08/01/2023 | EAEU Decisions
Recommendation of the Board of the Eurasian Economic Commission of May 21, 2019 No. 14 "On the Guidelines for Conducting Expert Examination of Safety, Quality and Efficacy of Medical Devices for the Purpose of Their Registration within the Framework of the Eurasian Economic Union"
BOARD OF THE EURASIAN ECONOMIC COMMISSION
RECOMMENDATION
of 21 May 2019 No. 14
ON METHODOLOGICAL GUIDELINES
FOR CONDUCTING THE SAFETY, QUALITY AND EFFICACY
ASSESSMENT OF MEDICAL DEVICES FOR THE PURPOSE
OF THEIR REGISTRATION WITHIN THE EURASIAN ECONOMIC UNION
The Board of the Eurasian Economic Commission, in accordance with Article 31 of the Treaty on the Eurasian Economic Union of 29 May 2014 and Article 4 of the Agreement on Uniform Principles and Rules for the Circulation of Medical Devices (Medical Products and Medical Equipment) within the Eurasian Economic Union of 23 December 2014,
for the purpose of establishing uniform approaches to conducting the safety, quality and efficacy assessment of medical devices within the Eurasian Economic Union,
recommends that the Member States of the Eurasian Economic Union, from the date of publication of this Recommendation on the official website of the Eurasian Economic Union, apply the Methodological Guidelines for Conducting the Safety, Quality and Efficacy Assessment of Medical Devices for the Purpose of Their Registration within the Eurasian Economic Union as set out in the Annex.
Chairman of the Board
of the Eurasian Economic Commission
T. SARKISYAN
Annex
to Recommendation
of the Board of the Eurasian
Economic Commission
of 21 May 2019 No. 14
METHODOLOGICAL GUIDELINES
FOR CONDUCTING THE SAFETY, QUALITY AND EFFICACY ASSESSMENT
OF MEDICAL DEVICES FOR THE PURPOSE OF THEIR REGISTRATION
WITHIN THE EURASIAN ECONOMIC UNION
1. These Methodological Guidelines are intended for use by experts of competent authorities (expert organisations) conducting the safety, quality and efficacy assessment of medical devices for the purpose of their registration within the Eurasian Economic Union (hereinafter — the Union) in accordance with the Rules for Registration and Assessment of the Safety, Quality and Efficacy of Medical Devices, approved by Decision of the Council of the Eurasian Economic Commission of 12 February 2016 No. 46 (hereinafter — the Registration Rules).
2. These Methodological Guidelines have been developed for the purpose of:
establishing uniform approaches to conducting the safety, quality and efficacy assessment of medical devices;
harmonising expert requirements for the type and content of evidentiary materials (documents) of the medical device manufacturer submitted for assessment in the course of collecting evidence of the safety and efficacy of the medical device and preparing the registration dossier.
3. For the purposes of applying these Methodological Guidelines, the following terms shall have the meanings set out below:
"first-party evidence" — the manufacturer's and/or authorised representative's own evidentiary materials (documents) (records of own tests (studies), including those issued by certification bodies and testing laboratories (centres) accredited within the national accreditation system of a Union Member State, results of clinical use, and other materials);
"evidence of authorised organisations" — test (study) reports issued by authorised organisations;
"clinical safety of a medical device" — the absence of unacceptable risk of harm to a patient when using the medical device in accordance with the instructions for use;
"configuration of a medical device" — a combination of components of a medical device specified in the registration dossier which, in accordance with the instructions for use, enables the intended purpose of the medical device to be achieved in accordance with the manufacturer's intended use;
"authorised organisations" — institutions, organisations or enterprises included in the unified register of authorised organisations entitled to conduct research (testing) of medical devices for the purpose of their registration.
Other terms are used in the meanings defined by acts of the Union bodies in the field of medical device circulation.
4. The safety, quality and efficacy of a medical device shall be confirmed by:
(a) review and assessment of registration dossier documents proving the medical device's compliance with the applicable provisions of the General Safety and Efficacy Requirements for Medical Devices, requirements for their labelling and operational documentation, approved by Decision of the Council of the Eurasian Economic Commission of 12 February 2016 No. 27 (hereinafter — the General Requirements);
(b) review of manufacturing inspection reports in accordance with the Requirements for the Implementation, Maintenance and Assessment of the Quality Management System for Medical Devices Depending on the Potential Risk of Their Application, approved by Decision of the Council of the Eurasian Economic Commission of 10 November 2017 No. 106;
(c) assessment of the manufacturer's plan for collecting and analysing post-market safety and efficacy data on the medical device (for medical devices submitted for registration), and information on identified adverse effects of the medical device during use (for medical devices with a market history);
(d) review of information on adverse events and market withdrawals of medical devices (for medical devices with a market history) and/or medical device safety notices, as well as information on corrective actions taken in such cases;
(e) review of post-registration clinical monitoring reports in accordance with the Rules for Conducting Safety, Quality and Efficacy Monitoring of Medical Devices, approved by Decision of the Board of the Eurasian Economic Commission of 22 December 2015 No. 174 (for registered medical devices).
5. A risk-based approach shall be applied when conducting the safety, quality and efficacy assessment of medical devices: expert requirements for the scope and level of detail of evidentiary materials (documents) in the registration dossier shall be proportional to the potential risk class of the medical device.
6. Documents confirming the safety and efficacy of a medical device, as provided for in paragraphs 4, 5, 8–10, 12–27 and 30 of Annex No. 4 to the Registration Rules, shall be submitted as separate documents within the registration dossier and may form part of the technical file.
