorisation by the
Member State(s) in which the clinical investigation is to be
conducted, in accordance with this Regulation, unless otherwise
stated;
(b)an ethics committee, set up in accordance with national law, has notissued a negative opinion in relation to the clinical investigation,
which is valid for that entire Member State under its national law;
(c)the sponsor, or its legal representative or a contact person pursuant to paragraph 2, is established in the Union;
(d)vulnerable populations and subjects are appropriately protected in accordance with Articles 64 to 68;
(e)the anticipated benefits to the subjects or to public health justify the foreseeable risks and inconveniences and compliance with this
condition is constantly monitored;
(f)the subject or, where the subject is not able to give informed
consent, his or her legally designated representative has given
informed consent in accordance with Article 63;
(g)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;
(h)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;
(i)the clinical investigation has been designed to involve as little pain,
discomfort, fear and any other foreseeable risk as possible for the
subjects, and both the risk threshold and the degree of distress are
specifically defined in the clinical investigation plan and constantlymonitored;
(j)the medical care provided to the subjects is the responsibility of an
appropriately qualified medical doctor or, where appropriate, a
qualified dental practitioner or any other person entitled by national law to provide the relevant patient care under clinical investigation conditions;
(k)no undue influence, including that of a financial nature, is exerted on the subject, or, where applicable, on his or her legally designated representatives, to participate in the clinical investigation;
(l)the investigational device(s) in question conform(s) to the applicablegeneral safety and performance requirements set out in Annex I
apart from the aspects covered by the clinical investigation and that, with regard to those aspects, every precaution has been taken to
protect the health and safety of the subjects. This includes, where
appropriate, technical and biological safety testing and pre-clinical
evaluation, as well as provisions in the field of occupational safety
and accident prevention, taking into consideration the state of the
art;
(m)the requirements of Annex XV are fulfilled.

5. Any subject, or, where the subject is not able to give informed consent, his or her legally designated representative, may, without any resulting detriment and without having to provide any justification, withdraw from the clinical investigation at any time by revoking his or her informed consent. Without prejudice to Directive 95/46/EC, the withdrawal of the informed consent shall not affect the activities already carried out and the use of data obtained based on informed consent before its withdrawal.

6. The investigator shall be a person exercising a profession which is recognised in the Member State concerned as qualifying for the role of investigator on account of having the necessary scientific knowledge and experience in patient care. Other personnel involved in conducting a clinical investigation shall be suitably qualified, by education, training or experience in the relevant medical field and in clinical research methodology, to perform their tasks.

7. The facilities where the clinical investigation is to be conducted shall be suitable for the clinical investigation and shall be similar to the facilities where the device is intended to be used.

MDR – Article 41 – Language requirements

Article 41

Language requirements

All documents required pursuant to Articles 38 and 39 shall be drawn up in a language or languages which shall be determined by the Member State concerned.

Member States, in applying the first paragraph, shall consider accepting and using a commonly understood language in the medical field, for all or part of the documentation concerned.

The Commission shall provide translations of the documentation pursuant to Articles 38 and 39, or parts thereof into an official Union language, such as is necessary for that documentation to be readily understood by the joint assessment team appointed in accordance with Article 39(3).

MDR – Article 36 – Requirements relating to notified bodies

Article 36

Requirements relating to notified bodies

1. Notified bodies shall fulfil the tasks for which they are designated in accordance with this Regulation. They shall satisfy the organisational and general requirements and the quality management, resource and process requirements that are necessary to fulfil those tasks. In particular, notified bodies shall comply with Annex VII.

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.

2. Notified bodies shall make available and submit upon request all relevant documentation, including the manufacturer’s documentation, to the authority responsible for notified bodies to allow it to conduct its assessment, designation, notification, monitoring and surveillance activities and to facilitate the assessment outlined in this Chapter.

3. In order to ensure the uniform application of the requirements set out in Annex VII, the Commission may adopt implementing acts, to the extent necessary to resolve issues of divergent interpretation and of practical application. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 114(3).