Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU (Text with EEA relevance. )

• — 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,

• — 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 52.

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 approved type of a device,

• — any substance incorporated in or utilised for the manufacturing of a device and being subject to the specific procedures in accordance with Section 4.5.5.

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,

• — 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,

• — to review vigilance data to which they have access under to Article 87 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 on 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 authorities' 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 that it adequately assesses the manufacturer's documentation on, and application of, the provisions on vigilance, the post-market surveillance and PMPF,

• — 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 performance evaluation as most recently updated by the manufacturer based on the manufacturer's post-market surveillance, on its PMPF 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,

• — ensure that the performance 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 performance evaluation, including the results of any performance studies and PMPF,

• (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 performance studies 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 PMPF activities undertaken since the previous certification or re-certification, including appropriate updates to manufacturers' performance evaluation reports.

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

ANNEX VIII

CLASSIFICATION RULES

1. IMPLEMENTING RULES

• 1.1. Application of the classification rules shall be governed by the intended purpose of the devices.

• 1.2. If the device in question is intended to be used in combination with another device, the classification rules shall apply separately to each of the devices.

• 1.3. Accessories for an in vitro diagnostic medical device shall be classified in their own right separately from the device with which they are used.

• 1.4. Software, which drives a device or influences the use of a device, shall fall within the same class as the device.

If the software is independent of any other device, it shall be classified in its own right.

• 1.5. Calibrators intended to be used with a device shall be classified in the same class as the device.

• 1.6. Control materials with quantitative or qualitative assigned values intended for one specific analyte or multiple analytes shall be classified in the same class as the device.

• 1.7. The manufacturer shall take into consideration all classification and implementation rules in order to establish the proper classification for the device.

• 1.8. Where a manufacturer states multiple intended purposes for a device, and as a result the device falls into more than one class, it shall be classified in the higher class.

• 1.9. If several classification rules apply to the same device, the rule resulting in the higher classification shall apply.

• 1.10. Each of the classification rules shall apply to first line assays, confirmatory assays and supplemental assays.

2. CLASSIFICATION RULES

2.1.   Rule 1

Devices intended to be used for the following purposes are classified as class D:

• — detection of the presence of, or exposure to, a transmissible agent in blood, blood components, cells, tissues or organs, or in any of their derivatives, in order to assess their suitability for transfusion, transplantation or cell administration;

• — detection of the presence of, or exposure to, a transmissible agent that causes a life-threatening disease with a high or suspected high risk of propagation;

• — determining the infectious load of a life-threatening disease where monitoring is critical in the process of patient management.

2.2.   Rule 2

Devices intended to be used for blood grouping, or to determine foeto-maternal blood group incompatibility, or for tissue typing to ensure the immunological compatibility of blood, blood components, cells, tissue or organs that are intended for transfusion or transplantation or cell administration, are classified as class C, except when intended to determine any of the following markers:

• — ABO system [A (ABO1), B (ABO2), AB (ABO3)];

• — Rhesus system [RH1 (D), RHW1, RH2 (C), RH3 (E), RH4 (c), RH5 (e)];

• — Kell system [Kel1 (K)];

• — Kidd system [JK1 (Jka), JK2 (Jkb)];

• — Duffy system [FY1 (Fya), FY2 (Fyb)];

in which case they are classified as class D.

2.3.   Rule 3

Devices are classified as class C if they are intended:

• (a) for detecting the presence of, or exposure to, a sexually transmitted agent;

• (b) for detecting the presence in cerebrospinal fluid or blood of an infectious agent without a high or suspected high risk of propagation;

• (c) for detecting the presence of an infectious agent, if there is a significant risk that an erroneous result would cause death or severe disability to the individual, foetus or embryo being tested, or to the individual's offspring;

• (d) for pre-natal screening of women in order to determine their immune status towards transmissible agents;

• (e) for determining infective disease status or immune status, where there is a risk that an erroneous result would lead to a patient management decision resulting in a life-threatening situation for the patient or for the patient's offspring;

• (f) to be used as companion diagnostics;

• (g) to be used for disease staging, where there is a risk that an erroneous result would lead to a patient management decision resulting in a life-threatening situation for the patient or for the patient's offspring;

• (h) to be used in screening, diagnosis, or staging of cancer;

• (i) for human genetic testing;

• (j) for monitoring of levels of medicinal products, substances or biological components, when there is a risk that an erroneous result will lead to a patient management decision resulting in a life-threatening situation for the patient or for the patient's offspring;

• (k) for management of patients suffering from a life-threatening disease or condition;

• (l) for screening for congenital disorders in the embryo or foetus;

• (m) for screening for congenital disorders in new-born babies where failure to detect and treat such disorders could lead to life-threatening situations or severe disabilities.