The conformity of the information contained in the documents required for registration of a medical device in accordance with Annex No. 4 to the Registration Rules with the technical file data structure for the medical device shall be confirmed by submitting information in accordance with the Annex.
7. The technical file may include any evidentiary materials (documents), including informational ones. They may be submitted as annexes or as separate documents.
8. Evidentiary materials (documents) of the technical file that are managed as standalone documents (e.g., the risk management file, instructions for use) shall be referenced in the relevant sections and/or clauses of the technical file.
If documents provided for in Annex No. 4 to the Registration Rules are submitted as part of the technical file, they shall be identified as standalone structural units of the technical file and may be managed as standalone documents.
If documents confirming the safety and efficacy of the medical device are submitted as part of the technical file, the conformity of its structure and content with Annex No. 3 to the Rules for Conducting Clinical and Clinical-Laboratory Tests (Studies) of Medical Devices, approved by Decision of the Council of the Eurasian Economic Commission of 12 February 2016 No. 29 (hereinafter — the Clinical Trials Rules), and with Annex No. 5 to the Requirements for the Implementation, Maintenance and Assessment of the Quality Management System for Medical Devices Depending on the Potential Risk of Their Application, shall be verified.
9. When reviewing the medical device description, the following shall be assessed:
(a) correctness of classification as a medical device. When assessing the correctness of classification as a medical device, the following shall be taken into account in order of priority: the definition of "medical device", the definition of "in vitro diagnostic medical device", and the criteria for classifying products as medical devices in accordance with Recommendation of the Board of the Eurasian Economic Commission of 12 November 2018 No. 25. The terms "medical device" and "in vitro diagnostic medical device" shall be applied taking into account the definition of "intended purpose of a medical device" established by the Clinical Trials Rules;
(b) correctness of determination of the potential risk class in accordance with the Rules for Classification of Medical Devices Depending on the Potential Risk of Application, approved by Decision of the Board of the Eurasian Economic Commission of 22 December 2015 No. 173. When indicating the potential risk class, the applicant may refer to the applicable clause of those Rules. When considering the correctness of classifying in vitro diagnostic medical devices that may be used as general laboratory devices into potential risk class 1, the possibility of their dual use in accordance with paragraph 40 of those Rules shall be verified;
(c) correctness of classification by type of medical device in accordance with the Union Nomenclature of Medical Devices. If the applicant provides the GMDN code for the type of medical device, its correspondence to the code of the medical device type in the Union Nomenclature of Medical Devices shall be verified or determined. When preparing the registration dossier, the applicant shall determine the type and code of the medical device type in accordance with the Union Nomenclature of Medical Devices published on the Union information portal on the Internet. If the Union Nomenclature of Medical Devices does not contain a corresponding type for the medical device being registered, the applicant shall, prior to submitting the registration dossier, ensure the inclusion of the new type of medical device in the Union Nomenclature of Medical Devices in the established manner;
(d) information placed on the labelling of the medical device and/or its components enabling identification of the medical device and/or its components in accordance with subsection 13 of Section III and subsection 11 of Section IV of the General Requirements.
Identifying features may include, for example, the name of the medical device and/or component and the name of the manufacturer, and/or model number, and/or modification (variant) number or name, and/or reference to the identifying number (article number) of the model and/or its components, as well as a combination of identifying features. During the assessment, the adequacy of the identifying features used by the manufacturer for unambiguous traceability of the medical device and/or its components to the registration dossier data shall be verified. If the medical device submitted for registration includes several modifications (variants) or several components, the labelling and instructions for use of a specific device shall indicate the name of the modification (variant), while the general name of the medical device in accordance with the registration application may be omitted. For multiple modifications (variants), fields for variable parameters in labelling drafts (layouts) may be left blank;
(e) description of modifications (variants) and/or configurations of the medical device under consideration. The configuration of a medical device may vary in accordance with the needs of a specific consumer within the limits indicated in the instructions for use;
(f) availability of characteristics contained in the instructions for use and other materials accessible to the end user, as well as characteristics used by the manufacturer to prove the medical device's compliance with the General Requirements. Conformity of characteristics specified in the instructions for use and in the registration dossier shall be assessed. No additional characteristics are required from the manufacturer. The product summary for the medical device shall indicate its functional characteristics as its brief description, which are contained in the instructions for use and other documents accessible to the end user;
(g) availability of a list of applied standards, if the manufacturer applies standards to ensure the safety and efficacy of the medical device;
(h) availability of a description of materials in direct or indirect contact with the human body for the purpose of performing the medical device's functions in accordance with its intended use (except for in vitro diagnostic medical devices).
For non-invasive medical devices of potential risk classes 1 and 2a, category A (short-term contact per GOST ISO 10993-1), the name of the material shall be indicated. For medical devices of potential risk class 2a, categories B and C (prolonged or permanent contact per GOST ISO 10993-1), and potential risk class 2a invasive medical devices and class 2b, category A (per GOST ISO 10993-1), the name and grade or specification of the material shall be indicated. For medical devices of potential risk class 2b, categories B and C (per GOST ISO 10993-1), as well as potential risk class 3, the name, grade or specification of the material, and its manufacturer shall be indicated;
(i) availability of a description of medicinal products contained in the medical device that exert an additional effect on the human body alongside the effect of the medical device, their influence on the medical device's functionality, the compatibility of the medicinal product with the medical device (except for in vitro diagnostic medical devices), as well as information on the authorisation for use of the medicinal product in the manufacturer's country;
(j) availability of a description of materials of animal or human origin, cultures of microorganisms and viruses incorporated into the medical device, information on the selection of sources (donors), material sampling, processing, storage, testing, validation of testing procedures, and handling of tissues, cells, substances of animal or human origin, cultures of microorganisms and viruses. The level of detail of this information shall be determined taking into account the results of risk analysis and risk management.
