Risk Management in the Manufacturing and Use of the Medical Product for <i>in vitro</i> Diagnostics: Reagent Kit “Lyophilized Erythrocyte Antigenic Tularemia Diagnosticum”

The aim of the work was to implement the risk management strategies in the manufacturing and use of medical products for in vitro diagnostics by the example of the experimental series of the reagent kit “Lyophilized erythrocyte antigenic tularemia diagnosticum”.Materials and methods. We tested experimental series of the reagent panel “Lyophilized erythrocyte antigenic tularemia diagnosticum”. To carry out the identification, assessment and analysis of risks regarding the considered medical product, failure mode and effects analysis (FMEA) was proposed and adapted under production conditions. Identification of risks associated with manufacturing and control of medical products for in vitro diagnostics was carried out using technological regulations, standard operational procedures and manufacturing notes.Results and discussion. The main outcome of the study is the development of a corrective actions system aimed at reducing the risks and ensuring consistent monitoring. The proposed schemes for carrying out the risk management process can be used as standard ones in the design and development of medical products for in vitro diagnostics, taking into account the specifics of each individual manufacturing. The reporting documents developed within the framework of the system are applicable during the inspection of good manufacturing practice and in terms of completing the registration profile of a diagnostic product with subsequent registration in the healthcare system of the Russian Federation

Волноводно-щелевая антенна на основе SIW-волновода

Introduction. Slotted waveguide antenna arrays are widely used across centimeter- and millimeter-wavelength ranges due to numerous advantages, including their good directional properties, compact dimensions, flat shape, convenience of power supply, and high efficiency. At the same time, the current trend toward miniaturization of electronic devices and their integration requires new solutions, such as the development of devices based on wave-guides integrated into the substrate (Substrate Integrated Waveguide – SIW).Aim. To simulate a SIW-based slotted antenna with characteristics similar to those of a conventional antenna array based on a hollow metal waveguide.Materials and methods. The Ansys HFSS software was used to simulate the structure under study and to carry out electro-magnetic modeling and analysis of its directional properties. The energy method was used to determine the coordinates of longitudinal slots on the wide wall of the SIW waveguide. Macros were developed in the Visual Basic Scripting Edition language to automate routine operations for creating and deleting objects of the same type when constructing a model. The Arlon AD300C microwave material was used to manufacture a printed version of the SIW waveguide.Results. The process of developing a SIW slotted antenna was carried out in the following stages: construction of a reference model based on a hollow metal waveguide followed by creating a transition model based on a waveguide completely filled with a dielectric and the final SIW-based model. At each stage, the radiation pattern was monitored to obtain the directional properties of the SIW slotted antenna with characteristics identical to those of an antenna based on the reference hollow metal waveguide.Conclusion. A SIW slotted antenna with the required characteristics was simulated and tested in the Ansys HFSS environment. Such an antenna employs one of the main advantages of the SIW technology, i.e., the possibility of integrating all components on a single substrate, including antenna arrays, passive components, and active elements. This approach provides the basis for reducing the size of microwave devices and their miniaturization.Введение. Волноводно-щелевые антенны широко применяются в диапазоне сантиметровых и миллиметровых волн из-за множества достоинств, среди которых высокие направленные свойства, компактные размеры, плоская форма, удобство подведения питания и высокая эффективность. Вместе с этим наблюдается стремление к уменьшению размеров СВЧ-устройств, их миниатюризации и повышению степени интеграции. Одним из вариантов решения этой задачи является переход к устройствам на основе волноводов, интегрированных в подложку (Substrate Integrated Waveguide – SIW).Цель работы. Разработка модели волноводно-щелевой антенны, построенной на основе SIW-волновода, с характеристиками, аналогичными антенне, выполненной по традиционной технологии на основе полого металлического волновода.Материалы и методы. Построение модели исследуемой структуры, электромагнитное моделирование и анализ ее направленных свойств проведены в САПР Ansys HFSS. Для определения координат продольных щелей.на широкой стенке SIW-волновода использован энергетический метод. Для автоматизации операций по созданию и удалению однотипных объектов при построении модели разработаны макросы на языке Visual Basic Scripting Edition. Для печатного исполнения SIW-волновода использован СВЧ-материал Arlon AD300C. Проектирование антенны на основе SIW-волновода выполнялось поэтапно: сначала была разработана эталонная модель на основе полого металлического волновода, затем переходная модель на основе волновода, полностью заполненного диэлектриком, и итоговая модель на основе SIW.Результаты. На каждом этапе контролировалась диаграмма направленности. В итоге смоделирована антенна на основе SIW-волновода с направленными свойствами, полностью совпадающими со свойствами антенны на основе эталонного полого металлического волновода.Заключение. На основе моделирования в САПР Ansys HFSS разработана и протестирована волноводно-щелевая антенна на основе SIW-волновода с требуемыми характеристиками. Антенна позволит использовать одно из главных преимуществ SIW-технологии – возможность интегрировать все компоненты на одной подложке, включая антенны, пассивные компоненты и активные элементы, что неизбежно приведет к уменьшению размеров СВЧ-устройств и их миниатюризаци