2.4.   Rule 4

• (a) Devices intended for self-testing are classified as class C, except for devices for the detection of pregnancy, for fertility testing and for determining cholesterol level, and devices for the detection of glucose, erythrocytes, leucocytes and bacteria in urine, which are classified as class B.

• (b) Devices intended for near-patient testing are classified in their own right.

2.5.   Rule 5

The following devices are classified as class A:

• (a) products for general laboratory use, accessories which possess no critical characteristics, buffer solutions, washing solutions, and general culture media and histological stains, intended by the manufacturer to make them suitable for in vitro diagnostic procedures relating to a specific examination;

• (b) instruments intended by the manufacturer specifically to be used for in vitro diagnostic procedures;

• (c) specimen receptacles.

2.6.   Rule 6

Devices not covered by the above-mentioned classification rules are classified as class B.

2.7.   Rule 7

Devices which are controls without a quantitative or qualitative assigned value are classified as class B.

ANNEX IX

CONFORMITY ASSESSMENT BASED ON A QUALITY MANAGEMENT SYSTEM AND ON ASSESSMENT OF TECHNICAL DOCUMENTATION

CHAPTER I

QUALITY MANAGEMENT SYSTEM

• 1. The manufacturer shall establish, document and implement a quality management system, as described in Article 10(8), and maintain its effectiveness throughout the life cycle of the devices concerned. The manufacturer shall ensure the application of the quality management system as specified in Section 2, and shall be subject to audit as laid down in Sections 2.3 and 2.4 and to surveillance as specified in Section 3.

• 1. 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 17 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 of 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 PMPF plan, and the procedures put in place to ensure compliance with the obligations resulting from the provisions on vigilance set out in Articles 82 to 87,

• — a description of the procedures in place to keep up to date the post-market surveillance system and, where applicable, the PMPF plan, and the procedures ensuring compliance with the obligations resulting from the provisions on vigilance set out in Articles 82 to 87, as well as the undertaking by the manufacturer to apply those procedures,

• — documentation on the performance evaluation plan, and

• — a description of the procedures in place to keep up to date the performance 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,
• — 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 into account and, where opted for, harmonised standards,
• — risk management as referred to in Section 3 of Annex I,
• — the performance evaluation, pursuant to Article 56 and Annex XIII, including PMPF,
• — 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;

• (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 B and C devices, the quality management system assessment shall be accompanied by the assessment of the technical documentation for devices selected on a representative basis as specified in Section 4. In choosing representative samples the notified body shall take into account the published guidance developed by the MDCG pursuant to Article 99 and in particular, the novelty of the technology, the potential impact on the patient and standard medical practice, similarities in design, technology, manufacturing and, where applicable, sterilisation methods, the intended purpose and the results of any previous relevant assessments 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.

• 1. Surveillance assessment

• 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,

• — the documentation on any findings and conclusions resulting from the application of the post-market surveillance plan, including the PMPF plan, for a representative sample of devices, and of the provisions on vigilance set out in Articles 82 to 87,

• — 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,

• — 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, the site 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. 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, notified bodies shall take samples of devices from the market to verify that the manufactured device is in conformity with the technical documentation. 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 B and C devices, the surveillance assessment shall also include an assessment of the technical documentation as specified in Section 4 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 third paragraph of Section 2.3.

• 3.6. Notified bodies 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 of class B, C and D devices and batch verification applicable to class D devices

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

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

In the case of devices for self-testing or near-patient testing, the application shall also include the aspects referred to in point (b) of Section 5.1.

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

• 4.4. The notified body shall review the clinical evidence presented by the manufacturer in the performance evaluation report and the related performance evaluation that was conducted. The notified body shall use employed device reviewers with sufficient clinical expertise and including external clinical experts with direct and current experience relating to the clinical application of the device in question for the purposes of that review.

• 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.

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

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

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

• 4.9. Before issuing an EU technical documentation assessment certificate, the notified body shall request an EU reference laboratory, where designated in accordance with Article 100, to verify the performance claimed by the manufacturer and the compliance of the device with the CS, where available, or with other solutions chosen by the manufacturer to ensure a level of safety and performance that is at least equivalent. The verification shall include laboratory tests by the EU reference laboratory as referred to in Article 48(5).

