Production of Viral Vaccines in High-Cell-Density Suspension Cultures
Process intensification for the production of various animal cell culture-based biopharmaceuticals is currently carried out through high-cell-density (HCD) cultivations. Cultivations in perfusion mode are commonly applied for manufacturing of recombinant proteins . Production of viral vaccines under HCD conditions, however, has been little explored in large scale production, and often a significant decrease in cell-specific yields (virus/cell) and/or volumetric productivity (virus/L·d) compared to conventional batch processes has been observed . Furthermore, due to virus-induced apoptosis and cell death, continuous virus production strategies in perfusion mode are challenging. Nevertheless, to increase virus yields, advanced process strategies suitable to overcome the intrinsic challenges of virus propagation in HCD cultures should be established and optimized.
Aims of the project
- Design and optimization of a perfusion-based process for the cultivaton of suspension cells at HCD using alternating tangential flow (ATF) and tangential flow filtration (TFF) systems.
- Monitoring of critical state variables to characterize cell growth and virus replication dynamics.
- Analysis of the impact of medium composition on virus quality and process yields.
- Establishment of mathematical models for control of cultivation conditions to increase process productivity.
- Identification of critical parameters for integration of upstream and downstream operations.
 Kompala, D.S. and S.S. Ozturk, Optimization of high cell density perfusion bioreactors. 2006: Taylor & Francis: New York.
 Genzel, Y., et al., High cell density cultivations by alternating tangential flow (ATF) perfusion for influenza A virus production using suspension cells. Vaccine, 2014. 32(24): p. 2770-81.