ANNEX IX

Conformity assessment based on a quality management system and on assessment of technical documentation

CHAPTER I

Quality management system

1. The manufacturer shall establish, document and implement a quality management system as described in Article 10(9) and maintain its effectiveness throughout the life cycle of the devices concerned. The manufacturer shall ensure the application of the quality management system as specified in Section 2 and shall be subject to audit, as laid down in Sections 2.3 and 2.4, and to surveillance as specified in Section 3.

2. Quality management system assessment

2.1. The manufacturer shall lodge an application for assessment of its quality management system with a notified body. The application shall include:

—the name of the manufacturer and address of its registered place of business and any additional manufacturing site covered by the quality management system, and, if the manufacturer’s application is lodged by its authorised representative, the name of the authorised representative and the address of the authorised representative’s registered place of business,
—all relevant information on the device or group of devices covered by the quality management system,
—a written declaration that no application has been lodged with any other notified body for the same device- related quality management system, or information about any previous application for the same device- related quality management system,
—a draft of an EU declaration of conformity in accordance with Article 19 and Annex IV for the device model covered by the conformity assessment procedure,
—the documentation on the manufacturer’s quality management system,
—a documented description of the procedures in place to fulfil the obligations arising from the quality management system and required under this Regulation and the undertaking by the manufacturer in question to apply those procedures,
—a description of the procedures in place to ensure that the quality management system remains adequate and effective, and the undertaking by the manufacturer to apply those procedures,
—the documentation on the manufacturer’s post-market surveillance system and, where applicable, on the PMCF plan, and the procedures put in place to ensure compliance with the obligations resulting from the provisions on vigilance set out in Articles 87 to 92,
—a description of the procedures in place to keep up to date the post-market surveillance system, and, where applicable, the PMCF plan, and the procedures ensuring compliance with the obligations resulting from the provisions on vigilance set out in Articles 87 to 92, as well as the undertaking by the manufacturer to apply those procedures,
—documentation on the clinical evaluation plan, and
—a description of the procedures in place to keep up to date the clinical evaluation plan, taking into account the state of the art.

2.2. Implementation of the quality management system shall ensure compliance with this Regulation. All the elements, requirements and provisions adopted by the manufacturer for its quality management system shall be documented in a systematic and orderly manner in the form of a quality manual and written policies and procedures such as quality programmes, quality plans and quality records.

Moreover, the documentation to be submitted for the assessment of the quality management system shall include an adequate description of, in particular:

(a)the manufacturer’s quality objectives;
(b)the organisation of the business and in particular:
— the organisational structures with the assignment of staff responsibilities in relation to critical procedures, the responsibilities of the managerial staff and their organisational authority,
— the methods of monitoring whether the operation of the quality management system is efficient and in particular the ability of that system to achieve the desired design and device quality, including control of devices which fail to conform,
— where the design, manufacture and/or final verification and testing of the devices, or parts of any of those processes, is carried out by another party, the methods of monitoring the efficient operation of the quality management system and in particular the type and extent of control applied to the other party, and
— where the manufacturer does not have a registered place of business in a Member State, the draft mandate for the designation of an authorised representative and a letter of intention from the authorised representative to accept the mandate;
(c)the procedures and techniques for monitoring, verifying, validating and controlling the design of the devices and the corresponding documentation as well as the data and records arising from those procedures and techniques. Those procedures and techniques shall specifically cover:
— the strategy for regulatory compliance, including processes for identification of relevant legal requirements, qualification, classification, handling of equivalence, choice of and compliance with conformity assessment procedures,
— identification of applicable general safety and performance requirements and solutions to fulfil those requirements, taking applicable CS and, where opted for, harmonised standards or other adequate solutions into account,
— risk management as referred to in Section 3 of Annex I,
— the clinical evaluation, pursuant to Article 61 and Annex XIV, including post-market clinical follow-up,
— solutions for fulfilling the applicable specific requirements regarding design and construction, including appropriate pre-clinical evaluation, in particular the requirements of Chapter II of Annex I,
— solutions for fulfilling the applicable specific requirements regarding the information to be supplied with the device, in particular the requirements of Chapter III of Annex I,
— the device identification procedures drawn up and kept up to date from drawings, specifications or other relevant documents at every stage of manufacture, and
— management of design or quality management system changes; and
(d)the verification and quality assurance techniques at the manufacturing stage and in particular the processes and procedures which are to be used, particularly as regards sterilisation and the relevant documents; and
(e)the appropriate tests and trials which are to be carried out before, during and after manufacture, the frequency with which they are to take place, and the test equipment to be used; it shall be possible to trace back adequately the calibration of that test equipment.

In addition, the manufacturer shall grant the notified body access to the technical documentation referred to in Annexes II and III.

2.3. Audit

The notified body shall audit the quality management system to determine whether it meets the requirements referred to in Section 2.2. Where the manufacturer uses a harmonised standard or CS related to a quality management system, the notified body shall assess conformity with those standards or CS. The notified body shall assume that a quality management system which satisfies the relevant harmonised standards or CS conforms to the requirements covered by those standards or CS, unless it duly substantiates not doing so.

