Monitoring Tools for the Development of High Cell Density Culture Strategies

Abstract

Biopharmaceuticals market has been constantly increasing during the last years, what is transforming the manufacturing industry of biomolecules. The efforts have been put into better understanding how bioprocesses are regulated in order to firstly, build the quality of the biopharmaceuticals into the bioprocess, and secondly, to be able to develop suitable culture strategies for the implementation of intensified bioprocess while preserving the product quality attributes (product quality). Both targets strongly depend on the development of reliable monitoring tools able to measure the key bioprocess variables and parameters. Among all the available monitoring tools, spectroscopic techniques are called to be the predominant as they can offer multicomponent mixtures composition. However, such techniques have not been widely incorporated due to its complexity which hampers their adoption by the industry. Alternatively, other “soft sensors” like oxygen uptake rate (OUR), have been successfully applied for the monitoring of cell activity, being very sensible to changes in metabolic behaviour or other biochemical changes suffered by the cells. Therefore, OUR has been applied to determine the key time points (Time of Action, TOA), for example the proper time for nutrients feeding in intensified cultures, or also the Time of Harvest in virus-host cells systems. TOAs detection would allow to automate and control the bioprocesses achieving higher productivities and product quality.