Experimental Peroxidase Conjugate for Detection of Specific Antibodies to Anthrax Agent in Enzyme Immunoassay

Anthrax poses a pressing issue for veterinary medicine and public health in many countries, including the Russian Federation, which necessitates the improvement and development of new, sensitive and specific diagnostic tools.The aim of the work was to create an experimental peroxidase conjugate for the detection of specific antibodies to the anthrax pathogen and to optimize the conditions for performing enzyme immunoassay (ELISA).Materials and methods. The peroxidase conjugate was constructed using horseradish peroxidase and Staphylococcus aureus protein A (Sigma-Aldrich, USA). Bacterial antigens isolated from strains of Bacillus anthracis 55ΔTPA-1Spo, B. anthracis Sterne 34 F2 were used as sensitizing agents. The developed experimental batches of the conjugate were tested in ELISA for the ability to bind antibodies in the blood sera of anthrax patients and vaccinated individuals. The sensitivity, specificity, and accuracy of the method were calculated using the built-in functions of the ROCR software package.Results and discussion. The peroxidase conjugate to detect specific antibodies to the anthrax pathogen in the study of clinical material has been developed; conditions for the ELISA performance have been optimized. To interpret the results of the study, a threshold value of the positivity coefficient was used, below which the result was considered negative, and at an equal or higher value, positive. The test demonstrated significant differences in the “positivity coefficient” indicator for the “Healthy”/“Sick” and “Healthy”/“Vaccinated” groups, while the differences between the “Sick”/“Vaccinated” groups were statistically insignificant. The maximum accuracy of the method was observed at blood serum dilutions of 1:250 and 1:500. 100 % intra-run, run-to-run and series-to-series reproducibility has been established for all positive samples. The sensitivity and specificity of the experimental peroxidase conjugates were 100 and 95.8 %, respectively, and the accuracy was 97.6 %

Influence of heat treatment on the structural and magnetic characteristics of (NdxPr1-x)2Fe14B-based magnetic material for low-temperature application

Sintered Pr-Nd-Fe-B-based permanent magnets with 10 and 13 wt. % of Pr were prepared by traditional technology and then subjected to various heat treatments. Stoichiometric composition of the matrix grains corresponds to (Pr0.3Nd0.7)2Fe14B and (Pr0.4Nd0.6)2Fe14B compounds, respectively. Conducted thermomagnetic analysis to samples of these magnets showed the presence of spin-reorientation transition in temperature 95 and 75 K, respectively. This makes the magnet potentially applicable for low temperatures. For these compounds, we have determined the optimum heat-treatment conditions. The magnetic domain structure of the magnet subjected to an optimum heat treatment has been studied. The effect of different low-temperature heat treatments on the magnetic properties of magnets has been demonstrated

Assessment of the Application of Erythrocytal Diagnosticum (Lyophilizate) in Detecting Tularemia Agent in Natural Foci