10. Information on the medical device's conformity with the General Requirements shall be submitted by the manufacturer in the form provided for in Annex No. 2 to the General Requirements.
11. Conformity of the medical device with the General Requirements shall be ensured by directly fulfilling the requirements set out therein or by fulfilling the requirements of the relevant sections of standards included in the list of standards, the voluntary application of which fully or partially ensures conformity of medical devices with the General Safety and Efficacy Requirements for Medical Devices, requirements for their labelling and operational documentation (hereinafter — the list) (Annex to Recommendation of the Board of the Eurasian Economic Commission of 4 September 2017 No. 17).
12. The safety and efficacy requirements for medical devices set out in paragraphs 3–11 of the General Requirements are applicable to all medical devices.
Table 1 provides recommendations for reviewing and assessing evidentiary materials (documents) submitted by the manufacturer to confirm conformity with those requirements.
Table 1
| Clause of the General Requirements | Content of the assessment |
|---|---|
| 3. Medical devices shall be designed and manufactured in such a way that, when used under conditions and for purposes corresponding to their intended use as determined by the manufacturer, and where necessary taking into account the technical knowledge, experience, education or special training, clinical and physical condition of the user, they shall perform as intended by the manufacturer and shall be safe for the user and third parties, provided that the risk associated with their use is acceptable when weighed against the benefit to the user. Interchangeability of medical devices shall not be restricted through the use of specific technical or software means or by other methods. | Assessment of conformity with the first paragraph of this clause shall be conducted (as applicable) on the basis of the manufacturer's risk analysis report, the conclusions of the clinical evidence report on the efficacy and safety of the medical device, clinical (clinical-laboratory) test (study) reports, and evidentiary materials (documents) confirming conformity with applicable standards. It shall be verified that hazards associated with the medical device have been identified, the associated risks assessed, and the overall residual risk is acceptable when weighed against the benefit in accordance with Section IV of these Methodological Guidelines. Conformity with the second paragraph of this clause shall be confirmed by a manufacturer's declaration that the technical or software means applied do not restrict the interchangeability of medical devices. |
| 4. Decisions made by the manufacturer in designing and manufacturing the medical device shall be consistent with safety principles taking into account the generally recognised state of the art. Where necessary, the manufacturer shall manage risks so that the residual risk associated with any hazard is acceptable. The manufacturer shall apply the following principles in order of priority: identification of known or foreseeable hazards and assessment of the associated risks arising from use of the medical device as intended and in cases of reasonably foreseeable misuse; elimination of risks through appropriate technical and technological design and manufacturing decisions; reduction of residual risks through adequate protective measures, including alarms; informing users of all residual risks. | The manufacturer's data on the methods applied to eliminate and/or reduce risks to an acceptable level in accordance with Section IV of these Methodological Guidelines shall be reviewed, and materials confirming conformity with applicable standards shall be assessed. It shall be verified that the labelling and/or instructions for use contain information on all residual risks that are unacceptable according to the criteria established in the risk management plan, provided that the benefit from the intended use of the medical device outweighs the residual risk. |
| 5. Medical devices shall be designed, manufactured and packaged in such a way that their performance characteristics and efficacy are not compromised during transport and storage in accordance with the instructions for use. | To confirm conformity with this requirement, the existence of transport and storage requirements shall be verified, and evidence from authorised organisations and first-party evidence confirming that performance characteristics (e.g., stability) and efficacy were not compromised during transport and storage in accordance with the instructions for use shall be reviewed. |
| 6. Medical devices shall be effective as intended by the manufacturer and shall be designed and manufactured so that, under normal conditions of use, they meet the intended purposes in accordance with the intended use as determined by the manufacturer. | Assessment of conformity shall be conducted (as applicable) on the basis of the clinical evidence report on the efficacy and safety of the medical device and the instructions for use (operational documentation). Additionally, materials confirming conformity with applicable standards shall be assessed. |
| 7. The performance characteristics and efficacy of the medical device shall not deteriorate to such a degree as to compromise the life and health of users and third parties during the service life determined by the manufacturer, provided that the medical device is subjected to conditions that may arise under normal conditions of use and maintenance is carried out in accordance with the instructions for use. | To confirm conformity with this requirement, the medical device stability study report, or data obtained from clinical use experience, or materials confirming conformity with applicable standards shall be assessed (as applicable). |
| 8. All known and foreseeable risks arising from the use of the medical device, and any undesirable effects of such use, shall be minimised and shall be acceptable when weighed against the benefit to users derived from the intended action of the medical device as determined by the manufacturer under normal conditions of use. | To confirm conformity with this requirement, the manufacturer's conclusions on the acceptability of the overall residual risk shall be reviewed in accordance with Section IV of these Methodological Guidelines. |
| 9. Each medical device shall be accompanied by information necessary to identify the medical device and its manufacturer, the country of origin, and information for the user (professional or non-professional) concerning the safety, functional properties and performance characteristics of the medical device. Such information may be located on the medical device itself, on its packaging or in the instructions for use. | Compliance with this requirement shall be verified against the labelling data submitted by the manufacturer in the registration dossier and the instructions for use (operational documents). The verification shall confirm that the information provided on the medical device itself, its packaging and in the instructions for use, taken together, is consistent with the registration documentation in accordance with the requirements of paragraph 9 of the General Requirements and is sufficient for its identification. |
