Farid, Suzanne; (2002) A decision-support tool for simulating the process and business perspectives of biopharmaceutical manufacture. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

With intensified competition in the biopharmaceutical industry, companies are facing conflicting pressures to compress drug development timescales and achieve cost reduction. This has triggered renewed interest in manufacturing and its contribution to a company's business performance. Computer simulation tools can help to bridge the gap between the process and business aspects of manufacturing. This thesis explores the possibility of creating a prototype decision-support tool that accomplishes this integration as well as incorporating risk analysis. An investigation of the commercial production methods for monoclonal antibodies enabled a generic process to be defined that was subsequently used as a basis for the unit operations to be incorporated into the tool. The tool, designated SIMBIOPHARMA, was built on top of G2 (Gensym Corporation, Cambridge, MA), an object-oriented programming environment. It provided a unique hierarchical framework for modelling both the operational and financial perspectives of biopharmaceutical batch manufacturing processes. The application of the tool for evaluating manufacturing strategies under uncertainty was demonstrated via case studies that focused on the large-scale production of therapeutic monoclonal antibodies using mammalian cell culture processes. The tool was used to address whether start-up companies should invest in a stainless steel pilot plant or use disposable equipment for early clinical trial material preparation. The cases utilised the Monte Carlo simulation technique to imitate the randomness inherent in manufacturing subject to uncertainties in product demand, titre and market success. The analyses highlighted the impact of each manufacturing option on the cost of goods and project throughput and the likelihood that they exceeded a critical threshold. Finally, a technique to combine the simulation results from the tool with other criteria pertinent to the decision was investigated using a multi-attribute decision-making technique that was extended to allow for uncertainty in parameters. The work in this thesis highlighted the benefits of adopting an integrated approach to the process-business interface in biopharmaceutical manufacture, so as to enhance the quality of decision-making and achieve cost-effective manufacture.

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