title: A decision-support model for evaluating changes in biopharmaceutical manufacturing processes.
abstract: A simulation is described that evaluates the impacts of altering bio-manufacturing processes. Modifications designed to improve production levels, times and costs were assessed, including increasing feed volumes/titres, replacing initial downstream stages with packed or expanded bed affinity steps and removing ion exchange steps. Options were evaluated for manufactured product mass, COG, batch times and development costs and timescales. Metrics were combined using multi-attribute-decision-making techniques generating a single assessment metric for each option. The utility of this approach was illustrated by application to an FDA-approved process manufacturing rattlesnake anti-venom (Protherics U.K.). Currently, ovine serum containing anti-venom IgG is purified by precipitation/centrifugation, prior to antibody proteolysis by papain. An ion exchanger removes F(C), before affinity chromatography yields the final anti-venom. An expanded bed affinity column operating with an 80% higher IgG titre, 66% higher feed volume and without the ion exchanger delivered the best multi-attribute-decision-making value, potentially providing the most desirable alternative.
authors.affiliation: The Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK.
authors.forename: S
authors.initials: S
authors.lastname: Chhatre
authors.forename: R
authors.initials: R
authors.lastname: Francis
authors.forename: K
authors.initials: K
authors.lastname: O'Donovan
authors.forename: N J
authors.initials: NJ
authors.lastname: Titchener-Hooker
authors.forename: A R
authors.initials: AR
authors.lastname: Newcombe
authors.forename: E
authors.initials: E
authors.lastname: Keshavarz-Moore
mesh_terms: D001702:Biopharmaceutics / Q000379:methods* / Q000639:trends; D003198:Computer Simulation; D004345:Drug Industry / Q000639:trends; D007074:Immunoglobulin G / Q000276:immunology; D015203:Reproducibility of Results
chemical_list: D007074:Immunoglobulin G