title: A prototype software methodology for the rapid evaluation of biomanufacturing process options.
abstract: A three-layered simulation methodology is described that rapidly evaluates biomanufacturing process options. In each layer, inferior options are screened out, while more promising candidates are evaluated further in the subsequent, more refined layer, which uses more rigorous models that require more data from time-consuming experimentation. Screening ensures laboratory studies are focused only on options showing the greatest potential. To simplify the screening, outputs of production level, cost and time are combined into a single value using multi-attribute-decision-making techniques. The methodology was illustrated by evaluating alternatives to an FDA (U.S. Food and Drug Administration)-approved process manufacturing rattlesnake antivenom. Currently, antivenom antibodies are recovered from ovine serum by precipitation/centrifugation and proteolyzed before chromatographic purification. Alternatives included increasing the feed volume, replacing centrifugation with microfiltration and replacing precipitation/centrifugation with a Protein G column. The best alternative used a higher feed volume and a Protein G step. By rapidly evaluating the attractiveness of options, the methodology facilitates efficient and cost-effective process development.
authors.affiliation: Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK. chhatre@ucl.ac.uk
authors.forename: Sunil
authors.initials: S
authors.lastname: Chhatre
authors.forename: Richard
authors.initials: R
authors.lastname: Francis
authors.forename: Kieran
authors.initials: K
authors.lastname: O'Donovan
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Titchener-Hooker
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Newcombe
authors.forename: Eli
authors.initials: E
authors.lastname: Keshavarz-Moore
mesh_terms: D001702:Biopharmaceutics / Q000379:methods*; D003198:Computer Simulation; D007221:Industry / Q000379:methods*; D008954:Models, Biological; D008956:Models, Chemical; D018803:Models, Economic; D010865:Pilot Projects; D012984:Software