The audit team of the notified body shall include at least one member with past experience of assessments of the technology concerned in accordance with Sections 4.3. to 4.5. of Annex VII. In circumstances where such experience is not immediately obvious or applicable, the notified body shall provide a documented rationale for the composition of that team. The assessment procedure shall include an audit on the manufacturer’s premises and, if appropriate, on the premises of the manufacturer’s suppliers and/or subcontractors to verify the manufacturing and other relevant processes.

Moreover, in the case of class IIa and class IIb devices, the quality management system assessment shall be accompanied by the assessment of technical documentation for devices selected on a representative basis in accordance with Sections 4.4 to 4.8. In choosing representative samples, the notified body shall take into account the published guidance developed by the MDCG pursuant to Article 105 and in particular the novelty of the technology, similarities in design, technology, manufacturing and sterilisation methods, the intended purpose and the results of any previous relevant assessments such as with regard to physical, chemical, biological or clinical properties, that have been carried out in accordance with this Regulation. The notified body in question shall document its rationale for the samples taken.

If the quality management system conforms to the relevant provisions of this Regulation, the notified body shall issue an EU quality management system certificate. The notified body shall notify the manufacturer of its decision to issue the certificate. The decision shall contain the conclusions of the audit and a reasoned report.

2.4. The manufacturer in question shall inform the notified body which approved the quality management system of any plan for substantial changes to the quality management system, or the device-range covered. The notified body shall assess the changes proposed, determine the need for additional audits and verify whether after those changes the quality management system still meets the requirements referred to in Section 2.2. It shall notify the manufacturer of its decision which shall contain the conclusions of the assessment, and where applicable, conclusions of additional audits. The approval of any substantial change to the quality management system or the device-range covered shall take the form of a supplement to the EU quality management system certificate.

3. Surveillance assessment applicable to class IIa, class IIb and class III devices

3.1. The aim of surveillance is to ensure that the manufacturer duly fulfils the obligations arising from the approved quality management system.

3.2. The manufacturer shall give authorisation to the notified body to carry out all the necessary audits, including on- site audits, and supply it with all relevant information, in particular:

—the documentation on its quality management system,
—documentation on any findings and conclusions resulting from the application of the post-market surveillance plan, including the PMCF plan, for a representative sample of devices, and of the provisions on vigilance set out in Articles 87 to 92,
—the data stipulated in the part of the quality management system relating to design, such as the results of analyses, calculations, tests and the solutions adopted regarding the risk-management as referred to in Section 4 of Annex I, and
—the data stipulated in the part of the quality management system relating to manufacture, such as quality control reports and test data, calibration data, and records on the qualifications of the personnel concerned.

3.3. Notified bodies shall periodically, at least once every 12 months, carry out appropriate audits and assessments to make sure that the manufacturer in question applies the approved quality management system and the post- market surveillance plan. Those audits and assessments shall include audits on the premises of the manufacturer and, if appropriate, of the manufacturer’s suppliers and/or subcontractors. At the time of such on-site audits, the notified body shall, where necessary, carry out or ask for tests in order to check that the quality management system is working properly. It shall provide the manufacturer with a surveillance audit report and, if a test has been carried out, with a test report.

3.4. The notified body shall randomly perform at least once every five years unannounced audits on the site of the manufacturer and, where appropriate, of the manufacturer’s suppliers and/or subcontractors, which may be combined with the periodic surveillance assessment referred to in Section 3.3. or be performed in addition to that surveillance assessment. The notified body shall establish a plan for such unannounced on-site audits but shall not disclose it to the manufacturer.

Within the context of such unannounced on-site audits, the notified body shall test an adequate sample of the devices produced or an adequate sample from the manufacturing process to verify that the manufactured device is in conformity with the technical documentation, with the exception of the devices referred to in the second subparagraph of Article 52(8). Prior to unannounced on-site audits, the notified body shall specify the relevant sampling criteria and testing procedure.

Instead of, or in addition to, sampling referred to in the second paragraph, the notified body shall take samples of devices from the market to verify that the manufactured device is in conformity with the technical documentation, with the exception of the devices referred to in the second subparagraph of Article 52(8). Prior to the sampling, the notified body in question shall specify the relevant sampling criteria and testing procedure.

The notified body shall provide the manufacturer in question with an on-site audit report which shall include, if applicable, the result of the sample test.

3.5. In the case of class IIa and class IIb devices, the surveillance assessment shall also include an assessment of the technical documentation as referred to in Sections 4.4 to 4.8 for the device or devices concerned on the basis of further representative samples chosen in accordance with the rationale documented by the notified body in accordance with the second paragraph of Section 2.3.

In the case of class III devices, the surveillance assessment shall also include a test of the approved parts and/or materials that are essential for the integrity of the device, including, where appropriate, a check that the quantities of produced or purchased parts and/or materials correspond to the quantities of finished devices.

