Council of the Eurasian Economic Commission Decision No. 29

Decision of the Council of the Eurasian Economic Commission
of February 12, 2016, No. 29
"On the Rules for Conducting Clinical and Clinical LaboratoryTrials (Studies) of Medical Devices"

(as amended by Decisions of the Council of the Eurasian Economic Commission
of December 24, 2021, No. 146, of January 26, 2024, No. 7)

In accordance with paragraph 2 of Article 31 of the Treaty on the Eurasian Economic Union of May 29, 2014, paragraphs 4 and 5 of Article 4 of the Agreement on Common Principles and Rules for the Circulation of Medical Devices (Medical Products and Medical Equipment) within the Eurasian Economic Union of December 23, 2014, paragraphs 105 and 106 of Annex No. 1 to the Rules of Procedure of the Eurasian Economic Commission, approved by Decision No. 98 of the Supreme Eurasian Economic Council of December 23, 2014, and Decision No. 109 of the Supreme Eurasian Economic Council of December 23, 2014, "On the Implementation of the Agreement on Common Principles and Rules for the Circulation of Medical Devices (Medical Products and Medical Equipment) within the Eurasian Economic Union," the Council of the Eurasian Economic Commission DECIDES:

1. To approve the attached Rules for Conducting Clinical and Clinical Laboratory Trials (Studies) of Medical Devices.

2. To establish that for medical devices of potential risk classes 3, 2b, and implantable medical devices (with the exception of medical devices for in vitro diagnostics and software that is a medical device), clinical trials (studies) for the purpose of registration, if it is not proven that the clinical efficacy and safety of the claimed medical device can be confirmed by other means, must be conducted in the form of multicenter trials (studies) and meet one of the following conditions:

a) Clinical trials (studies) conducted in accordance with the legislation of the member states of the Eurasian Economic Union and on their territories before January 1, 2022 (based on the date of the last visit of the last patient or test subject (study)) or were ongoing as of January 1, 2022 (with completed patient recruitment);

 b) Clinical trials (studies) conducted on the territories of states that are not members of the Eurasian Economic Union before January 1, 2022 (based on the date of the last visit of the last patient or test subject (study)) or were ongoing as of January 1, 2022 (with completed patient recruitment) in accordance with the recommendations of the International Medical Device Regulators Forum (IMDRF);

c) Clinical trials (studies) initiated after January 1, 2022, conducted in accordance with the law of the Eurasian Economic Union, while one of the clinical trials (studies) is conducted in one of the member states of the Eurasian Economic Union.

 

3. This Decision shall enter into force upon the expiration of 10 calendar days from the date of entry into force of the Protocol, signed on December 2, 2015, on the accession of the Republic of Armenia to the Agreement on Common Principles and Rules for the Circulation of Medical Devices (Medical Products and Medical Equipment) within the Eurasian Economic Union of December 23, 2014, but no earlier than upon the expiration of 10 calendar days from the date of official publication of this Decision.

Members of the Council of the Eurasian Economic Commission:

From the Republic of Armenia
V. Gabrielyan

From the Republic of Belarus
V. Matyushevsky

From the Republic of Kazakhstan
B. Sagintayev

From the Kyrgyz Republic
O. Pankratov

From the Russian Federation
I. Shuvalov

Approved
by Decision of the Council
of the Eurasian Economic Commission
of February 12, 2016, No. 29

RULES
FOR CONDUCTING CLINICAL AND CLINICAL LABORATORY TRIALS
(STUDIES) OF MEDICAL DEVICES

I. General Provisions

1. These Rules are developed in accordance with paragraph 2 of Article 31 of the Treaty on the Eurasian Economic Union of May 29, 2014, paragraphs 4 and 5 of Article 4 of the Agreement on Common Principles and Rules for the Circulation of Medical Devices (Medical Products and Medical Equipment) within the Eurasian Economic Union of December 23, 2014, and establish within the Eurasian Economic Union (hereinafter referred to as the Union) rules for conducting clinical and clinical laboratory trials (studies) of medical devices.

2. For the purposes of these Rules, the following concepts are used, which mean the following:

"Analyte" - a component of a sample with a measurable property;

"Analytical Efficiency of a Medical Device for In Vitro Diagnostics" - the ability of a medical device for in vitro diagnostics to detect the presence or determine the content of a specific analyte in a biological sample;

 "Biological Reference Population" - a homogeneous population of individuals in a well-defined state of health or disease;

 "Investigator's Brochure" - a summary statement of current clinical and non-clinical information about the test (investigated) medical device relating to a clinical trial (study) or clinical laboratory trial (study) (when conducting an interventional clinical study of effectiveness);

"Principal Investigator" - a qualified person responsible for conducting a clinical or clinical laboratory trial (study). If the trial (study) is conducted by a team of researchers, the head of that team is the principal investigator;

 "Double-Blinded Method" - a clinical trial (study) procedure in which the trial subjects (studies) and the researchers involved in obtaining and processing primary data are not aware of the actual application to the test subjects (studies) of the impact of the medical device;

  "Clinical Trial (Study) Design" - a methodology for conducting a clinical trial (study) with human participation as a test subject (study), with the help of which it is planned to obtain statistically reliable evidence of the clinical safety and effectiveness of the test (investigated) medical device, including the use of control groups of test subjects (study), and (or) the distribution of test subjects (studies) into groups randomly, and (or) the use of a single or double-blinded method, as well as the selection of primary and secondary endpoints;

"Secondary endpoint" - an indicator (or indicators) used to test a secondary hypothesis of a clinical trial (study)

"Legal representative" - a natural or legal person who, in accordance with the legislation of the Member State of the Union, has the right to give informed consent to participate in a clinical or clinical laboratory (during an interventional clinical effectiveness study) trial (study) on behalf of the potential test subject (study);

"Applicant" - the legal manufacturer of a medical device or its authorized representative;

"Individual Registration Card" - a document intended for entering all information about each test subject (study) provided for in the trial (study) program;

"Interventional Clinical Effectiveness Study" - a study of the clinical effectiveness of a medical device for in vitro diagnostics, the results of which affect decisions on patient management and (or) are used in the management of treatment to achieve the goals of the clinical study;

"Informed Consent" - a written document in which the test subject (study) or his legal representative confirms voluntary consent to participate in clinical or clinical laboratory (during interventional clinical effectiveness studies) trials (studies) based on the full information provided to him about the clinical or clinical laboratory trial (study);

"Test (Investigated) Medical Device" - a medical device that is evaluated for safety and (or) effectiveness during a clinical trial (study) or clinical laboratory trials (studies) for medical devices for in vitro diagnostics;

"Researcher" - a member of the research team appointed by the principal investigator to carry out the main procedures related to the clinical or clinical laboratory trial (study) or to make decisions related to the clinical or clinical laboratory trial (study) and subordinate to the principal investigator;

" Clinical Laboratory Trials (Studies) of a Medical Device for In Vitro Diagnostics" - systematic trials (studies) of analytical characteristics and, where applicable, clinical effectiveness, carried out to establish or confirm the conformity of a medical device for in vitro diagnostics to the purpose established by the manufacturer;

"Clinical Effectiveness of a Medical Device for In Vitro Diagnostics" - the ability of a medical device for in vitro diagnostics to show results that correlate with a specific clinical or physiological condition in the target population when used by the intended user;

"Clinical Data" - data on safety and/or effectiveness obtained during the clinical use of a medical device. Clinical data can be obtained by searching the scientific literature for data on the medical device, from the experience of clinical use of the medical device, as a result of clinical or clinical laboratory trials (studies), through the use of several of these methods, or in another way. Clinical data also include data on safety and/or effectiveness obtained during the clinical use of medical devices whose equivalence to the medical device under consideration can be proven;

"Clinical Evidence of the Effectiveness and Safety of a Medical Device" - the totality of clinical data confirming the clinical effectiveness and safety of a medical device when used as intended by the manufacturer, and their assessment;

"Clinical Evidence of the Effectiveness and Safety of a Medical Device for In Vitro Diagnostics" - a set of data confirming the scientific validity of the analyte, analytical effectiveness, and clinical effectiveness of a medical device for in vitro diagnostics when used as intended by the manufacturer, and their assessment;

"Clinical Trial (Study) of a Medical Device" - any trial (study) involving a human being as a test subject (study), conducted for the purpose of studying the safety and/or effectiveness of the test (investigated) medical device;

"Ethics Committee" - an independent expert body that operates in accordance with these Rules and the legislation of the Member State of the Union and considers issues of ensuring the rights, safety, and health of test subjects (studies);

"Control Medical Device" - a device used in a clinical trial (study) for comparison with the test (investigated) medical device;

"Coordinator-Researcher" - a researcher appointed by the applicant and responsible for coordinating work during a multicenter clinical (clinical laboratory) trial (study);

"Medical Organization (Clinical Center)" - an organization acting as a research center during clinical (clinical laboratory) trials (studies);

"Multicenter Trial (Study)" - a clinical (clinical laboratory) trial (study) that is conducted in two or more medical organizations (clinical centers) according to a single trial (study) program;

"Monitoring of a Clinical (Clinical Laboratory) Trial (Study)" - activities related to monitoring the progress of a clinical (clinical laboratory) trial (study) to verify that the data of the ongoing trial (study) are recorded, the monitoring report is formed in accordance with the trial (study) program, documented procedures, and these Rules;

"Scientific Validity of an Analyte" - the connection of an analyte with a clinical or physiological condition of the human body;