| 10. The information medium, its format, content and placement shall be appropriate for the medical device, its intended use, and the technical knowledge, experience, education or training of users. The information medium shall contain, as limitations on use, contraindications, precautions or warnings, information on the residual risks associated with the use of the medical device. The concept of "contraindications" is not applicable to in vitro diagnostic medical devices. | Compliance with this requirement shall be verified against the labelling data submitted by the manufacturer in the registration dossier, and in the instructions for use (operational documents) taking into account the risk analysis report data. |
| 11. The information provided for in paragraph 9 of these General Requirements shall be indicated on the labelling and in the instructions for use in Russian, and, where required by the legislation of Member States, in the official language(s) of the Member States. Such information may include symbols established by interstate standards, as well as those established by international standards (provided that the safety of the medical device is not compromised due to certain users' inability to understand the meaning of such symbols). | Compliance with this requirement shall be verified against the labelling data submitted by the manufacturer in the registration dossier, and in the instructions for use (operational documents). Additional labelling with information in the official language(s) of the EAEU Member States shall be required if the reference state or the state(s) of recognition selected are EAEU Member States whose legislation provides for such a requirement. For medical devices intended by the manufacturer for use by users with specialised medical training, any symbols whose use is provided for by the relevant standards included in the list may be applied. For medical devices intended by the manufacturer for use by users without specialised medical training, the meaning of symbols provided for by the relevant standards included in the list shall be explained in the instructions for use. |
13. Confirmation of medical device conformity with the General Requirements where the requirements set out therein are fulfilled directly, i.e., without reference to the requirements of a standard included in the list, shall be verified by reviewing the evidentiary materials (documents) indicated by the manufacturer in the list in the form provided for in Annex No. 2 to the General Requirements. Such evidentiary materials (documents) may include first-party evidence, evidence of authorised organisations, including test (study) results confirming conformity with applicable standards not included in the list.
14. The manufacturer may apply standards and methods not included in the list; however, their application does not create a presumption of medical device conformity with the General Requirements. In this case, the manufacturer shall provide justification for the validity of the applied standard and/or method for confirming medical device conformity with the General Requirements. During the assessment, the validity of the standards and/or methods used by the manufacturer to prove medical device conformity with the General Requirements shall be evaluated, including the effectiveness of those standards and/or methods, which shall not be inferior to the requirements of the standards included in the list.
15. If the manufacturer's documentation references standards that have not been adopted in the national standardisation systems of the reference state and/or state(s) of recognition, the relevant requirements of the standard shall be stated directly in the documentation without cross-references.
16. If, during the assessment, the validity of the requirements of the applied standard has been confirmed for proving the safety and efficacy of the medical device, the evidence of conformity with the applied standard shall be assessed taking into account the potential risk class of the medical device:
for medical devices of potential risk classes 1 and 2a, first-party evidence may be accepted;
for medical devices of potential risk classes 2b and 3, first-party evidence may be accepted together with an attached test (study) programme and justification of the selected methods.
17. Confirmation of conformity with the requirements of applicable standards included in the list is the guaranteed method of proving conformity with the General Requirements.
If the manufacturer applies standards included in the list to prove medical device conformity with the General Requirements, it shall provide a list of such standards applicable to the medical device.
If the manufacturer does not apply all structural elements of a standard included in the list to prove medical device conformity with the General Requirements, it shall provide justification for their non-application in the conformity information in the form provided for in Annex No. 2 to the General Requirements, as a note indicating the structural element of the standard in column 4 of the form. During the assessment, the justification for non-application of individual structural elements of the standard included in the list shall be evaluated to confirm that the exclusions do not reduce the safety and/or efficacy of the medical device under consideration.
If the manufacturer applies a later version of a standard included in the list, the presumption of medical device conformity with the General Requirements shall extend only to those norms and requirements of the applied standard that do not modify or reduce the requirements for the medical device compared to the requirements of the standard included in the list. In this case, the test (study) results shall be considered valid. To confirm that the norms and requirements of the applied standard do not reduce the requirements for the medical device compared to the requirements of the standard included in the list, the applicant shall provide a table of changes for the applied structural elements of the standard with an analysis of the differences.
18. The manufacturer may confirm medical device conformity with a standard included in the list by the following means:
(a) evidence of authorised organisations. Tests (studies) for conformity with the requirements of standards included in the list that are product standards shall be conducted by an authorised organisation using the test (study) methods contained in the relevant standards included in the list.
Test (study) results of authorised organisations shall be recognised provided they have been performed in accordance with the Rules for Conducting Technical Tests of Medical Devices, approved by Decision of the Council of the Eurasian Economic Commission of 12 February 2016 No. 28, and the Rules for Conducting Research (Tests) for the Purpose of Assessing the Biological Effects of Medical Devices, approved by Decision of the Council of the Eurasian Economic Commission of 16 May 2016 No. 38.
If tests (studies) have been conducted by authorised organisations in accordance with the aforementioned documents, but during the assessment facts are identified that cast doubt on the reliability of the results obtained, the competent authority (expert organisation) may inform the competent authority that submitted information on the authorised organisation to the Eurasian Economic Commission for inclusion in the unified register of authorised organisations entitled to conduct research (testing) of medical devices for registration purposes, and/or the accreditation body of the relevant Union Member State. However, this shall not affect the recognition of the test (study) report in respect of which such facts were identified;
(b) first-party evidence in cases where the relevant standard included in the list is applicable to medical devices but no standardised or officially validated test (study) method exists.
