Dynamic metabolic modeling for a MAB bioprocess.
Production of monoclonal antibodies (MAb) for diagnostic or therapeutic applications has become an important task in the pharmaceutical industry. The efficiency of high-density reactor systems can be potentially increased by model-based design and control strategies. Therefore, a reliable kinetic model for cell metabolism is required. A systematic procedure based on metabolic modeling is used to model nutrient uptake and key product formation in a MAb bioprocess during both the growth and post-growth phases. The approach combines the key advantages of stoichiometric and kinetic models into a complete metabolic network while integrating the regulation and control of cellular activity. This modeling procedure can be easily applied to any cell line during both the cell growth and post-growth phases. Quadratic programming (QP) has been identified as a suitable method to solve the underdetermined constrained problem related to model parameter identification. The approach is illustrated for the case of murine hybridoma cells cultivated in stirred spinners.
Gao
Jianying
J
Sanofi Pasteur Limited, Toronto, ON, Canada.
Gorenflo
Volker M
VM
Scharer
Jeno M
JM
Budman
Hector M
HM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000379:methods*; D003198:Computer Simulation; D051379:Mice; D008954:Models, Biological; D015202:Protein Engineering / Q000379:methods*; D015398:Signal Transduction / Q000502:physiology*
D000911:Antibodies, Monoclonal