Prospects for developing Biomedical Cellular Products in the Russian Federation.

Biomedical cellular product (BMCP) is a complex comprising cell line(s) and excipients or cell line(s) and excipients in combination with state-registered medicinal products for medical use (hereinafter – medicinal products) and (or) medical devices.  a Biomedical Cellular Product is a product that contains cultured human cells.  It divided biomedical cell products into several types: autologous (derived from the patient’s cells), allogeneic (derived from the cells of another person) and combined (derived from several people). With autologous products, BMCPs are being developed to treat musculoskeletal diseases (e.g., to repair cartilage damage to the joint surface), ophthalmology, cancer, and other diseases.

According to the FDA, there are17 BMCPs registered. The European Medicines Evaluation Agency’s database contains information on 16 BMCPs, and it has registered only four drugs in both the U.S. and the European Union. These BMCPs are intended to treat oncological diseases.

The Federal Law N 180-FZ “On Biomedical Cellular Products” was adopted in 2016 In Russia. In this article, we will look at the specifics of conducting clinical trials of biomedical cell products (BMCPs), as well as assess the prospects for the development of BMCPs in Russia.

Conducting clinical trials of BMCPs.

There is clinical trials of biomedical cell products in medical institutions accredited by the Russian Ministry of Health. The requirements for a medical organization to be accredited to conduct clinical trials of biomedical cellular products are:

• availability of a license to conduct medical activities;
• availability of intensive care and intensive care unit (wards) in case of clinical trials of biomedical cellular products to determine safety, tolerability, and efficacy of biomedical cellular products;
• availability of copies of regulatory legal acts governing the organization and conduct of clinical trials of biomedical cell products;
• ensuring the confidentiality of personal data of patients taking part in clinical trials of biomedical cell products;
• compliance with the rules of good clinical practice for biomedical cell products.

As with clinical trials of pharmaceuticals, if it detects any danger to the life and health of patients in conducting a clinical trial of a biomedical cell product, the head of a medical organization may suspend the trial. An allowed federal agency shall decide to suspend such research based on a written communication from the head of the medical organization in which the clinical trial of the biomedical cell product is being conducted.

A report on the results of a clinical trial of a biomedical cell product is prepared by the organizer of the clinical trial of the biomedical cell product and is submitted to the allowed federal executive body which issued the permission to conduct the trial, within three months from its completion.

According to the Appendix to the Order of the Ministry of Health of the Russian Federation of May 31, 2017. N 279n, the register of issued approvals to conduct clinical trials of biomedical cell products must contain the following information:

1. the number of the registry entry and the date of inclusion in the registry of information about the authorization issued to conduct a clinical trial of a biomedical cellular product;
2. date and number of permission to conduct a clinical trial of a biomedical cell product;
3. name and location address of the organization organizing the clinical trial of a biomedical cell product;
4. name of the legal entity engaged by the organization referred to in subparagraph 3 of this paragraph to organize the conduct of the clinical trial of a biomedical cell product (if any);
5. name of the biomedical cell product;
6. name of the protocol of clinical trial of a biomedical cell product;
7. purpose of the clinical trial of biomedical cell product;
8. terms of the clinical trial of biomedical cell product; 9) number of patients taking part in the clinical trial of biomedical cell product;
9. number of patients taking part in a clinical trial of a biomedical cell product;
10. list of medical organizations where clinical trials of biomedical cell product are supposed to be carried out, with the sign of location addresses and places of activity;
11. the current status of clinical trials of biomedical cell products (ongoing, completed, suspended, ended).

As of today, the registry of issued approvals to conduct clinical trials of biomedical cell products is not freely available on the website of the Russian Ministry of Health.

The list of medical organizations accredited to conduct clinical trials of biomedical cell products is on the website of the State Registry of Medicines https://grls.rosminzdrav.ru/.

The procedure for introducing BMCPs into the Russian market is quite time-consuming, lengthy, and requires serious financial expenses. According to experts, preclinical and clinical trials of BMCPs can take 9-11 years. The personnel issue also remains an open one. Pharmaceutical companies and research centers conduct training courses aimed at increasing the level of professionalism in this field.

Development of biomedical cell products in RF.

Roszdravnadzor issued Russia’s first license for the production of biomedical cellular products in 2020. Generium JSC is the only production site in Russia that has received a license to manufacture biomedical cellular products. Under the current license, Generium JSC plans to develop and produce several unique autologous, allogeneic and combined BMCP, as well as personalized therapy and diagnostic tools, including those aimed at fighting the pandemic coronavirus infection (COVID-19).

Russia is still at the initial stage of developing biomedical cellular products. It is necessary to continue improving the legal and regulatory framework, ensure quality training of specialists at all stages of work, create an association of BMCP producers, and prepare the infrastructure. Besides, it will be useful to turn to foreign experience in the development and implementation of BMPCs, because there are already about 30 registered preparations based on cell technology on the world market