Vaccines by different manufacturers are available for most of the vaccine-preventable infections covered by the National Immunisation Schedule of the Russian Federation. Determination of the possibility of replacing a vaccine in the case of routine or emergency vaccination still remains a challenging issue. The aim of the study was to substantiate the problem of vaccine interchangeability, outline specific challenges and ways of solving them, analyse criteria underlying evaluation of vaccine interchangeability in Russia, and international experience in this area. The procedure for determining the interchangeability of biological products, including vaccines, was established in the Decree of the Government of the Russian Federation of 5 September 2020, No. 1360 “On the procedure for determination of interchangeability of medicinal products for human use”. The paper analyses the applicability of the official criteria for interchangeability of biological products, including vaccines. It outlines the main problems of performing evaluation of vaccine interchangeability in accordance with the established criteria. It is concluded that the vaccine interchangeability criteria need to be clarified in order to allow for assessment of comparability of active substances, and comparison of efficacy, safety, and immunogenicity of vaccines, taking into account vaccination schedules for different age groups. The possibility of evaluating interchangeability based on the results of post-authorisation studies also needs clarification. It is also necessary to align patient information leaflets for interchangeable vaccines.

The pandemic of the new coronavirus (COVID-19) disease that began in December 2019 in China is still having a huge impact on all spheres of human life. The herd immunity, which is the most effective tool for preventing the spread of the disease, is formed in two ways: the passive way (i.e., the formation of a population not susceptible to re-infection due to the natural spread of the disease) and the active way (mass immunisation). High rates of COVID-19 vaccination were achieved thanks to the development and mass production of new vaccines. The selection of the most promising vaccine platforms is one of the key aspects of successful mass immunisation. The aim of the study was to compare the characteristics of COVID-19 vaccines used for mass immunisation. The paper analyses the vaccine technology platforms, efficacy of different types of vaccines based on clinical trial results, safety of vaccines for different population groups, and potential for scaling up vaccine production in order to ensure the necessary vaccination coverage. The vaccines currently used for mass immunisation are: BNT162b2 (Pfizer/BioNTech), mRNA1273 (Moderna), Gam-COVID-Vac (N.F. Gamaleya National Research Center for Epidemiology and Microbiology), Ad26.COV2.S (Johnson & Johnson), ChAdOx1-S (AZD1222) (AstraZeneca), BBIBP-CorV (Sinopharm), CoronaVac (Sinovac Biotech), and NVX-CoV2373 (Novavax). The comparison of the main characteristics of the vaccines demonstrated that the most promising types of vaccines for COVID-19 specific prophylaxis are RNA vaccines and recombinant adenovirus vector-based vaccines.

Current challenges to healthcare, i.e. the emergence of new diseases, lack of therapies for known diseases and life-threatening conditions, identification of patients who do not respond to standard treatment, on the one hand, and the evolution of scientific understanding of disease processes, medicines, therapies, causes of treatment failures, and implementation in clinical practice of innovations related to molecular biology and genetic engineering, on the other hand, create conditions and opportunities for the development of innovative medicinal products. A relatively new class of medicines is based on human cells and tissues (the term used in Russian legislation is biomedical cell products, BCP). However, the inability to accurately predict the efficacy and financial rewards of such medicines for pharmaceutical companies, as well as significant labour and financial costs associated with their development and clinical use, hinder their entry into the market. The aim of the study was to analyse the foreign regulatory setting for the development and launch of human cell- and tissue-based products, as well as approaches of foreign regulatory authorities to scientific advice, which can be drawn upon by the Russian expert authority when providing advice to BCP developers. The paper summarises the results of analysis of regulations establishing the procedure for providing scientific advice by EU, USA, and Russian regulatory authorities, and analyses the advice provided for the human cell- and tissue-based products which are now authorised in the EU and USA. The analysis of advice provided by foreign regulatory authorities shows that the largest number of consultations were given for medicinal products based on genetically modified cells for the treatment of cancer and genetic diseases. The questions were mainly related to the contents of specifications for finished pharmaceutical products, safety evaluation, curtailing of preclinical studies due to the lack of relevant animal/disease models, the number of subjects and efficacy endpoints in clinical studies, assessment of the appearance of replication-competent retroviruses.

