Toxicity testing of medical devices

In order to complete the mandatory state registration process, medical devices need to undergo toxicity testing. Only accredited laboratories are eligible to conduct these tests. At your request, the Moscow-based company Medalis can arrange the performance of toxicity testing at ElectrontestBio’s testing laboratory. The laboratory is part of Electrontest Group and it has been accredited by the Russian Federal Accreditation Service (Rosakkreditatsiya). The laboratory holds the Accreditation Certificate No. RA.RU.21ОМ13 for testing of medical devices and medicines for biological safety. The testing laboratory is equipped with state-of-the-art high-tech measuring instruments and testing equipment. It holds License No. 77.01.13.001.L.000083.11.21 issued by the Federal Service for Surveillance in Consumer Rights Protection and Human Wellbeing (Rospotrebnadzor), which allows it to work with Risk Group 3 and 4 microorganisms.

Components of toxicity testing

Toxicity testing means that non-food and non-pharmacological products intended for medical applications are tested by a laboratory to find out whether they are toxicologically safe for human use. The procedure for this category of testing is approved by the Order of the Ministry of Health of the Russian Federation. In the Eurasian Economic Union (EAEU), the process is referred to as “testing of medical devices for biological safety”. According to the Treaty on the EAEU, the results of toxicity testing are valid in five Member States of the EAEU: Armenia, Belarus, Kazakhstan, Kyrgyzstan, and Russia, which form a single market of goods and services.

Timeframe and causes of toxicity testing

One of the prerequisites for issuing a Registration Certificate is that the Applicant provides a package of documents confirming toxicological safety of the medical device in question. Toxicity testing of a medical device is conducted prior to the submission of a registration dossier to the Federal Service for Supervision of Healthcare (Roszdravnadzor).

The purpose of testing is to determine, to what degree it is safe to use a medical device. Achieving this goal involves meeting the following objectives:

• Assessment of sanitary chemical, physicochemical, and other factors of the biological impact that the subject medical device has on the human body;

• Determine whether or not documents and products are compliant with international standards and regulations.

According to the Order of the Ministry of Health, laboratories with a confirmed status from the Federal Accreditation Service are eligible to conduct toxicity testing. Our ElectrontestBio laboratory holds Accreditation Certificate No. RA.RU.21ОМ13.

Categories of medical devices to be tested for toxicity

Toxicity testing is compulsory for medical devices that are not themselves immunological, metabolic or pharmacological products, but can supplement them. These include apparatus, appliances, implants, devices, and materials that interact with the human body and are used in medicine for the following purposes:

• to replace lost/removed organs or parts of the body or compensate for the functions of damaged organs;
• for therapy, prevention and diagnosis, including sampling of biological material for testing purposes;
• to alleviate the course of the disease;
• as a means of contraception.

In terms of direct or indirect contact with the human body, medical devices subject to testing come into contact with the skin, mucous membranes, open wound surfaces, the internal milieu/internal organs, lymphoid fluid and blood.

Based on the duration of their contact with the body, medical devices are classified as follows:

• Permanent: from 30 days to lifelong;
• Long-term contact: from 24 hours to 30 days;
• Short-term contact: up to 24 hours.

Стоимость процедуры

Содержание	Стоимость по национальной системе	Стоимость по системе ЕАЭС
Организация и проведение токсикологических испытаний медицинского изделия.	от 295 до 1 200 т.р. т.р.	от 1 020 т.р.

*Стоимость проведения работ устанавливается лабораториями Электронтест и, во многом, зависит от:

• класса риска медицинского изделия;
• количества вариантов исполнения;
• степени контакта с тканями тела человека;
• сложности изделия;

Characteristics of medical devices to be checked by toxicity testing

Laboratory toxicity testing is conducted in accordance with GOST R 52770-2016 State Standard.

Any toxicity-testing program is approved by the head of the testing organization.

The testing laboratory of ElectrontestBio LLC has subdivisions for chemical analytical testing, microbiological testing, and toxicity testing.