In addition, the notified body shall, in the cases referred to in Article 48(6) of this Regulation, consult the relevant experts referred to in Article 106 of Regulation (EU) 2017/745 in accordance with the procedure laid down in Article 48(6) of this Regulation on the performance evaluation report of the manufacturer.

The EU reference laboratory shall provide a scientific opinion within 60 days.

The scientific opinion of the EU reference laboratory and, where applicable, the views of the experts consulted, pursuant to the procedure laid down in Article 48(6), and any possible updates shall be included in the documentation of the notified body concerning the device. The notified body shall, when making its decision, give due consideration to the views expressed in the scientific opinion of the EU reference laboratory, and, where applicable, to the views expressed by the experts consulted pursuant to Article 48(6). The notified body shall not deliver the certificate if the scientific opinion of the EU reference laboratory is unfavourable.

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

• 4.11. Changes to the approved device shall require approval from the notified body which issued the EU technical documentation assessment certificate, where such changes could affect the safety and performance of the device or the conditions prescribed for use of the device. Where the manufacturer plans to introduce any of the above-mentioned changes it shall inform the notified body which issued the EU technical documentation assessment certificate thereof. The notified body shall assess the planned changes and decide whether the planned changes require a new conformity assessment in accordance with Article 48 or whether they could be addressed by means of a supplement to the EU technical documentation assessment certificate. In the latter case, the notified body shall assess the changes, notify the manufacturer of its decision and, where the changes are approved, provide it with a supplement to the EU technical documentation assessment certificate.

Where the changes could affect compliance with the CS or with other solutions chosen by the manufacturer which were approved through the EU technical documentation assessment certificate, the notified body shall consult the EU reference laboratory that was involved in the initial consultation, in order to confirm that compliance with the CS or with other solutions chosen by the manufacturer, to ensure a level of safety and performance that is at least equivalent, is maintained.

The EU reference laboratory shall provide a scientific opinion within 60 days.

• 4.12. To verify conformity of manufactured class D devices, the manufacturer shall carry out tests on each manufactured batch of devices. After the conclusion of the controls and tests, it shall forward to the notified body, without delay, the relevant reports on those tests. Furthermore, the manufacturer shall make the samples of manufactured batches of devices available to the notified body in accordance with pre-agreed conditions and detailed arrangements which shall include that the notified body or the manufacturer shall send samples of the manufactured batches of devices to the EU reference laboratory, where such a laboratory has been designated in accordance with Article 100, to carry out appropriate tests. The EU reference laboratory shall inform the notified body about its findings.

• 4.13. The manufacturer may place the devices on the market, unless the notified body communicates to the manufacturer within the agreed timeframe, but not later than 30 days after reception of the samples, any other decision, including in particular any condition of validity of delivered certificates.

5. Assessment of the technical documentation of specific types of devices

5.1.   Assessment of the technical documentation of class B, C and D devices for self-testing and near-patient testing

• (a) The manufacturer of class B, C and D devices for self-testing and near-patient testing shall lodge with the notified body an application for the assessment of the technical documentation.

• (b) The application shall enable the design of the device characteristics and performance(s) to be understood and shall enable conformity with the design-related requirements of this Regulation to be assessed. It shall include:
• (i) test reports, including results of studies carried out with intended users;
• (ii) where practicable, an example of the device; if required, the device shall be returned on completion of the technical documentation assessment;
• (iii) data showing the suitability of the device in view of its intended purpose for self-testing or near patient-testing;
• (iv) the information to be provided with the device on its label and its instructions for use. The notified body may require the application to be completed by carrying out further tests or by providing further proof to allow assessment of conformity with the requirements of this Regulation.

• (c) The notified body shall verify the compliance of the device with the relevant requirements set out in Annex I of this Regulation.

• (d) The notified body shall assess the application, by using staff, employed by it, with proven knowledge and experience regarding the technology concerned and the intended purpose of the device and provide the manufacturer with a technical documentation assessment report.

• (e) If the device conforms to the relevant provisions of this Regulation, the notified body shall issue an EU technical documentation assessment certificate. The certificate shall contain the conclusions of the assessment, the conditions of its validity, the data needed for the identification of the approved devices and, where appropriate, a description of the intended purpose of the device.

