Assessment of Critical Parameters of the Cultivating Process in Biotechnology of Active Pharmaceutical Ingredients
Keywords:Biotechnology, Good manufacturing practice, Critical production stage, Fermenter, Hydrodynamics, V-blade mixer
Background. The production of medicines of a certain quality, efficiency, and safety has never lost its relevance. Modern quality assurance and quality management systems – Good manufacturing practice – take into account the existence of critical stages and critical process parameters. The production of biological drugs by cell culture methods or using classical fermentation refers to the critical stages and they need adequate methods of validating the cultivation processes in the original fermenters and equipment to which structural changes have been made.
Objective. The aim of the study is to test the methods for evaluating the hydrodynamic situation in a fermenter with a classic mixer and a specific V-blade mixer, in model environments and on various imitation objects, and to determine the dependence of the change in hydrodynamic characteristics on the main critical parameters of the process.
Methods. The hydrodynamic situation in the fermenter is characterized by specific parameters of the flows of the existing phases. To determine the specificity of the flows, methods of visualization and a method for equalizing the tracer concentration, the homogenization time, are proposed.
Results. The visualization methods carried out during high-speed photography revealed specific flow characteristics for various mixing devices. More adequate and convenient for assessing the hydrodynamic situation in the fermenter, with changing environmental factors, was the introduction of a chemical tracer and an estimate of the homogenization time from the pH changes.Conclusions. The possibility of using a simple and easily repeatable technique for the validation of fermentation equipment in assessing critical stages in the production of biological medicines by cell culture methods or using classical fermentation has been proved. The high efficiency of the V-blade agitator is shown in comparison with the conventional design.
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