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A Software Tool for Assessing the Financial and Technical Impacts of Changing Industrial Bio-Manufacturing Processes

Sunil A. Chhatre1, Richard Francis2, Kieran O'Donovan2, Nigel Titchener-Hooker1, Anthony R. Newcombe2, and Eli Keshavarz-Moore1. (1) The Advanced Centre for Biochemical Engineering, University College London, Torrington Place, London, United Kingdom, (2) Process Development Group, Protherics U.K. Limited, Blaenwaun, Ffostrasol, Llandysul, Wales, United Kingdom

Growing pressures in the bioprocess industries are driving the need for simulations that rapidly evaluate strategies for achieving improvements in large-scale production. This paper presents a prototype simulation that evaluates the financial and technical impacts of developing and implementing a range of manufacturing changes to a pre-existing industrial process. The simulation evaluates each option with respect to development costs and timescales as well as annual production mass, cost of goods and batch times. These metrics are integrated together using a multi-attribute decision making (MADM) technique to produce a single value that quantitatively evaluates each strategy. The methodology is applied to development strategies being considered for an industrial process operated by Protherics U.K. Limited that manufactures an FDA-approved polyclonal Fab preparation for the treatment of rattlesnake envenomation. In the current process, an ovine serum feed containing anti-venom IgG is subjected to sodium sulphate precipitation to sediment the antibodies. The precipitate is separated from the contaminating supernatant by disk stack centrifugation, after which the IgG molecules are enzymatically digested by papain into their Fab and Fc components. The latter is removed from the process stream by passing it through an ion exchange column, after which the venom-specific Fab is recovered in an affinity step. Process changes considered include replacing the precipitation and centrifugation stages by a synthetic Protein A column step operating in either packed or expanded modes, eliminating the ion exchanger, raising the volume of the ovine feed and increasing the venom-specific IgG titre. Of all the changes examined, using an expanded bed column with the highest increase in IgG titre that could be achieved and the greatest feed volume that could be handled within the facility, combined with the elimination of the ion exchanger results in the best MADM-based value. This would therefore be the most desirable alternative to current operation.