Model-based monitoring and control of a monoclonal antibody production process.
A structured mathematical model describing the dynamics of hybridoma growth and monoclonal antibody (mAb) production in suspension cultures is presented. The model fits well to experimental data obtained from batch, fed-batch, and continuous cultures with hybridoma cells. Applications of the model for process control are demonstrated. 1. An extended Kalman filter (EKF) was designed to estimate the state of the process. The oxygen consumption rate of the cell culture is monitored on-line and is used as the only measurement information for the EKF. This EKF is able to provide good estimates for living and dead cell densities and the medium composition. 2. The mathematical model can be applied for the optimization of fed-batch cultures.
Biener
R K
RK
Institut für Systemdynamik und Regelungstechnik, Universität Stuttgart, Germany.
Waldraff
W
W
Noé
W
W
Haas
J
J
Howaldt
M
M
Gilles
E D
ED
D000601:Amino Acids, Essential / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D002470:Cell Survival; D046508:Culture Techniques / Q000379:methods; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006825:Hybridomas / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007700:Kinetics; D008433:Mathematics; D051379:Mice; D008954:Models, Biological; D010101:Oxygen Consumption
D000601:Amino Acids, Essential; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D005973:Glutamine; D005947:Glucose