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.

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.

Development and improvement of biotechnological drugs currently more relevant than ever. Drugs obtained by means of biotechnology, have a number of positive qualities. Biotechnology allows you to create such products, which are currently impossible to synthesize by chemical means, in addition, the production of drugs using biotechnology meets the standards of quality, efficacy and safety and, more importantly, economically. Biotech drugs are used for treatment of infectious, autoimmune, cancer, are used to prevent, thereby finding wide application in medicine.

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 provides with the results of theoretical research on justification of the choice of methionine form of recombinant interferon alfa-2b substance to be certified as a reference standard for identification test by peptide mapping. At present non- methionine and methionine forms of interferon alfa-2b substance are produced in Russia. The reference standard of interferon alfa-2b CRS I0320301, recommended by the European Pharmacopoeia, is a non- methionine standard and is suitable for identification test by peptide mapping only for a non- methionine form of a protein. In order to choose the reference standard candidate for methionine form of interferon alfa-2b, the article provides with the comparative analysis of the range of criteria and methods used by domestic manufacturers to confirm the quality of substances, authorized in the Russian Federation. The theoretical research allowed to choose interferon alfa-2b substance as a reference standard candidate for identification test by peptide mapping.

The present article highlights the issues of standardization of diagnostic and therapeutic allergen extracts used for allergen-specific immunotherapy (ASIT) in Russia and abroad. Quality evaluation methods for finished immunobiologicals (allergens) in accordance with the regulatory documents and using biological, immunochemical and advanced physical and chemical analytical techniques (in vitro and in vivo diagnosis) have been considered. Basic standardization strategies for allergenic preparations (determination of total allergenic activity, biological activity, the content of major allergens) have been presented. Two systems of allergen standardization (allergen units and biological units) have been introduced. The potential for use of high-performance liquid chromatography combined with mass spectrometry (HPLC-MS) as the most promising method for the standardization of allergen extracts has been considered. The advantages and disadvantages of the mentioned method for the standardization of allergens has been described. The method of chromatographic analysis of the total extract of drooping birch pollen, developed by the experts of the Chair of Pharmaceutical and Toxicological Chemistry of the I. M. Sechenov First Moscow State Medical University, has been given as an example.

The article provides with the information on certification of an industrial reference standard (IRS) for determination of filgrastim activity. In order to confirm the quality of the IRS candidate, the following tests have been performed: biological activity, description, identification, clarity, colority, sterility, pH, foreign impurities, bacterial endotoxins, as well as the assay of: Filgrastim, Acetate ion, Polysorbate 80, residual Host Cell Proteins, residual Host Cell DNA. The results fully meet the requirements for filgrastim samples. The reference standard is certified for biological activity. The purpose of the IRS for determination of filgrastim activity is the assessment of acceptability of the results of biological activity tests in the quality control of substances and drugs based on filgrastim. Biological activity of the IRS candidate has been assessed by interlaboratory studies as compared against the second international standard NIBSC-09/136. The certified value for «Biological activity» of the IRS for determination of filgrastim activity has been set as 32.2±5.35 million IU/ml. The shelf-life under the storage conditions of 2 to 8^oC has been set as not less than 2 years. The results of long-term stability studies the IRS confirm its stability during the monitored period.

This article presents the data on pharmacodynamics evaluation of monoclonal antibodies to α4β1-integrin in guinea pigs. The effect on total content of peripheral blood leukocytes after a single intraperitoneal injection of three doses of the drug has been studied. It was shown that intraperitoneal injection of the drug at doses of 30, 60, and 120 mg/kg causes a twofold increase in the content of leukocytes in the first hours after the administration, reaching a maximum value to 6th day. Subsequently 11-18 days, depending on dose, leukocytes content gradually decreased to control values.

Test system for determining the presence of binding antibodies to interferon beta-1a (BAB to IFN beta-1a) in serum using ELISA has been developed. The validation included sensitivity, selectivity, specificity, precision and accuracy, robustness, stability, suitability of the test system studies. The applicability of the mentioned test system has been approved for the use in clinical studies for the evaluation of interferon beta-1a immunogenicity (pegylated and non-pegylated forms).