Ecological safety and prospects of development of low-waste technologies in the biotechnology industry

Environmental pollution with industrial waste is an urgent problem today. A special place in the list of pollutants belongs to waste from biotechnological enterprises and industries, whose activities are related to the production of various drugs. Russian Research Anti-Plague Institute «Microbe» is the only manufacturer of unique immunobiological drugs in the Russian Federation – bivalent chemical cholera vaccine and rabies immunoglobulin from horse blood serum (AIG). At present, the institute actively uses fibrin as a basis for nutrient media – a waste in the production of AIG; a technology for the regeneration of alcohol waste has been developed; biologically active substances were obtained from the production waste of specific components of the cholera vaccine. The aim of the work was to assess the prospects of using waste products from the production of specific components of cholera vaccine (cholerogen-toxoid – X-AT, and O-antigen – O-AG) – formalized detoxified microbial-free filtrate (FMF), as a nutrient medium for the cultivation of industrial strains of microorganisms. It has been shown that the best methods for reducing formalin concentration are autoclaving and chemical neutralization with aqueous ammonia. During low-volume cultivation of Vibrio cholerae 569B and V. cholerae M-41 strains on all variants of experimental media based on PBP, an increase in biomass was noted. The production of Vibrio cholerae antigens at a level comparable to that of growing on a control nutrient medium was recorded in a medium variant based on O-AG production waste. The use of FMF as a nutrient medium in the future will reduce the volume of waste generated and reduce the load on the treatment facilities of the Institute, which will increase the environmental safety of production.

ESTIMATION OF THE EFFICIENCY OF THE DISINFECTANT «BIOLOK» IN PRODUCTION CONDITIONS

The article presents the results of laboratory and production tests of a new domestic composite preparation «Biolok» (manufactured by «Biosfera»). Laboratory studies were carried out on smooth and rough surfaces. Museum cultures of E. coli (stream 1257), Staphylococcus aurous (stream 209 Р), Mycobacteria (stream B 5), B. cereus (stream 96) were used as test microorganisms. Inactivated horse blood serum was taken to simulate the natural contamination of the surfaces. Production tests were carried out at the objects of veterinary supervision in the Republic Dagestan. As a result of the test, it was found that Biolok has antimicrobial activity and can be recommended for preventive and forced disinfection in case of infectious diseases of farm animals and poiltry.

REGISTRATION DOCUMENTATION AND AMENDMENTS TO IT AS AN ELEMENT OF A QUALITY MANAGEMENT SYSTEM IN PRODUCTION OF ANTI-RABIES IMMUNOGLOBULIN (REVIEW)

Introduction. Documentation is an integral part of the quality management system, a key element of production and quality control of medicines. A necessary condition for the Rules of good manufacturing practice and guaranteed production of quality products is compliance with the requirements set out in the documents of the registration dossier for the drug. During the life cycle of a drug, post-registration changes in the dossier may be required. Text. This work is an analytical review of changes in the documents of the registration dossier for the drug «Immunoglobulin antirabic from horse blood serum liquid», solution for injections, reflecting the improvement of biotechnology of drug production and methods of its control in the post – registration period. The first post-registration changes in the regulatory documentation were administrative in nature and did not require examination of samples of the drug. The next group of changes in the documents of the registration dossier was due to the expansion of production, reconstruction of technological sites and the introduction of innovative technologies in order to comply with the requirements of GMP, as well as improving the consumer properties of the drug. The last group of changes concerned the revision of methods of quality control of finished products associated with the introduction of modern analytical equipment, expanding the list of standards and bringing into compliance with the requirements of the state Pharmacopoeia XIII edition. Conclusion. The timely introduction of changes into documents of the registration dossier allows you to optimize the procedure for the conduct of internal and external control of rabies immunoglobulin, as well as to avoid violations related to the actualization of the technological documentation. The analysis of changes in the documents of the registration dossier for the drug «Immunoglobulin antirabic from horse blood serum liquid», solution for injections, reflecting the improvement of biotechnology of drug production and methods of its control in the post-registration period. Timely changes in the documents of the registration dossier allow to optimize the procedure of internal and external quality control of anti-rabies immunoglobulin, as well as to avoid violations associated with the updating of technological documentation.

An experience in the clinical use of specific immunoglobulin from horse blood serum for prophylaxis of Ebola haemorrhagic fever

The aim of this work was to estimate the efficacy and safety of single intramuscular introduction of specific heterologous immunoglobulin as prophylactic drug against Ebola hemorrhagic fever. Materials and methods. The specific heterologous immunoglobulin was introduced as a special prophylactic drug to 28 patients in epidemic situations, after skin hurt with infectious materials or contact with infectious blood. Clinico-laboratory observation was performed in 24 subjects after single intramuscular introduction of heterologous immunoglobulin Ebola. The samples of blood serum were investigated for immunoglobulin Ebola and antibodies to horse gamma-globulin on the 30th and 60th days after prophylaxis. Results. None of the subjects of the study contracted Ebola fever. There were no anaphylactic reactions after special prophylaxis with specific heterologous immunoglobulin. Among the subjects with normal allergic state 31% responded with local reactions; 13%, with a general reaction (mild case of the serum disease). Almost no reaction was observed in patients with unfavorable allergic state subjected to desensitizing therapy; in the absence of desensitizing therapy, 50% of patients with unfavorable allergic state exhibited local reactions; 17%, mild cases of the serum disease; 33%, moderate cases of the serum disease. In summary, if the tactics of immunoglobulin application was right, the quantity of local allergic reactions was 28%; of wide spread reactions, 6%. Weak serum disease was observed in 11% of the subjects. The prognostic period of resistance to Ebola fever was less than 30 days. Conclusion. The prophylactic use of specific immunoglobulin from horse blood serum against hemorrhagic Ebola fever is effective and relatively safe in patients subjected to desensitizing therapy.

Variability of albumin in blood serum as a possible reflection of evolutional influence of diluvial horses on population of native mountain horse in Serbia

Native mountain horse is an autochthonous ungulata with a domicile extending to the whole mountaneous region of Serbia, south of the Sava and Danube rivers. Along with native horses of other Balkan countries it is classified as Mediterranean pony, but unlike Balkan horses such as Skiros, Pinea, Pindos, Karakachan, Bosnian mountineous horse etc., mountineous horses in Serbia neither have been morphologically described nor were of concern to the scientific community till the end of the twentieth century. Investigations of albumin polymorphism in blood serum of native mountain horse were taken within a comprehensive reserch on morphologic, physiologic and genetic structure of this autochtonous ungulata breed. On the basis of the results obtained by electrophoretic separation of albumine types in native mountaneous horse blood serum, there were determined four albumine phenotypes: AA, AB, BB and BI which are inherited by three autosomal alleles AlA, Alb, All . The appearance of All allele in native mountaneous horse population points out to diluvial forest horse impact on process of microevolution of autochtonous native mountaneous horse. Occidental- specific albumin isoforms presence indicate the necessity of thorough study of evolution position and historic influence of different ancestors, and especially occidental horses on native mountain horse population in Serbia.