During the assessment, the justification provided by the medical device manufacturer and/or the manufacturer's authorised representative regarding the validity of the applied test (study) method for confirming conformity with the standard included in the list shall be evaluated, taking into account the potential risk class of the medical device:
for medical devices of potential risk classes 1 and 2a, first-party evidence may be accepted;
for medical devices of potential risk classes 2b and 3, first-party evidence may be accepted together with an attached test (study) programme and justification of the selected methods.
19. Where the manufacturer applies pharmacopoeial articles (monographs) of the Union Pharmacopoeia or the pharmacopoeias of Union Member States to prove medical device conformity with the General Requirements, the evidentiary materials (documents) and the applicability of the pharmacopoeial articles to the medical device shall be assessed during the expert review.
20. In accordance with GOST ISO 14971, risk analysis includes hazard identification and estimation of associated risks. Pursuant to paragraph 4 of the General Requirements, the manufacturer shall confirm that it assesses and manages risks so that residual risks are acceptable.
21. The manufacturer shall provide a summary report containing:
(a) documented information on all cases of intended use and reasonably foreseeable misuse, as well as all qualitative and quantitative characteristics ensuring the prevention of unacceptable risk (with their maximum permissible values indicated where necessary);
(b) a list of known or foreseeable hazards associated with the use of the medical device both under normal conditions and in the event of a malfunction;
(c) a list of hazardous situations and reasonably foreseeable sequences or combinations of events leading to hazardous situations. Determination of hazardous situations and associated risks may not be required where the potential harm from the hazards under consideration is minimal;
(d) risk estimation for each hazardous situation. For hazardous situations where the probability of harm cannot be determined, a list of possible consequences of medical device use shall be prepared for use in risk evaluation and management. For hazards and hazardous situations covered by product safety standards applied by the manufacturer that are included in the list, the associated risks need not be determined and/or evaluated. In such cases, the risks shall be considered acceptable;
(e) risk control measures required to reduce risks to an acceptable level in accordance with the criteria established in the risk management plan.
22. If the residual risk, based on the criteria established in the risk management plan, is deemed unacceptable and further risk reduction is not practicable, the manufacturer shall conduct a risk-benefit analysis on the basis of all available data. If the analysis indicates that the benefit of the intended use of the medical device outweighs the residual risk, the risk shall be considered acceptable.
23. During the assessment of the report, the absence of unacceptable risks shall be verified, thereby confirming the safety of the medical device. If the assessment concludes that risks have been underestimated and/or the risk reduction measures taken are ineffective to such a degree that they fall within the unacceptable zone of the risk matrix, the expert report shall indicate the reasons leading to higher risks (e.g., increased severity and/or probability of harm) that result in an unacceptable risk.
| Note: By Decision of the Council of the EEC of 26.01.2024 No. 7, the Clinical Trials Rules have been set out in a new edition. For clinical efficacy evidence, see paragraph 6 of the new edition of the Rules. |
24. In accordance with paragraph 7 of the Clinical Trials Rules, where clinical data are used to prove medical device conformity with the General Requirements, the clinical evidence of efficacy and safety of the medical device shall be documented in a report and shall include all clinical data on which it is based.
25. For in vitro diagnostic medical devices, the clinical evidence report on efficacy and safety shall be prepared where the in vitro diagnostic medical device is subject to analytical performance indicators (such as sensitivity, specificity, accuracy, repeatability, reproducibility, limit of detection and measurement range) or clinical performance characteristics (such as diagnostic sensitivity and diagnostic specificity). For in vitro diagnostic medical devices of potential risk class 1, preparation of the clinical evidence report on efficacy and safety is not mandatory.
26. The clinical evidence report on the efficacy and safety of the medical device shall be kept up to date in accordance with the document management rules adopted by the enterprise, taking into account data obtained from post-market surveillance and/or new confirmed information from scientific literature sources relating to its safety and efficacy.
27. Recommendations on the structure of the clinical evidence report on the efficacy and safety of the medical device and the content of the assessment are set out in Table 2.
The information and data contained in the clinical evidence report on the efficacy and safety of the medical device shall allow assessment of the correctness of the statistical data analysis methods used and the statistical reliability of the test (study) results.
