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At the beginning of 2020, humanity faced the pandemic of a novel coronavirus infection – COVID-19. The disease has become one of the most contagious for the entire history of mankind. Among medical means of protection, which can be used for prophylactics and treatment of COVID-19, non-specific medical medical protection means play an important role. The aim of this work is to analyze and evaluate the effectiveness of non-specific medical protection means against COVID-19. These medications are divided in two groups in accordance with the targets of their actions. The medications of the first group either block the virus from entering the cell, or inhibit the enzymes involved in viral RNA replication. The other group of medications affects the immune system of a macroorganism, which plays a crucial role in infection resistance, or blocks inflammatory processes in the lungs. Favipiravir is an example of a broad-spectrum antiviral drug with an established activity against SARS-CoV-2 in particular. During the development of new non-specific medical protection means against COVID-19, a comprehensive validation in representative randomized clinical trials is an important condition for their implementation in medical practice.

The paper presents the data on safety and efficacy assessment of adjuvants and vaccines with adjuvants at the stages of development and preclinical studies based on international recommendations. The presence of an adjuvant in vaccine content ensures higher expressing and prolonged specific immunity. The origin and nature of adjuvants currently used for various vaccines are different. Adjuvants can be classified by origin, mechanism of action, physical and chemical properties. The finished vaccine may contain one or more adjuvants which can be intended for one antigen or a number of antigens in vaccine content. Antigen-adjuvant combination is a key part in the production of a vaccine with an adjuvant. Due to the diversity of adjuvant nature and their physical and chemical properties and mechanisms of action, as well as to antigens in adjuvant vaccines content, it is rather complicated to plan and to conduct preclinical studies. The present article describes various aspects of preclinical studies of adjuvants and vaccines with adjuvants based on the analysis of current guidelines and requirements.

The analysis of patent and scientific literature on the production of biomedical cell-based products (BMCP) showed that the main patentable developments in this sphere are focused on organ and tissue recovery, preventing transplant rejection and characterization of cell line viability. The researchers have revealed recent tendency for replacing the clinical use of BMCP based on unmodified cells and human cell lines by their genetically modified derivatives. Several dozens of Western companies are the principal developers, holding key patents in this field. At the same time, the analysis of patent activity showed that the technology of BmCp reached its peak of the development in 2000-2010, but many issues related to their safety clinical practice has not been solved yet. The examples of the mentioned issues are low efficiency of implanted cell differentiation maintanance; the possibility of BMCP contamination with infectious agents; nonspecific immunosuppressive effect on recipient organism; poor control of gene expression in transplant cell lines differentiated in a target organ and some

Quality evaluation of biologicals entails some specific considerations and problems associated with inherent variability of biological systems. This has implications not only for biological and immunological test methods, but for physical and physico-chemical methods as well. Usage of reference standards (RSs) has an important role to play in the improvement of evaluation of biologicals’ quality. Absence of some industry RSs, which have the status of national RSs, makes it impossible to standardize corresponding products and to assess comparability of test results obtained by different manufacturers for similar (similarly named) products. The first step in the creation of the national system of RSs for medicines is the analysis of the demand for RSs used in quality evaluation of medicines, including biologicals. The analysis of the range of RSs demonstrated that existing industry RSs are not sufficient for performing quality evaluation of available biologicals. At present new industry RSs are being developed.

The problems of quality and safety products derived from human blood plasma and hyperimmune animal sera as well as recombinant blood products resolved strict government regulation of their production processes. The risk of implications is minimized by plasma fractionation and purification of a specific drugs from various impurities (immunoglobulin aggregates, protease, plasmin, plasminogen, prekallikrein activator, IgA and IgM etc.). Viral safety is achieved by multi-step manufacturing process that includes at least two independent methods (treatment with solvent/detergent + incubation at low pH or pasteurization, combined with polyethylene glycol processing). It was justified that for today the technological process of the development of plasma preparations and hyperimmune animal sera has reached its limit. Their further development is the most likely to refer to specific improvements. The improvements will relate to increasing the efficiency of manufacturing technologies and methods of clinical use (preparations for subcutaneous administration, combinations of different immunoglobulin preparations, etc.), viral safety, ways to eliminate component, that were previously not considered to be able to influence the outcome of clinical use (soluble molecules CD4, CD8, HLA, thrombin, trace amounts of blood clotting factors VIII, IX, X, XI, XII etc.). At the same time new genetic engineered preparations with well-characterized molecular composition and a high selectivity for target impact are expected to appear on the market because of these unsolved issues. These are recombinant blood factors with altered properties; cocktails of recombinant antibodies and Fab-fragments of IgG, highly affine for toxin epitopes, etc. Therefore, in the upcoming years it is necessary to create in Russia a new system for assessing the quality, efficacy and safety of blood products, taking into account the future course of their development.

The safety of biological products derived from animal cells is associated with the properties of the cells themselves or their components, as well as with the possible presence of contaminants of microbial and viral origin. The suitability of cell substrate for production of prophylactic preparations is often determined by the features of the production process, which allows to benefit/risk ratio of the product. One of the common contaminants of cell substrates are mycoplasmas, type Mollicutes. As distinguished from other microorganisms they don’t have cell membranes, and parasitize a wide range of animals and plants, on the surface or inside the cells. Some mycoplasma species of are potentially pathogenic to humans, they compete for nutrients with cells in vitro , cause chromosomal aberrations, interfere with normal cell metabolism. The detection of mycoplasma contamination in cell substrates when manufacturing prophylactic preparations is required by regulatory documents.

The article presents the results of a retrospective analysis of experimental data on the protective properties of the three seed lots of tuberculosis vaccines which have been used in the production of BCG and BCG-M vaccines since 1984. It was shown that these seed lots have comparable characteristics of viability, which accounts for their equivalent immunogenicity. An additional study of the protective properties of the preparations was carried out in guinea pigs vaccinated with production batches of tuberculosis vaccines containing a different amount of viable BCG cells in the vaccine dose. Exposure of animals to a virulent strain of M. tuberculosis 2.5 months after the vaccination demonstrated high immunogenicity of the tuberculosis vaccines. It was established that a fivefold reduction in the dose of a vaccine with a high content of viable BCG cells only slightly reduces the degree of protection of the animals from disseminated tuberculosis. Thus, the data obtained confirmed that the 30 % reduction of the upper limit of the viability (viable BCG) of the BCG and BCG-M tuberculosis vaccines aimed at reducing their reactogenicity does not affect the protective properties of the preparation. It is important to note that previous post-marketing surveillance of such improved vaccines has shown a significant reduction in the number of post-vaccination complications in children.