• (f) Changes to the approved device shall require approval from the notified body which issued the EU technical documentation assessment certificate, where such changes could affect the safety and performance of the device or the conditions prescribed for use of the device. Where the manufacturer plans to introduce any of the above-mentioned changes, it shall inform the notified body which issued the EU technical documentation assessment certificate thereof. The notified body shall assess the planned changes and decide whether the planned changes require a new conformity assessment in accordance with Article 48 or whether they could be addressed by means of a supplement to the EU technical documentation assessment certificate. In the latter case, the notified body shall assess the changes, notify the manufacturer of its decision and, where the changes are approved, provide it with a supplement to the EU technical documentation assessment certificate.

5.2.   Assessment of the technical documentation of companion diagnostics

• (a) The manufacturer of a companion diagnostic shall lodge with the notified body an application for the assessment of the technical documentation. The notified body shall assess that application in accordance with the procedure laid down in Sections 4.1 to 4.8 of this Annex.

• (b) The application shall enable the characteristics and performance of the device to be understood, and shall enable conformity with the design-related requirements of this Regulation to be assessed, in particular, with regard to the suitability of the device in relation to the medicinal product concerned.

• (c) The notified body shall, before issuing an EU technical documentation assessment certificate for the companion diagnostic and on the basis of the draft summary of safety and performance and the draft instructions for use, seek a scientific opinion from one of the competent authorities designated by the Member States in accordance with Directive 2001/83/EC or from the EMA, either of which to be referred to in this Section as ‘the medicinal products authority consulted’ depending on which has been consulted under this point, regarding the suitability of the device in relation to the medicinal product concerned. Where the medicinal product falls exclusively within the scope of the Annex to Regulation (EC) No 726/2004 of the European Parliament and of the Council ([^E0009]), the notified body shall seek the opinion of the EMA. If the medicinal product concerned is already authorised, or if an application for its authorisation has been submitted, the notified body shall consult the medicinal products authority, or the EMA, that is responsible for the authorisation.

• (d) The medicinal products authority consulted shall provide its opinion, within 60 days of receipt of all the necessary documentation. This 60-day period may be extended once for a further 60 days on justified grounds. The opinion and any possible update shall be included in the documentation of the notified body concerning the device.

• (e) The notified body shall give due consideration to the scientific opinion referred to in point (d) when making its decision. The notified body shall convey its final decision to the medicinal products authority consulted. The EU technical documentation assessment certificate shall be delivered in accordance with point (e) of Section 5.1.

• (f) Before changes affecting the performance and/or the intended use and/or the suitability of the device in relation to the medicinal product concerned are made, the manufacturer shall inform the notified body of the changes. The notified body shall assess the planned changes and decide whether the planned changes require a new conformity assessment in accordance with Article 48 or whether they could be addressed by means of a supplement to the EU technical documentation assessment certificate. In the latter case, the notified body shall assess the changes and seek the opinion of the medicinal products authority consulted. The medicinal products authority consulted shall give its opinion within 30 days of receipt of the all the necessary documentation regarding the changes. A supplement to the EU technical documentation assessment certificate shall be issued in accordance with point (f) of Section 5.1.

CHAPTER III

ADMINISTRATIVE PROVISIONS

• 1. The manufacturer or, where the manufacturer does not have a registered place of business in a Member State, it's authorised representative shall, for a period ending no sooner than 10 years after the last device has been placed on the market, keep at the disposal of the competent authorities:

• — 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 Sections 4.2. and point (b) of Section 5.1., and

• — the decisions and reports from the notified body as referred to in this Annex.

• 1. Each Member State shall require that the documentation referred to in Section 6 is kept at the disposal of competent authorities for the period indicated in that Section in case a manufacturer, or its authorised representative, established within its territory goes bankrupt or ceases its business activity prior to the end of that period.

ANNEX X

CONFORMITY ASSESSMENT BASED ON TYPE-EXAMINATION

• 1. EU type-examination is the procedure whereby a notified body ascertains and certifies that a device, including its technical documentation and relevant life cycle processes and a corresponding representative sample of the device production envisaged, fulfils the relevant provisions of this Regulation.