3.6. The notified body shall ensure that the composition of the assessment team is such that there is sufficient experience with the evaluation of the devices, systems and processes concerned, continuous objectivity and neutrality; this shall include a rotation of the members of the assessment team at appropriate intervals. As a general rule, a lead auditor shall neither lead nor attend audits for more than three consecutive years in respect of the same manufacturer.

3.7. If the notified body finds a divergence between the sample taken from the devices produced or from the market and the specifications laid down in the technical documentation or the approved design, it shall suspend or withdraw the relevant certificate or impose restrictions on it.

CHAPTER II

Assessment of the technical documentation

4. Assessment of the technical documentation applicable to class III devices and to the class IIb devices referred to in the second subparagraph of Article 52(4)

4.1. In addition to the obligations laid down in Section 2, the manufacturer shall lodge with the notified body an application for assessment of the technical documentation relating to the device which it plans to place on the market or put into service and which is covered by the quality management system referred to in Section 2.

4.2. The application shall describe the design, manufacture and performance of the device in question. It shall include the technical documentation as referred to in Annexes II and III.

4.3. The notified body shall examine the application by using staff, employed by it, with proven knowledge and experience regarding the technology concerned and its clinical application. The notified body may require the application to be completed by having further tests carried out or requesting further evidence to be provided to allow assessment of conformity with the relevant requirements of the Regulation. The notified body shall carry out adequate physical or laboratory tests in relation to the device or request the manufacturer to carry out such tests.

4.4. The notified body shall review the clinical evidence presented by the manufacturer in the clinical evaluation report and the related clinical evaluation that was conducted. The notified body shall employ device reviewers with sufficient clinical expertise and, if necessary, use external clinical experts with direct and current experience relating to the device in question or the clinical condition in which it is utilised, for the purposes of that review.

4.5. The notified body shall, in circumstances in which the clinical evidence is based partly or totally on data from devices which are claimed to be equivalent to the device under assessment, assess the suitability of using such data, taking into account factors such as new indications and innovation. The notified body shall clearly document its conclusions on the claimed equivalence, and on the relevance and adequacy of the data for demonstrating conformity. For any characteristic of the device claimed as innovative by the manufacturer or for new indications, the notified body shall assess to what extent specific claims are supported by specific pre-clinical and clinical data and risk analysis.

4.6. The notified body shall verify that the clinical evidence and the clinical evaluation are adequate and shall verify the conclusions drawn by the manufacturer on the conformity with the relevant general safety and performance requirements. That verification shall include consideration of the adequacy of the benefit-risk determination, the risk management, the instructions for use, the user training and the manufacturer’s post-market surveillance plan, and include a review of the need for, and the adequacy of, the PMCF plan proposed, where applicable.

4.7. Based on its assessment of the clinical evidence, the notified body shall consider the clinical evaluation and the benefit-risk determination, and whether specific milestones need to be defined to allow the notified body to review updates to the clinical evidence that result from post-market surveillance and PMCF data.

4.8. The notified body shall clearly document the outcome of its assessment in the clinical evaluation assessment report.

4.9. The notified body shall provide the manufacturer with a report on the technical documentation assessment, including a clinical evaluation assessment report. If the device conforms to the relevant provisions of this Regulation, the notified body shall issue an EU technical documentation assessment certificate. The certificate shall contain the conclusions of the technical documentation assessment, the conditions of the certificate’s validity, the data needed for identification of the approved design, and, where appropriate, a description of the intended purpose of the device.

4.10. Changes to the approved device shall require approval from the notified body which issued the EU technical documentation assessment certificate where such changes could affect the safety and performance of the device or the conditions prescribed for use of the device. Where the manufacturer plans to introduce any of the above- mentioned changes it shall inform the notified body which issued the EU technical documentation assessment certificate thereof. The notified body shall assess the planned changes and decide whether the planned changes require a new conformity assessment in accordance with Article 52 or whether they could be addressed by means of a supplement to the EU technical documentation assessment certificate. In the latter case, the notified body shall assess the changes, notify the manufacturer of its decision and, where the changes are approved, provide it with a supplement to the EU technical documentation assessment certificate.

5. Specific additional procedures

5.1. Assessment procedure for certain class III and class IIb devices

(a)For class III implantable devices, and for class IIb active devices intended to administer and/or remove a medicinal product as referred to in Section 6.4. of Annex VIII (Rule 12), the notified body shall, having verified the quality of clinical data supporting the clinical evaluation report of the manufacturer referred to in Article 61(12), prepare a clinical evaluation assessment report which sets out its conclusions concerning the clinical evidence provided by the manufacturer, in particular concerning the benefit-risk determination, the consistency of that evidence with the intended purpose, including the medical indication or indications and the PMCF plan referred to in Article 10(3) and Part B of Annex XIV.

The notified body shall transmit its clinical evaluation assessment report, along with the manufacturer’s clinical evaluation documentation, referred to in points (c) and (d) of Section 6.1 of Annex II, to the Commission.

