title: Application of a decision-support tool to assess pooling strategies in perfusion culture processes under uncertainty.
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.
authors.affiliation: The Advanced Centre for Biochemical Engineering, Department of Biochemical Engineering, University College London, Torrington Place, London WC1E 7JE, UK.
authors.forename: Ai Chye
authors.initials: AC
authors.lastname: Lim
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhou
authors.forename: John
authors.initials: J
authors.lastname: Washbrook
authors.forename: Andrew
authors.initials: A
authors.lastname: Sinclair
authors.forename: Brendan
authors.initials: B
authors.lastname: Fish
authors.forename: Richard
authors.initials: R
authors.lastname: Francis
authors.forename: Nigel John
authors.initials: NJ
authors.lastname: Titchener-Hooker
authors.forename: Suzanne S
authors.initials: SS
authors.lastname: Farid
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001709:Biotechnology / Q000191:economics / Q000295:instrumentation / Q000379:methods* / Q000458:organization & administration; D002478:Cells, Cultured; D003365:Costs and Cost Analysis; D003657:Decision Making; D004345:Drug Industry / Q000191:economics / Q000295:instrumentation / Q000379:methods* / Q000458:organization & administration; D004355:Drug Stability; D008322:Mammals; D009010:Monte Carlo Method; D010477:Perfusion
chemical_list: D000911:Antibodies, Monoclonal