• 1. Application

The manufacturer shall lodge an application for assessment with a notified body. The application shall include:

• — the name of the manufacturer and the address of its registered place of business and, if the application is lodged by the authorised representative, the name of the authorised representative and the address of its registered place of business,

• — the technical documentation referred to in Annexes II and III. The applicant shall make a representative sample of the device production envisaged (‘type’) available to the notified body. The notified body may request other samples as necessary,

• — in the case of devices for self-testing or near-patient testing, test reports, including results of studies carried out with intended users, and data showing the handling suitability of the device in relation to its intended purpose for self-testing or near patient-testing,

• — where practicable, an example of the device. If required, the device shall be returned on completion of the technical documentation assessment;

• — data showing the suitability of the device in relation to its intended purpose for self-testing or near-patient testing,

• — the information to be provided with the device on its label and its instructions for use, and

• — a written declaration that no application has been lodged with any other notified body for the same type, or information about any previous application for the same type that was refused by another notified body or was withdrawn by the manufacturer or its authorised representative before that other notified body made its final assessment.

• 1. Assessment

The notified body shall:

• (a) examine the application, by using staff with proven knowledge and experience in the evaluation of the technology, and the devices concerned and the evaluation of clinical evidence. The notified body may require the application to be completed by having further tests carried out or requesting further evidence to be provided to allow assessment of conformity with the relevant requirements of this Regulation. The notified body shall carry out adequate physical or laboratory tests in relation to the device or request the manufacturer to carry out such tests;

• (b) examine and assess the technical documentation for conformity with the requirements of this Regulation that are applicable to the device and verify that the type has been manufactured in conformity with that documentation; it shall also record the items designed in conformity with the applicable standards referred to in Article 8 or with applicable CS, and record items not designed on the basis of the relevant standards referred to in Article 8 or of the relevant CS;

• (c) review the clinical evidence presented by the manufacturer in the performance evaluation report in accordance with Section 1.3.2 of Annex XIII. The notified body shall employ device reviewers with sufficient clinical expertise and, if necessary, use external clinical experts with direct and current experience relating to the clinical application of the device in question for the purposes of that review;

• (d) in circumstances in which the clinical evidence is partly or totally based on data from devices which are claimed to be similar or equivalent to the device under assessment, assess the suitability of using such data, taking into account factors such as new indications and innovation. The notified body shall clearly document its conclusions on the claimed equivalence, and on the relevance and adequacy of the data for demonstrating conformity;

• (e) clearly document the outcome of its assessment in the performance evaluation assessment report referred to in Section 4.8 of Annex IX;

• (f) carry out or arrange for the appropriate assessments and the physical or laboratory tests necessary to verify whether the solutions adopted by the manufacturer meet the general safety and performance requirements laid down in this Regulation in the event that the standards referred to in Article 8 or the CS have not been applied. Where the device has to be connected to another device or devices in order to operate as intended, proof shall be provided that it conforms to the general safety and performance requirements when connected to any such device or devices having the characteristics specified by the manufacturer;

• (g) carry out or arrange for the appropriate assessments and the physical or laboratory tests necessary to verify whether, in the event that the manufacturer has chosen to apply the relevant harmonised standards, those standards have actually been applied;

• (h) agree with the applicant on the place where the necessary assessments and tests are to be carried out;

• (i) draw up an EU type-examination report on the results of the assessments and tests carried out under points (a) to (g);

• (j) in the case of class D devices, request the EU reference laboratory, where designated in accordance with Article 100, to verify the performance claimed by the manufacturer and the compliance of the device with the CS, where available, or with other solutions chosen by the manufacturer to ensure a level of safety and performance that is at least equivalent. The verification shall include laboratory tests by the EU reference laboratory in accordance with Article 48(5). In addition, the notified body shall, in the cases referred to in Article 48(6) of this Regulation, consult the relevant experts referred to in Article 106 of Regulation (EU) 2017/745 following the procedure laid down in Article 48(6) of this Regulation on the performance evaluation report of the manufacturer. The EU reference laboratory shall provide a scientific opinion within 60 days. The scientific opinion of the EU reference laboratory and, where the procedure laid down in Article 48(6) is applicable, the views of the experts consulted, and any possible updates shall be included in the documentation of the notified body concerning the device. The notified body shall give due consideration to the views expressed in the scientific opinion of the EU reference laboratory, and, where applicable, to the views expressed by the experts consulted in accordance with Article 48(6), when making its decision. The notified body shall not deliver the certificate if the scientific opinion of the EU reference laboratory is unfavourable;

