Biopharmaceutical production levels can vary up to 65% regarding productivity. However, this is widely accepted due to the complexities of living cells. Offline measurement methods often miss critical real-time changes in cell culture, which can lead to reduced cell viability. Giovanni Campolongo, Senior Market Manager at Hamilton, advocated for real-time monitoring in cell culture.
Real-time monitoring is important in cell culture because it reduces the risk of contamination and real-time data can also improve the yield and quality of cell cultures. Campolongo introduced two technologies that contribute to cell viability calculations, Incyte’s Impedance Spectroscopy and Hamilton’s IR technology. By combining these tools scientists can calculate cell viability and total cell density.
Campolongo mentioned that the CO2 level is an often overlooked factor in cell culture, but research from Roche demonstrated that finding the optimal CO2 target level doubled productivity in a set of cell culture experiments.
However, Campolongo addressed the challenges associated with CO2 density, specifically the scale-up. He stated: “CO2 is not oxygen. CO2 is 32 times heavier and stays in the bioreactor. The problem is in a 2-litre bioreactor you can strip CO2 quite easily. In a 12,000 or 4,000 litre bioreactor, you can’t.” As a result, scientists have to
add more base to compensate which causes osmolality to rise and cell productivity and viability decrease.
To overcome this, Campolongo suggested using a double sparge strategy to combat CO2 accumulation in perfusion systems. Integrating real-time sensors with digital platforms enables predictive analytics and enhanced process control. Soft sensors combine several signals to generate a ‘golden batch prediction’. Furthermore, sensor diagnostics in real-time help prevent drift, ensuring reliable data and reducing downtime.
Hamilton’s ARC technology gives insights into how well sensors measure. Campolongo said: “You don’t just want to have real-time measurements; you also want to know how well the sensor is measuring in real-time.” Moreover, Hamilton is collaborating with Siemens to incorporate the ARC technology into control systems.
Overall, real-time monitoring minimises errors and reduces variability. Campolongo outlined how advanced sensors, digital twins, and predictive analytics can work alongside one another to provide a comprehensive framework for addressing the complexities of cell culture to ensure higher productivity and high-quality standards.
