Multi-Stage Population Balance Model To Understand The Dynamics Of Fed-Batch Cho Cell Culture

Monoclonal antibodies are crucial in the treatment of a broad spectrum of critical illnesses such as cancer and autoimmune diseases. These biopharmaceuticals are industrially produced in fed-batch animal cell culture bioreactors to achieve high cell density and product titre. At the end of the culture, the valuable product is selectively separated from a wide range of impurities also present in the supernatant, most of which are released by the host cells. A better insight into the dynamics of host cell impurity accumulation would facilitate optimisation and control of process pertbnnance and product quality. A multi-stage population balance model was developed to simulate cell growth, viability and the lysis of dead cells in an effort to trace the profile of a particular class of host cell impurities known as host cell proteins (HCPs). The model was informed by data from antibody producing Chinese hamster ovary (CHO) cell cultures. The simulation results support that more than 20% of dead cells lyse in the interval between consecutive cell counts, releasing a variety of HCPs into the supernatant. The model also calculates that approximately 20% of the total HCP amount found extracellularly are likely to be secreted by viable cells during culture. The proposed model can be used in process development to gain estimates of HCP concentration under different process conditions, such as different feeding strategies, culture temperature and harvest time. These conditions can also be optimised in silico to decrease the level of cell-derived impurities.