• (k) for companion diagnostics, seek the opinion, on the basis of the draft summary of safety and performance and the draft instructions for use, of one of the competent authorities designated by the Member States in accordance with Directive 2001/83/EC or the EMA (either of which to be hereinafter referred to as ‘the medicinal products authority consulted’ depending on which has been consulted under this point) on the suitability of the device in relation to the medicinal product concerned. Where the medicinal product falls exclusively within the scope of the Annex of Regulation (EC) No 726/2004, the notified body shall consult the EMA. If the medicinal product concerned is already authorised, or if an application for its authorisation has been submitted, the notified body shall consult the medicinal products competent authority, or the EMA, that is responsible for the authorisation. The medicinal products authority consulted shall deliver its opinion within 60 days of receipt of all the necessary documentation. This 60-day period may be extended once for a further 60 days on justified grounds. The opinion of the medicinal products authority consulted and any possible update shall be included in the documentation of the notified body concerning the device. The notified body shall give due consideration to the opinion expressed by the medicinal products authority consulted when making its decision. It shall convey its final decision to the medicinal products authority consulted; and

• (l) draw up an EU type-examination report on the results of the assessments and tests carried out, and scientific opinions provided under, points (a) to (k), including a performance evaluation assessment report for class C or class D devices or covered by the third indent of Section 2.

• 1. Certificate

If the type conforms to this Regulation, the notified body shall issue an EU type-examination certificate. The certificate shall contain the name and address of the manufacturer, the conclusions of the type examination assessment, the conditions of certificate's validity and the data needed for identification of the type approved. The certificate shall be drawn up in accordance with Annex XII. The relevant parts of the documentation shall be annexed to the certificate and a copy kept by the notified body.

• 1. Changes to the type

• 5.1. The applicant shall inform the notified body which issued the EU type-examination certificate of any planned change to the approved type or of its intended purpose and conditions of use.

• 5.2. Changes to the approved device including limitations of its intended purpose and conditions of use shall require further approval from the notified body which issued the EU type-examination certificate where such changes may affect conformity with the general safety and performance requirements or with the conditions prescribed for use of the product. The notified body shall examine the planned changes, notify the manufacturer of its decision and provide him with a supplement to the EU type-examination report. The approval of any change to the approved type shall take the form of a supplement to the EU type-examination certificate.

• 5.3. Changes to the intended purpose and conditions of use of the approved device, with the exception of limitations of the intended purpose and conditions of use, shall necessitate a new application for a conformity assessment.

• 5.4. Where the changes could affect the performance claimed by the manufacturer or compliance with the CS or with other solutions chosen by the manufacturer which were approved through the EU type-examination certificate, the notified body shall consult the EU reference laboratory that was involved in the initial consultation, in order to confirm that compliance with the CS, when available, or with other solutions chosen by the manufacturer to ensure a level of safety and performance that is at least equivalent are maintained.

The EU reference laboratory shall provide a scientific opinion within 60 days.

• 5.5. Where the changes affect the performance or the intended use of a companion diagnostic approved through the EU type-examination certificate or its suitability in relation to a medicinal product, the notified body shall consult the medicinal products competent authority that was involved in the initial consultation or the EMA. The medicinal products authority consulted shall give its opinion, if any, within 30 days after receipt of the valid documentation regarding the changes. The approval of any change to the approved type shall take the form of a supplement to the initial EU type-examination certificate.

• 1. Administrative provisions

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

• — the documentation referred to in the second indent of Section 2,

• — information on the changes referred to in Section 5,

• — copies of EU type-examination certificates, scientific opinions and reports and their additions/supplements.

Section 7 of Annex IX shall apply.

ANNEX XI

CONFORMITY ASSESSMENT BASED ON PRODUCTION QUALITY ASSURANCE

• 1. The manufacturer shall ensure that the quality management system approved for the manufacture of the devices concerned is implemented, shall carry out final verification, as specified in Section 3, and shall be subject to the surveillance referred to in Section 4.

• 1. When the manufacturer fulfils the obligations laid down in Section 1, it shall draw up and keep an EU declaration of conformity in accordance with Article 17 and Annex IV for the device covered by the conformity assessment procedure. By issuing an EU declaration of conformity, the manufacturer shall be deemed to ensure, and to declare, that the device concerned meets the requirements of this Regulation which apply to the device, and in the case of class C and class D devices that undergo a type examination, conforms to the type described in the EU type-examination certificate.

• 1. Quality management system

• 3.1. The manufacturer shall lodge an application for assessment of its quality management system with a notified body.

The application shall include:

• — all elements listed in Section 2.1 of Annex IX,

• — the technical documentation referred to in Annexes II and III for the types approved,

• — a copy of the EU type-examination certificates referred to in Section 4 of Annex X; if the EU type-examination certificates have been issued by the same notified body with which the application is lodged, a reference to the technical documentation and its updates and the certificates issued shall also be included in the application.

