Developing the biofacility of the future based on continuous processing and single-use technology

Stephan Klutz, Jorgen Magnus, Martin Lobedann, Peter Schwan, Benjamin Maiser, Jens Niklas, Maike Temming, Gerhard Schembecker

To maintain or strengthen their market position, biopharmaceutical producers have to adapt their production facilities to a drastically changed market environment. Contrary to currently used large scale batch-wise operated production facilities, where stainless steel equipment is widely applied, small scale and flexible production processes are desired. Consequently, the concept of the "biofacility of the future" has been developed, which combines the attributes fast, flexible, small, inexpensive and sustainable. Four design principles build the facilitýs basis and are presented within this work: continuous processing, 100 % single-use equipment, closed processing and adopting the ballroom concept. However, no publication presents a completely continuously operated platform process for the production of monoclonal antibodies up to now. Therefore, this work establishes the proof of concept regarding continuous antibody manufacturing. A pilot plant for the production of monoclonal antibodies has been built 100 % in single-use equipment. It was operated fully continuous and automated in the upstream and the downstream part. The concepts that allow continuously operating the pilot plant are presented within this work, i.e. continuously operated filtration, continuously operated viral inactivation, continuously operated chromatography and a continuously operated formulation. Analytics showed that the produced product was within specification limits of industrial bulk drug substances.