Application of a Decision-Support Tool to Assess Pooling Strategies in Perfusion Culture Processes under Uncertainty

Authors

  • Ai Chye Lim,

    1. The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK
    Search for more papers by this author
  • Yuhong Zhou,

    1. The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK
    Search for more papers by this author
  • John Washbrook,

    1. Department of Computer Science, University College London, Gower Street, London WC1E 6BT, UK
    Search for more papers by this author
  • Andrew Sinclair,

    1. Biopharm Services Ltd., Lancer House, East Street, Chesham, Bucks HP5 1DG, UK
    Search for more papers by this author
  • Brendan Fish,

    1. Cambridge Antibody Technology, Milstein Building, Granta Park, Cambridge CB1 6GH, UK
    Search for more papers by this author
  • Richard Francis,

    1. Protherics Plc, 2 Burgon Street, London EC4V 5DR, UK
    Search for more papers by this author
  • Nigel John Titchener-Hooker,

    1. The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK
    Search for more papers by this author
  • Suzanne S. Farid

    Corresponding author
    1. The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK
    • The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK. Tel: +44 (0)20 7679 4415. Fax: +44 (0)20 7916 3943
    Search for more papers by this author

Abstract

Biopharmaceutical manufacture is subject to numerous risk factors that may affect operational costs and throughput. This paper discusses the need for incorporating such uncertainties in decision-making tools in order to reflect the inherent variability of process parameters during the operation of a biopharmaceutical plant. The functionalities of a risk-based prototype tool to model cost summation, perform mass balance calculations, simulate resource handling, and incorporate uncertainties in order to evaluate the potential risk associated with different manufacturing strategies are demonstrated via a case study. The case study is based upon the assessment of pooling strategies in the perfusion culture of mammalian cells to deliver a therapeutic protein for commercial use. Monte Carlo simulations, which generate random sample behaviors for probabilistic factors so as to imitate the uncertainties inherent in any process, have been applied. This provides an indication of the range of possible output values and hence enables trends or anomalies in the expected performance of a process to be determined.

Ancillary