"Single-Blinded Method" - a clinical trial (study) procedure in which the trial subjects (studies) are not aware of the actual application of the impact of the medical device to them;

"Primary Endpoint" - an indicator (indicators) used to test the main hypothesis of a clinical trial (study);

"Report on a Clinical Laboratory Trial (Study) of a Medical Device" - a written description of a clinical laboratory trial (study) of a medical device using samples and specimens, including those obtained by genetic engineering, combining clinical laboratory and statistical descriptions, data presentation and analysis, in the prescribed form;

"Report on a Clinical Trial (Study) of a Medical Device" - a written description of a clinical trial (study) of a medical device with human participation as a test subject (study), combining clinical and statistical descriptions, data presentation and analysis, in the prescribed form;

"Primary Data" - any information in the form of original records or certified copies of original records on clinical facts, observations, and other events during clinical (clinical laboratory) trials (studies), necessary for monitoring and evaluating the results of clinical (clinical laboratory) trials (studies);

"Intended User" - a specific group (groups) of persons, designated in the accompanying documentation for the medical device, who can use the medical device in accordance with its intended purpose;

"Trial (Study) Program" - a document that establishes the rationale, objectives, design of the clinical (clinical laboratory) trial (study) and the intended analysis, methodology, monitoring, requirements for maintaining records of the clinical (clinical laboratory) trial (study), and describes the conduct of the clinical (clinical laboratory) trial (study);

"Test Subject (Study)" - a natural person participating in a clinical or clinical laboratory (during an interventional clinical effectiveness study) trial (study) as part of a group to which the test (investigated) medical device is applied, or as part of a control group;

"Technical File" - documented data confirming the conformity of a medical device to the General Safety and Performance Requirements for Medical Devices, the requirements for their labeling and operational documentation, approved by Decision No. 27 of the Council of the Eurasian Economic Commission of February 12, 2016;

"Vulnerable Test Subjects (Studies)" - persons whose desire to participate in a clinical or clinical laboratory (during an interventional clinical effectiveness study) trial (study) may be influenced by the expectation (justified or unjustified) of certain advantages associated with participation in the trial (study), or possible sanctions from superiors in case of refusal to participate in the trial (study). Vulnerable test subjects (studies) include students of higher and secondary medical, pharmaceutical and dental educational institutions, junior staff of medical institutions and laboratories, military personnel and prisoners, as well as patients suffering from incurable diseases, persons in care homes, low-income and unemployed persons, stateless persons, patients in an emergency condition, representatives of national minorities, homeless people, vagrants, refugees, minors, and persons under guardianship or trusteeship, as well as persons unable to give informed consent.

Other concepts used in these Rules shall be applied in the meanings defined by acts in the sphere of circulation of medical devices, which are part of the law of the Union. 

 

II. Justification of Clinical Effectiveness and Safety of Medical Devices, Except for Medical Devices for In Vitro Diagnostics

3. To prove the clinical effectiveness and safety of a medical device, the manufacturer must:

 a) Determine the requirements from the General Safety and Performance Requirements for Medical Devices, the requirements for their labeling and operational documentation (hereinafter referred to as the General Requirements), evidence of compliance with which must be based on clinical data;

b) Determine the clinical data relating to the medical device and its intended use, which are obtained by searching scientific literature, from experience of clinical use, or from clinical trials (studies) of the medical device;

c) Evaluate the clinical data for the possibility of using them to prove the clinical effectiveness and safety of the medical device;

 d) Conduct clinical trials (studies) on those aspects of the safety and effectiveness of medical devices for which there is insufficient available clinical data;

 e) Analyze both favorable and unfavorable clinical data obtained by searching scientific literature, from experience of clinical use, or as a result of conducting clinical trials (studies), and make a reasoned conclusion about the clinical evidence of the effectiveness and safety of the medical device in the form of a report. The analysis is carried out taking into account the class of potential risk of use, purpose, and specific features of the application of the medical device. The report on the clinical evidence of effectiveness and safety of the medical device must be agreed upon with a specialist in the field of medical application of the medical device. The qualification of such a specialist is confirmed by a document on education in the field of medicine and on the specialty in accordance with the field of medical application of the medical device (specialist certificate and (or) diploma, etc.), publications of the medical specialist (scientific articles, and (or) monographs, and (or) dissertations in the field of medical application of the medical device). This report is part of the documentation of the medical device manufacturer.

 

4. Justification of the clinical effectiveness and safety of a medical device is based on clinical data obtained during clinical trials (studies) for:

 medical devices (except for software that is a medical device) if it is not proven that the clinical effectiveness and safety of the claimed medical device can be confirmed in another way;

medical devices (except for software that is a medical device) whose functional characteristics, principle of operation, intended purpose, indications for medical use, or features of medical use have not been previously investigated;

medical devices containing new materials in contact with the human body that have not been previously studied in terms of biological effects, or known materials that contact those organs or tissues of the human body for which there is no experience of their medical use, or if such contact is more prolonged than previously studied.

Clinical trials (studies) of medical devices of potential risk classes 3, 2b, and implantable medical devices (except for software that is a medical device) initiated after January 1, 2022, shall be conducted in the form of multicenter trials (studies), including in one of the Member States of the Union (hereinafter referred to as the Member States).

 

5. Obtaining clinical data for software that is a medical device, including software using artificial intelligence technologies, shall be carried out using patient medical data verified by a medical organization (clinical center) obtained during diagnosis, treatment, and rehabilitation.

6. Clinical data obtained during clinical trials (studies) or during the use of a medical device in states that are not members of the Union shall be recognized as a source of clinical data on the medical device if one of the following conditions is met:

 a) The clinical data are confirmed by publications in specialized journals or reports of the World Health Organization on the medical device safety and effectiveness control program ("The WHO prequalification project"), posted on the World Health Organization website on the information and telecommunications network "Internet" (hereinafter referred to as the "Internet");

 b) The results of clinical trials (studies) are presented in accordance with the recommendations of the International Medical Device Regulators Forum (IMDRF). Evidence of compliance of the conducted clinical trials (studies) with international requirements must be verifiable.

 

7. Clinical data obtained for another medical device may be accepted for consideration only if evidence of its equivalence to the claimed medical device is presented while simultaneously meeting the following conditions:

 a) The medical devices under consideration have the same intended purpose, including (as applicable) in relation to:

indications for use;

intended user;

severity and stage of the disease or condition of patients;

group of patients for whom the medical device is intended;

parts of the human body that are affected by or in contact with the medical device;

type of contact;

duration of use or contact with the body;

conditions of use (for example, medical facility, for home use);

frequency of use, including any restrictions on the number or duration of repeated use;

 

b) The technical characteristics (including the principle of operation, basic parameters, materials, and design features of the device) and biological characteristics (including biocompatibility of materials and the biological effect of the medical device) of the medical devices under consideration are the same to the extent that guarantees the absence of differences in their clinical effectiveness and safety;

c) The medical device declared as equivalent is registered in accordance with the law of the Union or the legislation of the Member State.

 

8. The report on the clinical evidence of the effectiveness and safety of the medical device must be kept up to date, taking into account data obtained during post-market monitoring and/or when new confirmed information relating to its safety and effectiveness appears in the scientific literature.

For medical devices of potential risk class 3, as well as for medical devices of potential risk class 2b implanted in the human body, the medical device manufacturer or its authorized representative is obliged to conduct post-registration clinical monitoring of the safety and effectiveness of medical devices in accordance with the plan included in the report on clinical evidence of effectiveness and safety of the medical device, submitted in accordance with the Rules for Monitoring the Safety, Quality and Effectiveness of Medical Devices, approved by Decision No. 174 of the Board of the Eurasian Economic Commission of December 22, 2015.

 

III. Requirements for Conducting Clinical Trials (Studies) of Medical Devices, Except for Medical Devices for In Vitro Diagnostics

 

9. Clinical trials (studies) of medical devices are conducted in accordance with the principles of the Helsinki Declaration of the World Medical Association of 1964 "Ethical Principles for Medical Research Involving Human Subjects."

Clinical trials (studies) of medical devices in the territories of the Member States are conducted in the medical organizations (clinical centers) selected by the applicant, information about which is included in the unified register of authorized organizations that have the right to conduct research (tests) of medical devices for the purpose of their registration (hereinafter - the register of authorized organizations).

 

10. Medical organizations (clinical centers) that conduct clinical trials (studies), as well as specialists of these organizations who conduct clinical trials (studies), may not be with the medical device manufacturer, the authorized representative of the manufacturer, or other persons interested in the results of the trials (studies) in relationships that affect their impartiality.

Commercial, financial, or other pressure that puts the impartiality of the medical organization (clinical center) conducting clinical trials (studies) at risk is not allowed.

 

11. Clinical trials (studies) of medical devices are conducted on the basis of trial (study) programs in such a way that the results of the trials (studies) can confirm or disprove the clinical effectiveness and safety of medical devices declared by the manufacturer. The number of observations made must be sufficient to ensure statistical reliability, reproducibility of results, and scientific validity of the conclusions.

Trials (studies) of medical devices intended for use by persons without medical education are conducted under conditions that simulate the conditions of use of these medical devices as intended.

12.Clinical trials (studies) of medical devices are conducted under the conditions established by the manufacturer for the use of these medical devices and as specified in the test (study) protocols.

13. The researcher is responsible for conducting the clinical trial (study) of the medical device. The researcher must have access to all available technical and clinical data on the test (investigated) medical device.

14. To provide researchers with the necessary amount of information about the medical device, the applicant submits an investigator's brochure, the content of which complies with the requirements in accordance with Appendix No. 1.

