Lutsenko T. Biotechnology of preparations of recombinant human interleukin-7 and its standardization

The purpose of the work was to provide scientific substantiation and development of biotechnology of substance of rIL-7 and nasal preparation of rIL-7, as well as parameters of its technological and analytical standardization. To achieve the goal, the following tasks were set. To develop a technology for the production of a substance of rIL-7, suitable for the manufacture of non-sterile drugs from it. To develop the technology of obtaining the finished preparation of nasal application on the basis of the substance of rIL-7. To investigate the biological activity of rIL-7 on various in vitro models as a basis for biological standardization of preparations. To substantiate the parameters of analytical standardization of various preparations of rIL-7, to develop methods to control its quality and to validate it. Conduct a study of the stability of various drugs of rIL-7. To carry out the perspective validation of the technology of manufacturing the finished preparation of rIL-7 on the basis of risk assessment of the manufacturing process. An optimized biosynthesis technology, isolation and purification of rIL-7 with high biological activity in vitro were developed. For the first time, the presence of direct antiviral activity of rIL-7 in relation to the hepatitis C virus in vitro and the possibility of using an appropriate method for standardizing drugs based on rIL-7was demonstrated. For the first time, the technology of obtaining the nasal form of the drug on the basis of the received rIL-7, as well as the principles of its analytical standardization with the use of physico-chemical, microbiological and immunological methods, is scientifically substantiated. The results of the work were supplemented with modern scientific and methodical approaches for the preparation of preparations of recombinant proteins for therapeutic purposes. The adaptation and validation of the method of determining the biological activity of rIL-7 with the use of mononuclear cells of human peripheral blood has been carried out, which allowed using the proposed method for routine analytical quality control of drugs based on rIL-7. Perspective validation of the technology for the preparation of nasal spray on the basis of rIL-7 with the use of the system of risk analysis and critical control points has been proven, which confirmed the stability of the process and its compliance with the eligibility criteria.