Registration of medical devices for in vitro diagnostics in Russia

State registration of medical devices for in vitro diagnostics has some distinctive features. In this article, we will discuss in detail the procedure, stages and specific features that distinguish it from the registration procedure for other medical devices.

First, let us determine which medical devices and equipment are classified as medical devices for in vitro diagnostics.

Intended purpose of medical devices for in vitro diagnostics

Medical device for in vitro diagnostics (in vitro diagnostic medical device, IVD) is a product, such as reagents, calibrators, control materials, sample bottles, software and associated tools, equipment or other devices, which, whether used alone or in combination, is intended by the manufacturer for in vitro testing of human body samples solely or primarily to provide information for the purposes of diagnosis, monitoring or compatibility assessment.

Since we are talking about samples only, in vitro studies are studies carried out under controlled conditions outside a living organism!

One can also often find the following abbreviated name: medical devices for IVD.

There is a huge variety of in vitro diagnostic medical devices. As of now, the nomenclature classifier contains 34,216 records of types of medical devices, where 15,980 are intended for in vitro diagnostics. That is almost a half!

The most common types (in a broad sense) are:

analyzers (hematological, biochemical, immunological, luminescent, amperometric, coagulological, bacteriological, cytometers, spectrophotometers, mass spectrometers, chromatographs, gas analyzers, ion-selective analyzers, pH meters, densitometers, osmometers, urine analyzers, PCR analyzers, sequencers, cell morphology analyzers, blood rheological properties analyzers, monitoring systems, etc.);
individual reagents and reagent kits (for enzyme immunoassay, radioimmunoassay, chemiluminescent assay, fluorescent assay, multiplex analysis, PCR analysis, tissue typing, genetic analysis);
calibrators used to establish reference values;
control samples used to confirm the analysis quality;
ancillary reagents (used to prepare samples for analysis, including extraction and isolation of the analyte, removal of interfering components, modification of the environment, preservation);
express tests, cartridges, biochips;
nutrient media (agars, broths, selective media, transport media);
IVD software;
reagents for visualization and staining (of cells, tissues, inter- and intracellular structures, etc.);
containers, test tubes, bottles, cups, glass slides, kits for sampling/collection of samples;
general laboratory products for IVD, other equipment and consumables (micropipettes, devices for microplates movement, containers, washing devices, heaters, stands, devices for preparation of samples for analysis: shakers, separators, sample freezers, microtomes, devices for preparation and staining of mixtures, etc.).

Procedure for registration of medical devices for in vitro diagnostics

Considering the importance of tasks resolved with the help of IVD products (diagnosis, health monitoring, tissue compatibility), the state has developed a thorough procedure to control their quality, safety and effectiveness as part of the state registration.

Let us look at its implementation at each stage.

During the first stage, the Applicant develops registration dossier documents, as well as collects evidence of the quality, effectiveness and safety of the device for in vitro diagnostics. This stage also includes the assessment of the conformity of a medical device for in vitro diagnostics in the form of various tests and trials. After that, the manufacturer (or their representative) submits an application for state registration and the registration dossier documents.

The detailed description of steps taken during the first stage is given in the flowchart below.

During the second stage, the expert institution of Roszdravnadzor examines the Applicant’s documents and evaluates the quality, effectiveness and safety of the medical device for in vitro diagnostics. An expert opinion is then prepared based on the examination results. The steps carried out at this stage are given in the flowchart.

Examination of medical devices, where the conformity assessment requires clinical trials with human participation, is divided into two stages:

stage 1 – examination of the application for registration and the registration dossier documents to determine the possibility (impossibility) of conducting clinical trials;
stage 2 – examination of completeness and results of technical tests, toxicological tests, clinical trials, as well as tests for the purpose of confirming the type of measuring instruments.

However, the examination of all in vitro diagnostic medical devices is carried out in one stage!

Based on the results of the examination, an expert opinion is prepared. Its form is established by Appendix 3 of the Order of the Ministry of Health of the Russian Federation N 206n, dated March 20, 2020. You can download it You can download it here.

During the third stage, Roszdravnadzor assesses the compliance of the expert opinion with the task and decides, whether to register or to deny the registration of the medical device for in vitro diagnostics. Please see the flowchart for more details.

Now let us look at the main issues considered during the state registration procedure.

Technical testing of medical devices for in vitro diagnostics

The main task of technical testing is to assess the quality and safety of a in vitro diagnostic medical device when it is being used in accordance with its intended purpose specified in the manufacturer’s documentation.

Technical tests are conducted in authorized testing laboratories and centers that have a valid accreditation certificate from the Federal Accreditation Service.

Toxicological testing of in vitro diagnostic medical devices

Toxicological tests are the tests for assessment of the biological safety of a medical device for in vitro diagnostics (i.e. biological effects of the device). These tests are only necessary if the intended use of an IVD medical device involves direct or indirect contact with human skin, mucous membranes or internal media.

As a rule, IVD devices used in medical institutions are not subjected to toxicological tests, since they are used while wearing gloves or other protective equipment that prevent such contact.

