Scaling Up Progressive Expression Systems

Greenovation Biotech, a company that focuses on the production of biopharmaceuticals in plants, has unique scale-up considerations that are specific to the process. The company produces glycoproteins in moss using a state-of-the-art wave-bag bioreactor system operated by its partner Biomeva. The production of moss also requires the use of photo bioreactors, which are not always readily available at contract manufacturing firms. “Effective illumination is the central limiting process parameter in production of biopharmaceuticals with moss,” notes Thomas Frischmuth, PhD, CEO of Greenovation. “For small-scale production and R&D there are different illuminated bioreactors commercially available, but scaled-up and regulatory compliant versions that are ready to use in photoautotrophic production of biopharmaceuticals are currently missing [from] the market.”

Although Frischmuth added that although it may eventually become standard procedure for contract manufacturing organizations to run a photoautrophic bioreactor production unit, few offer this technology. For a moss-based system, new illumination-based technologies will be crucial for the successful scale-up of fermentation volumes. In addition, moss processes have to be scaled-up exclusively in disposable bioreactors. Frischmuth says because of difficulties associated with clean-in-place protocols, production in a GMP-compliant stainless-steel bioreactor was not possible. He adds, “The use of single-use bioreactors was a key element to transfer the production technology in a GMP-compliant environment.”