Techno-economic analysis of semicontinuous bioreactor production of biopharmaceuticals in transgenic rice cell suspension cultures

Abstract

Biopharmaceutical protein production using transgenic plant cell bioreactor processes offers advantages over microbial and mammalian cell culture platforms due to the ability to produce complex biologics, use of simple chemically-defined, animal component-free media, robustness of host cells, and biosafety. A disadvantage of plant cells from a traditional batch bioprocessing perspective is their slow growth rate which has motivated us to develop semicontinuous and/or perfusion processes. Although the economic benefits of plant cell culture bioprocesses are often mentioned in the literature, to our knowledge no rigorous techno-economic models or analyses have been published. Here we present techno-economic models in SuperPro Designer® for the large-scale production of recombinant butyrylcholinesterase (BChE), a prophylactic/therapeutic bioscavenger against organophosphate nerve agent poisoning, in inducible transgenic rice cell suspension cultures. The base facility designed to produce 25 kg BChE per year utilizing two-stage semicontinuous bioreactor operation manufactures a single 400 mg dose of BChE for $263. Semicontinuous operation scenarios result in 4-11% reduction over traditional two-stage batch operation scenarios. In addition to providing a simulation tool that will be useful to the plant-made pharmaceutical community, the model also provides a computational framework that can be used for other semicontinuous or batch bioreactor-based processes.

Effects of Kifunensine on Production and N-Glycosylation Modification of Butyrylcholinesterase in a Transgenic Rice Cell Culture Bioreactor

“…At the laboratory scale, we produced ~16 mg of rrBChE in a 2 L working volume during a 12-day batch run, corresponding to a volumetric productivity of 0.680 mg L −1 day −1 . A technoeconomic model developed for semicontinuous large-scale production (25 kg/year) of rrBChE (without kifunensine addition) at a higher volumetric productivity (1.5 mg L −1 day −1 ) showed that the process could be cost-effective with a cost-of-goods sold of ~$660/gram, less than 3% of the estimated cost of plasma-derived hBChE at ~$25,000/gram [ 54 ].…”