Machine learning-based model predictive controller design for cell culture processes.

Journal: Biotechnology and bioengineering
PMID:

Abstract

The biopharmaceutical industry continuously seeks to optimize the critical quality attributes to maintain the reliability and cost-effectiveness of its products. Such optimization demands a scalable and optimal control strategy to meet the process constraints and objectives. This work uses a model predictive controller (MPC) to compute an optimal feeding strategy leading to maximized cell growth and metabolite production in fed-batch cell culture processes. The lack of high-fidelity physics-based models and the high complexity of cell culture processes motivated us to use machine learning algorithms in the forecast model to aid our development. We took advantage of linear regression, the Gaussian process and neural network models in the MPC design to maximize the daily protein production for each batch. The control scheme of the cell culture process solves an optimization problem while maintaining all metabolites and cell culture process variables within the specification. The linear and nonlinear models are developed based on real cell culture process data, and the performance of the designed controllers is evaluated by running several real-time experiments.

Authors

  • Mohammad Rashedi
    Operations Digital Strategy & Capabilities, Amgen Inc., Thousand Oaks, California, USA.
  • Mina Rafiei
    Operations Digital Strategy & Capabilities, Amgen Inc., Thousand Oaks, California, USA.
  • Matthew Demers
    Operations Digital Strategy & Capabilities, Amgen Inc., West Greenwich, Rhode Island, USA.
  • Hamid Khodabandehlou
    Digital Integration & Predictive Technologies, Amgen Inc., Thousand Oaks, California.
  • Tony Wang
    Imedacs, Ann Arbor, MI.
  • Aditya Tulsyan
    Digital Integration and Predictive Technologies, Amgen, Inc., Cambridge, Massachusetts.
  • Cenk Ündey
    Digital Integration and Predictive Technologies, Amgen, Inc., Thousand Oaks, California.
  • Christopher Garvin
    Digital Integration and Predictive Technologies, Amgen, Inc., West Greenwich, Rhode Island.