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 summarizes the existing knowledge on the infection caused by Haemophilus influenzae type b (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.

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 article analyses the main principles of and approaches to software and hardware solutions and platforms that could be used in the development of data management systems for biological collections. The authors summarise the key requirements for functional capabilities of the software which could be used to support biological resources databases and which is a prerequisite for maintaining a highly organized biological collection. The article sums up the main approaches to restricting access to information on biological collections as required by the patent procedure and biological safety principles. The authors identified specific aspects of developing information support systems for public biological collections.

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 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 TCID 50 /ml for type 1 and 10 6.7±0.48 TCID 50 /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.

Genotyping efficiency depends on resolution of methods which provided by the target sequence of genome, efficiency of enzymes, primers and conditions of DNA restriction and PCR amplification. The most differential tools are methods involving the high evolutionary markers. They are methods MST, MLVA, DGE, HRM against to the method MLST based on the slow evolutionary marker. Methods PFGE, AFLP, DNA chips exploit the preliminary information of genome and have the better resolution than ribotyping and RFLP-PCR limited by certain loci. Monitoring of local outbreaks may be carried out using a rapidly evolving markers (methods RAPD-PCR, MST, or MLVA, DGE, HRM). The most suitable methods for prolongated epidemiological or population researches are MLST, PFGE, ribotyping and pyrosequencing analysis. Polymicrobial samples are investigated with DNA specific methods PCR-RFLP, MLVA, DGE, HRM, MLST, MST, DNA chips. The metagenomic analysis is the most informative to identify the species of bacterium from the polymicrobial sample. It is essential to use the conservative DNA sequences, for example 16S rRNA. The modern genotyping assays provide the informative and technological platform for phylogenetic studies of bacterial strains even through the several generations. The important results are figures of genetic distances between strains involving in complex of epidemiological characteristics: virulence, antibiotic resistance and the others. The computing tools for integration the phenotyping and sequencing data have developed. Whole-genome sequencing is the optimal method for bacterial genotyping. But there are several crucial restrictions of this method. It is still rather expensive and needs to operate with high quality DNA.

Pharmacopoeial analytical methods involving reference standards (RS) are used for manufacture and quality control of medicinal products, including biologicals, these RS should now to be called pharmacopoeal. The introduction of the mentioned term reflects special drug characteristics, which are regulated not by the State Union Standards but by the Russian State Pharmacopoeia in terms of quality control. Drug and RS special characteristics require the establishment of legal and methodological framework. The recommendations stated in ISO REMCO are general do not fully cover the special aspects of the certification of reference standards for each specific area. The documents of the Federal Agency for Technical Regulating and Metrology (Rosstandart) on reference standards can not be used for biological medicinal products due to their specificity as the test methods do not allow to separate systematic and random components of uncertainty of test results, as required by Rosstandart. The regulatory framework for biological RS should be developed on the basis of WHO and ICH Guidelines. The classification of drug reference standards and the list of priority documents required for the elaboration of normative and procedural framework regulating their development, certification, approval and use is considered in the article. The development of the documents for the mentioned system is exemplified by a new pattern for an RS certificate.

The results of the tests for the quality assessment of live tularemia vaccine under the Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation in 2011-2015 were analyzed in the present article. There were 14 batches (of 34) which did not comply with the requirements of regulatory documents (RD) in terms of «Specific activity (percentage of live microbial cells)», «Number of cutaneous doses» and «Thermal stability». The experimental results had confirmed the irregularity of tularemia vaccine batch samples in terms of «Specific activity (percentage of live microbial cells)» which, respectively, led to differences in vaccine samples in terms of the number of cutaneous and intradermal doses. It was confirmed that FT-agar is a nutrient providing all the necessary conditions for cultivating Francisella tularensis strain. Possible causes of irregular quality of the batches released in 2011 was considered in the present article. Test results for 93 batches of tularemia vaccine manufactured in 2012-2015 shown their full compliance with the requirements of RD. Consistent quality assurance of tularemia vaccine became the basis for the possibility of choice, certification and approval of new drug batches as industrial reference standards.