Team members of the Chemical Analytical Testing Division test medical devices to assess their physical and chemical parameters (physical chemistry of the materials from which medical devices and accessories are made) and sanitary chemical parameters using liquid and gas chromatography and atomic absorption spectrometry. The Microbiological Testing Division tests both sterile and non-sterile medical devices to assess the sterility and microbiological contamination of samples. Also, they have in place methods to assess bacterial permeability of facemasks and medical wear. The scope of accreditation of the testing laboratory of EletrontestBio comprises reference documents for testing materials for resistance to mold-line fungi. The Toxicity Testing Division conducts testing to assess the irritation action, pyrogenicity, acute systemic toxicity indicators, cytotoxicity, hemocompatibility and the content of endotoxins in medical devices and pharmaceuticals.

Main stages of toxicity testing

The testing process comprises three stages: preparation, laboratory testing of medical devices, and obtaining results.

The preparation stage involves the following:

• Sampling for testing;
• Collecting documents for the medical devices to be tested, including reports on any previous tests, if any, and a permit for import products in case of foreign manufacturers;
• Submitting the documents to the testing organization;
• Having the package of documents reviewed by laboratory experts;
• Developing and coordinating a toxicity testing program with the customer and its approval by the test manager;
• Delivery of samples to the laboratory.

The laboratory stage begins with sanitary chemical testing (physical and chemical tests, analysis of integral indicators). Based on the data obtained, products that are clinically unsafe to be used can be rejected. If the results are unsatisfactory, no toxicity testing will take place. If the results are satisfactory, toxicity testing will be conducted. Depending on applications of medical products, toxicity testing will involve:

• Assessment of cytotoxic, mutagenic and sensitizing factors;
• Hemolysis screening testing;
• Pyrogenicity testing;
• Sterility testing and identification of contaminants.

Toxicity testing uses hematological, physiological, biochemical, immunological, and pathomorphological methods, in vivo experiments (with laboratory animals), and in vitro testing of cell cultures.

The third stage involves issuing a package of documents fully ready for the submission to Roszdravnadzor.

Documents to be provided for toxicity testing

The following documents are to be provided to an accredited testing organization:

• Application;
• Technical and operational documentation (drawings, tables, diagrams, etc.);
• Regulatory documents indicating applicable national standards (GOST R ISO);
• Information on the materials used to manufacture the medical device;
• Information on medicinal products used as part of the medical device;
• Reports on previous toxicity tests (including those completed abroad).

Information in foreign languages must be provided with a notarized translation.

Testing results

Upon completion of toxicity testing, the testing organization will issue a package of documents in the prescribed format, including the following:

• Report listing results of toxicity testing;
• Testing program;
• Assessment report.

The results are considered negative/unsatisfactory if:

• It is found that the sample of the medical device or its component provided for testing fails to conform to the national standards and any related documentation (technical, legal, or operational documentation);
• The documentation provided turns out to be false or erroneous and fails to confirm that the medical device is safe to use (the medical device fails to conform to the declared level of safety).

If the results of testing are positive/satisfactory, the product and its registration dossier will be sent to Roszdravnadzor for state registration. The end point is for the Customer to receive a Registration Certificate.

Advantages of working with Medalis

We will undertake the preparation and development of documents at all stages, and arrange all necessary tests with a view to obtaining a Registration Certificate for your medical device.

Medalis is a member of Electrontest Group which has licensed technical, toxicological and clinical diagnostic laboratory assets accredited with Roszdravnadzor. Medalis team closely collaborates with Electrontest Group, thereby allowing for a quicker response to customers’ requests without extra fees being charged. Moreover, we have access to laboratories that test products from top-of-the-line manufacturers of medical devices, equipment and consumables. Our experts know how long it would take to complete toxicity testing, what the quality will be, and how much it will cost in each laboratory. The up-to-date database enables us to quickly find an organization that fits the customer’s needs in terms of specialization and pricing.

We welcome collaboration with all medical device manufacturers (including foreign ones) who are seeking to enter the Russian and EAEU markets.

Laboratory Certificates