Search

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.

Introduction. This publication describes the design and implementation sequence of technological procedures for labeling immunobiological medicinal products produced by the FGHI RusRAPI "Microbe" of the Rospotrebnadzor. In light of meeting the requirements of the Federal Act "On the Circulation of Pharmaceutical Products", the materials of this study are undoubtedly relevant.Text. The paper presents a step-by-step sequence of introducing technological procedures for labeling and interaction with the system for monitoring the movement of pharmaceutical products (MMPP) into the production process of medicines. At the preparatory stage, the following main issues were addressed: verification of the identity of information about medicinal products in the State Register of Medicines and in the automatic identification system "UNISCAN/GS1 RUS"; determination of the method and possibility of applying the identification means onto the secondary packaging; amendments to the pharma-copoeial monographs of the enterprise for each type of drug. Stage 2 [development of requirements for the system of labeling, serialization, verification and aggregation (LSVAS)] included the following activities: development of a functional model of the labeling process in the FGHI RusRAPI "Microbe" and determination of the responsible for the implementation of this scheme units; determination of the method of secondary packaging (manual or automatic), as well as the required degree of aggregation and the required automation of the process, based on the analysis of the functional model and the technological process of labeling; analysis of the experience of introducing drug labeling systems; analysis of the existing IT-structure of the FGHI RusRAPI "Microbe"; monitoring of the market of hardware and software manufacturers; development of technical requirements for the created system of marking, serialization, verification and aggregation. Stage 3 (implementation of the labeling, serialization, verification and aggregation system at the production sites) included the following activities: equipment supply and commissioning; equipment qualification (IQ/OQ); training of the personnel; amendments to regulatory documents. In the materials devoted to the implementation of the final stage, the issues of validation of technological procedures for drug labeling and interaction with the system of labeling, serialization, verification and aggregation are considered.Conclusion. The works performed made it possible to produce medicines in accordance with the requirements of the Federal Act "On the Circulation of Pharmaceutical Products" and the Decree of the Government of the Russian Federation dated December 14, 2018 № 1556 "On Approval of the Regulation on the System for Monitoring the Movement of Drugs for Medical Use". The material presented may be of interest to manufacturers who produce medicines in small amounts.

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.

The paper contains the data on the development of quality control sample (QCS) for determination of specific activity of heterologous anti-rabies immunoglobulin in neutralization test on white mice. Given are the results on QCS attestation in reference to international standard samples of human immunoglobulin against rabies. The quality control sample is put on the register of QCSs approved for application in experimental-production subdivisions and in the department of biological and technical control. It is deployed for final quality control of anti-rabies immunoglobulin preparation in commercial batches.

Objective of the study was to assess analytical and diagnostic sensitivity and specificity of the “Reagent kit. Erythrocytic coccidioidomycosal and histoplasmosal immunoglobulin dry diagnosticum”, designed for identification of causative agents of coccidioidomycosis and histoplasmosis in isolated cultures of micromycetes, as well as in clinical and biological samples using indirect hemagglutination test.Materials and methods. The investigation included 264 positive samples (216 samples of micromycete suspensions, 48 samples of biological and clinical material) containing pathogens of histoplasmosis and coccidioidomycosis concentrated up to 3,12·106 and 1,56·106 cells/ml, respectively, and 128 negative samples containing heterologous microorganisms in concentrations equal to 5·106 cells/ml. The study was carried out using biological samples that were artificially contaminated with stated pathogens of particularly dangerous mycoses and samples, obtained from bioassay animals with experimental infection.Results and conclusions. It is established that diagnostic sensitivity of the reagent kit is not less than 99,0 %. The diagnostic specificity is not less than 98,0 %. Reproducibility of the results in all cases was 100 %. The results obtained testify to the prospect of introduction of the developed kit into the health care practice.