The Commission shall immediately transmit those documents to the relevant expert panel referred to in Article 106.

(b)The notified body may be requested to present its conclusions as referred to in point (a) to the expert panel concerned.
(c) The expert panel shall decide, under the supervision of the Commission, on the basis of all of the following criteria:
(i) the novelty of the device or of the related clinical procedure involved, and the possible major clinical or health impact thereof;
(ii) a significantly adverse change in the benefit-risk profile of a specific category or group of devices due to scientifically valid health concerns in respect of components or source material or in respect of the impact on health in the case of failure of the device;
(iii) a significantly increased rate of serious incidents reported in accordance with Article 87 in respect of a specific category or group of devices,
whether to provide a scientific opinion on the clinical evaluation assessment report of the notified body based on the clinical evidence provided by the manufacturer, in particular concerning the benefit-risk determination, the consistency of that evidence with the medical indication or indications and the PMCF plan. That scientific opinion shall be provided within a period of 60 days, starting on the day of receipt of the documents from the Commission as referred to in point (a). The reasons for the decision to provide a scientific opinion on the basis of the criteria in points (i), (ii) and (iii) shall be included in the scientific opinion. Where the information submitted is not sufficient for the expert panel to reach a conclusion, this shall be stated in the scientific opinion.
(d)The expert panel may decide, under the supervision of the Commission, on the basis of the criteria laid down in point (c) not to provide a scientific opinion, in which case it shall inform the notified body as soon as possible and in any event within 21 days of receipt of the documents as referred to in point (a) from the Commission. The expert panel shall within that time limit provide the notified body and the Commission with the reasons for its decision, whereupon the notified body may proceed with the certification procedure of that device.
(e)The expert panel shall within 21 days of receipt of the documents from the Commission notify the Commission, through Eudamed whether it intends to provide a scientific opinion, pursuant to point (c), or whether it intends not to provide a scientific opinion, pursuant to point (d).
(f)Where no opinion has been delivered within a period of 60 days, the notified body may proceed with the certification procedure of the device in question.
(g)The notified body shall give due consideration to the views expressed in the scientific opinion of the expert panel. Where the expert panel finds that the level of clinical evidence is not sufficient or otherwise gives rise to serious concerns about the benefit-risk determination, the consistency of that evidence with the intended purpose, including the medical indication(s), and with the PMCF plan, the notified body shall, if necessary, advise the manufacturer to restrict the intended purpose of the device to certain groups of patients or certain medical indications and/or to impose a limit on the duration of validity of the certificate, to undertake specific PMCF studies, to adapt the instructions for use or the summary of safety and performance, or to impose other restrictions in its conformity assessment report, as appropriate. The notified body shall provide a full justification where it has not followed the advice of the expert panel in its conformity assessment report and the Commission shall without prejudice to Article 109 make both the scientific opinion of the expert panel and the written justification provided by the notified body publicly available via Eudamed.
(h)The Commission, after consultation with the Member States and relevant scientific experts shall provide guidance for expert panels for consistent interpretation of the criteria in point (c) before 26 May 2020.

5.2. Procedure in the case of devices incorporating a medicinal substance

(a)Where a device incorporates, as an integral part, a substance which, if used separately, may be considered to be a medicinal product within the meaning of point 2 of Article 1 of Directive 2001/83/EC, including a medicinal product derived from human blood or human plasma and that has an action ancillary to that of the device, the quality, safety and usefulness of the substance shall be verified by analogy with the methods specified in Annex I to Directive 2001/83/EC.
(b)Before issuing an EU technical documentation assessment certificate, the notified body shall, having verified the usefulness of the substance as part of the device and taking account of the intended purpose of the device, seek a scientific opinion from one of the competent authorities designated by the Member States in accordance with Directive 2001/83/EC or from the EMA, either of which to be referred to in this Section as ‘the medicinal products authority consulted’ depending on which has been consulted under this point, on the quality and safety of the substance including the benefit or risk of the incorporation of the substance into the device. Where the device incorporates a human blood or plasma derivative or a substance that, if used separately, may be considered to be a medicinal product falling exclusively within the scope of the Annex to Regulation (EC) No 726/2004, the notified body shall seek the opinion of the EMA.
(c)When issuing its opinion, the medicinal products authority consulted shall take into account the manufacturing process and the data relating to the usefulness of incorporation of the substance into the device as determined by the notified body.
(d)The medicinal products authority consulted shall provide its opinion to the notified body within 210 days of receipt of all the necessary documentation.
(e)The scientific opinion of the medicinal products authority consulted, and any possible update of that opinion, shall be included in the documentation of the notified body concerning the device. The notified body shall give due consideration to the views expressed in the scientific opinion when making its decision. The notified body shall not deliver the certificate if the scientific opinion is unfavourable and shall convey its final decision to the medicinal products authority consulted.
(f)Before any change is made with respect to an ancillary substance incorporated in a device, in particular related to its manufacturing process, the manufacturer shall inform the notified body of the changes. That notified body shall seek the opinion of the medicinal products authority consulted, in order to confirm that the quality and safety of the ancillary substance remain unchanged. The medicinal products authority consulted shall take into account the data relating to the usefulness of incorporation of the substance into the device as determined by the notified body, in order to ensure that the changes have no negative impact on the risk or benefit previously established concerning the incorporation of the substance into the device. The medicinal products authority consulted shall provide its opinion within 60 days after receipt of all the necessary documentation regarding the changes. The notified body shall not deliver the supplement to the EU technical documentation assessment certificate if the scientific opinion provided by the medicinal products authority consulted is unfavourable. The notified body shall convey its final decision to the medicinal products authority consulted.
(g)Where the medicinal products authority consulted obtains information on the ancillary substance, which could have an impact on the risk or benefit previously established concerning the incorporation of the substance into the device, it shall advise the notified body as to whether this information has an impact on the risk or benefit previously established concerning the incorporation of the substance into the device. The notified body shall take that advice into account in reconsidering its assessment of the conformity assessment procedure.