• 3.2. Implementation of the quality management system shall be such as to ensure that there is compliance with the type described in the EU type-examination certificate and with the provisions of this Regulation which apply to the devices at each stage. 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.

That documentation shall, in particular, include an adequate description of all elements listed in points (a), (b), (d) and (e) of Section 2.2. of Annex IX.

• 3.3. The first and second paragraphs of Section 2.3 of Annex IX shall apply.

If the quality management system is such that it ensures that the devices conform to the type described in the EU type-examination certificate and conform to the relevant provisions of this Regulation, the notified body shall issue an EU production quality assurance certificate. The notified body shall notify the manufacturer of its decision to issue the certificate. That decision shall contain the conclusions of the notified body's audit and a reasoned assessment.

• 3.4. Section 2.4 of Annex IX shall apply.

• 1. Surveillance

Section 3.1, the first, second and fourth indents of Section 3.2, Sections 3.3, 3.4, 3.6 and 3.7 of Annex IX shall apply.

• 1. Verification of manufactured class D devices

• 5.1. In the case of class D devices, the manufacturer shall carry out tests on each manufactured batch of devices. After the conclusion of the controls and tests, it shall forward to the notified body without delay the relevant reports on those tests. Furthermore, the manufacturer shall make samples of manufactured devices or batches of devices available to the notified body in accordance with pre-agreed conditions and detailed arrangements which shall include that the notified body or the manufacturer, shall send samples of the manufactured devices or batches of devices to an EU reference laboratory, where such a laboratory has been designated in accordance with Article 100, to carry out appropriate laboratory tests. The EU reference laboratory shall inform the notified body about its findings.

• 5.2. The manufacturer may place the devices on the market, unless the notified body communicates to the manufacturer within the agreed timeframe, but not later than 30 days after reception of the samples, any other decision, including in particular any condition of validity of delivered certificates.

• 1. Administrative provisions

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

• — the EU declaration of conformity,

• — the documentation referred to in the fifth indent of Section 2.1 of Annex IX,

• — the documentation referred to in the eighth indent of Section 2.1 of Annex IX, including the EU type-examination certificate referred to in Annex X,

• — information on the changes referred to in Section 2.4 of Annex IX, and

• — the decisions and reports from the notified body as referred to in Sections 2.3., 3.3. and 3.4. of Annex IX.

Section 7 of Annex IX shall apply.

ANNEX XII

CERTIFICATES ISSUED BY A NOTIFIED BODY

CHAPTER I

GENERAL REQUIREMENTS

• 1. Certificates shall be drawn up in one of the official languages of the Union.

• 1. Each certificate shall refer to only one conformity assessment procedure.

• 1. Certificates shall only be issued to one manufacturer. The name and address of the manufacturer included in the certificate shall be the same as that registered in the electronic system referred to in Article 27.

• 1. The scope of the certificates shall unambiguously describe the device or devices covered:
• (a) EU technical documentation assessment certificates and EU type-examination certificates shall include a clear identification, including the name, model and type, of the device or devices, the intended purpose as indicated by the manufacturer in the instructions for use and in relation to which the device has been assessed in the conformity assessment procedure, risk classification and the Basic UDI-DI as referred to in Article 24(6).
• (b) EU quality management system certificates and EU production quality assurance certificates shall include the identification of the devices or groups of devices, the risk classification and the intended purpose.

• 1. The notified body shall be able to demonstrate on request, which (individual) devices are covered by the certificate. The notified body shall set up a system that enables the determination of the devices, including their classification, covered by the certificate.

• 1. Certificates shall contain, if applicable, a note that, for the placing on the market of the device or devices it covers, another certificate issued in accordance with this Regulation is required.

• 1. EU quality management system certificates and EU production quality assurance certificates for class A sterile devices shall include a statement that the audit by the notified body was limited to the aspects of manufacture concerned with securing and maintaining sterile conditions.

• 1. Where a certificate is supplemented, modified or re-issued, the new certificate shall contain a reference to the preceding certificate and its date of issue with identification of the changes.