15. The content of the clinical trial (study) program of the medical device must comply with the requirements in accordance with Appendix No. 2.

16. The description of the clinical trial (study) design must include:

a) A strategy to ensure the clinical significance and scientific validity of the results with justification for its choice;

b) Primary and secondary endpoints with justification for their choice and measurement.

 

17. The clinical trial (study) program is agreed upon with medical organizations (clinical centers) and the coordinator-researcher during a multicenter trial (study) and is approved by the applicant.

18. To conduct a clinical trial (study) of a medical device, the applicant submits to the medical organization (clinical center) the following information and documents, drawn up in accordance with the legislation of the Member State in whose territory the clinical trial (study) is conducted:

a) Permission from the authorized body (expert organization) to conduct a clinical trial (study) of a medical device (with the exception of software that is a medical device) or the details of the registry entry in the register in which information about issued permits and submitted notifications on conducting clinical or clinical laboratory trials (studies) of medical devices is entered (hereinafter - the register of permits);

b) An application for conducting a clinical trial (study) of a medical device;

c) Written confirmation that this medical device meets all applicable safety and effectiveness requirements, with the exception of those properties and characteristics that must be investigated during the ongoing clinical trial (study) of the medical device;

d) Investigator's brochure;

e) Trial (study) program, drawn up in accordance with the requirements provided for in Appendix No. 2 to these Rules;

f) Samples (sample) of the medical device together with accessories necessary for the use of the medical device as intended (if accessories are available);

g) Information on compliance of the medical device with the General Requirements;

h) Instructions for use of the medical device (operational documentation);

i) Technical file for the medical device, the content of which complies with the requirements in accordance with Appendix No. 3 (for medical devices other than software and medical devices for in vitro diagnostics) or Appendix No. 4 (for software that is a medical device), with the exception of the properties and characteristics of safety and effectiveness of the medical device, which must be determined as a result of the ongoing clinical trial (study);

j) Conclusion of the Ethics Committee on the conduct of a clinical trial (study) of the medical device;

k) A copy of the document on the terms of insurance or reimbursement (compensation) of possible harm in the event of adverse events (incidents), carried out in accordance with the legislation of the Member State in whose territory the clinical trial (study) of the medical device is conducted;

l) A form of informed consent, including all necessary explanatory materials, as well as other information provided to the test subject (study);

m) Forms of individual registration cards, diaries, and questionnaires to be filled out by researchers;

n) A form of report on adverse events (incidents);

o) A form of report on defects of the medical device;

p) Forms of reports on the clinical trial (study) of the medical device, including an interim report;

q) Materials (including advertising) used to attract potential test subjects (studies).

 

19. During clinical trials (studies) of medical devices, the following are carried out:

a) Procedures in accordance with trial (study) programs;

b) Maintaining unambiguously identifiable records on the results of the conducted clinical trials (studies);

c) Evaluation and analysis of data obtained during clinical trials (studies) of medical devices;

d) Finalization of the manufacturer's operational documentation for the medical device based on the results of trials (studies) (if necessary);

e) Preparation and issuance to the applicant of a report on the clinical trial (study) of the medical device.

 

20. The report on the clinical trial (study) of the medical device (with the attachment of summary tables (graphs) of the results of the trials (studies) with appropriate statistical processing and comments on them) must contain a critical assessment of all data obtained during the trial (study), including negative data. Such a report shall be drawn up in the form according to Appendix No. 5, signed by the researchers, and approved by the head of the medical organization (clinical center).

When conducting multicenter clinical trials (studies), a general report is drawn up, which is signed by the researchers and heads of medical organizations (clinical centers) and approved by the coordinator-researcher.

 

21. The applicant has the right to control the conduct of the clinical trial (study) of the medical device at all stages by appointing persons with the appropriate qualifications and conducting monitoring procedures or independent conformity assessment in order to obtain reliable data.

 

IV. Justification of Clinical Effectiveness and Safety of Medical Devices for In Vitro Diagnostics

 

22. Proof of compliance of medical devices for in vitro diagnostics with the General Requirements includes justification of the clinical effectiveness and safety of medical devices for in vitro diagnostics.

Justification of clinical effectiveness and safety is drawn up in the form of a report on the clinical evidence of effectiveness and safety of the medical device and, where applicable, is based on the determination or confirmation of the scientific validity of the analyte, analytical effectiveness, and clinical effectiveness of the medical device for in vitro diagnostics when used as intended by the manufacturer. The inapplicability of these characteristics shall be justified in the report on clinical evidence of effectiveness and safety of the medical device.

23. Determining or confirming the scientific validity of the analyte is not necessary if the connection of the analyte with the clinical or physiological condition of the human body is well known and is based on available information.

24. For a new analyte or a new purpose of a medical device for in vitro diagnostics, the scientific validity of the analyte shall be established during clinical laboratory trials (studies) of the medical device for in vitro diagnostics, unless it is proven that the scientific validity of the analyte can be established in another way, for example, based on:

a) Data obtained from the clinical experience of using medical devices for in vitro diagnostics in the Member States that determine the same analyte by the same method and have the same purpose;

b) Data obtained from scientific literature on medical devices for in vitro diagnostics that determine the same analyte by the same method and have the same purpose.

 

25. The analytical effectiveness of a medical device for in vitro diagnostics must be confirmed by the results of clinical laboratory trials (studies) for the claimed medical device for in vitro diagnostics.

26. Determining or confirming clinical effectiveness during clinical laboratory trials (studies) of a medical device for in vitro diagnostics is not necessary for medical devices for in vitro diagnostics if the clinical effectiveness of this device is fully determined by analytical effectiveness and this fact is well known and substantiated in the report on clinical evidence of effectiveness and safety of the medical device.

27. Clinical effectiveness of a medical device for in vitro diagnostics shall be established during clinical laboratory trials (studies) of the medical device for in vitro diagnostics, unless it is proven that the clinical effectiveness of the medical device can be established in another way, for example, based on:

a) Data obtained from peer-reviewed scientific literature on the use of the medical device on samples obtained from a biological reference population;

b) Data obtained from the clinical experience of using a medical device for in vitro diagnostics in the Member States or published data on the clinical experience of using a medical device on samples obtained from a biological reference population.

 

V. Requirements for Conducting Clinical Laboratory Trials (Studies) of Medical Devices for In Vitro Diagnostics

 

28. Clinical trials (studies) in relation to medical devices for in vitro diagnostics shall be conducted in the form of clinical laboratory trials (studies).

Clinical laboratory trials (studies) of medical devices shall be conducted in the medical organizations (clinical centers) selected by the applicant, information about which is included in the register of authorized organizations.

 

29. Medical organizations (clinical centers) that conduct clinical laboratory trials (studies), as well as specialists of these organizations who conduct clinical laboratory trials (studies), may not be with the medical device manufacturer, the authorized representative of the manufacturer, or other persons interested in the results of the trials (studies) in relationships that affect their impartiality.

Commercial, financial, or other pressure that puts the impartiality of the medical organization (clinical center) conducting clinical laboratory trials (studies) at risk is not allowed.

 

30. Clinical laboratory trials (studies) of medical devices for in vitro diagnostics are conducted on the basis of trial (study) programs in such a way that the results of the trials (studies) can confirm or disprove the analytical effectiveness and clinical effectiveness of medical devices for in vitro diagnostics declared by the manufacturer. The number of laboratory tests performed must be sufficient to ensure the statistical reliability of the trial (study) results.

31. The content of the program of a clinical laboratory trial (study) of a medical device for in vitro diagnostics must comply with the requirements in accordance with Appendix No. 6.

32. Trials (studies) of medical devices for in vitro diagnostics intended for use by persons without medical education in the field of clinical laboratory diagnostics shall be conducted under conditions that simulate the conditions of use of these medical devices as intended.

33. Clinical laboratory trials (studies) of medical devices for in vitro diagnostics intended for use in combination with each other in the form of analytical systems may be conducted as part of one trial (study) (together with the accessories necessary for using the medical device as intended).

34. Samples used in clinical laboratory trials (studies) of medical devices for in vitro diagnostics may be collected from several sources, including residual samples, archived samples, or purposefully selected samples.

Residual samples are considered to be remnants of samples collected during the diagnostic and therapeutic process.

Archived samples or specimens include characterized samples or specimens that were previously selected and obtained from repositories (including tissue banks, standard panels, museum test strains, and other collections).

Purposefully selected samples are samples that were taken from patients specifically for use in a particular trial (study).

When conducting trials (studies) of medical devices for in vitro diagnostics using purposefully selected samples, informed consent must be obtained.

 

35. The results of testing samples during clinical laboratory trials (studies) of a medical device for in vitro diagnostics (except in cases of an interventional clinical effectiveness study) shall not be used for other purposes other than assessing its analytical and/or clinical effectiveness, unless ethical considerations, fully shared by all researchers participating in the trial (study), suggest otherwise (including the need to inform the test subjects (studies) of the test results). In this case, the researcher assumes full responsibility for the consequences of other uses of the data obtained.

36. Clinical laboratory trials (studies) of medical devices for in vitro diagnostics of new or particularly dangerous infectious diseases, including natural focal infectious diseases, may be carried out under laboratory conditions using archived samples and/or samples obtained by genetic engineering.

