title: Closed-loop optimization of chromatography column sizing strategies in biopharmaceutical manufacture.
abstract: BACKGROUND
  This paper considers a real-world optimization problem involving the identification of cost-effective equipment sizing strategies for the sequence of chromatography steps employed to purify biopharmaceuticals. Tackling this problem requires solving a combinatorial optimization problem subject to multiple constraints, uncertain parameters, and time-consuming fitness evaluations.
  
  
  RESULTS
  An industrially-relevant case study is used to illustrate that evolutionary algorithms can identify chromatography sizing strategies with significant improvements in performance criteria related to process cost, time and product waste over the base case. The results demonstrate also that evolutionary algorithms perform best when infeasible solutions are repaired intelligently, the population size is set appropriately, and elitism is combined with a low number of Monte Carlo trials (needed to account for uncertainty). Adopting this setup turns out to be more important for scenarios where less time is available for the purification process. Finally, a data-visualization tool is employed to illustrate how user preferences can be accounted for when it comes to selecting a sizing strategy to be implemented in a real industrial setting.
  
  
  CONCLUSIONS
  This work demonstrates that closed-loop evolutionary optimization, when tuned properly and combined with a detailed manufacturing cost model, acts as a powerful decisional tool for the identification of cost-effective purification strategies. © 2013 The Authors. Journal of Chemical Technology & Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
authors.affiliation: The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London Torrington Place, London, WC1E 7JE, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Allmendinger
authors.affiliation: The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London Torrington Place, London, WC1E 7JE, UK.
authors.forename: Ana S
authors.initials: AS
authors.lastname: Simaria
authors.affiliation: MedImmune Limited, Milstein Building Granta Park, Cambridge, CB1 6GH, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Turner
authors.affiliation: The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London Torrington Place, London, WC1E 7JE, UK.
authors.forename: Suzanne S
authors.initials: SS
authors.lastname: Farid
keywords: antibody purification technologies; biopharmaceutical manufacture; closed-loop optimization; downstream processing design; evolutionary computation; process economics