Table 2
| Section title | Content recommendations (as applicable) | Assessment of the information provided |
|---|---|---|
| 1. General information on the report | the report shall contain the date of preparation and information on the persons who prepared it (full name, position) | the presence of the report date and information on the persons who prepared it shall be verified |
| 2. General information on the medical device | identification of the medical device and its modifications (variants) covered by the report | the medical device shall be identified in accordance with the requirements of paragraph 9 of the General Requirements. The report shall be verified to contain information on all declared modifications (variants) of the medical device |
| name and address of the manufacturer and (if applicable) its authorised representative | the name and address of the manufacturer and (if applicable) its authorised representative shall correspond to the data indicated in the registration application and other registration dossier documents | |
| brief description of the medical device, its modifications (variants), possible configurations, including key functional characteristics, and information on materials in contact with the patient's body | the presence of the information and its conformity with the registration dossier documents shall be verified | |
| intended use of the medical device, description of the properties and/or characteristics that enable the intended purpose of the medical device to be achieved in accordance with the manufacturer's intended use | the conformity of the intended use and stated characteristics with the data provided in the registration dossier documents shall be verified | |
| information on users and target groups | the presence of information on users (e.g., patient, healthcare professional, individual using the medical device as intended by the manufacturer) and target groups, and its conformity with the evidentiary materials (documents) shall be verified | |
| indications and contraindications for use, residual risks (if any) | the presence of information on indications, contraindications and residual risks (as applicable) shall be verified. Contraindications and residual risks (if any) shall be stated unambiguously and clearly. The concept of "contraindications" is not used for in vitro diagnostic medical devices | |
| classification characteristics of the medical device (as applicable): frequency of use (single-use, reusable); invasiveness (invasive, surgically invasive, non-invasive, implantable); microbiological status (sterile, non-sterile, sterilisable, pyrogenic, apyrogenic) | classification characteristics shall be indicated as applicable (where a characteristic is not applicable, information on it may be omitted). The stated classification characteristics shall correspond to the data provided in other registration dossier documents | |
| information on the circulation of the medical device in third countries and the market history of the device | the information is provided at the applicant's discretion; such data may be used to support clinical efficacy evidence | |
| 3. Clinical aspects of medical device use | description of the medical field of application of the medical device | the field of application shall be described in accordance with the intended use specified in the registration dossier documents |
| brief information describing the medical technologies applied to achieve the intended purpose of the medical device in accordance with the manufacturer's intended use and to ensure clinical safety. References to data sources used may be included where necessary | the data overview presented shall relate to the medical device submitted for registration | |
| description of clinical conditions (diseases) relevant to the medical device's field of application | the presence of a description of clinical conditions (diseases) relevant to the medical device's field of application shall be verified | |
| 4. Methods applied by the manufacturer to prove clinical efficacy and safety of the medical device | based on clinical data obtained: through a literature search for the medical device under consideration or for a medical device whose equivalence to the medical device under consideration has been demonstrated pursuant to item 8 of this table; from clinical use experience of the medical device under consideration; from clinical tests (studies); from a combination of the above methods; by other means | the justification for the choice of methods for proving clinical efficacy and safety of the medical device under consideration shall be verified if another method is used |
| 5. Clinical data obtained through a literature search (if the manufacturer applies this method) | an overview of clinical data on the medical device under consideration or an equivalent device shall be provided, including the objectives and goals of the search for relevant clinical efficacy and safety data with indication of data sources. The overview may include questions, keywords, and selection criteria for the data found for the purpose of clinical efficacy and safety evidence. The following databases may be used for the search, for example: MEDLINE — bibliographic database of medical science articles, covering approximately 75% of world medical publications; PubMed — public version of the MEDLINE database; EMBASE/Excerpta Medica — European database of biomedical and pharmacological publications; ClinicalTrials.gov — clinical trials (studies) database; Cochrane central trials register — clinical trials (studies) database; WHO International Clinical Trials Registry Platform — WHO clinical trials (studies) database. The overview shall ensure traceability of data sources | the validity of the data provided for proving clinical efficacy and safety shall be verified. Where necessary, full (unabridged) copies in the original language with a translation into Russian may be requested (for non-Russian language sources) |
| 6. Clinical data obtained from clinical use experience (if the manufacturer applies this method) | the manufacturer's materials on the collection and analysis of post-market efficacy and safety data on the medical device under consideration shall be provided. Such materials may include, inter alia, summary reports on adverse events and market withdrawals relative to the number of medical devices supplied, data on corrective and preventive actions taken in response to such events, consumer feedback on experience with the medical device, results of user surveys, identifiable records of oral survey results, and any forms and reports pursuant to the documented customer feedback procedure provided for by the enterprise's quality management system. For in vitro diagnostic medical devices, the manufacturer's materials on the collection and analysis of post-market efficacy and safety data are applicable for confirming analytical and clinical performance | the validity of the data provided for proving clinical efficacy and safety shall be verified |
| 7. Clinical data obtained from clinical tests (studies) (if the manufacturer applies this method) | results and conclusions of clinical (clinical-laboratory) tests (studies) shall be provided | the following shall be verified: conformity of clinical and clinical-laboratory tests (studies) conducted in Union Member States with the Clinical Trials Rules (if the data obtained are used in the report), for the purpose of recognising their results; conformity of clinical and clinical-laboratory tests (studies) conducted in non-Union Member States with the criteria of the Clinical Trials Rules, for the purpose of recognising their results as a source of clinical data on the medical device |