CHAPTER II

MINIMUM CONTENT OF THE CERTIFICATES

• 1. name, address and identification number of the notified body;

• 1. name and address of the manufacturer and, if applicable, of the authorised representative;

• 1. unique number identifying the certificate;

• 1. if already issued, the SRN of the manufacturer referred to in Article 28(2);

• 1. date of issue;

• 1. date of expiry;

• 1. data needed for the unambiguous identification of the device or devices where applicable as specified in Section 4 of this Annex;

• 1. if applicable, reference to any previous certificate as specified in Section 8 of Chapter I;

• 1. reference to this Regulation and the relevant Annex in accordance with which the conformity assessment has been carried out;

• 1. examinations and tests performed, e.g. reference to relevant CS, harmonised standards, test reports and audit report(s);

• 1. if applicable, reference to the relevant parts of the technical documentation or other certificates required for the placing on the market of the device or devices covered;

• 1. if applicable, information about the surveillance by the notified body;

• 1. conclusions of the notified body's conformity assessment with regard to the relevant Annex;

• 1. conditions for or limitations to the validity of the certificate;

• 1. legally binding signature of the notified body in accordance with the applicable national law.

ANNEX XIII

PERFORMANCE EVALUATION, PERFORMANCE STUDIES AND POST-MARKET PERFORMANCE FOLLOW-UP

PART A

PERFORMANCE EVALUATION AND PERFORMANCE STUDIES

1. PERFORMANCE EVALUATION

Performance evaluation of a device is a continuous process by which data are assessed and analysed to demonstrate the scientific validity, analytical performance and clinical performance of that device for its intended purpose as stated by the manufacturer. To plan, continuously conduct and document a performance evaluation, the manufacturer shall establish and update a performance evaluation plan. The performance evaluation plan shall specify the characteristics and the performance of the device and the process and criteria applied to generate the necessary clinical evidence.

The performance evaluation shall be thorough and objective, considering both favourable and unfavourable data.

Its depth and extent shall be proportionate and appropriate to the characteristics of the device including the risks, risk class, performance and its intended purpose.

1.1.   Performance evaluation plan

As a general rule, the performance evaluation plan shall include at least:

• — a specification of the intended purpose of the device;

• — a specification of the characteristics of the device as described in Section 9 of Chapter II of Annex I and in point (c) of Section 20.4.1. of Chapter III of Annex I;

• — a specification of the analyte or marker to be determined by the device;

• — a specification of the intended use of the device;

• — identification of certified reference materials or reference measurement procedures to allow for metrological traceability;

• — a clear identification of specified target patient groups with clear indications, limitations and contra-indications;

• — an identification of the general safety and performance requirements as laid down in Sections 1 to 9 of Annex I that require support from relevant scientific validity and analytical and clinical performance data;

• — a specification of methods, including the appropriate statistical tools, used for the examination of the analytical and clinical performance of the device and of the limitations of the device and information provided by it;

• — a description of the state of the art, including an identification of existing relevant standards, CS, guidance or best practices documents;

• — an indication and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the intended purpose or purposes and for the analytical and clinical performance of the device;

• — for software qualified as a device, an identification and specification of reference databases and other sources of data used as the basis for its decision making;

• — an outline of the different development phases including the sequence and means of determination of the scientific validity, the analytical and clinical performance, including an indication of milestones and a description of potential acceptance criteria;

• — the PMPF planning as referred to in Part B of this Annex.

Where any of the above mentioned elements are not deemed appropriate in the Performance Evaluation Plan due to the specific device characteristics a justification shall be provided in the plan.

1.2.   Demonstration of the scientific validity and the analytical and clinical performance:

As a general methodological principle the manufacturer shall:

• — identify through a systematic scientific literature review the available data relevant to the device and its intended purpose and identify any remaining unaddressed issues or gaps in the data;

• — appraise all relevant data by evaluating their suitability for establishing the safety and performance of the device;

• — generate any new or additional data necessary to address outstanding issues.

1.2.1.   Demonstration of the scientific validity

The manufacturer shall demonstrate the scientific validity based on one or a combination of the following sources:

• — relevant information on the scientific validity of devices measuring the same analyte or marker;

• — scientific (peer-reviewed) literature;

• — consensus expert opinions/positions from relevant professional associations;

• — results from proof of concept studies;

• — results from clinical performance studies.

The scientific validity of the analyte or marker shall be demonstrated and documented in the scientific validity report.

1.2.2.   Demonstration of the analytical performance

The manufacturer shall demonstrate the analytical performance of the device in relation to all the parameters described in point (a) of Section 9.1 of Annex I, unless any omission can be justified as not applicable.

As a general rule, the analytical performance shall always be demonstrated on the basis of analytical performance studies.