For medical devices for in vitro diagnostics of potential risk classes 1, 2a, and 2b, whose clinical laboratory trials (studies) were conducted under the specified conditions, as well as for medical devices for in vitro diagnostics of rare diseases, the manufacturer, in agreement with the authorized body (expert organization), shall conduct post-registration clinical monitoring of the safety and effectiveness of medical devices in accordance with the Rules for Monitoring the Safety, Quality and Effectiveness of Medical Devices in order to obtain statistically reliable characteristics of their analytical and/or clinical effectiveness.

 

37. The clinical laboratory test (study) protocol for an in vitro diagnostic medical device is agreed upon with the medical organizations (clinical centers) and approved by the applicant.

38. To conduct a clinical laboratory trial (study) of a medical device for in vitro diagnostics, the applicant submits to the medical organization (clinical center) the following information and documents, drawn up in accordance with the legislation of the Member State in whose territory the clinical laboratory trial (study) is conducted:

a) An application for conducting a clinical laboratory trial (study) of a medical device for in vitro diagnostics;

b) Written confirmation that this medical device for in vitro diagnostics meets all applicable safety and effectiveness requirements, with the exception of those properties and characteristics that must be investigated during the clinical laboratory trial (study) of the medical device for in vitro diagnostics;

c) A trial (study) program, drawn up in accordance with the requirements provided for in Appendix No. 6 to these Rules;

d) Samples (sample) of the medical device for in vitro diagnostics together with accessories necessary for the use of the medical device as intended (if accessories are available);

e) Information on compliance of the medical device for in vitro diagnostics with the General Requirements;

f) Instructions for use of the medical device for in vitro diagnostics (operational documentation);

g) A technical file for the medical device for in vitro diagnostics, which meets the requirements provided for in Appendix No. 5 to the Requirements for the Implementation, Maintenance and Evaluation of a Quality Management System for Medical Devices Depending on the Potential Risk of Their Use, approved by Decision No. 106 of the Council of the Eurasian Economic Commission of November 10, 2017, with the exception of the properties and characteristics of safety and effectiveness of the medical device, which must be determined as a result of the ongoing clinical laboratory trial (study);

h) Permission from the authorized body (expert organization) to conduct a clinical laboratory trial (study) (when conducting an interventional clinical effectiveness study) or the details of the registry entry in the register of permits;

i) Conclusion of the Ethics Committee on the conduct of a clinical laboratory trial (study) (when conducting an interventional clinical effectiveness study);

j) Investigator's brochure (when conducting an interventional clinical effectiveness study);

k) A form of informed consent, including all necessary explanatory materials, as well as other information provided to the test subject (study) (when conducting an interventional clinical effectiveness study);

l) A copy of the document on the terms of insurance or reimbursement (compensation) of possible harm in the event of adverse events (incidents), carried out in accordance with the legislation of the Member State in whose territory the clinical laboratory trial (study) of the medical device for in vitro diagnostics is conducted (when conducting an interventional clinical effectiveness study);

m) Forms of individual registration cards, diaries, and questionnaires to be filled out by researchers (when conducting an interventional clinical effectiveness study);

n) A form of report on adverse events (incidents) (when conducting an interventional clinical effectiveness study);

o) A form of report on defects of the medical device for in vitro diagnostics (when conducting an interventional clinical effectiveness study);

p) Materials (including advertising) used to attract potential test subjects (studies) (when conducting an interventional clinical effectiveness study).

 

39. During clinical laboratory trials (studies) of medical devices for in vitro diagnostics, the following are carried out:

a) Procedures in accordance with trial (study) programs;

b) Maintaining unambiguously identifiable records on the assessment of functional characteristics, containing all measurement results;

c) Evaluation and analysis of the data obtained in order to confirm their compliance with the stated characteristics;

d) Finalization of the manufacturer's operational documentation for the medical device for in vitro diagnostics based on the results of trials (studies) (if necessary).

 

40. The results of a clinical laboratory trial (study) of a medical device for in vitro diagnostics are considered negative if they indicate that the analytical and/or clinical effectiveness of the specified medical device does not meet the requirements declared by the manufacturer.

41. The report on a clinical laboratory trial (study) of a medical device for in vitro diagnostics must contain a critical assessment of all data obtained during the trial (study), including negative data. Such a report shall be drawn up in the form according to Appendix No. 7, signed by the researchers, and approved by the head of the medical organization (clinical center).

In the case of conducting multicenter clinical laboratory trials (studies) of a medical device for in vitro diagnostics, a general report is drawn up, which is signed by the researchers and heads of medical organizations (clinical centers) and approved by the coordinator-researcher.

 

VI. Ethics Committee

 

42. In order to protect the life, health, and rights of subjects of a trial (study) during clinical or clinical laboratory trials (studies) (in the case of an interventional clinical efficacy study) of medical devices, Ethics Committees operate in the member states, including at the level of the medical organization (clinical center).

43. In its work, the Ethics Committee is guided by the principles of the World Medical Association's 1964 Declaration of Helsinki, "Ethical Principles for Medical Research Involving Human Subjects," and the legislation of the member states.

44. The main principles of the Ethics Committee's activities are:

 a) Ensuring the rights, safety, and health of individuals participating in clinical or clinical laboratory trials (studies) (in the case of an interventional clinical efficacy study) of medical devices;

b) Adherence to moral and ethical standards and norms of public morality;

c) Observance of the principles of humanity;  

d) Independence of judgment;

e) Maintaining the confidentiality of received information;

f) Compliance with professional ethical standards;

g) Prevention of conflicts of interest.

 

45. The main functions of the Ethics Committee are:

a) Reviewing programs for clinical or clinical laboratory trials (studies) (in the case of an interventional clinical efficacy study);

b) Issuing an opinion on the ethical justification or ethical lack of justification for conducting clinical or clinical laboratory trials (studies) (in the case of an interventional clinical efficacy study) of medical devices within the framework of submitted draft programs of clinical or clinical laboratory trials (studies);

c) Assessing the suitability of the researcher's qualifications for participation in the proposed trial (study).

 

46. All documents and information necessary for a complete and thorough examination of the planned study are submitted to the Ethics Committee. These documents and information should include:

a) An application for review;

b) A draft program of the planned trial (study);

c) Forms for individual registration cards, diaries, and questionnaires to be completed by researchers;

g) A description of the safety data for the medical device that is planned for trial (study), as well as its technical specifications, data from conducted technical tests and studies (trials) for the purpose of assessing biological effects, and a description of clinical experience with the medical device;

d) The Investigator's Brochure;

e) The researcher's resume and/or other materials confirming their qualifications;

f) Materials (including advertising) used to attract potential subjects of the trial (study);

g) A form of informed consent, including all necessary explanatory materials, as well as other information provided to the subject of the trial (study);

h) A description of all compensation for participation in the trial (study) for participants in the trial (study), including coverage of expenses and medical care;

i) Information about the terms of payments and compensation to subjects of the trial (study);

j) A description of the conditions of insurance for participants in the trial (study);

k) A statement of agreement to follow the ethical principles outlined in the relevant guidelines;

l) Previous decisions made by ethics committees (if any).

 

47. The Ethics Committee considers the issue of conducting the proposed clinical or clinical laboratory trial (study) (in the case of an interventional clinical efficacy study) within 30 working days from the date of receipt of the documents and information provided for in paragraph 46 of these Rules, and issues a written opinion in which the trial (study) must be identified, indicating the documents reviewed and the date of the decision:

a) On approval (issuance of an opinion) of the conduct of the trial (study);

b) On the need to make changes to the submitted documentation to obtain approval (issuance of an opinion) for the conduct of the trial (study);

c) On refusal to approve (issue an opinion) for the conduct of the trial (study);

d) On the cancellation (suspension) of a previously made approval (issued opinion) for the conduct of the trial (study).

 

48. The composition of the Ethics Committee includes persons who collectively possess the necessary qualifications and experience to consider and expert assess the scientific, medical, and ethical aspects of the planned trial (study).

49. The Ethics Committee operates in accordance with documented procedures.

50. The Ethics Committee is responsible for ensuring that it acts entirely in the interests of potential subjects of the trial (study), taking into account the interests and needs of vulnerable subjects of the trial (study), as well as the availability of legal representatives if necessary.

 

VII. Authorization to Conduct Clinical or Clinical Laboratory Trials (Studies)

 

51. To conduct a clinical or clinical laboratory trial (study) (in the case of an interventional clinical efficacy study) of a medical device, authorization must be obtained from the authorized body (expert organization) of the member state in whose territory these trials (studies) are planned (hereinafter in this section - the authorized body (expert organization)).

The authorization is issued on paper or by making an entry in the register of authorizations.

For conducting a clinical laboratory trial (study) of a medical device for in vitro diagnostics (excluding an interventional clinical efficacy study) and clinical trials (studies) of software that is a medical device, a notification in free form must be sent to the authorized body (expert organization) within 10 working days from the date of commencement of procedures in accordance with the trial (study) program, and information about it is entered in the register of authorizations.

 

52. Expenses related to obtaining authorization to conduct clinical or clinical laboratory trials (studies) (in the case of an interventional clinical efficacy study) or to making an entry in the register of authorizations for these trials (studies) are borne by the applicant in accordance with the legislation of the member state. Tariffs for carrying out relevant actions are determined in the manner established by the legislation of the member state.

Inclusion in the register of authorizations of information on notifications of clinical laboratory trials (studies) of medical devices for in vitro diagnostics (excluding interventional clinical efficacy studies) or clinical trials (studies) of software that is a medical device is carried out by the authorized body (expert organization) free of charge.