5.3. Procedure in the case of devices manufactured utilising, or incorporating, tissues or cells of human or animal origin, or their derivatives, that are non-viable or rendered non-viable

5.3.1. Tissues or cells of human origin or their derivatives

(a)For devices manufactured utilising derivatives of tissues or cells of human origin that are covered by this Regulation in accordance with point (g) of Article 1(6) and for devices that incorporate, as an integral part, tissues or cells of human origin, or their derivatives, covered by Directive 2004/23/EC, that have an action ancillary to that of the device, the notified body shall, prior to issuing an EU technical documentation assessment certificate, seek a scientific opinion from one of the competent authorities designated by the Member States in accordance with Directive 2004/23/EC (‘human tissues and cells competent authority’) on the aspects relating to the donation, procurement and testing of tissues or cells of human origin or their derivatives. The notified body shall submit a summary of the preliminary conformity assessment which provides, among other things, information about the non-viability of the human tissues or cells in question, their donation, procurement and testing and the risk or benefit of the incorporation of the tissues or cells of human origin or their derivatives into the device.
(b)Within 120 days of receipt of all the necessary documentation, the human tissues and cells competent authority shall provide to the notified body its opinion.
(c)The scientific opinion of the human tissues and cells competent authority, and any possible update, shall be included in the documentation of the notified body concerning the device. The notified body shall give due consideration to the views expressed in the scientific opinion of the human tissues and cells competent authority when making its decision. The notified body shall not deliver the certificate if that scientific opinion is unfavourable. It shall convey its final decision to the human tissues and cells competent authority concerned.
(d)Before any change is made with respect to non-viable tissues or cells of human origin or their derivatives incorporated in a device, in particular relating to their donation, testing or procurement, the manufacturer shall inform the notified body of the intended changes. The notified body shall consult the authority that was involved in the initial consultation, in order to confirm that the quality and safety of the tissues or cells of human origin or their derivatives incorporated in the device are maintained. The human tissues and cells competent authority concerned shall take into account the data relating to the usefulness of incorporation of the tissues or cells of human origin or their derivatives into the device as determined by the notified body, in order to ensure that the changes have no negative impact on the established benefit-risk ratio of the addition of the tissues or cells of human origin or their derivatives in the device. It shall provide its opinion within 60 days of receipt of all the necessary documentation regarding the intended changes. The notified body shall not deliver a supplement to the EU technical documentation assessment certificate if the scientific opinion is unfavourable and shall convey its final decision to the human tissues and cells competent authority concerned.

5.3.2. Tissues or cells of animal origin or their derivatives

In the case of devices manufactured utilising animal tissue which is rendered non-viable or utilising non-viable products derived from animal tissue, as referred to in Regulation (EU) No 722/2012, the notified body shall apply the relevant requirements laid down in that Regulation.

5.4. Procedure in the case of devices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body

(a)The quality and safety of devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed by, or locally dispersed in, the human body, shall be verified where applicable and only in respect of the requirements not covered by this Regulation, in accordance with the relevant requirements laid down in Annex I to Directive 2001/83/EC for the evaluation of absorption, distribution, metabolism, excretion, local tolerance, toxicity, interaction with other devices, medicinal products or other substances and potential for adverse reactions.
(b)In addition, for devices, or their products of metabolism, that are systemically absorbed by the human body in order to achieve their intended purpose, the notified body shall seek a scientific opinion from one of the competent authorities designated by the Member States in accordance with Directive 2001/83/EC or from the EMA, either of which to be referred to in this Section as ‘the medicinal products authority consulted’ depending on which has been consulted under this point, on the compliance of the device with the relevant requirements laid down in Annex I to Directive 2001/83/EC.
(c)The opinion of the medicinal products authority consulted shall be drawn up within 150 days of receipt of all the necessary documentation.
(d)The scientific opinion of the medicinal products authority consulted, and any possible update, shall be included in the documentation of the notified body concerning the device. The notified body shall give due consideration to the views expressed in the scientific opinion when making its decision and shall convey its final decision to the medicinal products authority consulted.

