Integrated design of biopharmaceutical manufacturing processes: Operation modes and process configurations for monoclonal antibody production. (October 2021)

• Record Type: Journal Article
• Authors: Badr, Sara; Okamura, Kozue; Takahashi, Nozomi; Ubbenjans, Vera; Shirahata, Haruku; Sugiyama, Hirokazu
• Is Part Of: Computers & chemical engineering. Volume 153(2021)
• Publication Date: 2021-10
• Subjects: Chinese hamster ovary cells (CHO) -- kinetic model -- perfusion cultivation -- Periodic counter current (PCC) chromatography -- Continuous manufacturing -- Techno-economic assessment; Chemical engineering -- Data processing -- Periodicals; 660.0285
• DOI: 10.1016/j.compchemeng.2021.107422
• Languages: English
• ISSNs: 0098-1354

Abstract

Highlights: Comparison of batch, continuous and hybrid modes in monoclonal antibody production. A modified kinetic model for the main cultivation unit. Model validation with experimental data from literature and a pilot facility. Analysis of production cost and time for individual units and integrated scenarios. Analysis for production scales from clinical to commercial with single-use equipment. Abstract: Monoclonal antibodies are leading the growing biopharmaceutical markets. To sustain the increasing demand, manufacturing processes should be optimized to increase efficiency and flexibility. This work investigates the impacts of the application of single-use equipment in batch, continuous, and hybrid scenarios. Operating costs and time are compared at different production scales from clinical to commercial manufacturing for individual unit operations and for the final integrated scenarios. A modified kinetic model is presented for the main cultivation unit. The model is validated using experimental data from literature and from a pilot facility using Chinese hamster ovary cells. Integrated scenarios with fed-batch cultivation and continuous capture have the lowest operating costs. The selection of operating modes across production scales is discussed along with further considerations for the design of integrated processes. The presented models could be used for the development of process design, control, and scheduling efforts for achieving sustainable biopharmaceutical manufacturing.