Analysis of XI and XII editions of the State Pharmacopoeia of the Russian Federation proved the necessity and relevance of elaborating quality standards for immunobiological medicinal products as well as methods of their control. Assurance of safety and efficacy of this group of medicines could be achieved only by fulfilling the requirements of modern standards of quality and assuming that methods used for assessment of quality parameters of biologicals are adequate and informative. Top priorities addressed during the preparation of the XIII edition of the State Pharmacopoeia of the Russian Federation were: systematization of quality standards for biologicals on the basis of product types and methods of analysis, and harmonization of requirements for quality parameters with those of the leading world pharmacopoeias, primarily with the European Pharmacopoeia.

The Russian system of standardization of HP including biological medicines is based on the State Pharmacopoeia of the Russian Federation numbering more than the 250th summer history of the development. Requirements of general the farmakopoeia and the farmakopoeia of articles included in the State Pharmacopoeia of the Russian Federation are obligatory for all organizations which are engaged in the territory of the Russian Federation in production, production, quality control, storage and use of medicines. Historical development the farmakopoeia of the quality standards on biological medicines is reflected in article, starting with the first publications of articles editions (1910) and to GF Programme of the Russian Federation editions (2015) in which are provided are included in GF VI of Russia 57 OFS and 56 FS on the biological medicines allowing to provide standardization of requirements to their quality. Further enhancement and development of various directions in the immunobiology, immunobiological technologies which are based on a joint of immunology and molecular biology, and also genetic engineering and as a result of it, development of new BLP requires further development and the standardization of these HP guaranteeing their quality at all stages of lifecycle.

The review provides with the information, related to the development, research and registration of new biological preparations, including the issues of terminology and classification. It also highlights the issues of and prospects for genetically engineered drugs, specific aspects of comparative studies to prove the similarity of a biosimilar and the original (reference) medicine, clinical use and interchangeability of preparations, prospects for the development of biotechnological medicines, expert evaluation of the quality of biological/ biotechnological medicines, modern methods of immunotherapy of allergic diseases by recombinant medicines, as well as the issues of cell technology and tissue engineering. The review also describes the topics discussed at the 14th International Conference «High Medical Technologies of 21st Century» (October 24-31, 2015, Spain), related to fundamental and applied research, development and introduction of new technologies and modern medicines into clinical practice.

The article presents the results obtained in the study of a new batch of a candidate branch reference standard for live tularemic vaccine (vaccine BRS). The candidate vaccine BRS was represented by a commercial batch of a product that met all applicable requirements of the manufacturer’s monograph (MM) for live tularemic vaccine’s quality attributes. The candidate vaccine BRS was certified for specific activity including a range of parameters, such as: microbial cells concentration, percentage of living microbial cells, dissociation degree (percent of SR (white) immunogenic colonies from the total number of colonies grown), as well as immunogenicity. Results of analysis that addressed the use of this batch of vaccine BRS and its quality attributes made it possible to extend the shelf-life of the product for 6 months.

Blood products were first represented in the State Pharmacopoeia of the USSR IX and X editions (1961 and 1968) by a single monograph Gamma globulin for the prevention of measles. During the next 50 years there were no general monographs (GM) or individual monographs (IM) in the State Pharmacopoeia of the Russian Federation that laid down regulatory requirements for the quality of human blood products. In this regard, there came a need to develop GMs and IMs on human blood products taking into account modern approaches, specific features of a complex multi-level production technology and modern harmonized requirements for blood products, ensuring their quality, efficacy and safety in humans. The Order of the Ministry of Health of the Russian Federation On the adoption of general monographs and individual monographs” No. 768 of 21.11.2014 brought into effect 32 GMs and IMs on blood products, including 11 GMs and 5 IMs that have been introduced into the national pharmacopoeial texts for the first time. The monographs were developed with due regard to modern pharmacopoeial methods of analysis that account for a high level of quality control of this type of products.