Chinese hamster ovary (CHO) cells are the most commonly used mammalian host organism for the production of high‐value therapeutic monoclonal antibodies (mAbs). The process performance of CHO cell cultures strongly depends on the cultivation conditions prevailing in the bioreactor. Critical process parameters (CPPs) in bioprocessing include pH, temperature, dissolved oxygen (DO), agitation rate, and concentration of nutrients and metabolites.
Process Analytical Technology (PAT) plays a crucial role in the design, analysis, and control of manufacturing bioprocesses based on timely in-process measurements of critical quality and performance attributes with the goal of ensuring final product quality. The incorporation of PAT tools provides the opportunity for faster decision-making as well as a finer level of process understanding. Raman spectroscopy has gained popularity as a very powerful PAT tool due to its ability to measure multiple variables non‐destructively, in situ, and with low interference from water in cell culture process.
The application of our self-developed Raman-based monitoring system coupled with multi-variate data analysis enables us to measure various CPPs such as glucose, amino acids or cell density in real-time during cell cultivation without the need of taking a physical sample from the bioreactor and increasing the risk of contamination. This opens the door to automatization and designing of dynamic feeding strategies where nutrient replenishment can be performed according to the culture conditions prevailing in the reactor (e.g., cell growth, nutrient consumption or production of metabolic waste products). Moreover, it enables to establish a well-controlled cultivation environment during the process thus improving cell growth and productivity, and ensuring consistent product quality.