The article compares results reported in national and foreign literature concerning tuberculosis detection by various in vivo (skin tests such as the Mantoux test and Diaskintest^® (a skin test with a recombinant tuberculosis allergen)) and in vitro methods (IGRA tests). A positive reaction to the Mantoux test, which has been used for over 100 years as part of mass immunization against tuberculosis, can be indicative of both earlier vaccination and of infection caused by virulent Mycobacteria tuberculosis. Given the mass scale of BCG vaccination, the positive reaction to tuberculin loses its predictive value for assessing the risk of tuberculosis. Diaskintest^®, a recombinant tuberculosis allergen, was developed in Russia in early 2000s, authorized in 2008 and has been used in the national healthcare system since 2009. This is a recombinant fusion protein ESAT6-CFP10 produced using Echerichia coli BL21(DE3)/pCFP-ESAT. Differential diagnosis between post vaccination (BCG) and bacterial allergic reactions using Diaskintest^® demonstrated high efficacy of the product - detection of tuberculosis in people with a positive reaction to the test was much higher than that of the Mantoux test. Both Diaskintest^® and IGRA tests usually do not produce false negative reactions. Therefore no additional examination of non-infected people is needed, and the preventive therapy is given only to those people who have a high risk of developing tuberculosis.

The article summarizes the existing knowledge on the infection caused by Haemophilus influenzaetypeb (Hib-infection). It examines clinical immunology aspects of vaccination against Hib-infection. The authors cite data on the incidence of invasive Hib-infections in the Russia and other countries. Special attention is given to preventive vaccination against Hib-infection. The article describes properties of polysaccharide and conjugate vaccines against Hib-infection and examines different immunization schedules, therapeutic indications and contraindications, potential adverse reactions, and the vaccination procedure.

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 article presents the results of a long-term study of biological and genetic stability of tick-borne encephalitis strain 205 which is used by the FSUE «SPA «Microgen» to produce tick-borne encephalitis vaccines EnceVir (for adults) and EnceVir Neo for children, both of which are tissue cultured, inactivated, purified, and sorbed. The biological stability of strain 205 was studied at the seed lot stage using passages on outbred white mice: initial production strain 205 and production «stock strain». Lyophilisates of production seed lots were studied at different storage intervals at -20 °С (up to 9 years of storage and more). Biological activity parameters (tick-borne encephalitis virus (TBEV) titre in log LD₅₀/ml) were studied by using different ways of infecting outbred white mice, and strain 205 identification (specificity) was determined by comparing it to a reference strain in a biological neutralization assay (BNA) according to the manufacturer’s specifications for the vaccines concerned. The same materials and a batch of TBEV vaccine produced from the production «stock strain» (lyophilisate of 1986) were analyzed by polymerase chain reaction (PCR) and sequencing for genetic stability during passaging and long-term storage. The results of the study made it possible to demonstrate the biological and genetic stability of strain 205 during production of TBEV vaccines.

Reliable evaluation of blood products sterility is a very important and one of the most complex and critical control methods in the context of microbiological safety. The membrane filtration method that uses a closed-circuit system has, for many years, been the main and the most preferable sterility test method for all known medicinal products. However, Russian manufacturers perform sterility testing of heterologous serum products by direct inoculation method only. The present study was aimed at exploring the feasibility of performing sterility testing of heterologous serum products by membrane filtration. It was shown that sample preparation could be modified by dilution of samples to, on average, 1.5-2 times the initial volume with a sterile 0.9 % sodium chloride solution followed by membrane filtration at a geared-up rate which lowers protein sorption by the membrane filter. The study helped to determine the range of protein impact on the membrane when testing serum products according to the State Pharmacopoeia 13th ed. It was shown that various types of filter elements from mixed cellulose esters and Durapore^® (PVDF) could be used to test serum products by membrane filtration with a protein impact range of up to 12 g of protein per membrane. The results of heterologous serum products sterility testing by direct inoculation method and by membrane filtration were found to be comparable. Adaptation of the procedure to protein-containing products makes it possible to perform sterility testing by a more reliable and modern method. The authors can recommend the incorporation of the above-cited test procedure into quality standards for products concerned together with the currently used direct inoculation method.

The article gives an account of the stability study performed for two batches of human immunoglobulin reference standard (RS) used for determination of anticomplementary activity (industry reference standard, IRS 42-28-430). The first batch of human immunoglobulin reference standard used for determination of anticomplementary activity showed sustainable results during 30 months of storage at (5±3) °C which makes it possible to extend the RS shelf life from 18 months (corresponding to the initial monitoring period) to 30 months from the date of determining the certified parameter, given the acceptable range of more than 50 % for the positive control and less than 50 % for the negative control. Based on the results obtained, the re-certification was performed for the second RS batch after 18 months of storage. The main certified parameter (anticomplementary activity) of the negative control was within the range of 41.6±7.2 %, and of the positive control 75.7±6.8 % for the confidence level of 0.95. Therefore, the shelf life of the second batch of the human immunoglobulin reference standard used for determination of anticomplementary activity (IRS 42-28-430) was extended until February 2018, which makes 30 months.

The article gives an account of certification performed for a new batch of a Reference standard to be used with the test system for determination of the fractional (antigenic) composition of human serum products by immunoelectrophoresis -industry reference standard (IRS) 42-28-77 - in accordance with existing requirements. A candidate reference standard was represented by a batch of normal human serum intended for diagnostic purposes (more than 500 donors) and a batch of immunoelectrophoresis serum against human serum proteins (antiserum against human serum proteins). In accordance with the certification programme, the fractional (antigenic) composition of the reference standard was determined by immunoelectrophoresis using «KliniTest-EF» buffer and 0.05 M borate buffer solution and the modes stipulated in the general monograph 1.8.2.0002.15 Agar gel immunoelectrophoresis. The reaction between the antiserum against human serum proteins and the normal human serum components of the reference standard produced at least 15 precipitation lines. The study demonstrated that the bromphenol blue dye could be used together with «KliniTest-EF» buffer to assess albumin migration, and the pyronin B dye could be used together with «KliniTest-EF» buffer and 0.05 M borate buffer solution to assess immunoglobulin migration. The study confirmed the applicability of the certified reference standard designed for the test system for determination of the fractional (antigenic) composition of human serum products by immunoelectrophoresis, and set the criteria for its use in the context of human serum products identification (species specificity) testing not only by immunoelectrophoresis, but also by agar-gel immunodiffusion.

The standardization and control of «BiVac polio» (live attenuated bivalent oral polio vaccine type 1 and 3) developed by M. P. Chumakov Institute of Poliomyelitis and Viral Encephalitides of the Russian Academy of Medical Sciences, called for establishment of an industry reference standard (IRS) to be used in determination of infectious units for each type of the poliovirus in a vaccine dose, according to the requirements of the quality standard. The article gives an account of certification performed for the first batch of a live attenuated bivalent oral polio vaccine type 1 and 3 IRS. The following parameters were tested: Clarity, Colourity, рН, Sterility, Identification, Specific activity, Thermal stability. Identification, Specific activity and Thermal stability of the candidate reference standard were assessed in comparison with the vaccine poliovirus type 1 IRS (IRS 42-28-362-2016) and vaccine poliovirus type 3 IRS (IRS 42-28-372-2015). The IRS certified parameter was found to be: 10^7.38±0.38 TCID₅₀/ml for type 1 and 10^6.7±0.48 TCID₅₀/ml for type 3. The IRS was assigned with the number IRS 42-28-434-2016 and a shelf life of 1.5 years. The IRS can be used in specific activity testing of «BiVac polio» commercial batches.