title: Economic analysis of uricase production under uncertainty: Contrast of chromatographic purification and aqueous two-phase extraction (with and without PEG recycle).
abstract: Uricase is the enzyme responsible for the breakdown of uric acid, the key molecule leading to gout in humans, into allantoin, but it is absent in humans. It has been produced as a PEGylated pharmaceutical where the purification is performed through three sequential chromatographic columns. More recently an aqueous two-phase system (ATPS) was reported that could recover Uricase with high yield and purity. Although the use of ATPS can decrease cost and time, it also generates a large amount of waste. The ability, therefore, to recycle key components of ATPS is of interest. Economic modelling is a powerful tool that allows the bioprocess engineer to compare possible outcomes and find areas where further research or optimization might be required without recourse to extensive experiments and time. This research provides an economic analysis using the commercial software BioSolve of the strategies for Uricase production: chromatographic and ATPS, and includes a third bioprocess that uses material recycling. The key parameters that affect the process the most were located via a sensitivity analysis and evaluated with a Monte Carlo analysis. Results show that ATPS is far less expensive than chromatography, but that there is an area where the cost of production of both bioprocesses overlap. Furthermore, recycling does not impact the cost of production. This study serves to provide a framework for the economic analysis of Uricase production using alternative techniques.
authors.affiliation: Centro De Biotecnología-FEMSA, Tecnológico De Monterrey, Campus Monterrey, NL, 64849, México.|Dept. of Biochemical Engineering, The Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London, WC1E 7JE, U.K.
authors.forename: Mario A
authors.initials: MA
authors.lastname: Torres-Acosta
authors.affiliation: Centro De Biotecnología-FEMSA, Tecnológico De Monterrey, Campus Monterrey, NL, 64849, México.
authors.forename: José M
authors.initials: JM
authors.lastname: Aguilar-Yáñez
authors.affiliation: Centro De Biotecnología-FEMSA, Tecnológico De Monterrey, Campus Monterrey, NL, 64849, México.
authors.forename: Marco
authors.initials: M
authors.lastname: Rito-Palomares
authors.affiliation: Dept. of Biochemical Engineering, The Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London, WC1E 7JE, U.K.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Titchener-Hooker
mesh_terms: D002845:Chromatography / Q000191:economics*; D006801:Humans; D059625:Liquid-Liquid Extraction / Q000191:economics*; D009010:Monte Carlo Method; D011092:Polyethylene Glycols / Q000737:chemistry; D012984:Software; D014503:Urate Oxidase / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification*
chemical_list: D011092:Polyethylene Glycols; D014503:Urate Oxidase
keywords: Monte Carlo simulation; PEG back-extraction; aqueous two-phase system; economic analysis under uncertainty; uricase