title: Developing the biofacility of the future based on continuous processing and single-use technology.
abstract: 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 facility's 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.
authors.affiliation: Invite GmbH, Chempark Leverkusen, Building W32, 51373 Leverkusen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Klutz
authors.affiliation: Bayer Technology Services GmbH, Chempark Leverkusen, Building E41, 51373 Leverkusen, Germany. Electronic address: jorgen.magnus@bayer.com.
authors.forename: Jorgen
authors.initials: J
authors.lastname: Magnus
authors.affiliation: Invite GmbH, Chempark Leverkusen, Building W32, 51373 Leverkusen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Lobedann
authors.affiliation: Bayer Technology Services GmbH, Chempark Leverkusen, Building E41, 51373 Leverkusen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schwan
authors.affiliation: Bayer Technology Services GmbH, Chempark Leverkusen, Building E41, 51373 Leverkusen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Maiser
authors.affiliation: Bayer Technology Services GmbH, Chempark Leverkusen, Building E41, 51373 Leverkusen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Niklas
authors.affiliation: Bayer Technology Services GmbH, Chempark Leverkusen, Building E41, 51373 Leverkusen, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Temming
authors.affiliation: TU Dortmund University, BCI, Plant and Process Design, 44227 Dortmund, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schembecker
mesh_terms: D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D001709:Biotechnology; D002845:Chromatography; D004345:Drug Industry; D005160:Facility Design and Construction; D005374:Filtration; D006863:Hydrogen-Ion Concentration; D013205:Staphylococcal Protein A / Q000737:chemistry; D038301:Virus Inactivation
chemical_list: D000911:Antibodies, Monoclonal; D013205:Staphylococcal Protein A
keywords: Ballroom concept; Closed processing; Continuous countercurrent diafiltration; Continuous processing; Monoclonal antibody; Single-use