6. Batch verification in the case of devices incorporating, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma as referred to in Article 1(8)

Upon completing the manufacture of each batch of devices that incorporate, as an integral part, a medicinal substance which, if used separately, would be considered to be a medicinal product derived from human blood or human plasma as referred to in the first subparagraph of Article 1(8), the manufacturer shall inform the notified body of the release of the batch of devices and send it the official certificate concerning the release of the batch of human blood or plasma derivative used in the device, issued by a Member State laboratory or a laboratory designated for that purpose by a Member State in accordance with Article 114(2) of Directive 2001/83/EC.

CHAPTER III

Administrative provisions

7. The manufacturer or, where the manufacturer does not have a registered place of business in a Member State, its authorised representative shall, for a period ending no sooner than 10 years, and in the case of implantable devices no sooner than 15 years, after the last device has been placed on the market, keep at the disposal of the competent authorities:

—the EU declaration of conformity,
—the documentation referred to in the fifth indent of Section 2.1 and in particular the data and records arising from the procedures referred to in point (c) of the second paragraph of Section 2.2,
—information on the changes referred to in Section 2.4,
—the documentation referred to in Section 4.2, and
—the decisions and reports from the notified body as referred to in this Annex.

8. Each Member State shall require that the documentation referred to in Section 7 is kept at the disposal of competent authorities for the period indicated in that Section in case a manufacturer, or its authorised representative, established within its territory goes bankrupt or ceases its business activity prior to the end of that period.

ANNEX III

Technical documentation on post-market surveillance

The technical documentation on post-market surveillance to be drawn up by the manufacturer in accordance with Articles 83 to 86 shall be presented in a clear, organised, readily searchable and unambiguous manner and shall include in particular the elements described in this Annex.

1.1. The post-market surveillance plan drawn up in accordance with Article 84.

The manufacturer shall prove in a post-market surveillance plan that it complies with the obligation referred to in Article 83.

(a)The post-market surveillance plan shall address the collection and
utilization of available information, in particular:
— information concerning serious incidents, including information
from PSURs, and field safety corrective actions;
— records referring to non-serious incidents and data on any
undesirable side-effects;
— information from trend reporting;
— relevant specialist or technical literature, databases and/or
registers;
— information, including feedbacks and complaints, provided by
users, distributors and importers; and
— publicly available information about similar medical devices.
(b)The post-market surveillance plan shall cover at least:
— a proactive and systematic process to collect any information
referred to in point (a). The process shall allow a correct
characterisation of the performance of the devices and shall also
allow a comparison to be made between the device and similar
products available on the market;
— effective and appropriate methods and processes to assess the
collected data;
— suitable indicators and threshold values that shall be used in the
continuous reassessment of the benefit- risk analysis and of the riskmanagement as referred to in Section 3 of Annex I;
— effective and appropriate methods and tools to investigate
complaints and analyse market-related experience collected in the
field;
— methods and protocols to manage the events subject to the trend
report as provided for in Article 88, including the methods and
protocols to be used to establish any statistically significant increase in the frequency or severity of incidents as well as the observation
period;
— methods and protocols to communicate effectively with
competent authorities, notified bodies, economic operators and
users;
— reference to procedures to fulfil the manufacturers obligations
laid down in Articles 83, 84 and 86;
— systematic procedures to identify and initiate appropriate
measures including corrective actions;
— effective tools to trace and identify devices for which corrective
actions might be necessary; and
— a PMCF plan as referred to in Part B of Annex XIV, or a
justification as to why a PMCF is not applicable.

1.2. The PSUR referred to in Article 86 and the post-market surveillance report referred to in Article 85.

ANNEX II (PART 2)

Technical documentation

6. PRODUCT VERIFICATION AND VALIDATION

The documentation shall contain the results and critical analyses of all verifications and validation tests and/or studies undertaken to demonstrate conformity of the device with the requirements of this Regulation and in particular the applicable general safety and performance requirements.

6.1. Pre-clinical and clinical data

(a)results of tests, such as engineering, laboratory, simulated use and
animal tests, and evaluation of published literature applicable to the device, taking into account its intended purpose, or to similar
devices, regarding the pre-clinical safety of the device and its
conformity with the specifications;
(b)detailed information regarding test design, complete test or study
protocols, methods of data analysis, in addition to data summaries
and test conclusions regarding in particular:
— the biocompatibility of the device including the identification of all materials in direct or indirect contact with the patient or user;
— physical, chemical and microbiological characterisation;
— electrical safety and electromagnetic compatibility;
— software verification and validation (describing the software
design and development process and evidence of the validation of
the software, as used in the finished device. This information shall
typically include the summary results of all verification, validation
and testing performed both in-house and in a simulated or actual
user environment prior to final release. It shall also address all of
the different hardware configurations and, where applicable,
operating systems identified in the information supplied by the
manufacturer);
— stability, including shelf life; and
— performance and safety.