However, many self-test devices are used by non-professional users and may require such contact. When considering how to assess the conformity of an IVD medical device, pay special attention to this aspect, because it determines, whether there is a need for toxicological testing.

Clinical trials of medical devices for in vitro diagnostics

Since clinical trials of IVD medical devices are conducted under laboratory conditions using samples of patient biomaterial taken during the diagnosis and treatment process (including archival samples and museum strains of microorganisms), they are called clinical laboratory tests.

The main goal of clinical laboratory tests is to verify the functional characteristics and (or) effectiveness of a medical device when it is being used in accordance with its intended purpose specified in the manufacturer’s documentation.

These tests can only be conducted by organizations that are included by Roszdravnadzor in the List of medical organizations conducting clinical trials of medical devices.

In addition, the list of works (services) in accordance with the license to carry out medical activities of such organizations should include laboratory diagnostics.

Another important aspect of conducting clinical trials of medical devices for in vitro diagnostics is that such trials do not require a permission from Roszdravnadzor.

Clinical laboratory tests of medical devices for in vitro diagnostics in the form of analytical systems, carried out for a medical device along with its accessories, reagents kits and calibrators necessary for the intended use of the medical device, can be conducted within one test.

What information is required in the application for the state registration of medical devices for in vitro diagnostics

In accordance with clause 9 of the Decree of the Government of the Russian Federation No. 1416, dated December 27, 2012, the Application includes:

name of the medical device (with inclusion of the accessories necessary for its intended use). In addition, the trademark and other means of individualization of the medical device should be indicated if they are applied to its packaging;
in relation to the developer of the IVD medical device – full and (if available) abbreviated name, including company name, organizational and legal form of the legal entity. For an individual entrepreneur – the location address or last name, first name and (if any) patronymic name, details of an identity document, address of residence. As well as telephone numbers and (if available) email address of the legal entity or the individual entrepreneur;
in relation to the manufacturer (producer) of the IVD medical device – full and (if any) abbreviated name, including company name, organizational and legal form of the legal entity. For an individual entrepreneur – the location address or last name, first name and (if any) patronymic name, details of an identity document, address of residence. As well as telephone numbers and (if available) email address of the legal entity or the individual entrepreneur;
in relation to an authorized representative of the manufacturer (producer) – full and (if any) abbreviated name, including company name, organizational and legal form of the legal entity. For an individual entrepreneur – the location address or last name, first name and (if any) patronymic name, details of an identity document, address of residence. As well as telephone numbers and (if available) email address of the legal entity or the individual entrepreneur;
in relation to the person in whose name a registration certificate may be issued – full and (if any) abbreviated name, including company name, organizational and legal form of the legal entity. For an individual entrepreneur – the location address or last name, first name and (if any) patronymic name, details of an identity document, address of residence. As well as telephone numbers and (if available) email address of the legal entity or the individual entrepreneur;
place of manufacture of the medical device. Please indicate the exact address in accordance with the document which establishes ownership of the premises;
intended use of the medical device established by the manufacturer (producer);
type of the medical device in accordance with the nomenclature classification of medical devices;
class of potential application risk of the medical device in accordance with the nomenclature classification of medical devices;
code of the All-Russian Classifier of Products by Type of Economic Activity (OKPD 2);
method of obtaining a registration certificate, as well as information related to the state registration procedure. By mail, courier, etc.

Documents required for the registration of in vitro diagnostic medical devices

In accordance with paragraph 10 of the Decree No. 1416, dated December 27, 2012, the Applicant submits the following documents along with the application:

wdt_ID	Item No.	Document name	Commentary
1	1	Copy of a document confirming the authority of an authorized representative of the manufacturer (producer)	Provided for the devices of foreign origin. Information about the functions of an authorized representative can be found here
2	2	Information on regulatory documentation for medical devices for in vitro diagnostics
3	3	Manufacturer’s (producer’s) technical documentation for the medical device
4	4	Manufacturer’s (producer’s) operational documentation for the medical device for in vitro diagnostics, such as instructions for use or operation manual for the medical device
5	5	Photographic images of the general appearance of the device together with accessories necessary for its intended use (at least 18 by 24 centimeters in size)
6	6	Photographic images of electronic media and software interface (at least 18 by 24 centimeters in size) (for the software medical device, including software with artificial intelligence technologies)	Provided if the medical device includes (or is) software
7	7	Documents confirming the results of technical tests of the medical device	Certificate of assessment of the results of technical tests of the medical device for in vitro diagnostics
8	8	Documents confirming the results of toxicological tests of the medical device, the use of which involves contact with the human body	Conclusion based on the results of toxicological tests
9	9	Documents confirming the results of the medical device tests for the purpose of approval of the type of measuring instruments	For medical devices related to measuring instruments in the field of state regulation to ensure the uniformity of measurements. Their list is approved by the Ministry of Health of the Russian Federation
10	10	Information confirming the clinical effectiveness and safety of the medical device for in vitro diagnostics	Certificate of evaluation of the results of clinical trials of the medical device for in vitro diagnostics
11	11	Information on permits issued by the registration authority for the import of medical devices for the purpose of their state registration	For medical devices of foreign origin, with the exception of software medical devices, including software with artificial intelligence technologies
12	12	Copies of documents confirming the quality of the drug, pharmaceutical substance, biological material and/or other substances, which are used to manufacture the medical device or are included in its composition, and which are intended for use only taking into account the intended purpose of the medical device, determined by the manufacturer, and issued in accordance with the legislation of the country where the drug, pharmaceutical substance, biological material or other substance has been produced
13	13	Inventory list	Download the inventory form