 

53. To obtain authorization to conduct a clinical or clinical laboratory trial (study) (in the case of an interventional clinical efficacy study) of a medical device, the applicant sends to the authorized body (expert organization) an application for such authorization (hereinafter - the application for authorization) in the form according to Appendix No. 8 or 9, respectively, with the following documents and information attached:

a) A statement from the manufacturer of the medical device that the medical device meets the applicable safety and performance requirements, with the exception of the properties and characteristics of the safety and performance of the medical device that must be investigated in the course of clinical or clinical laboratory trials (studies) (in the case of an interventional clinical efficacy study), and that precautions have been taken in relation to them to protect the health and safety of the subjects of the trials (studies);

b) The manufacturer's agreement with the manufacturer's authorized representative or a copy thereof (if the application is submitted by the manufacturer's authorized representative)

c) The Ethics Committee opinion issued in accordance with these Rules, or a copy thereof certified by the applicant;

d) The Investigator's Brochure, the content of which complies with the requirements provided for in Appendix No. 1 to these Rules;

e) A sample of the individual registration card of the subject of the trial (study);

f) The technical file for the medical device, the content of which complies with the requirements provided for in Appendix No. 3 to these Rules (for medical devices other than software and medical devices for in vitro diagnostics), or Appendix No. 4 to these Rules (for software that is a medical device), or Appendix No. 5 to the Requirements for the Implementation, Maintenance and Evaluation of a Quality Management System for Medical Devices depending on the potential risk of their use (for medical devices for in vitro diagnostics), with the exception of the properties and characteristics of the safety and performance of the medical device that must be determined as a result of the clinical or clinical laboratory trials (studies);

g) The trial (study) program, the content of which complies with the requirements provided for in Appendix No. 2 or 6 to these Rules, respectively, with a justification for the number of medical devices submitted for clinical or clinical laboratory (in the case of an interventional clinical efficacy study) trial (study), and the duration of its conduct;

h) A list of adverse events (incidents), in the event of which it is necessary to report to the authorized body (indicating the deadlines for submitting the report);

i) A copy of the document on the conditions of insurance or reimbursement (compensation) for possible harm in the event of adverse events (incidents) in accordance with the legislation of the member state in whose territory the clinical or clinical laboratory (in the case of an interventional clinical efficacy study) trial (study) is conducted;

j) Copies of documents confirming payment for actions related to the issuance of authorization to conduct clinical (clinical laboratory) trials (studies) or to making an entry in the register of authorizations.

 

54. The applicant submits information and documents drawn up in accordance with the legislation of the member state in whose territory the clinical or clinical laboratory trial (study) is conducted.

55. The authorized body (expert organization) conducts a check of the completeness and reliability of the information contained therein within 7 working days from the date of receipt of the application for authorization, documents, and information specified in paragraph 53 of these Rules.

56. If the application for authorization is submitted in violation of the requirements of these Rules, or if it contains false information, or if the documents specified in paragraph 53 of these Rules are not submitted in full, the authorized body (expert organization), within 7 working days from the date of receipt of such application and documents, sends the applicant, in the manner indicated in the application, a notification of the need to eliminate the identified violations and (or) submit the missing documents within 30 working days from the date of sending this notification.

If, after 30 working days, the applicant has not eliminated the identified violations and (or) submitted the missing documents and information, the authorized body (expert organization), within 3 working days, decides to return the application for authorization and the attached documents to the applicant (with a justification for the reasons for the return).

 

57. Within 3 working days from the date of completion of the verification provided for in paragraph 55 of these Rules (in the case of submitting an application for authorization and documents that comply with the requirements of these Rules), as well as in the event of eliminating the identified violations within the prescribed period and (or) submitting documents that comply with the requirements of these Rules, the authorized body (expert organization) decides to consider the specified application and documents.

58. If, during the examination of the application for authorization and the documents specified in paragraph 53 of these Rules, after a decision has been made to consider these documents, it is revealed that the materials and information are insufficient to make a decision on the possibility (impossibility) of conducting a clinical or clinical laboratory trial (study) (in the case of an interventional clinical efficacy study), the authorized body (expert organization) sends the applicant a corresponding request (indicating the nature of the comments and ways to eliminate them). The request is sent once in the manner indicated in the application for authorization.

The applicant is obliged to submit a response to the request within 60 working days from the date of its receipt. If a response is not submitted within the specified period, the authorized body (expert organization) makes a decision regarding the possibility of conducting clinical or clinical laboratory trials (studies) (in the case of an interventional clinical efficacy study) of the medical device based on the documents at its disposal.

If the authorized body (expert organization) detects unreliable data in the documents submitted by the applicant in response to the request, the authorized body (expert organization), within 2 working days from the date of receipt of such documents, hands over to the applicant, in the manner indicated in the application for authorization, a decision to return the specified documents (with a justification for the reasons for the return and a message about the possibility of the applicant re-submitting the documents before the expiration of the period specified in the second paragraph of this clause).

The time from the date the authorized body (expert organization) sends the request to the date of receipt of the response to the request or notification of non-submission of a response to the request is not taken into account when calculating the deadline for the authorized body (expert organization) to make a decision regarding the possibility of conducting clinical or clinical laboratory trials (studies) (in the case of an interventional clinical efficacy study).

 

59. The authorized body (expert organization) conducts an examination of the submitted documents and draws up an expert opinion in the form according to Appendix No. 10 within 30 working days from the date it makes a decision to consider the application for authorization and the documents specified in paragraph 53 of these Rules. The conclusions contained in the expert opinion must be unambiguous and understandable.

60. The authorized body (expert organization), within 5 working days from the date of preparation of the expert opinion:

a) Makes a decision on the possibility (impossibility) of conducting clinical or clinical laboratory trials (studies) (in the case of an interventional clinical efficacy study) of the medical device, which is оформляется by an order of the authorized body (expert organization), and notifies the applicant of the decision made;

b) Issues (sends by registered mail with notification of delivery or in the form of an electronic document signed with an electronic signature) the applicant authorization to conduct clinical or clinical laboratory trials (studies) of the medical device and (or) enters the relevant information in the register of authorizations, or issues the applicant a notification of the impossibility of conducting them with an attachment of the expert opinion (with a justification for the reasons for refusing authorization to conduct clinical or clinical laboratory trials (studies) of the medical device).

 

61. The authorization (registry entry) for conducting a clinical or clinical laboratory trial (study) of a medical device contains the following information:

a) The number and date of such authorization (registry entry);

b) The name of the applicant, its location (legal address) - for a legal entity, or the last name, first name, patronymic (if any), place of residence - for an individual registered as an individual entrepreneur, information on the state registration of the legal entity or individual as an individual entrepreneur, as well as the applicant's contact information (telephone number, email address);

c) The name of the medical device (indicating the model (brand) of the medical device, its composition, accessories necessary for using the medical device for its intended purpose);

d) The name of the manufacturer, its location (legal address) - for a legal entity, or the last name, first name, patronymic (if any), place of residence - for an individual registered as an individual entrepreneur;

e) The name of the manufacturer's authorized representative (if any), its location (legal address) - for a legal entity, or the last name, first name, patronymic (if any), place of residence - for an individual registered as an individual entrepreneur;

f) The name and address of the location of the production site (production sites) carrying out the entire production process of the medical device or its certain stages;

g) The names and addresses of medical organizations (clinical centers) in which the clinical or clinical laboratory trial (study) (in the case of an interventional clinical efficacy study) of the medical device is conducted, information about which is included in the register of authorized organizations.

 

62. The grounds for the authorized body (expert organization) to issue an opinion on the impossibility of conducting clinical or clinical laboratory trials (studies) (in the case of an interventional clinical efficacy study) of a medical device are:

a) Non-confirmation by the relevant documents and information provided by the applicant of the acceptability of the risks associated with clinical or clinical laboratory trials (studies) (in the case of an interventional clinical efficacy study);

b) Failure to eliminate the identified violations and (or) failure to submit documents and information upon request. 

 

VIII. Requirements for Medical Organizations (Clinical Centers) Conducting Clinical and Clinical Laboratory Trials (Studies) of Medical Devices

 

63. The formation and maintenance of the register of authorized organizations is carried out by the Eurasian Economic Commission (hereinafter referred to as the Commission) in accordance with the Procedure for the Formation and Maintenance of an Information System in the Field of Circulation of Medical Devices, approved by the Decision of the Council of the Eurasian Economic Commission of February 12, 2016 No. 30, based on information submitted by authorized bodies, using the means of the integrated information system of the Union.

64. The register of authorized organizations includes information about medical organizations (clinical centers) that conduct clinical trials (studies) of medical devices and meet the following requirements:

a) Registration of the medical organization (clinical center) as a legal entity in the territory of the member state in accordance with its legislation;

b) Having a permit (license) to carry out medical activities (with an indication of the list of works (services) constituting medical activity) corresponding to the purpose and scope of application of medical devices for which trials (studies) are conducted, if such a requirement exists in the legislation of the member state;

c) Having documents (standard operating procedures) regulating the conduct of clinical trials (studies) of medical devices, including those defining:

Qualification requirements and procedure for personnel training;

Interaction with the ethics committee;

Obtaining informed consent;

Procedure for conducting clinical trials (studies);

Registration and submission to the authorized body of reports on adverse events (incidents);

Maintenance and accounting of documentation on clinical trials (studies);

Ensuring the protection of confidential information;

 

d) Having the conditions for conducting the declared profile of clinical trials (studies) of medical devices;

e) Having the conditions for intensive care and resuscitation;

f) Having personnel with medical education and a document confirming completion of training in the rules for conducting clinical trials (studies) (good clinical practice).