Where applicable, conformity with the provisions of Directive 2004/10/EC of the European Parliament and of the Council (1) shall be demonstrated.

Where no new testing has been undertaken, the documentation shall incorporate a rationale for that decision. An example of such a rationale would be that biocompatibility testing on identical materials was conducted when those materials were incorporated in a previous version of the device that has been legally placed on the market or put into service;

(c)the clinical evaluation report and its updates and the clinical
evaluation plan referred to in Article 61(12) and Part A of Annex
XIV;
(d)the PMCF plan and PMCF evaluation report referred to in Part B of
Annex XIV or a justification why a PMCF is not applicable.

6.2. Additional information required in specific cases

(a)Where a device incorporates, as an integral part, a substance which,if used separately, may be considered to be a medicinal product within the meaning of point 2 of Article 1 of Directive 2001/83/EC,
including a medicinal product derived from human blood or human plasma, as referred to in the first subparagraph of Article 1(8), a
statement indicating this fact. In this case, the documentation shall
identify the source of that substance and contain the data of the tests conducted to assess its safety, quality and usefulness, taking accountof the intended purpose of the device.
(b)Where a device is manufactured utilising tissues or cells of human
or animal origin, or their derivatives, and is covered by this
Regulation in accordance with points (f) and (g) of Article 1(6, and
where a device incorporates, as an integral part, tissues or cells of
human origin or their derivatives that have an action ancillary to
that of the device and is covered by this Regulation in accordance
with the first subparagraph of Article 1(10), a statement indicating
this fact. In such a case, the documentation shall identify all
materials of human or animal origin used and provide detailed
information concerning the conformity with Sections 13.1. or 13.2.,
respectively, of Annex I.
(c)In the case of devices that are composed of substances or
combinations of substances that are intended to be introduced into
the human body and that are absorbed by or locally dispersed in thehuman body, detailed information, including test design, complete
test or study protocols, methods of data analysis, and data
summaries and test conclusions, regarding studies in relation to:
— absorption, distribution, metabolism and excretion;
— possible interactions of those substances, or of their products of
metabolism in the human body, with other devices, medicinal
products or other substances, considering the target population, andits associated medical conditions;
— local tolerance; and
— toxicity, including single-dose toxicity, repeat-dose toxicity,
genotoxicity, carcinogenicity and reproductive and developmental
toxicity, as applicable depending on the level and nature of exposure to the device.

In the absence of such studies, a justification shall be provided.

(d)In the case of devices containing CMR or endocrine-disrupting
substances referred to in Section 10.4.1 of Annex I, the justification
referred to in Section 10.4.2 of that Annex.
(e)In the case of devices placed on the market in a sterile or defined
microbiological condition, a description of the environmental
conditions for the relevant manufacturing steps. In the case of
devices placed on the market in a sterile condition, a description of
the methods used, including the validation reports, with respect to
packaging, sterilisation and maintenance of sterility. The validation
report shall address bioburden testing, pyrogen testing and, if
applicable, testing for sterilant residues.
(f)In the case of devices placed on the market with a measuring
function, a description of the methods used in order to ensure the
accuracy as given in the specifications.
(g)If the device is to be connected to other device(s) in order to operate as intended, a description of this combination/configuration
including proof that it conforms to the general safety and
performance requirements when connected to any such device(s)
having regard to the characteristics specified by the manufacturer.

(1) Directive 2004/10/EC of the European Parliament and of the Council of 11 February 2004 on the harmonisation of laws, regulations and administrative provisions relating to the application of the principles of good laboratory practice and the verification of their applications for tests on chemical substances (OJ L 50, 20.2.2004, p. 44).

ANNEX II (PART 1)

Technical documentation

The technical documentation and, if applicable, the summary thereof to be drawn up by the manufacturer shall be presented in a clear, organised, readily searchable and unambiguous manner and shall include in particular the elements listed in this Annex.

1. DEVICE DESCRIPTION AND SPECIFICATION, INCLUDING VARIANTS AND ACCESSORIES

1.1. Device description and specification

(a)product or trade name and a general description of the device
including its intended purpose and intended users;
(b)the Basic UDI-DI as referred to in Part C of Annex VI assigned by
the manufacturer to the device in question, as soon as identificationof this device becomes based on a UDI system, or otherwise a clear
identification by means of product code, catalogue number or otherunambiguous reference allowing traceability;
(c)the intended patient population and medical conditions to be
diagnosed, treated and/or monitored and other considerations such
as patient selection criteria, indications, contra-indications,
warnings;
(d)principles of operation of the device and its mode of action,
scientifically demonstrated if necessary;
(e)the rationale for the qualification of the product as a device;
(f)the risk class of the device and the justification for the classification
rule(s) applied in accordance with Annex VIII;
(g)an explanation of any novel features;
(h)a description of the accessories for a device, other devices and otherproducts that are not devices, which are intended to be used in
combination with it;
(i)a description or complete list of the various configurations/variants
of the device that are intended to be made available on the market;
(j)a general description of the key functional elements, e.g. its parts/
components (including software if appropriate), its formulation, its
composition, its functionality and, where relevant, its qualitative and quantitative composition. Where appropriate, this shall include
labelled pictorial representations (e.g. diagrams, photographs, and
drawings), clearly indicating key parts/components, including
sufficient explanation to understand the drawings and diagrams;
(k)a description of the raw materials incorporated into key functional
elements and those making either direct contact with the human
body or indirect contact with the body, e.g., during extracorporeal
circulation of body fluids;
(l)technical specifications, such as features, dimensions and
performance attributes, of the device and any variants/
configurations and accessories that would typically appear in the
product specification made available to the user, for example in
brochures, catalogues and similar publications.