Objective of the study was to develop and then conduct medical trials of the “Monoclonal immune-enzyme test-system for the detection of plague agent (“EIAPESTF1-M”).Materials and methods. Utilized were materials for carrying out sandwich EIA. MCA 1B3 to Y. pestis F1 served as diagnostic immune-reagent. To determine sensitivity and specificity of the designed immune-enzyme test-system, investigated were samples of 24 natural and genetically modified pFra+ and pFra– Y. pestis strains and 56 strains of heterologous bacteria Enterobacteriaceae family.Results and conclusions. Based on monoclonal antibodies to Yersinia pestis capsular antigen, constructed was “Monoclonal immune-enzyme test-system for the detection of plague agent (“EIAPESTF1-M”), which is characterized by high specificity and allows for the detection of encapsulated plague agent strains in biological samples and for identification of pure cultures with sensitivity of 5·105 – 1·106 mc/ml. It is highly competitive with comparator drug – “Diagnostic fluorescent absorbed equine plague immunoglobulins”, lyophilizate for diagnostic purposes, by RusRAPI “Microbe”. It possesses such advantages as objective result recording and capability of result documentation. “EIAPESTF1-M” is registered in the RF Federal Service for Surveillance in the Sphere of Healthcare and Social Development, reference No 2013/711, dated 31.05.2013 and approved for use in the territory of the Russian Federation.

Objective of the study is to experimentally substantiate the possibility to improve manufacturing efficiency by means of mass reduction of a vaccine tablet from 300 to 100 mg. Materials and methods. Inaba O-antigen lyophilizate serves as the specific immunogenic component of the vaccine. Results and conclusions. It is identified that it is expedient to produce tablets of 6 mm in diameter. Justified is the quantitative content of additive substances (lactose monohydrate, micro-crystal cellulose, and polyvinylpyrolidone). Moreover, the studies have specified target values for technological parameters of such processes as fluid bed granulation of the formula with overfeed of the binder, tablet compression and enteric-coating (Acryl-eze) application to finished dosage form. Using Inaba O-antigen lyophilizate manufactured has been model experimental series of the vaccine. Investigated have been its characteristics. Verified vaccine quality indicators testify to the compliance of the product with the requirements of manufacturer’s pharmacopoeial monograph. The studies exercised showed the possibility in principle to enhance manufacturing efficacy through the decrement of additives amounts, and thus the mass of a vaccine tablet from 300 up to 100 mg.

mc/ml. Additionally, this test-system has been proving for acquisition of sustainable results after 6 months of storing (the observation period). Medical trials of the panel of reagents “Monoclonal dot-immuno-enzyme test-system for tularemia microbe detection” have shown it to be a prospective preparation for implementation into the national healthcare practices both under stationary and field conditions.

– for environmental objects. Application of the preparation for practical purposes was considered to be promising, and it was recommended for State registration as a product of medical application.

Presented is a comprehensive approach to utilization of the wastes that appear in the process of heterologous anti-rabies immunoglobulin production (packed red cells, fibrin, and alcohol-containing products). Specific immunoglobulin is extracted from the surface of red blood cells using desorption technique. Additional yields of immunoglobulin after exposure of erythrocytes to non-ionic detergent amount to 10-19 % of the output. Rich protein supplement feeding for horses-producers is obtained from spray-dried packed red cells. Solid nutritious substrate for microbiological media production is obtained from fibrin using enzymic hydrolysis method. The efficiency of the fibrin hydrolysate-based media is 1.5-2 times higher in comparison with that of the media based on the digest of meat and casein, as demonstrated by the results of Vibrio cholerae scaled cultivation. Furthermore, worked out is the technology of ethanol regeneration after the rivanol-ethanolic precipitation of gamma globulin, alcohol content by volume being (93±1) % after the regeneration. It is demonstrated that the regenerated alcohol can be used as a precipitator in the process of anti-rabies serum fractioning. All in all, the developed techniques make it possible to utilize the wastes of anti-rabies immunoglobulin production and provide for further use of derivatives while producing medical immunobiological preparations.

Presented is the information on technical and medical trials of new generation preparations for gene diagnostics of Dengue fever and cholera, based on the multiple factor analysis. Application of these preparations makes it possible not only to detect pathogen but also to carry out its expedited identification in accordance with epidemiological significance and taxonomic status.

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.