 

65. The register of authorized organizations includes information about medical organizations (clinical centers) that conduct clinical laboratory trials (studies) of medical devices for in vitro diagnostics and meet the following requirements:

a) Registration of the medical organization (clinical center) as a legal entity in the territory of the member state in accordance with its legislation;

b) Having a permit (license) to carry out medical activities in the field of laboratory diagnostics (clinical laboratory diagnostics), if such a requirement exists in the legislation of the member state;

c) Having documents (standard operating procedures) regulating the conduct of clinical laboratory trials (studies) of medical devices for in vitro diagnostics, including those defining:

Qualification requirements and procedure for personnel training;

Procedure for verification and calibration of equipment;

Procedure for conducting clinical laboratory trials (studies);

Maintenance and accounting of documentation on clinical laboratory trials (studies);

Ensuring the protection of confidential information;

Interaction with the ethics committee (in the event that the medical organization (clinical center) has declared the possibility of conducting interventional clinical efficacy studies).

 

66. The authorized body, within 20 working days from the date of receipt of an application from a medical organization (clinical center) for inclusion in the register of authorized organizations, considers the specified application and informs the medical organization (clinical center) of the decision made in writing by handing over the notification in person against the signature of its representative, or sends it by registered mail with notification of delivery, or transmits it electronically via telecommunication channels or in the form of an electronic document signed with a digital signature.

In the event that the authorized body makes a decision to include a medical organization (clinical center) in the register of authorized organizations, information about the medical organization (clinical center) is sent to the Commission using the means of the integrated information system of the Union for inclusion in the register of authorized organizations, and may also be posted on the official website of the authorized body on the Internet.

In the event of non-compliance of the medical organization (clinical center) with one of the criteria specified in paragraph 64 or 65 of these Rules, respectively, and a decision to refuse to include the medical organization (clinical center) in the register of authorized organizations, the authorized body notifies the medical organization (clinical center) of the reasons for the refusal in writing by handing over the notification in person against the signature of its representative, or sends it by registered mail with notification of delivery, or transmits it electronically via telecommunication channels or in the form of an electronic document signed with a digital signature.

 

67. Appealing the decision of the authorized body is carried out in accordance with the legislation of its member state.

68. In the event of changes in the information contained in the register of authorized organizations, the medical organization (clinical center) included in the register of authorized organizations (hereinafter referred to as the authorized organization), within 30 calendar days, submits to the authorized body an application for making changes to the specified information, as well as documents confirming these changes.

The authorized body, within 10 working days from the date of submission by the authorized organization of an application for making changes to the information contained in the register of authorized organizations:

Considers the submitted application and documents;

 Sends the relevant information to the Commission using the means of the integrated information system of the Union (in the event that the authorized body makes a decision to make changes), and may also post it on its official website on the Internet;

Informs the authorized organization of the decision made in writing by handing over the notification in person against the signature of its representative, or sends it by registered mail with notification of delivery, or transmits it electronically via telecommunication channels or in the form of an electronic document signed with a digital signature.

 

69. Exclusion of a medical organization (clinical center) from the register of authorized organizations is carried out by the authorized body in the following cases:

a) Receipt of an application for the exclusion of the medical organization (clinical center) from the register of authorized organizations, signed by the head of the medical organization (clinical center);

b) Detection of non-compliance by the medical organization (clinical center) with the requirements of these Rules as a result of control carried out by the authorized body;

c) Liquidation of the medical organization (clinical center) or termination of the validity of the permit (license) to carry out medical activities (if such a requirement exists in the legislation of the member state);

d) Late submission or non-submission of information and documents provided for in paragraph 68 of these Rules.

 

70. The authorized body, within 3 working days from the date of making a decision on excluding information from the register of authorized organizations, submits the relevant information to the Commission using the means of the integrated information system of the Union, and may also post it on its official website on the Internet.

71. The storage, systematization and modification of information about authorized organizations, as well as protection from unauthorized access to it, are ensured by the authorized bodies.

72. The register of authorized organizations is published on the information portal of the Union.

73. Control over compliance by medical organizations (clinical centers) that have the right to conduct clinical or clinical laboratory trials (studies) of medical devices with the requirements of these Rules is carried out by the authorized body in accordance with the legislation of its state.

74. The provision of information to interested parties about organizations included in the register of authorized organizations is carried out by the authorized bodies in accordance with the legislation of the member states.

 

Appendix No. 1

to the Rules for Conducting Clinical

and Clinical Laboratory Trials

(Studies) of Medical Devices

 

REQUIREMENTS
FOR THE CONTENT OF THE INVESTIGATOR'S BROCHURE ON A MEDICAL DEVICE

 

I. General Description of the Medical Device

1. The Investigator's Brochure on a medical device must contain the following information:

a) The name of the medical device;

b) Description and intended use of the medical device;

c) Information allowing the identification of the medical device, including the model number (brand) of the medical device (if available) or an indication of the identifying number of the model (brand) of the medical device;

d) Type of medical device in accordance with the nomenclature of medical devices used within the Eurasian Economic Union;

e) Information about intended users;

f) Principles of operation of the medical device;

g) Class of potential application risk and applicable classification rules in accordance with the Rules for Classifying Medical Devices Depending on the Potential Application Risk, approved by the Decision of the Board of the Eurasian Economic Commission of December 22, 2015 No. 173;

h) Description of new properties and characteristics of the medical device;

i) A description of accessories and medical devices intended for use in combination with the medical device being studied;

j) A description and/or list of models (brands) of the medical device (if available);

k) A description of the main functional elements of the medical device (diagrams, photographs and drawings showing the main parts (components) of the medical device and including explanatory captions for the diagrams, photographs and drawings);

l) A description of the materials in direct or indirect contact with the human body.

 

II. Use of the Medical Device

 

2. The Investigator's Brochure must contain the following information about the use of the medical device:

a) The intended use of the medical device;

b) Installation (commissioning) instructions;

c) Instructions for use, including transport and storage conditions.

 

III. Information on Trials (Studies) of the Medical Device

 

3. The Investigator's Brochure must contain the following information on previously conducted trials (studies) of the medical device:

a) Results of preclinical trials (studies);

b) Available clinical data, including:

Scientific literature data (indicating data sources, as well as information ensuring their traceability) containing information on the design, safety, effectiveness and intended use of similar or equivalent medical devices;

Scientific literature data (indicating data sources, as well as information ensuring their traceability) containing information on the design, safety, effectiveness and intended use of similar or equivalent medical devices of the same manufacturer, including data on the time they have been on the market, as well as information on identified problems related to the safety of use of the medical device and its effectiveness and corrective actions taken;

 

c) Results of risk analysis, information on side effects and contraindications;

d) A list of possible adverse events (incidents) and adverse effects arising from the use of the medical device;

e) A list of standards applied in full or in part.

 

Appendix N 2

to the Rules for Conducting Clinical

and Clinical Laboratory Trials

(Studies) of Medical Devices

 

REQUIREMENTS

FOR THE CONTENT OF THE CLINICAL TRIAL (STUDY) PROTOCOL

OF A MEDICAL DEVICE

I. General Description of the Medical Device

1. The clinical trial (study) protocol for a medical device shall contain the following information:

a) Name of the medical device;

b) Name of the manufacturer, its location (legal entity address) - for a legal entity, or last name, first name, patronymic (if any), place of residence - for an individual registered as an individual entrepreneur;

c) Name of the applicant, its location (legal entity address) - for a legal entity, or last name, first name, patronymic (if any), place of residence - for an individual registered as an individual entrepreneur, information on the state registration of a legal entity or an individual registered as an individual entrepreneur, as well as the applicant's contact details (phone number, email address);

d) Name of the manufacturer's authorized representative (if any), its location (legal entity address) - for a legal entity, or last name, first name, patronymic (if any), place of residence - for an individual registered as an individual entrepreneur;

e) Information allowing identification of the medical device, including the model number (brand) of the medical device (if any) or indication of the identifying model number (brand) of the medical device;

f) Type of medical device in accordance with the nomenclature of medical devices used within the Eurasian Economic Union;

g) Class of potential risk of use and applicable classification rules in accordance with the Rules for Classification of Medical Devices Depending on the Potential Risk of Use, approved by Decision of the Board of the Eurasian Economic Commission dated December 22, 2015 N 173;

h) Purpose of the medical device;

i) Description of the medical device;

j) Explanation of new properties and characteristics of the medical device;

k) Description of materials that come into direct or indirect contact with the human body;

l) Information on control medical devices, including permits for their circulation in the country where the trials (studies) are conducted;

m) Description of how traceability is achieved during and after the clinical trial (study) of the medical device (by assigning a series number, batch number, factory serial numbers, or other means);

n) Subjects of clinical trials (studies) (patient group) and medical indications for which the medical device is intended.