Tularemia is a zoonotic disease with a wide geographical dissemination, and its causative agent Francisella tularensis can be used as a bioterrorism agent. The aim of the study was to evaluate the use of a set of reagents “Erythrocytic immunoglobulin dry tularemia diagnosticum” (“DET-Ig”) with the help of control test strains and field material from natural tularemia foci. Materials and methods. Using the introduced erythrocyte diagnosticum, we studied the decontaminated cultures of test strains (F. tularensis Miura, F. tularensis 55, F. tularensis Schu, F. tularensis 15 NIIEG, Brucella abortus 544, B. melitensis 16-M, B. suis 1330, and Yersinia enterocolitica 64, Y. enterocolitica 178, Y. enterocolitica 383) and environmental samples suspected of containing F. tularensis. Results and discussion. It has been proven that the developed diagnosticum is specific, sensitive, and easy to use for routine diagnostics of tularemia. In the course of laboratory tests of the experimental series of the DET-Ig reagent kit, the possibility of qualitative determination of the tularemia agent in bacterial cultures, biological material and environmental samples in the reaction of indirect hemagglutination was demonstrated. Comparison of the results of use of erythrocyte diagnosticum in liquid and lyophilized forms showed the advantages of drugs after lyophilization: the possibility of transportation and long-term storage at any temperature conditions in various climatic conditions; the setting of the reaction is possible without the use of special diluents. The guaranteed storage term is set for two years (observation period). The results obtained indicate the prospects of introducing the developed drug into healthcare practice

Qualitative Indicators of Experimental Brucellosis Antigen Preparations Designed for Cellular Tests in vitro

In order to develop the most diagnostically informative methods for carrying out antigen-stimulated cellular tests in vitro a careful selection of stimulating agent (antigen) is required, possessing an adequate activating potential and providing specificity of the reaction.Objective of the study was to identify the qualitative indicators of experimental batches of brucellosis antigen preparations designed for cellular tests in vitro.Materials and methods. Initially we produced antigen complexes of brucellosis microbe on the basis of the vaccine strains of three epidemically significant Brucella species (B. abortus, B. melitensis, B. suis). Quantitative determination of WsAg and PPBC proteins of experimental preparation series was performed applying capillary electrophoresis. Qualitative composition was assessed through ion exchange liquid chromatography with refractometric detection.Results and discussion. We have specified physical-chemical features, investigated chromatographic profiles and composition of protein fractions, as well as tried the produced experimental batches of brucellosis antigen preparations. After analyzing the defined protein and polysaccharide composition of the obtained WsAg samples, one can conclude that WsAg preparation cannot be used for cellular tests as the probability of non-specific lymphocyte reaction manifestation in vitro was experimentally proven. By contrast, complex brucellosis antigen preparation PPBC has an expressed specific activity and specificity under in vitro conditions and the prospects to be used when developing methodological approaches for laboratory diagnosis of brucellosis and assessment of de facto immunity rate in risk contingents after vaccination. The obtained parameters will allow for proper quality provision when manufacturing the developed experimental PPBC preparation designed for cellular tests in vitro, taking into account modern validation and standardization regulations

Influence of heat treatment on the structural and magnetic characteristics of (Nd_xPr_1-x)₂Fe₁₄B-based magnetic material for low-temperature application

Sintered Pr-Nd-Fe-B-based permanent magnets with 10 and 13 wt. % of Pr were prepared by traditional technology and then subjected to various heat treatments. Stoichiometric composition of the matrix grains corresponds to (Pr_0.3Nd_0.7)₂Fe₁₄B and (Pr_0.4Nd_0.6)₂Fe₁₄B compounds, respectively. Conducted thermomagnetic analysis to samples of these magnets showed the presence of spin-reorientation transition in temperature 95 and 75 K, respectively. This makes the magnet potentially applicable for low temperatures. For these compounds, we have determined the optimum heat-treatment conditions. The magnetic domain structure of the magnet subjected to an optimum heat treatment has been studied. The effect of different low-temperature heat treatments on the magnetic properties of magnets has been demonstrated