Development and Implementation of the Quality Management System as Applied to the Production of Medical Immunobiological Preparations at the Russian Research Anti-Plague Institute Microbe

Developed are the methodical approaches for design and implementation of quality management system(QMS) in the production of preventive and diagnostic medical immunobiological preparations manufactured at the Russian Research Anti-Plague Institute Microbe. Analyzed and generalized is the current legislative-normative framework of Russian Federation in the sphere of quality control and quality assurance. Factors influencing the quality management system are revealed. QMS is certified in conformity with the requirements of international standard ISO 9001

Deployment of Ultrafiltration for Concentrating and Purification of Antigens

Represented is domestic and foreign literature review dedicated to usage of ultrafiltration for concentrating and purification of antigens. Discussed are the issues of deployment of various ultrafiltration techniques. It is determined that filtering in the tangential mode by means of modules with flat-frame filtering elements is among the prospective ones. Demonstrated is the impact of such technological specifications as concentration rate, pressure, temperature, and membrane nominal cut-off on molecular mass on the quality of target products, the time elapsed, and preparation losses decrease (increase). Literature data analysis proves to be useful for the selection of the proper procedure for concentrating and purification of protective antigens of bacterial and viral origins. In addition, it allows for taking into account the parameters under discussion when developing specific manufacturing technologies for diagnostic and preventive medical immunobiological preparation production

Methods and Technologies of Cholera Vibrio Cultivation (Scientific Review)

Displayed is the review of domestic and foreign literature sources devoted to matters of cholera vibrio cultivation. Discussed is the information concerning the following methods utilized in the technological process of vibrio growth stimulation: batch cultivation, fed-batch, fermentation and dialysis, periodic and continuous cultivation. Analyzed is the impact of such parameters as dissolved oxygen concentration, count of carbon nutrition source, medium pH, temperature rate , concentration and physiological condition of inoculate, duration of technological process, affecting the growth of this microorganism and synthesis of its antigens. Consequently, literature data analysis has contributed to the selection of proper method for cholera vibrio cultivation and consideration of the factors mentioned above for the development of manufacture technology applied to the production of medical immunoglobulin preparations for diagnostics and prophylaxis of cholera

Enhancement of the Technology for Live Tularemia Vaccine Production

Objective of the study was to develop and test new biotechnological approaches for live tularemia vaccine production.Materials and methods: Francisella tularensis 15 NIIEG strain was used as producer-strain; Francisella tularensis 503 strain – as test infecting one. Producer strain was cultivated on solid and liquid nutrient media. Tangential ultrafiltration was performed with the help of microfiltration module “Viva-flow”. Lyophilization was conducted using drying installation – Free Zone 2.5 L.Results and discussion: Application of the designed liquid nutrient medium on the basis of enzymatic fibrin hydrolysate and submerged cultivation of the producer-strain has allowed for a significant biomass yield increment. At the stage of tularemia microbe culture concentration via microfiltration through filtering membranes with pore size of 0.2 μm, in the mode of tangential liquid flow, increased has been the content of microbe cells; the nutrient media residues – removed. Comparative analysis of the obtained in accordance with experimental technique laboratory series of the vaccine and commercial preparation of live tularemia vaccine has demonstrated their conformity with the specific normative properties. It is established that application of modified liquid nutrient medium, submerged cultivation conditions, methods of biomass concentration and separation has no negative influence on the main properties of live tularemia vaccine and will provide for considerable produce-ability increase in the future

Development of an in-house reference standard for anti-rabies immunoglobulin potency, to be used in the virus neutralisation test in a Vero cell culture

The development and use of new methods of quality control of medicines involve the use of a lot of reference materials in quality control testing. Specialists of the Russian Research Antiplague Institute “Microbe” have proposed an alternative methodological approach to determination of potency of anti-rabies immunoglobulin in cell culture, which requires the development of an in-house reference standard (RS) certified against the biological reference preparation (BRP) of the European Pharmacopoeia human rabies immunoglobulin. The aim of the study was to develop and evaluate the metrological characteristics of an in-house RS for anti-rabies immunoglobulin potency, to be used in the virus neutralisation test in a Vero cell culture. Materials and methods: The following materials were used in the study: equine rabies immunoglobulin, Vero continuous cell culture, fixed rabies virus (Moscow 3253Vero strain), human rabies immunoglobulin BRP of the European Pharmacopoeia. The potencies of the candidate in-house RS and rabies immunoglobulin samples were determined in the neutralisation test in cell culture. The results were recorded using a fluorescent microscope. Statistical processing was carried out in accordance with general chapter 1.1.0014.15 of the State Pharmacopoeia of the Russian Federation, 14th edition. Results: the certified value of the in-house RS potency was 180.8±18.8 IU/mL. The confidence limits were determined at the 0.95 probability level. The shelf life of the in-house RS is 1.5 years (when stored according to the sanitary regulation SanPiN 3.3686-21). The certified in-house RS was assigned with the number 41-01-20. A set of technical and operational documentation was developed and approved for the in-house RS. The developed in-house RS can be used for in vitro determination of anti-rabies immunoglobulin potency, expressed in international units, to confirm its compliance with the product specification file. Conclusions: the authors developed an in-house RS for anti-rabies immunoglobulin potency, to be used in the virus neutralisation test in cell culture, certified against the human rabies immunoglobulin BRP of the European Pharmacopoeia

Optimization of Specifications for Scaled-Up Fixed Rabies Virus Cultivation (“Moscow 3253” Strain) in Vero Cell Culture

/cell, using maintenance media 199 with admixture of 0.1 % human serum albumin or 2 % bovine serum. Optimum media volume in the roll-bottle for fixed rabies virus strain, “Moscow 3253”, cultivation is 200-400 ml. It depends upon the proliferating surface area. Specifications stated above provide for the obtainment of culture liquid with rabies virus titer - 1:256 - 1:512, if assayed in ELISA. This cultural virus is recommended as a basis for immunization material obtainment with a view to produce anti-rabies immunoglobulin from equine blood serum

Assessment of Stability of Chemical Cholera Vaccine in a New Primary Packaging

The bivalent chemical cholera vaccine is the only drug for the prevention of cholera registered in the Russian Federation. The vaccine has been produced in glass bottles containing 210 tablets. At the same time, modern trends dictate the need to produce the drug in varying dispensing and more practical packaging for the convenience of the consumer.The aim of the work was to study the stability of the properties of the immunobiological medicinal product “Bivalent chemical cholera vaccine” with modified filling and in new primary packaging.Materials and methods. When studying the quality of bivalent chemical cholera vaccine batches, physicochemical parameters, formaldehyde content, specific activity and safety, abnormal toxicity, immunogenicity, and microbiological purity were assessed. Stability in terms of “specific activity” was evaluated using dot immunoassay.Results and discussion. As a result of this work, the use of several dispensing options and new primary packaging of cholera vaccine has been experimentally substantiated. The stability of the finished vaccine preparation has been established in the “accelerated aging” test and during long-term storage. The possibility of using dot immunoassay with a conjugate based on staphylococcal protein A, labeled with colloidal gold, to monitor the stability of cholera vaccine has been experimentally demonstrated