Control systems technology in the advanced manufacturing of biologic drugs

The paper focuses on systems engineering challenges for biomanufacturing, as exemplified by the Integrated and Scalable Cyto-Technology (InSCyT) bio-manufacturing platform under the Defense Advanced Research Projects Agency (DARPA) Biologically-derived Medicines on Demand (Bio-MOD) program. One goal of the project is to apply modeling and simulation techniques to the design, control, and optimization of biomanufacturing operations. In this paper, we present models and control strategies for the unit operations within the InSCyT platform, including a perfusion bioreactor, several packed bed and membrane chromatography steps, and a conductivity- and pH-controlled buffer mixing unit.