(683e) Investigation of Bio-Capacitance Driven Process Variation in a Site to Site Large Scale Technology Transfer Campaign

Bio-capacitance in cell culture processing allows for more automated process controls and on-line biomass monitoring. Here we presented a case study where the large-scale manufacture process (15,000L) is monitored and nutrient-fed based on the dual bio-capacitance automation driven protocol. In one of the batches, unexpected process variation was observed. Higher amount of feed, out of trend nutrient concentration and accumulative waste level were observed during the process which can be a signature of nutrient overfeed. Our investigation suggested that the primary and backup bio-capacitance reading have significant deviation especially at the earlier days. When bio-capacitance reading deviation happened, viable cell volume (VCV), calculated by Viable cell density (VCD) and cell diameter, was used to justify which probe signal to use. This is because capacitive signal is to measure the dielectric properties in the membrane of viable cell. Historical VCV/bio-capacitance ratio is referenced as process control strategy to translate the online bio-capacitance reading and offline Vi-cell measurement. In conclusion, the variation of Vi-cells to Vi-cells in addition to deviation of dual capacitance readings, created the signal to demand for higher feed volume. As a result, it might cause negative impact on the product quality such as glycosylation. Based on this large-scale process experience, we developed a more robust bio-capacitance control strategies to facilitate the site-to-site process transfer in the future.