title: Very-large-scale production of antibodies in plants: The biologization of manufacturing.
abstract: Gene technology has facilitated the biologization of manufacturing, i.e. the use and production of complex biological molecules and systems at an industrial scale. Monoclonal antibodies (mAbs) are currently the major class of biopharmaceutical products, but they are typically used to treat specific diseases which individually have comparably low incidences. The therapeutic potential of mAbs could also be used for more prevalent diseases, but this would require a massive increase in production capacity that could not be met by traditional fermenter systems. Here we outline the potential of plants to be used for the very-large-scale (VLS) production of biopharmaceutical proteins such as mAbs. We discuss the potential market sizes and their corresponding production capacities. We then consider available process technologies and scale-down models and how these can be used to develop VLS processes. Finally, we discuss which adaptations will likely be required for VLS production, lessons learned from existing cell culture-based processes and the food industry, and practical requirements for the implementation of a VLS process.
authors.affiliation: Institute for Molecular Biotechnology, Worringerweg 1, RWTH Aachen University, 52074 Aachen, Germany; Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstraße 6, 52074 Aachen, Germany. Electronic address: johannes.buyel@rwth-aachen.de.
authors.forename: J F
authors.initials: JF
authors.lastname: Buyel
authors.affiliation: TRM Ltd, PO Box 463, York YO11 9FJ, United Kingdom. Electronic address: richard@twymanrm.com.
authors.forename: R M
authors.initials: RM
authors.lastname: Twyman
authors.affiliation: Institute for Molecular Biotechnology, Worringerweg 1, RWTH Aachen University, 52074 Aachen, Germany; Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Forckenbeckstraße 6, 52074 Aachen, Germany. Electronic address: fischer@molbiotech.rwth-aachen.de.
authors.forename: R
authors.initials: R
authors.lastname: Fischer
mesh_terms: D000911:Antibodies, Monoclonal; D001709:Biotechnology; D058634:Molecular Farming; D030821:Plants, Genetically Modified / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal
keywords: Biologization; Molecular farming; Monoclonal antibodies; Plant-based production; Process economy; Very-large-scale production