| 8. Proof of equivalence of another medical device to the device under consideration (if clinical data for another medical device are used to prove clinical efficacy and safety) | in accordance with the Clinical Trials Rules for Medical Devices, evidence shall be provided that: the medical devices under consideration have the same intended use; the technical and biological characteristics of the medical devices under consideration are identical to the extent that guarantees the absence of differences in their clinical efficacy and safety; for this purpose: comparative photographs of the medical devices under consideration shall be provided where they come into contact with the patient's body; data confirming that both medical devices have the same operating principle shall be provided; data confirming that both medical devices have identical biocompatibility properties shall be provided; all differences between the devices shall be identified, those that do not significantly affect clinical efficacy and safety shall be determined, and the reasons why these differences do not affect clinical efficacy and safety shall be explained; those differences that may significantly affect clinical efficacy and safety shall be identified. If such differences exist, to prove equivalence the manufacturer may conduct comparative technical tests, and/or biological effect evaluation tests, and/or clinical (clinical-laboratory) tests (studies) of medical devices, including with the involvement of certification bodies and testing laboratories (centres) accredited within the national accreditation system of a Union Member State | the justification for the equivalence of another medical device to the device under consideration shall be verified (if clinical data for another medical device are used to prove clinical efficacy and safety) |
| 9. Analysis of clinical data | all clinical data shall be summarised, a critical analysis of both favourable and unfavourable clinical data shall be conducted, and conclusions on clinical efficacy and safety shall be drawn, including justification of the acceptability of residual risks compared to the benefit of using the medical device | the following shall be verified: justification of clinical efficacy and safety for all indications submitted for use. The presence or absence of contraindications shall also be confirmed by the report materials; the presence of justification for extending the report's conclusions to all modifications (variants) and configurations, if the medical device under consideration has various modifications (variants) and configurations in accordance with the instructions for use (operational documentation); the adequacy of the report materials to confirm medical device conformity with paragraphs 3, 6 and 8 of the General Requirements, taking into account the requirements for post-registration clinical monitoring in accordance with the Rules for Conducting Safety, Quality and Efficacy Monitoring of Medical Devices, approved by Decision of the Board of the Eurasian Economic Commission of 22 December 2015 No. 174 |
28. When reviewing manufacturing inspection reports for medical devices submitted as part of the registration dossier, the applicability of such reports to the medical device being registered shall be verified by analysing the following information:
(a) availability of a manufacturing inspection report for the medical device;
(b) availability of a positive conclusion on the conformity of the quality management system for medical devices with the Requirements for the Implementation, Maintenance and Assessment of the Quality Management System for Medical Devices Depending on the Potential Risk of Their Application;
(c) conformity of the medical device being registered with the group (subgroup) of medical devices covered by the manufacturing inspection report;
(d) conformity of the list of manufacturing sites and their addresses indicated in the registration dossier with the corresponding list in the manufacturing inspection report.
29. Amendments to the registration dossier made during the validity period of the registration certificate that do not require new registration may be introduced on the grounds set out in Annex No. 8 to the Registration Rules.
Other changes in the manufacturer's documentation, including the technical file, the risk management file, the clinical evidence report on the efficacy and safety of the medical device, the list of applied standards, and information on the medical device's conformity with the safety and efficacy requirements, do not require amendments to the registration dossier.
30. Where indications for use, field of application, contraindications or side effects are changed, an assessment of the updated clinical evidence report on the efficacy and safety of the medical device shall be conducted in the manner described in Section V of these Methodological Guidelines.
31. Where changes are made to the technical specifications and/or operational documentation relating to the properties and/or characteristics of the medical device, an assessment shall be conducted of the information on the medical device's conformity with the safety and efficacy requirements, submitted in the form provided for in Annex No. 2 to the General Requirements, in respect of the changes introduced within the framework of the updated regulatory documentation submitted. Based on the results of the review, confirmation shall be obtained that the medical device continues to conform with the General Requirements in connection with the changes introduced. Assessment of the evidentiary materials (documents) used by the manufacturer to prove medical device conformity with the General Requirements shall be carried out in accordance with Section III of these Methodological Guidelines.
32. Where changes are not related to the properties and/or characteristics of the medical device, the assessment shall be limited to reviewing the application for amendments to the medical device registration dossier.
33. When reviewing information on the medical device's conformity with the safety and efficacy requirements in accordance with paragraph 31 of these Methodological Guidelines, the currency of the standards included in the list that are referenced in such information and whose conformity was used to prove compliance with the General Requirements shall also be verified. The availability of updated evidentiary materials (documents) for updated standards in respect of confirming conformity with the new and/or amended requirements of those standards shall also be verified.
Where standards included in the list are updated, evidentiary materials (documents) shall be provided by the manufacturer only in respect of those requirements that were used to prove medical device conformity with the General Requirements and that were changed in the new (current) version of the standard. Assessment of the evidentiary materials (documents) used by the manufacturer to prove medical device conformity with the updated standards included in the list shall be carried out in accordance with subsection 3 of Section III of these Methodological Guidelines.
