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Dynamic metabolic modeling for a MAB bioprocess.
Jianying Gao1, Volker M Gorenflo, Jeno M Scharer
1Sanofi Pasteur Limited, Toronto, ON, Canada.
Biotechnology Progress
|February 3, 2007
Summary
This study presents a metabolic modeling approach to enhance monoclonal antibody (MAb) production in bioprocesses. The method accurately models cell metabolism for improved reactor efficiency and product formation.
Area of Science:
- Biotechnology
- Biochemical Engineering
- Cellular Metabolism
Background:
- Monoclonal antibody (MAb) production is crucial for pharmaceutical applications.
- High-density reactor systems require efficient model-based control strategies.
- Reliable kinetic models of cell metabolism are essential for optimizing bioprocesses.
Purpose of the Study:
- To develop a systematic metabolic modeling procedure for MAb bioprocesses.
- To model nutrient uptake and product formation during growth and post-growth phases.
- To integrate cellular regulation and control into a comprehensive metabolic network.
Main Methods:
- Utilized a systematic metabolic modeling approach.
- Combined stoichiometric and kinetic modeling principles.
- Employed quadratic programming (QP) for parameter identification.
- Applied the model to murine hybridoma cells in stirred spinners.
Main Results:
- Developed a comprehensive metabolic network model for MAb bioprocesses.
- Successfully modeled nutrient uptake and MAb production across different cell phases.
- Demonstrated the applicability of the QP method for parameter identification.
- Validated the model's effectiveness using murine hybridoma cell cultures.
Conclusions:
- The proposed metabolic modeling procedure enhances MAb bioprocess efficiency.
- The integrated model accurately captures cell metabolism and product formation.
- This approach is adaptable to various cell lines and bioprocess phases.
- Optimized bioprocess control can be achieved through reliable metabolic modeling.
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