According to generally accepted international standards, the characterization and confirmation of the quality of biological pharmaceutical substances requires the use of not only a combination of physicochemical and biological tests, but also an in-depth knowledge of the production process and its control. The study of such an industrial process involves considerable expenditure of time and material resources. Gaining a deep knowledge of the production process is greatly facilitated by using laboratory models of industrial installations that effectively reproduce large-scale processes in a research laboratory. On the basis of a laboratory bioreactor for the cultivation of eukaryotic cells with a working volume of 2 L, a scale-down model of a pilot bioreactor has been developed, linearly scalable to a production volume of 1000 L. The laboratory model reproduces the key parameters of cultivation on a pilot scale: the ratio of the geometric dimensions of the reactor, the peripheral speed of the mixer, the specific power input, the coefficient of oxygen mass transfer, the type and intensity of aeration, strategies for defoaming, feeding and maintaining the pH level. Experiments using the developed model showed high similarity in the kinetics of cell growth, productivity and quality of the expressed monoclonal antibodies in laboratory and pilot bioreactors.
Key words: cultivation, CHO cells, monoclonal antibodies, scale-down model
Development and fine-tuning of a scale down model for process characterization studies of a monoclonal antibody upstream production process