Annex
to the Methodological Guidelines
for Conducting the Safety, Quality
and Efficacy Assessment of Medical Devices
for the Purpose of Their Registration
within the Eurasian Economic Union
INFORMATION
ON THE CONFORMITY OF THE DATA CONTAINED IN THE DOCUMENTS
REQUIRED FOR REGISTRATION OF A MEDICAL DEVICE
WITH THE TECHNICAL FILE DATA STRUCTURE FOR THE MEDICAL DEVICE
| Clause No. <*> | Document title <*> | Structural element of the technical file for medical devices (other than in vitro diagnostics) <**> | Structural element of the technical file for in vitro diagnostic medical devices <***> |
|---|---|---|---|
| 4 | copies of certificates for the quality management system of the medical device manufacturer (ISO 13485 or the equivalent regional or national standard of an EAEU Member State) (if available) | Section VII "Manufacturing Sites" | Section VII "Manufacturing Sites" |
| 5 | declaration of conformity with the safety and efficacy requirements for medical devices or equivalent document (if available) | Section VIII "General Requirements Conformity Information" | Subparagraph (d) of paragraph 9 of Section VIII "Verification and Validation Activities" |
| 8 | medical device product summary describing the field of application, intended use, brief description, variants and accessories (in prescribed form) | Section I "General Description of the Medical Device" | Paragraph 1 of Section I "General Requirements for the Content of the Technical File for an In Vitro Diagnostic Medical Device" |
| 9 | labelling and packaging data (full-colour packaging and label layouts, labelling text in Russian and the official languages of the EAEU Member States) | Section IV "Accompanying Information" | Subparagraph (a) of paragraph 3 of Section II "Accompanying Information" |
| 10 | information on design and manufacture: manufacturing process flowcharts, key manufacturing stages, packaging, testing and finished product release procedure | Section V "Medical Device Design and Development", Section VI "Manufacturing Processes" | Section V "In Vitro Diagnostic Medical Device Design and Development", Section VI "Manufacturing Processes" |
| 12 | marketing information (where the device has been on the market for more than 2 years) (if available) | Subparagraph (f) of paragraph 11 of Section X "Verification and Validation Activities" | Subparagraph (g) of paragraph 9 of Section VIII "Verification and Validation Activities" |
| 13 | reports on incidents and withdrawals (information is not provided for newly developed and designed medical devices): list of adverse events or incidents related to the use of the device, with indication of the time period during which such events occurred; if adverse events are too numerous, brief summaries for each type of event and the total number of events of each type reported shall be provided; list of market withdrawals of medical devices and/or advisory notices and a description of the approach taken by manufacturers to address and resolve such issues in each case; description of the analysis and/or corrective actions taken in response to such events | Subparagraph (f) of paragraph 11 of Section X "Verification and Validation Activities" | Subparagraph (g) of paragraph 9 of Section VIII "Verification and Validation Activities" |
| 14 | list of standards with which the medical device complies (with details thereof) | Section II "Description of the Medical Device" | Subparagraph (a) of paragraph 9 of Section VIII "Verification and Validation Activities" |
| 15 | information on the medical device's conformity with the general safety and efficacy requirements for medical devices, requirements for their labelling and operational documentation | Section III "Reference to Similar and Previous Modifications of the Medical Device", Section VIII "General Requirements Conformity Information" | Section III "General Safety and Efficacy Requirements Conformity Information" |
| 16 | document establishing requirements for the technical characteristics of the medical device | Section II "Description of the Medical Device" | Section I "General Requirements for the Content of the Technical File for an In Vitro Diagnostic Medical Device" (for equipment), paragraph 10 of Section VIII "Verification and Validation Activities" |
| 17 | technical test reports conducted for the purpose of proving conformity with the general requirements | Section X "Verification and Validation Activities" | Subparagraphs (b) and (c) of paragraph 9 of Section VIII "Verification and Validation Activities" |
| 18 | biological effect evaluation study (test) reports conducted for the purpose of proving conformity with the general requirements | Section X "Verification and Validation Activities" | — |
| 19 | clinical evidence report on the efficacy and safety of the medical device | Subparagraph (f) of paragraph 11 of Section X "Verification and Validation Activities" | Subparagraph (g) of paragraph 9 of Section VIII "Verification and Validation Activities" |
| 20 | risk analysis report | Section IX "Risk Analysis and Management Results" | Section IV "Risk Analysis and Management Results" |
| 21 | data on medicinal products incorporated in the medical device (composition of the medicinal product, quantity, data on the compatibility of the medicinal product with the medical device, registration of the medicinal product in the country of manufacture) | Section X "Verification and Validation Activities" | — |
| 22 | biological safety data (if available) | Section X "Verification and Validation Activities" | Paragraph 9 of Section VIII "Verification and Validation Activities" |
| 23 | data on the sterilisation procedure, including process validation information, bioburden testing results, pyrogenicity and sterility testing results (where required) with indication of test methods, and packaging validation data (for sterile devices) | Section X "Verification and Validation Activities" | Paragraph 14 of Section VIII "Verification and Validation Activities" |
| 24 | information on special software (if available): manufacturer's data on software validation | Section X "Verification and Validation Activities" | Paragraph 15 of Section VIII "Verification and Validation Activities" |
| 25 | stability study report with an authentic translation into Russian of the test results and conclusions, for devices with a shelf life | Section X "Verification and Validation Activities" | Paragraph 13 of Section VIII "Verification and Validation Activities" |
| 26 | operational document or instructions for use of the medical device in the official languages of the states of recognition (where required) and in Russian | Section IV "Accompanying Information" | Subparagraph (b) of paragraph 3 of Section II "Accompanying Information" |
| 27 | service manual (in respect of medical device components) — where such data are absent from the operational documentation (if available) | Section IV "Accompanying Information" | Subparagraph (b) of paragraph 3 of Section II "Accompanying Information" |
| 30 | documents confirming the results of type approval testing of medical devices classified as measuring instruments (the list of which is approved by the Eurasian Economic Commission) (where required) | Section X "Verification and Validation Activities" | Subparagraph (b) of paragraph 9 of Section VIII "Verification and Validation Activities" |
<*> In accordance with Annex No. 4 to the Rules for Registration and Assessment of the Safety, Quality and Efficacy of Medical Devices, approved by Decision of the Council of the Eurasian Economic Commission of 12 February 2016 No. 46.
<**> In accordance with Annex No. 3 to the Rules for Conducting Clinical and Clinical-Laboratory Tests (Studies) of Medical Devices, approved by Decision of the Council of the Eurasian Economic Commission of 12 February 2016 No. 29.
<***> In accordance with Annex No. 5 to the Requirements for the Implementation, Maintenance and Assessment of the Quality Management System for Medical Devices Depending on the Potential Risk of Their Application, approved by Decision of the Council of the Eurasian Economic Commission of 10 November 2017 No. 106.