(683b) Control of Glycosylation and Titer in Fed-Batch Monoclonal Antibody Production
- Conference: AIChE Annual Meeting
- Year: 2019
- Proceeding: 2019 AIChE Annual Meeting
- Group: Pharmaceutical Discovery, Development and Manufacturing Forum
- Time: Thursday, November 14, 2019 - 12:55pm-1:20pm
Here we present an overall model-based strategy for meeting productivity and product quality requirements in the manufacture of mAbs. The proposed multivariate cascade control system consists of two nested control loops. The outer loop, which is responsible for controlling product attributes such as mAb titer, cell density, and the relative abundance of dominant glycans, uses a model predictive controller (MPC) to determine the setpoints for the inner loop. The inner loop in turn employs multiple PI controllers to sustain the cell culture by maintaining the levels of nutrients, pH, temperature, etc., at desired values. Because measurements of glycan distribution are not available frequently enough, the outer loop incorporates a state observer which uses available sensor measurements and model predictions to reconstruct the complete system state that the MPC uses, along with the process model, to determine the desired control policies.
As a first step toward implementing on-line control of industrial fed-batch mAb manufacturing processes, we tested the complete control system in a MATLAB simulation, investigating a variety of industrially relevant process conditions under several operating sensor configurationsâfrequencies, qualities, and delays. The simulation results offer insight into optimal sensing strategy as well as the usefulness and limitations of the proposed control system.