Reasons for refusal of state registration of an IVD medical device

In accordance with paragraph 35 of Government Decree No. 1416, dated December 27, 2012, the reasons for denying the state registration are:

an expert institution issues a negative expert opinion based on the results of examination of the quality, effectiveness and safety of the medical device. A negative expert opinion indicates that the quality and (or) effectiveness and (or) safety of the medical device is not confirmed by the provided data, and (or) that the risk of harm to the health of citizens and medical workers as a result of medical device application exceeds its effectiveness;
based on the results of state control over the circulation of medical devices, Roszdravnadzor has identified inconsistencies of the data on the effectiveness and safety of the medical device to the data on the medical device provided in the registration application and the registration dossier documents.

Which IVD medical devices are not subject to registration?

In general (true for all medical devices) the following devices are not subject to registration:

medical devices manufactured according to individual orders of patients, which are subject to special requirements for the prescription of medical professionals and are intended exclusively for personal use by a specific patient. This exception generally does not apply to IVD medical devices;
medical devices that are intended for use in the territory of an international medical cluster or the territories of innovative scientific and technological centers.

A number of regulatory documents have been developed exclusively for medical devices for in vitro diagnostics, allowing the use of unregistered devices. These documents establish the following criteria:

the financial costs of registration are not commensurate with the existing need for diagnostic testing;
the impossibility of determining the statistically reliable sensitivity and (or) specificity of a diagnostic test is justified, determined by the need to conduct such diagnostic test in accordance with the frequency of occurrence of the disease (condition) for which such IVD device is used.

More details on these criteria are given in paragraph 3 of Appendix 5 of Decree of the Government of the Russian Federation No. 2026, dated November 24, 2021.

Permission to use such medical devices can be obtained from Roszdravnadzor. They should be used exclusively by the medical organization that manufactured them.

Formally, such permission is valid indefinitely but requires confirmation every 5 years!

The decision to grant or confirm permission is made based on the results of an examination of the quality, safety and effectiveness of an unregistered medical device for in vitro diagnostics, carried out by the federal state budgetary institution subordinate to Roszdravnadzor (as is the case with the general Registration Rules).

For granting permission to use an unregistered medical device for in vitro diagnostics, a state fee of 9,500 rubles is paid. The fee for conducting an examination of the quality, safety and effectiveness of the device in order to grant permission for use is 65,800 rubles.

The decision to grant or deny permission is made by Roszdravnadzor within a period not exceeding 50 working days from the date when the decision to begin examination of the application for a permit was made.

Labeling of medical devices for in vitro diagnostics

Labeling of medical devices for IVD also has its own specific features: GOST R ISO 15223-1-2020 contains specific symbols that are applied only to them.

Symbol indicating that the medical device is intended for in vitro diagnostics.

Symbol that is applied to the control material which is intended to verify the performance of another IVD product.

Negative control. This is a sample that does not contain the analyte (or contains trace amounts that do not result in an analytical signal). It is intended to test results within the expected negative range.

Positive control. This is a sample that contains the analyte in sufficient concentration to produce a positive result. It is intended to control the results within the expected positive range.

Symbol indicates the cumulative number of in vitro tests that can be performed with this device. The number of tests is indicated next to the symbol.

test tube for the evaluation of the characteristics

Symbol indicates that this product is intended only for the evaluation of the functional characteristics of an IVD medical device (prior to its release to the market, for example, during clinical trials).

OUR SERVICES

For manufacturers and importers of medical devices for in vitro diagnostics, we offer the following services:

state registration in accordance with the Government Decree No. 1416, dated December 27, 2012
registration in the Eurasian Economic Union in accordance with the Decision No. 46, dated February 12, 2016
accelerated registration of devices used for prevention and control of coronavirus infection, in accordance with Government Decree No. 430, dated April 3, 2020
facilitated registration of devices for which there is a risk of shortage due to restrictive sanctions, in accordance with Government Decree No. 552, dated 04/01/2022
making amendments to the registration certificate and the registration dossier of the medical device registered in accordance with the above mentioned procedures
receiving a copy of the registration certificate, a copy of the registration dossier
obtaining permits to import devices for the purpose of their registration, issuing refusal letters for products similar to medical devices
planning, arranging and supporting technical, clinical, laboratory and toxicological tests in authorized laboratories and centers
preparing declarations and certificates of conformity for the medical devices for in vitro diagnostics
developing individual registration dossier documents (technical and operational documentation, reports on sterilization validation and packaging validation, shelf life confirmation, risk management file, etc.)
preparing responses to letters from Roszdravnadzor, supporting control activities and eliminating identified violations

If you are interested in our services, just leave a request, and we will contact you and provide free consultation on any of the issues.

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