 

II. Data on the Clinical Trial (Study) of the Medical Device

2. The clinical trial (study) protocol for a medical device shall contain the following information regarding the clinical trial (study) procedure:

a) Name and identification data of the clinical trial (study);

 b) Name and address of the medical organization (clinical center) (medical organizations (clinical centers)) conducting the clinical trial (study);

c) Data on the researchers, coordinating investigator (if any);

d) Requirements for the professional training and education of medical specialists;

e) Process for obtaining informed consent from subjects of clinical trials (studies);

f) Description of the ethical aspects of the clinical trial (study), including the interests of vulnerable subjects of the clinical trial (study);

g) Overall expected duration of the clinical trial (study);

h) Description of special surgical and other medical procedures associated with the use of the medical device;

i) Description of the conditions for conducting the clinical trial (study) specified by the manufacturer;

j) Description of the risks and benefits of using the medical device during the clinical trial (study);

k) Description of accessories, other medical devices, and non-medical products intended for use in combination with the medical device;

l) Description of the clinical trial (study) design;

m) Objectives and hypotheses of the clinical trial (study);

n) Primary and secondary endpoints of the clinical trial (study);

o) Sample size of subjects of the clinical trial (study);

 p) Sample size calculation, including the expected dropout rate of subjects of the clinical trial (study);

q) Inclusion criteria, exclusion criteria for subject selection, criteria and procedures for termination or suspension of participation of subjects of the clinical trial (study);

r) Number of investigational medical devices used (with justification);

s) Description of clinical trial (study) procedures;

t) Description of procedures for reporting any deviations from the original clinical trial (study) protocol;

u) Monitoring plan for the conduct of clinical trials (studies), indicating the frequency of visits, the number of monitors, and their contact information;

v) Statistical methods for data analysis.

 Appendix N 3

to the Rules for Conducting Clinical

and Clinical Laboratory Trials

(Studies) of Medical Devices

 

REQUIREMENTS

FOR THE CONTENT OF THE TECHNICAL FILE FOR A MEDICAL DEVICE

(EXCLUDING SOFTWARE AND MEDICAL DEVICES

FOR IN VITRO DIAGNOSTICS)

I. General Description of the Medical Device

 

1. The technical file for a medical device (excluding software and medical devices for in vitro diagnostics) shall contain the following information:

a) Name of the medical device;

b) General description and intended purpose of the medical device;

c) Information allowing identification of the medical device, including the model number (brand) of the medical device (if any) or indication of the identifying model number (brand) of the medical device;

d) Type of medical device in accordance with the nomenclature of medical devices used within the Eurasian Economic Union;

e) Intended users;

f) Principles of operation of the medical device;

g) Class of potential risk of use and applicable classification rules in accordance with the Rules for Classification of Medical Devices Depending on the Potential Risk of Use, approved by Decision of the Board of the Eurasian Economic Commission dated December 22, 2015 N 173;

h) Explanation of the properties and characteristics of the medical device;

i) Description of accessories, other medical devices, and non-medical products intended for use in combination with the medical device under consideration;

j) Description and/or list of models (brands) of the medical device (if any);

k) Description of the main functional elements of the medical device (diagrams, photographs, and drawings demonstrating the main parts (components) of the medical device, including explanatory labels for diagrams, photographs, and drawings);

l) Description of materials that come into direct or indirect contact with the human body.

 

II. Description of the Medical Device

2. The technical file shall contain a list of the main characteristics, dimensions, and operating instructions for the medical device, its models (brands), and accessories, which are available in the technical documentation of the medical device and other materials accessible to the end user, as well as a list of standards applied by the manufacturer.

 

III. History of Circulation of the Medical Device, Information on Similar and Previous Modifications of the Medical Device

 

3. The technical file shall contain information on the presence or absence of a history of circulation of the medical device on international markets, including information on marketing, occurrences of adverse events (incidents) associated with the use of the medical device, and recalls of the medical device from the market, as well as a description of corrective actions taken in response to said occurrences and/or analysis thereof.

4. In the event that information on similar or previous modifications of the medical device is used to demonstrate compliance with the General Requirements for Safety and Effectiveness of Medical Devices, Requirements for their Labeling and Operational Documentation, approved by Decision of the Council of the Eurasian Economic Commission dated February 12, 2016 N 27 (hereinafter - General Requirements), the technical file shall contain a brief description of:

a) Previous modifications of the medical device (if any);

b) Similar modifications of medical devices in circulation within the Eurasian Economic Union and on international markets.

 

IV. Accompanying Information

5. The technical file shall contain:

a) Data on the labeling of the medical device and its packaging (labeling designs);

b) Instructions for use of the medical device (operational documentation).

 

V. Design and Development of the Medical Device

6. The technical file shall contain information that allows for a general understanding of the main stages of the design and development of the medical device. This information may be presented in the form of a process flow diagram.

VI. Manufacturing Processes

7. The technical file shall contain information that allows for a general understanding of the manufacturing processes. This information may be presented in the form of a process flow diagram, providing a general overview of the manufacturing, assembly, final testing (studies) of the medical device, and final packaging of the finished medical device.

VII. Manufacturing Sites

8. The technical file shall identify the manufacturing sites where manufacturing activities related to the medical device are carried out. If quality management system certificates or equivalent documents are available for these sites, copies thereof shall be attached to the technical file.

VIII. Information on Compliance with General Requirements

9. The technical file shall include information on the compliance of the medical device with the General Requirements.

 

IX. Results of Risk Analysis and Management

10. The technical file shall contain a brief list of risks identified during the risk analysis process and a description of how these risks are managed to reduce them to an acceptable level.

 

X. Verification and Validation Activities

11. The technical file shall contain the following information and documents on verification and validation that were used to demonstrate compliance of the medical device with the General Requirements (including regarding the applicability of the General Requirements):

a) Results of tests (studies) in testing laboratories (centers) and medical organizations (clinical centers);

b) Results of the manufacturer's own laboratory and/or factory tests (studies) of the medical device, including results of tests (studies) under simulated operational conditions;

c) Results of laboratory animal tests to confirm the correctness of the concept of the finished medical device;

d) Declaration(s) of conformity to standards from the list of standards, the voluntary application of which ensures full or partial compliance with the Essential Safety and Performance Requirements for medical devices, the requirements for their labeling and user documentation (appendix to Recommendation of the Board of the Eurasian Economic Commission of September 4, 2017 No. 17), or other standards with justification for their use;

e) A review of published literature containing information about the medical device or a similar medical device.

 

12. The technical file must contain:

а) Information on biocompatibility;

b) Information on medicinal products included in the medical device;

c) Information on the biological safety of medical devices including cells, tissues or their derivatives taken from humans or animals;

d) Information on sterilization methods;

e) Information on verification and validation of software in the design of the medical device;

f) A report on the justification of the clinical effectiveness and safety of the medical device.

 

13. The presentation of the results of clinical trials (studies), in addition to the conclusions, must include full reports (protocols) of the trials (studies).

14. The technical file must contain a list of materials that are in direct or indirect contact with the human body. In order to determine the physical, chemical, toxicological and biological characteristics of the material, it is necessary, in accordance with the results of the risk analysis, to conduct trials (studies) of biocompatibility.

The technical file should include detailed information on the trials (studies) conducted, the standards applied, test (study) protocols, analysis of the data obtained, and a summary of the test (study) results.

 

15. If the medical device includes medicinal products, the technical file must contain detailed information about the medicinal products used, their manufacturer(s), the reason for inclusion in the medical device, the safety of use and the mechanism of action as part of the device for its intended use, as well as a document confirming the registration of the medicinal product in the country of the medicinal product manufacturer.

16. The technical file must contain a list of materials of animal or human origin used in the medical device, as well as detailed information about these materials, indicating the selection of sources (donors), sampling, processing, storage, testing, and handling of tissues, cells, and substances of animal or human origin.

The technical file should also include the results of the process validation, confirming the existence of manufacturing procedures that minimize biological risks, in particular with regard to viruses and other pathogens.

It should also include a description of the record-keeping system allowing traceability from the sources of materials to the finished medical device.

 

17. If the medical device is supplied in a sterile condition, the technical file must contain information on the validation of the sterilization process (including trials (studies) for bioburden, the presence of pyrogenic substances, the presence of residual sterilizing agent) and on the validation of the packaging process. Validation information should include the method used, the achieved sterility assurance level, the standards applied, the sterilization protocol developed in accordance with these standards, and a summary of the results obtained.

18. The technical file must contain information on the process of designing and developing software and validating the software used in the finished medical device. This information includes a summary of the results of verification, validation, and test (study) activities performed in the manufacturing organization, as well as information on available hardware and operating system configurations contained in the accompanying documentation.

19. The technical file must contain information on animal testing (studies) conducted to confirm compliance with the Essential Requirements (if any). The technical file should describe the objectives of these studies, methodology, results, analysis, and conclusions.

 

Appendix No. 4

 to the Rules for Conducting Clinical 

and Clinical Laboratory Trials (Studies) 

of Medical Devices

REQUIREMENTS FOR THE CONTENT OF THE TECHNICAL FILE FOR SOFTWARE THAT IS A MEDICAL DEVICE

 

1. General description of the software that is a medical device

 

1. The technical file for software that is a medical device (hereinafter referred to as software) must contain the following information:

1. Name of the software;

2. General description and intended purpose of the software;

3. Information about the intended users of the software;

4. Information to identify the software, including information about the models (brands) of the software and its version(s);

5. Explanation of the version numbering scheme of the software;

6. Information about possible changes to the software that affect (or do not affect) the invariability of its functional purpose and/or principle of operation (if any);

7. Type of medical device according to the nomenclature of medical devices used within the Eurasian Economic Union;

8. Class of potential application risk and applicable classification rules in accordance with the Rules for Classification of Medical Devices based on Potential Application Risk, approved by Decision of the Board of the Eurasian Economic Commission of December 22, 2015 No. 173 (with justification for the selected class of potential application risk);

9. Principles of operation of the software;

10. Information on the interpretation function, data set source, hardware platform, method of software deployment, and method of access to the software;

11. Description of the components, modules, blocks of the software, which may be accompanied by structural diagrams of the software architecture;

12. Information on the presence (or absence) of artificial intelligence technologies in the software and their description;

13. Description of the characteristics of software accessories, medical devices or non-medical products intended for use in combination with the software, as well as a description of special equipment and/or software, test databases developed by the manufacturer for use with the software (if any).