1.2. Reference to previous and similar generations of the device

(a)an overview of the previous generation or generations of the deviceproduced by the manufacturer, where such devices exist;
(b)an overview of identified similar devices available on the Union or
international markets, where such devices exist.

2. INFORMATION TO BE SUPPLIED BY THE MANUFACTURER

A complete set of:

—the label or labels on the device and on its packaging, such as single unit packaging, sales packaging, transport packaging in case of
specific management conditions, in the languages accepted in the
Member States where the device is envisaged to be sold; and
—the instructions for use in the languages accepted in the Member
States where the device is envisaged to be sold.

3. DESIGN AND MANUFACTURING INFORMATION

(a)information to allow the design stages applied to the device to be
understood;
(b)complete information and specifications, including the
manufacturing processes and their validation, their adjuvants, the
continuous monitoring and the final product testing. Data shall be
fully included in the technical documentation;
(c)identification of all sites, including suppliers and sub-contractors,
where design and manufacturing activities are performed.

4. GENERAL SAFETY AND PERFORMANCE REQUIREMENTS

The documentation shall contain information for the demonstration of conformity with the general safety and performance requirements set out in Annex I that are applicable to the device taking into account its intended purpose, and shall include a justification, validation and verification of the solutions adopted to meet those requirements. The demonstration of conformity shall include:

(a)the general safety and performance requirements that apply to the
device and an explanation as to why others do not apply;
(b)the method or methods used to demonstrate conformity with each
applicable general safety and performance requirement;
(c)the harmonised standards, CS or other solutions applied; and
(d)the precise identity of the controlled documents offering evidence of conformity with each harmonised standard, CS or other method
applied to demonstrate conformity with the general safety and
performance requirements. The information referred to under this
point shall incorporate a cross-reference to the location of such
evidence within the full technical documentation and, if applicable,
the summary technical documentation.

5. BENEFIT-RISK ANALYSIS AND RISK MANAGEMENT

The documentation shall contain information on:

(a)the benefit-risk analysis referred to in Sections 1 and 8 of Annex I,
and
(b)the solutions adopted and the results of the risk management
referred to in Section 3 of Annex I.

MDR – Article 45 – Review of notified body assessment of technical documentation and clinical evaluation documentation

Article 45

Review of notified body assessment of technical documentation and clinical evaluation documentation

1. The authority responsible for notified bodies, as part of its ongoing monitoring of notified bodies, shall review an appropriate number of notified body assessments of manufacturers’ technical documentation, in particular the clinical evaluation documentation as referred to in points (c) and (d) of Section 6.1 of Annex II to verify the conclusions drawn by the notified body based on the information presented by the manufacturer. The reviews by the authority responsible for notified bodies shall be conducted both off-site and on-site.

2. The sampling of files to be reviewed in accordance with paragraph 1 shall be planned and representative of the types and risk of devices certified by the notified body, in particular high-risk devices, and be appropriately justified and documented in a sampling plan, which shall be made available by the authority responsible for notified bodies to the MDCG upon request.

3. The authority responsible for notified bodies shall review whether the assessment by the notified body was conducted appropriately and shall check the procedures used, associated documentation and the conclusions drawn by the notified body. Such checking shall include the technical documentation and clinical evaluation documentation of the manufacturer upon which the notified body has based its assessment. Such reviews shall be conducted utilising CS.

4. Those reviews shall also form part of the re-assessment of notified bodies in accordance with Article 44(10) and the joint assessment activities referred to in Article 47(3). The reviews shall be conducted utilising appropriate expertise.

5. Based on the reports of the reviews and assessments by the authority responsible for notified bodies or joint assessment teams, on input from the market surveillance, vigilance and post-market surveillance activities described in Chapter VII, on the continuous monitoring of technical progress, or on the identification of concerns and emerging issues concerning the safety and performance of devices, the MDCG may recommend that the sampling, carried out under this Article, cover a greater or lesser proportion of the technical documentation and clinical evaluation documentation assessed by a notified body.

6. The Commission may, by means of implementing acts, adopt measures setting out the detailed arrangements, associated documents for, and coordination of, the review of assessments of technical documentation and clinical evaluation documentation, as referred to in this Article. Those implementing acts shall be adopted in accordance with the examination procedure referred to in Article 114(3).