With the onset of the COVID-19 pandemic, a number of molecular-based tests have been developed to diagnose SARS-CoV-2 infection. However, numerous available serological tests lack sufficient sensitivity or specificity. They do not detect specific antibodies in a significant proportion of patients with PCR-confirmed COVID-19. There is evidence that some convalescents have a relatively short-lived humoral immunity. In contrast, a number of publications have shown that T-cell response to human coronaviruses, including SARS-CoV-1, MERS, and SARS-CoV-2, can be strong and long-term. Assessment of T-cell immunity to SARS-CoV-2 is important not only for stratification of risks and identification of potentially protected populations with immunity acquired as a result of previous infection, but also for determining immunogenicity and potential efficacy of vaccines under development. The existing methods of quantitative or semi-quantitative assessment of specific T-cell response are mainly used in scientific research and are not standardised. The aim of the study was to develop and verify experimentally a test kit to be used in a standardised procedure for in vitro determination of T-cells specific to SARS-CoV-2 antigens, in human peripheral blood. Materials and methods: the TigraTest^® SARS-CoV-2 kit developed by GENERIUM, which determines the number of T-cells secreting interferon gamma in vitro, was tested in the study. Samples of venous blood of volunteers from three different groups were analysed in the study: presumably healthy volunteers; COVID-19 convalescents; individuals vaccinated against SARS-CoV-2. Results: the authors developed the TigraTest^® SARS-CoV-2 kit for in vitro determination of T-cells specific to SARS-CoV-2 antigens in human peripheral blood, demonstrated its specificity and performed preliminary assessment of its sensitivity. The study analysed the range and magnitude of the T-cell response in convalescent and vaccinated individuals. A pronounced T-cell response was also shown in some individuals with no symptoms or with unconfirmed diagnosis. It was discovered that the mean T-cell response to peptides of the spike protein (S-protein) was higher in the vaccinated individuals than in the convalescent patients. A correlation was determined between the severity of the disease and the level of T-cell response. Specific contributions of various groups of antigens to the T-cell response after COVID-19 infection were also determined. Conclusions: the TigraTest^® SARS-CoV-2 kit is a specific and sensitive tool for the assessment of T-cell immunity to the SARS-CoV-2 virus, which can also be used for vaccinated individuals. The kit may be used in clinical practice for comprehensive assessment of immunity to SARS-CoV-2.

Phenol is used as a preservative in a number of biological products. Methods that are used for quantitative determination of phenol differ a lot. Current requirements for accredited laboratories include continuous internal quality control. Reference standards with a certified content of the analyte are an effective metrological tool for ensuring such control. The aim of the study was to develop and certify reference standards for phenolic content in biological products, based on comparison of results obtained by GLC, HPLC, spectrophotometric, and colorimetric methods. Materials and methods: diluent for allergens by (candidate reference standard), 2.5 and 5 mg/mL phenol solutions, and 2.5 mg/mL 2-phenoxyethanol solution were used in the study. The experiments were performed using spectrophotometric, colorimetric, HPLC, and GLC procedures. The statistical analysis of results included calculation of the arithmetic mean, standard deviation, coefficient of variation, and analysis of variance with Student’s t-test and Fisher’s F-test. Results: the results of phenolic content determination by the spectrophotometric, colorimetric, and HPLC methods were statistically comparable. The F value obtained for equal sample sizes (n = 40) was F = 0.9343, given the critical value F_crit = 3.96. A reference standard certified by one of these methods can be used to control the consistency of phenol determination by a relevant method. The results of phenolic content determination by the GLC method showed statistically significantly differences: F = 17.47, given F_crit = 3.96, which demonstrated the need for certification of another reference standard. Conclusions: two reference standards were certified in the study: reference standard 42-28-449 with the certified phenolic content of 2.56‒3.32 mg/mL, to be used with the spectrophotometric, colorimetric, and HPLC methods; and reference standard 42-28-451 with the certified phenolic content of 2.92‒3.28 mg/mL, to be used with the GLC method.

The development of technologies for preparation of protein nutritional bases for microbiological nutrient media, from production waste of mainly readily available or non-food products, is a promising area in biotechnology. Researchers of Vyatka State Agrotechnological University assume that non-food secondary raw materials, such as waste chick embryos (WCEs) used in the production of anti-influenza products, could be used for these purposes, after removal of the virus-containing allantoic fluid. The aim of the study was to develop a technology for preparation of WCE enzymatic hydrolysate (WCEEH), and to evaluate growth properties of the hydrolysate-based solid nutrient medium, using Escherichia coli M-17 and Pseudomonas alcaligenes IP-1 test strains. Materials and methods: the authors offer methodological approaches to obtaining WCEEH and substantiate hydrolysis parameters. The obtained WCEEH was characterised in terms of physico-chemical properties: pH, amine nitrogen, total nitrogen, sodium chloride, degree of protein cleavage. The growth properties of the hydrolysate-based nutrient medium were studied using E. coli M-17 and Ps. alcaligenes IP-1 test strains. Results: the experiments demonstrated the feasibility of performing enzymatic hydrolysis of WCEs, and assessed physico-chemical properties of the prepared WCEEH batches. The study demonstrated the possibility of using the prepared hydrolysate as a component of solid nutrient media for growing the selected test strains. Conclusions: the study substantiated the optimal technological parameters for WCE enzymatic hydrolysis: pH (7.6 ± 0.3), duration (48 ± 2 h), temperature (49 ± 1) °C. The loading of hydrolysis components was optimised: mass fraction of the substrate—500 g/L, mass fraction of the hydrolysing agent—100 g/L. The physico-chemical properties of WCEEH make it suitable for preparation of microbiological media; the hydrolysate-based solid nutrient medium consistently ensures the growth of E. coli M-17 and Ps. alcaligenes IP-1 test strains with standard properties. The growth properties of the experimental medium are comparable to those of the meat-peptone broth-based nutrient medium.