 

II. Software Description

 

2. The technical file must contain a list of key characteristics, including the following informationa:

a) Description of the technical specifications of the software;

b) Description of the hardware system requirements necessary for the software to function (specifying supported operating systems, hardware platforms, required RAM, required disk space, additional software and hardware requirements);

 c) Data exchange protocols for using the software with other medical devices and/or accessories;

d) Performance parameters established by the manufacturer based on the intended use of the software, and taking into account the current level of development in the relevant field;

 e) Description of the software installation and uninstallation procedure;

f) List of requirements for the professional training or qualifications of individuals who perform software installation and uninstallation (if any);

g) List of measures and means of protection against unauthorized access to the software, as well as measures to ensure its cybersecurity, including:

Information on potential cybersecurity threat risks (identification of assets, threats, and vulnerabilities, etc.);

Information on access control procedures for all levels, indicating the methods by which such control is achieved (access only for trusted users, access through user authentication);

The degree and potential impact of threats and vulnerabilities on the functionality of the software and intended users;

Information on the use of automatic synchronization methods for terminating sessions in the system, if necessary for the software's operating environment;

Information on the use of a multi-level authorization model and differentiation of rights based on user role or device role;

Information on technical and software protection measures used in the software;

Procedure for user authentication before allowing software updates, including those affecting the operating system and applications;

Information on the need for systematic procedures for authorized users when installing and updating software;

Information on the necessity of using malware protection tools (antivirus software), if such tools are not provided by the manufacturer of the software that is to be used in conjunction with other software;

Information on the use of cryptographic information protection tools (if any);

 Information on the necessity of using the archiving, backup (duplication) function of data on the organization's servers using an authenticated privileged user;

 Information on the means used for protection against illegal distribution (if any);

 

h) Clinical guidelines used by the software algorithm (if any);

i) Indication of how the user can obtain information about the current version of the software and the procedure for updating it;

j) List of standards applied by the software manufacturer.

 

III. History of Software Circulation, Information About Similar and Previous Versions of Software

3. The technical file must contain information on the presence or absence of a history of software circulation in international markets, including information on marketing, adverse events (incidents) related to the use of the software, and software recalls from the market, as well as a description of corrective actions taken in response to these cases, and/or their analysis.

4. If information about similar or previous versions of the software is used to prove compliance with the General Safety and Performance Requirements for Medical Devices, requirements for their labeling and operational documentation approved by Decision No. 27 of the Council of the Eurasian Economic Commission of February 12, 2016 (hereinafter referred to as the General Requirements), the technical file must contain a brief description of:

(a) Previous versions of the software (if any);

(b) Similar versions of the software circulating within the Eurasian Economic Union and in international markets.

 

IV. Accompanying Information

5. The technical file must contain:

(a) Data on the labeling of the software, its electronic medium, and packaging (labeling drafts);

 (b) Instructions for use (operational documentation) of the software.

 

V. Software Design and Development

6. The technical file must contain information about the software lifecycle processes, including information about the main stages of software design and development, which may be accompanied by schemes, drawings, diagrams, and other explanations.

 

VI. Manufacturing Processes

7. The technical file must contain information that provides a general understanding of the manufacturing processes. This information can be presented in the form of a process flow chart, giving a general overview of the production, final testing (research) of the software, and final packaging of the electronic software medium (if applicable).

 

VII. Manufacturing Sites

8. The technical file must identify the manufacturing sites where production activities for the software are carried out. If quality management system certificates, reports on inspections carried out to verify system compliance with standard requirements, or equivalent documents are available for these sites, copies of them must be attached to the technical file.

 

VIII. Information on Compliance with the General Requirements

9. The technical file must include information on the software's compliance with the General Requirements.

 

IX. Results of Risk Analysis and Management

10. The technical file must contain a brief list of risks identified in the risk analysis process and a description of how these risks are managed to reduce them to an acceptable level.

 

X. Verification and Validation Activities

11. The technical file must contain the following information and documents on verification and validation that were used to demonstrate the software's compliance with the General Requirements (including on the applicability of the General Requirements):

(a) Results of tests (research) in testing laboratories (centers) and medical organizations (clinical centers);

(b) Protocols of preliminary tests (research) of the software (including reports on testing, validation, and verification of the software), tests (research) of the software on test databases;

(c) Declaration(s) of conformity of the software to standards from the list of standards, the application of which on a voluntary basis ensures full or partial compliance of medical devices with the General Safety and Performance Requirements for Medical Devices, requirements for their labeling and operational documentation (appendix to Recommendation

No. 17 of the Board of the Eurasian Economic Commission dated September 4, 2017), or other standards with justification for their application;

(d) Review of published literature sources containing information on the software in question or similar software.

 

12. The technical file must contain a report justifying the clinical efficacy and safety of the software.

 13. The technical file must contain information about conducted clinical trials (studies), excluding conclusions, which must include the full reports and protocols of the trials (studies).

 

Appendix N 5

to the Rules for Conducting Clinical

and Clinical Laboratory Trials

(Research) of Medical Devices

 

FORM OF REPORT

ON A CLINICAL TRIAL (RESEARCH) OF A MEDICAL DEVICE

 

 

 

 

 

 

 

Appendix N 6

to the Rules for Conducting Clinical 

and Clinical Laboratory Trials (Studies) 

of Medical Devices

REQUIREMENTS
FOR THE CONTENT OF A CLINICAL LABORATORY TRIAL (STUDY) PROTOCOL
OF A MEDICAL DEVICE FOR IN VITRO DIAGNOSTICS

 

1. General Description of the Medical Device for In Vitro Diagnostics

            1. The clinical laboratory trial (study) protocol for a medical device for in vitro diagnostics must contain the following information:

a) Name of the medical device for in vitro diagnostics;

b) Name of the manufacturer, its location (legal entity address) - for a legal entity, or last name, first name, patronymic (if applicable), place of residence - for an individual registered as an individual entrepreneur;

c) Name of the applicant, its location (legal entity address) - for a legal entity, or last name, first name, patronymic (if applicable), place of residence - for an individual registered as an individual entrepreneur, information about the state registration of the legal entity or individual registered as an individual entrepreneur, as well as the applicant's contact information (phone number, email address);

 d) Name of the authorized representative of the manufacturer (if applicable), its location (legal entity address) - for a legal entity, or last name, first name, patronymic (if applicable), place of residence - for an individual registered as an individual entrepreneur;

e) Description and intended use of the medical device for in vitro diagnostics;

f) Information allowing identification of the medical device for in vitro diagnostics, including the model (brand) number of the medical device (if applicable) or an indication of the identifying number of the model (brand) of the medical device for in vitro diagnostics;

g) Type of the medical device for in vitro diagnostics in accordance with the nomenclature of medical devices used within the Eurasian Economic Union;

h) Characteristics of the samples or specimens used in the clinical laboratory trial (study);

i) Class of potential risk of use and applicable classification rules in accordance with the Rules for the Classification of Medical Devices Based on Potential Risk of Use, approved by Decision No. 173 of the Collegium of the Eurasian Economic Commission dated December 22, 2015;

j) Explanation of new properties and characteristics of the medical device for in vitro diagnostics.

 

II. Data on the Clinical Laboratory Trial (Study) of a Medical Device for In Vitro Diagnostics

2. The clinical laboratory trial (study) protocol for a medical device for in vitro diagnostics must contain the following information:

a) Purpose and objectives of the clinical laboratory trial (study);

 b) Name and address of the medical organization (clinical center) (medical organizations (clinical centers)) participating in the clinical laboratory trial (study);

c) Location(s) where measurements (analysis) are performed (if different from the address of the medical organization (clinical center));

d) Methods of data analysis;

e) Statistical significance levels;

f) Sample size for assessing clinical performance;

g) Biological reference population;

h) Specimen suitability criteria, sample volume, and specimen exclusion criteria;

i) Details of the pre-analytical phase;

j) Blind testing procedures;

k) Consideration of the effects of interfering factors caused by specimen collection conditions or the donor's pathological (physiological) condition or treatment;

l) Selection and justification of the method of comparison;

m) Calibration procedures, including traceability data for calibrators;

n) Criteria for retesting and data exclusion;

o) Appropriate measures to prevent the risk of user infection.

Appendix N 7

to the Rules for Conducting Clinical 

and Clinical Laboratory Trials (Studies)

 of Medical Devices

REPORT FORM

ON THE CLINICAL LABORATORY TRIAL (STUDY) OF A MEDICAL DEVICE FOR IN VITRO DIAGNOSTICS

 

 

 

 

 

Appendix N 8
to the Rules for Conducting Clinical and
Clinical Laboratory Trials
(Studies) of Medical Devices

(Form)

 

 

 

  

 

 

 

 

 

 

 
Appendix N 9
to the Rules for Conducting Clinical and
Clinical Laboratory Trials
(Studies) of Medical Devices

(Form)

 

 

APPLICATION
for Obtaining Permission to Conduct Clinical Laboratory Trials (Studies) of a Medical Device (when conducting an interventional clinical performance study)

I. Information about the Medical Device

 

 

 

 

 

 

 

 

 

 

 

Appendix N 10
to the Rules for Conducting Clinical and
Clinical Laboratory Trials
(Studies) of Medical Devices

(Form)